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Clinics, Volume: 76, Published: 2021
  • Scarce Resource Allocation for Critically ill Patients During the COVID-19 Pandemic: A Public Health Emergency in São Paulo Brazil Editorial

    Lin, Chin An; Franco, Juliana Bertoldi; da Costa Ribeiro, Sabrina Correa; Dadalto, Luciana; Letaif, Leila Suemi Harima
  • Relationship between the coronavirus disease 2019 pandemic and immobilization syndrome Editorial

    Plapler, Pérola Grinberg; Souza, Daniel Rubio de; Kaziyama, Helena Hideko Seguchi; Battistella, Linamara Rizzo; Barros-Filho, Tarcisio Eloy Pessoa de
  • Information technology challenges in a public hospital during the COVID-19 pandemic Editorial

    Yamamoto, Jorge Futoshi; Souza, Izabel Oliva Marcílio de; Letaif, Leila Suemi Harima; Cobello-Júnior, Vilson
  • Decreased Glasgow Coma Scale score in medical patients as an indicator for intubation in the Emergency Department: Why are we doing it? Editorial

    Ribeiro, Sabrina Correa da Costa
  • Reopening borders: protocols for resuming travel during the COVID-19 pandemic Editorial

    Nali, Luiz Henrique da Silva; Salvador, Felipe Scassi; Bonani, Graciela dos Santos Soares; Andrade Júnior, Heitor Franco de; Luna, Expedito José de Albuquerque; Fujita, Dennis Minoru
  • Insights into the Classification of Cardiomyopathies: Past, Present, and Future Directions Editorial

    Salemi, Vera Maria Cury; Mohty, Dania; Altavila, Sonia Lages Lustosa de; Melo, Marcelo Dantas Tavares de; Kalil Filho, Roberto; Bocchi, Edimar Alcides
  • Considerations about ethical and legal aspects at the end of life during the COVID-19 pandemic Editorial

    Miziara, Ivan Dieb; Miziara, Carmen Silvia Molleis Galego
  • Guselkumab: widened action in psoriatic disease Editorial

    Arnone, Marcelo; Carvalho, André Vicente Esteves de; Fabricio, Lincoln Zambaldi; Romiti, Ricardo
  • Global Health in the medical curriculum Editorial

    Gouveia, Nelson; Ayres, José Ricardo de Carvalho Mesquita
  • Lessons learned from a home-based exercise program for adolescents with pre-existing chronic diseases during the COVID-19 quarantine in Brazil Editorial

    Marques, Isabela Gouveia; Astley, Camilla; Sieczkowska, Sofia Mendes; Iraha, Amanda Yuri; Franco, Tathiane Christine; Smaira, Fabiana Infante; Mazzolani, Bruna Caruso; Miranda, Luana Cristina do Amaral; Ihara, Bianca Pires; Pereira, Rosa Maria R.; Queiroz, Ligia Bruni; Silva, Clovis Artur; Gualano, Bruno
  • Energy-based devices in gynecology: the new frontier for the treatment of genitourinary syndrome of postmenopause? Editorial

    Soares-Júnior, José Maria; Barbosa, Maricy Tacla Alves; Aguiar, Lana Maria; Seganfredo, Isadora Braga; Pereyra, Elsa Aida Gay de; Melo, Nilson Roberto de; Haddad, Jorge Milhem; Baracat, Edmund Chada
  • Obstetric Observatory BRAZIL - COVID-19: 1031 maternal deaths because of COVID-19 and the unequal access to health care services Editorial

    Francisco, Rossana Pulcineli Vieira; Lacerda, Lucas; Rodrigues, Agatha S.
  • CoronaVac can induce the production of anti-SARS-CoV-2 IgA antibodies in human milk Editorial

    Calil, Valdenise Martins Laurindo Tuma; Palmeira, Patricia; Zheng, Yingying; Krebs, Vera Lúcia Jornada; Carvalho, Werther Brunow de; Carneiro-Sampaio, Magda
  • Cardiac manifestations in pediatric COVID-19 Editorial

    Capucho, Ana Carolina Marques do Vale; Resende, Paola Laureza Silva; Mascarenhas, Daniel Alves; Silva, Camila Lino Martins Rodrigues da; Sawamura, Karen Saori Shiraishi; Menezes, Carolina da Rocha Brito; Diniz, Maria de Fátima Rodrigues; Lianza, Alessandro Cavalcanti; Carvalho, Werther Brunow de; Silva, Clovis Artur Almeida da; Leal, Gabriela Nunes
  • Lock or Down: Effectiveness of Isolation Measures Against COVID-19 Editorial

    Fujita, Dennis Minoru; Nali, Luiz Henrique da Silva; Salvador, Felipe Scassi; Luna, Expedito José de Albuquerque
  • Reflections on the need for a vaccine strategy against COVID-19 for pregnant and postpartum women Editorial

    Cabar, Fábio Roberto; Francisco, Rossana Pulcineli Vieira
  • New paths in pediatrics - The implementation of a Unit of Integrative Pediatrics at the Institute of Children and Adolescents, University of Sao Paulo Editorial

    Pasqualucci, Paula Lage; Polastrini, Rita Tiziana Verardo; Seifert, Georg; Carneiro-Sampaio, Magda; Odone Filho, Vicente; Santos, Angélica Carreira dos
  • Scientific legacy of COVID-19 at the FMUSP-HC academic health system: current status and implications for the future Editorial

    Busatto, Geraldo Filho; Silva, Clovis Artur; Pereira, Antonio José Rodrigues; Bonfá, Eloisa; Barros-Filho, Tarcísio Eloy Pessoa de
  • Association of serum chemokine ligand 21 levels with asthma control in adults Original Article

    Lou, Yueyan; Zheng, Yu; Xu, Yanhua; Lu, Hui; Wang, Yiwei; Guo, Yinshi

    Abstract in English:

    OBJECTIVES: The chemokine ligand (CCL) 21 regulates the maturation, migration, and function of dendritic cells, and has been implicated in the pathogenesis of asthma. This study aimed to investigate the association between serum CCL21 levels and asthma control. METHODS: The serum levels of CCL21 and other inflammatory cytokines were analyzed in patients with asthma (n=44) and healthy controls (n=35) by enzyme-linked immunosorbent assay. IgE levels and eosinophil counts were determined by turbidimetric inhibition immunoassay and fully automatic blood analysis, respectively. The Asthma Control Test (ACT) questionnaire was used, and spirometry and fractional exhaled nitric oxide (FENO) measurements were performed. A multiple unpaired Student’s t-test was performed to analyze the differences in CCL21 and interleukin levels between patients with asthma and healthy controls. The correlation of CCL21 levels with disease severity was evaluated using the Pearson’s rank correlation test. RESULTS: Serum CCL21 levels were lower in patients with asthma (254.78±95.66 pg/mL) than in healthy controls (382.95±87.77 pg/mL) (p<0.001). Patients with asthma had significantly higher levels of IL-1β (19.74±16.77 vs. 2.63±5.22 pg/mL), IL-6 (7.55±8.65 vs. 2.37±2.47 pg/mL), and tumor necrosis factor-α (12.70±12.03 vs. 4.82±3.97 pg/mL) compared with the controls. CCL21 levels were positively correlated with the ACT score (rs=0.1653, p=0.0062), forced expiratory volume in 1s (FEV1)/forced vital capacity (rs=0.3607, p<0.0001), and FEV1 (rs=0.2753, p=0.0003), and negatively correlated with FENO (rs=0.1060, p=0.0310). CCL21 levels were negatively correlated with serum IgE levels (rs=0.1114, p=0.0268) and eosinophil counts (rs=0.3476, p<0.0001). CONCLUSIONS: Serum CCL21 levels may be a new biomarker for assessing asthma control.
  • Symptoms of anxiety and depression and their relationship with barriers to physical activity in patients with intermittent claudication Original Article

    Ragazzo, Luciana; Puech-Leao, Pedro; Wolosker, Nelson; de Luccia, Nelson; Saes, Glauco; Ritti-Dias, Raphael M.; Cucato, Gabriel Grizzo; Ferreira Kamikava, Debora Yumi; Zerati, Antonio Eduardo

    Abstract in English:

    OBJECTIVES: Although the practice of physical exercise in patients with intermittent claudication (IC) is often encouraged, adherence is low. The difficulty in performing physical training may be related to the psychological characteristics of patients with claudication. To verify the association between anxiety and depression symptoms and barriers to physical exercise and walking capacity in patients with IC. METHODS: One-hundred and thirteen patients with a clinical diagnosis of IC were included in the study. Patients underwent clinical evaluation by a vascular surgeon, answered the Beck Depression Inventory, and Beck Anxiety Inventory tests were applied by the psychologist. The patients performed the 6-minute test and reported their barriers to physical activity practice in a questionnaire. RESULTS: Patients with signs of depression had a shorter pain-free walking distance (p=0.015) and total walking distance (p=0.035) compared to patients with no signs of depression. Pain-free walking distance (p=0.29) and total walking distance (p=0.07) were similar between patients with and without signs of anxiety. Patients with symptoms of moderate to severe depression reported more barriers to physical activity practice compared to patients without signs of depression. CONCLUSION: Symptoms of anxiety and depression are prevalent among patients with peripheral arterial occlusive disease (PAD). Depression symptoms are associated with personal barriers to exercise, while anxiety symptoms are not. The main barriers to physical activity among patients with IC are exercise-induced pain and the presence of other diseases.
  • Obesity as an additional factor for autonomic imbalance and poor sleep behavior in chronic obstructive pulmonary disease: a case-control study Original Article

    Mostarda, Cristiano; Barboza, Catarina de Andrade; Cutrim, Ana Lídia; Silva-Filho, Antonio Carlos; Dias, Carlos José; Brito-Monzani, Janaina De Oliveira; Rodrigues, Bruno

    Abstract in English:

    OBJECTIVES: We compared the autonomic modulation and sleep behavior of eutrophic and overweight patients with chronic obstructive pulmonary disease (COPD). METHODS: COPD participants were divided into the overweight and eutrophic groups. Pulmonary function, blood pressure, body composition, autonomic modulation, and the Pittsburgh Sleep Quality Index score were assessed. Participants performed the six-minute walk test for functional assessment. RESULTS: Spirometric variables obtained in eutrophic and overweight individuals with COPD showed no statistically different results. We observed that the SDNN index indicated lower overall variability (p=0.003), and root mean square of successive differences between normal heart beats (RMSSD) (p=0.04) indicated lower parasympathetic modulation in the overweight group than observed in the eutrophic group. The indexes of the frequency domain presented lower values of total variability (p<0.01), low frequency bands (p<0.01), and high frequency (p=0.02), suggesting a higher sympathetic modulation and reduced parasympathetic modulation of the overweight group compared to eutrophic group. The overweight group also showed reduced sleep quality than the eutrophic group. CONCLUSION: Overweight COPD patients showed lower autonomic modulation and impaired sleep quality, latency, and efficiency as compared eutrophic subjects. These results reinforce the importance of weight control and the acquisition of healthy habits in this population.
  • Clinical Efficacy of Controlled-Release Morphine Tablets Combined with Celecoxib in Pain Management and the Effects on WNK1 Expression Original Article

    Li, Jian; Luan, Fanghai; Song, Jiangfeng; Dong, Jianhua; Shang, Mingfu

    Abstract in English:

    OBJECTIVES: This study was designed to evaluate the clinical efficacy of controlled-release morphine tablets combined with celecoxib in relieving osteocarcinoma-related pain and the effects of the combination on WNK1 expression. METHODS: A total of 110 patients with osteocarcinoma-related pain were selected and divided into two groups based on the treatment administered, including the control group (treated with controlled-release morphine tablets alone) and the study group (treated with a combination of controlled-release morphine tablets and celecoxib). We compared the treatment efficacy, pain level (visual analog scale (VAS)), time of onset of breakthrough pain (BTP), dose of morphine, incidence of adverse events, quality of life (QOL) score, and With-no-lysine 1 (WNK1) expression in the peripheral blood (PB) as determined with qRT-PCR before and after treatment, of the two groups. RESULTS: The total effective rate of the study group was higher than that of the control group, while the VAS score, time of onset of BTP, dose of morphine, incidence of adverse events, QOL score, and relative WNK1 expression in the PB were lower than those of the control group (p<0.05). CONCLUSION: Combination treatment with controlled-release morphine tablets and celecoxib can be extensively used in the clinical setting because it effectively improves the symptoms, QOL score, and adverse effects in patients with osteocarcinoma-related pain.
  • Effects of sympathectomy on myocardium remodeling and function Original Article

    Jordão, Maurício Rodrigues; Pessoa, Fernanda G.; Fonseca, Keila C.B.; Zanoni, Fernando; Salemi, Vera M.C.; Souza, Leandro E.; Ribeiro, Orlando N.; Fernandes, Fábio; Irigoyen, Maria Claudia; Moreira, Luiz Felipe P.; Mady, Charles; Ramires, Felix Jose Alvarez

    Abstract in English:

    OBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.
  • Hemodynamics and cardiac autonomic modulation after an acute concurrent exercise circuit in older individuals with pre- to established hypertension Original Article

    Cordeiro, Ricardo; Mira, Pedro Augusto; Monteiro, Walace; Cunha, Felipe; Laterza, Mateus C.; Pescatello, Linda S.; Martinez, Daniel G.; Farinatti, Paulo

    Abstract in English:

    OBJECTIVES: Few studies have investigated whether post-exercise hypotension (PEH) after concurrent exercise (CEX) is related to changes in cardiac output (Q) and systemic vascular resistance (SVR) in older individuals. We tested whether PEH after a single bout of CEX circuits performed in open-access facilities at the Third Age Academies (TAA) in Rio de Janeiro City (Brazil) would be concomitant with decreased Q and SVR in individuals aged ≥60 years with prehypertension. Moreover, we assessed autonomic modulation as a potential mechanism underlying PEH. METHODS: Fourteen individuals (age, 65.8±0.9 y; systolic/diastolic blood pressure [SBP/DBP], 132.4±12.1/72.8±10.8 mmHg; with half of the patients taking antihypertensive medications) had their blood pressure (BP), heart rate (HR), Q, SVR, HR variability (HRV), and spontaneous baroreflex sensitivity (BRS) recorded before and 50 min after CEX (40-min circuit, including seven stations of alternate aerobic/resistance exercises at 60-70% HR reserve) and non-exercise control (CONT) sessions. The study protocol was registered in a World Health Organization-accredited office (Trial registration RBR-7BWVPJ). RESULTS: SBP (Δ=−14.2±13.1 mmHg, p=0.0001), DBP (Δ=−5.2±8.2 mmHg, p= 0.04), Q (Δ=−2.2±1.5 L/min, p=0.0001), and BRS (Δ=−3.5±2.6 ms/mmHg; p=0.05) decreased after CEX as compared with the CONT session. By contrast, the HR increased (Δ=9.4±7.2 bpm, p<0.0001), and SVR remained stable throughout the postexercise period as compared with the CONT session (Δ=0.10±0.22 AU, p=0.14). We found no significant difference between the CEX and CONT with respect to the HRV indexes reflecting autonomic modulation. CONCLUSION: CEX induced PEH in the older individuals with prehypertension status. At least in the first 50 min, PEH occurred parallel to the decreased Q and increased HR, while SVR was not different. The changes in autonomic outflow appeared to be unrelated to the acute cardiac and hemodynamic responses.
  • Implications for Clinical Practice from a Multicenter Survey of Heart Failure Management Centers Original Article

    Bocchi, Edimar Alcides; Moreira, Henrique Turin; Nakamuta, Juliana Sanajotti; Simões, Marcus Vinicius; ,

    Abstract in English:

    OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.
  • Radiotherapy for early and advanced stages Follicular Lymphoma Original Article

    Mauro, Geovanne Pedro; Medici, Carolina Trindade Mello; Casimiro, Lucas Coelho; Weltman, Eduardo

    Abstract in English:

    OBJECTIVES To evaluate the results of radiotherapy (RT) for follicular lymphoma (FL) under different management scenarios. METHODS We retrospectively assessed consecutive patients with FL who had undergone irradiation between 2010 and 2018. All patients had biopsy-proven FL and were positron emission tomography-staged, although some (35.3%) were reassessed with computed tomography after treatment alone. Rituximab was only available to FL patients after 2016. RESULTS Thirty-four patients were selected, with a mean age at diagnosis of 61.6 years (34-89 years). The median follow-up duration was 49.4 months. Most patients were female (58.8%) and showed good performance on the Eastern Cooperative Oncology Group (ECOG) scale (ECOG 0-55.9%). The mean overall survival (OS) and progression-free survival were 48.7 and 33.6 months, respectively, with four deaths reported. OS rates at 2 and 3 years were 94.1% and 91.2%, respectively. Four patients showed transformation into aggressive lymphomas and underwent rituximab-based systemic treatment. Transformation-free survival was 47.8 months, and all patients with transformed disease were alive at assessment. Five patients had in-field relapse, all of them also relapsed elsewhere, and the mean relapse-free survival time was 40.3 months. No median end points were reached on assessment. CONCLUSION FL is an indolent disease. Our findings show good outcomes for patients treated with radiation, with a low transformation rate and excellent management of relapsed disease. RT is an important part of these results.
  • Comparison of Different Ultrasound Classification Systems of Thyroid Nodules for Identifying Malignant Potential: A Cross-sectional Study Original Article

    Chen, Hua; Ye, Jun; Song, Jianming; You, Yuguang; Chen, Weihua; Liu, Yanna

    Abstract in English:

    OBJECTIVE: In our organization, it has been necessary in our organization to calculate the risk categories according to the American Thyroid Association (ATA), the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) classification systems for each patient, from the year 2019; these are also required to be registered in the database. This creates a barrier to medical collaboration in everyday radiological practice because using multiple rating systems can be confusing for both readers and patients. For the change in routine practice, this study aimed to compare diagnostic parameters of the ATA, AACE/ACE/AME, and ACR TIRADS classification systems for the detection of suspicious thyroid nodule(s) considering the results of fine-needle aspiration cytopathology as the reference standard. METHODS: Data on ultrasound characteristics (2,000 nodules) and fine-needle aspiration cytopathology (39 nodules) were included in the analysis. The decision making of fine-needle aspiration biopsies was evaluated from the ultrasound characteristics as per the ATA, AACE/ACE/AME, and ACR TIRADS classification systems. RESULTS: The ATA, AACE/ACE/AME, and ACR TIRADS recommended 26, 32, and 37 nodules for fine-needle aspiration biopsies, respectively. Considering the results of fine-needle aspiration cytopathology as the reference standard, the ATA, AACE/ACE/AME, and ACR TIRADS classification systems had 0.993, 0.996, and 0.998 sensitivity, respectively. The accuracies were 0.641, 0.795, and 0.923, respectively. CONCLUSION: The ACR TIRADS classification system is less invasive and can identify suspicious nodules more accurately than that of ATA and AACE/ACE/AME.
  • miRNA-195 expression in the tumor tissues of female Brazilian breast cancer patients with operable disease Original Article

    de Sales, Alexandre Cesar Vieira; da Silva, Isaura Isabelle Fonseca Gomes; Leite, Matheus Carvalho Brito; de Lima Coutinho, Leandro; de Albuquerque Cavalcante Reis, Renata Bezerra; Martins, Danyelly Bruneska Gondin; de Lima Filho, José Luiz; Oliveira Souto, Fabrício

    Abstract in English:

    OBJECTIVE: This study aimed to assess miRNA-195 expression in the tumor tissues from a cohort of Brazilian female breast cancer patients undergoing neoadjuvant chemotherapy (NAC) and evaluate its correlation with various clinicopathological markers. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the miRNA-195 expression in tumor tissues from a cohort of female breast cancer patients undergoing NAC. This expression was then correlated with the occurrence of several distinct breast cancer molecular subtypes and other clinicopathological variables. RESULTS: A total of 55 patients were included in this study, 28 (50.9%) of whom were treated using NAC. Tumor miRNA-195 expression was suppressed in breast cancer patients, regardless of their exposure to systemic treatments, histological grade, size, nodal status, and tumor-node-metastasis (TNM) staging. This was more pronounced in luminal and triple-negative patients, and patient’s response to NAC was correlated with an increase in miRNA-195 expression. CONCLUSION: miRNA-195 is downregulated in the tumor tissues of Brazilian breast cancer patients regardless of NAC exposure; this reinforces its role as a tumor suppressor and a potential biomarker for chemotherapy response.
  • Exploration of the risk factors of essential hypertension with hyperhomocysteinemia: A hospital-based study and nomogram analysis Original Article

    Wang, Jufang; Du, Jinman; Fan, Rui

    Abstract in English:

    OBJECTIVES: To explore the risk factors of essential hypertension with hyperhomocysteinemia (H-type hypertension) and design a nomogram to predict this risk. METHODS: A hospital-based study was conducted on 1,712 individuals, including 282 patients with H-type hypertension, 105 patients with simple hypertension, 645 individuals with hyperhomocysteinemia, and 680 healthy controls. Logistic regression and nomogram models were applied to evaluate the risk factors. RESULTS: Logistic regression showed that advanced age, male sex, high body mass index (BMI), high total cholesterol levels, high glucose levels, and high creatinine levels were risk factors of H-type hypertension in the healthy population and were integrated into the nomogram model. Advanced age, male sex, high BMI, high total cholesterol levels, and high glucose levels were shown to be risk factors of H-type hypertension in the hyperhomocysteinemia population. Male sex and high creatinine levels were shown to be risk factors of H-type hypertension in the hypertension population. Nomogram analysis showed that the total factor score ranged from 106 to 206, and the corresponding risk rate ranged from 0.05 to 0.95. CONCLUSIONS: Men are more likely to have H-type hypertension, and advanced age, high BMI, high total cholesterol levels, and high glucose levels are risk factors of H-type hypertension in healthy and hyperhomocysteinemia populations. Furthermore, high creatinine level is a risk factor of H-type hypertension in healthy and hypertension populations. Nomogram models may be used to intuitively evaluate H-type hypertension risk and provide a basis for personalized interventions.
  • Thoracic aortic size in Brazilian smokers: measures using low-dose chest computed tomography anatomical and epidemiological assessment Original Article

    Lembrança, Lucas; Teivelis, Marcelo Passos; Tachibana, Adriano; dos Santos, Ricardo Sales; Joo, Richard Wonuh; Zippo, Emanuela; Wolosker, Nelson

    Abstract in English:

    OBJECTIVES: Thoracic aortic aneurysms (TAAs) represent one-third of the hospitalizations for aortic diseases. The prevalence rate depends on the definition of the normal size of the aorta, which is quite variable, depending on the population studied. The aim of this study was to evaluate the characteristics of the thoracic aorta of Brazilian smokers, identifying the normal size of the aorta, presence of anatomical variations, and prevalence of TAA. MATERIALS AND METHODS: A total of 711 patients underwent radiological evaluation with low-dose computed tomography (CT) from January 2013 to July 2014 with the initial objective of lung nodule tracking. Two examiners evaluated these images, and measurements of maximum and serial diameters were performed manually in true orthogonal planes. Serial diameter measurements were taken every 2 cm in the ascending aorta and 5 cm in the descending segment. We searched for anatomical variations, aortic arch type, and correlations between anatomical characteristics, sex, body mass index, and body surface area (BSA). RESULTS: The maximum diameters were 33.61 (standard deviation [SD] 3.88), 28.66 (SD 2.89), and 28.36 mm (SD 3.09) for the ascending segment, aortic arch, and descending segment, respectively. A positive correlation was found between male sex, age, and BSA and aorta diameter. The bovine arch was the most common variation of the aortic arch type, and we found one (0.14%) case of TAA. CONCLUSIONS: This study with low-dose CT allowed the determination of the mean diameters of the ascending aorta, aortic arch, and descending aorta in Brazilian smokers and TAA prevalence.
  • The mutational repertoire of uterine sarcomas and carcinosarcomas in a Brazilian cohort: A preliminary study Original Article

    da Costa, Leonardo Tomiatti; dos Anjos, Laura Gonzalez; Kagohara, Luciane Tsukamoto; Torrezan, Giovana Tardin; De Paula, Claudia A. Andrade; Baracat, Edmund Chada; Carraro, Dirce Maria; Carvalho, Katia Candido

    Abstract in English:

    OBJECTIVES: The present study aimed to contribute to the catalog of genetic mutations involved in the carcinogenic processes of uterine sarcomas (USs) and carcinosarcomas (UCSs), which may assist in the accurate diagnosis of, and selection of treatment regimens for, these conditions. METHODS: We performed gene-targeted next-generation sequencing (NGS) of 409 cancer-related genes in 15 US (7 uterine leiomyosarcoma [ULMS], 7 endometrial stromal sarcoma [ESS], 1 adenosarcoma [ADS]), 5 UCS, and 3 uterine leiomyoma (ULM) samples. Quality, frequency, and functional filters were applied to select putative somatic variants. RESULTS: Among the 23 samples evaluated in this study, 42 loss-of-function (LOF) mutations and 111 missense mutations were detected, with a total of 153 mutations. Among them, 66 mutations were observed in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. TP53 (48%), ATM (22%), and PIK3CA (17%) were the most frequently mutated genes. With respect to specific tumor subtypes, ESS showed mutations in the PDE4DIP, IGTA10, and DST genes, UCS exhibited mutations in ERBB4, and ULMS showed exclusive alterations in NOTCH2 and HER2. Mutations in the KMT2A gene were observed exclusively in ULM and ULMS. In silico pathway analyses demonstrated that many genes mutated in ULMS and ESS have functions associated with the cellular response to hypoxia and cellular response to peptide hormone stimulus. In UCS and ADS, genes with most alterations have functions associated with phosphatidylinositol kinase activity and glycerophospholipid metabolic process. CONCLUSION: This preliminary study observed pathogenic mutations in US and UCS samples. Further studies with a larger cohort and functional analyses will foster the development of a precision medicine-based approach for the treatment of US and UCS.
  • Predictors and reference equations for augmentation index, an arterial stiffness marker, in healthy children and adolescents Original Article

    Santos, Luzia Maria dos; Gomes, Isabel Cristina; Pinho, José Felippe; Neves-Alves, Claudia Marotta; Magalhães, Giselle Santos; Campagnole-Santos, Maria José; da Glória Rodrigues-Machado, Maria

    Abstract in English:

    OBJECTIVES: To investigate predictors and propose reference equations for the augmentation index normalized to 75 bpm heart rate (AIx@75) in healthy children and adolescents. METHODS: This was a cross-sectional, observational study involving 134 healthy children and adolescents aged 9 to 19 years old. Participants were categorized into child (n=53) and adolescent (n=81) groups, as well as into male (n=69) and female (n=65) groups. We evaluated AIx@75, vascular and hemodynamic parameters, anthropometric data, physical activity profile, and quality of life (Peds-QL4.0; physical, emotional, social and school domains). RESULTS: The predictors of AIx@75 in the whole sample were age, peripheral diastolic blood pressure (pDBP), mean arterial pressure, pulse pressure amplification (PPA), systolic volume (SV), cardiac index (CI), and pulse wave velocity (PWV; R2=80.47%). In the male group, the predictors of AIx@75 were SV, CI, total vascular resistence (TVR), and PWV (R2=78.56%), while in the female group, they were pDBP, PPA, SV, and PWV (R2=82.45%). In the children, they were pDBP, PPA, SV, and PWV (R2=79.17%), while in the adolescents, they were body mass index, pDBP, PPA, SV, TVR, and PWV (R2=81.57%). CONCLUSION: In the present study, we used a representative sample from Belo Horizonte to establish normality values of AIx@75. We also identified, for the first time, independent predictors of AIx@75 in healthy children and adolescents categorized by sex and age. Determining AIx@75 reference equations may facilitate the early diagnosis of preclinical atherosclerosis and allow an objective measure of the vascular effects of therapeutic interventions aimed at modifying cardiovascular risk factors.
  • Effects of Raloxifene Combined with Low-dose Conjugated Estrogen on the Endometrium in Menopausal Women at High Risk for Breast Cancer Original Article

    Carneiro, Andrea Lucia Bastos; Spadella, Ana Paula Curi; Souza, Fabiola Amaral de; Alves, Karen Borelli Ferreira; Araujo-Neto, Joaquim Teodoro de; Haidar, Mauro Abi; Dardes, Rita de Cássia de Maio

    Abstract in English:

    OBJECTIVES: To compare the effects of low-dose conjugated estrogen (CE), raloxifene, and the combination thereof on the endometrium of postmenopausal women. METHODS: Postmenopausal women between 45 and 60 years of age, with Gail score≥1.67 and no endometrial disorders, were randomly assigned to receive low-dose CE (0.3 mg), raloxifene (60 mg), or combined therapy for 1 year. Transvaginal ultrasound was performed at baseline and every 3 months; the Kupperman Index was assessed at baseline and every 6 months. Endometrial biopsies were performed if endometrial thickness (ET) was ≥5 mm or if vaginal bleeding occurred. The primary outcome was the occurrence of ET≥5 mm over the one-year period. RESULTS: Seventy-three women were randomly assigned and analyzed on an intent-to-treat basis. Eight, three, and four women in the CE, raloxifene, and combination groups, respectively, exhibited ET≥5 mm. No genital bleeding was reported in the combination group. Endometrial biopsy revealed atrophy or polyps in all groups, with one patient in the CE group exhibiting a proliferative endometrium without atypia. At 6 months, there was a progressive increase in mean ET in the CE group, but not in the other two groups, with statistically significant differences at 6, 9, and 12 months. Mean scores for vasomotor symptoms and Kupperman Index favored the CE and combination groups over raloxifene. CONCLUSION: Combined raloxifene and low-dose CE decreased the severity of menopausal symptoms to a similar extent as CE alone and had similar effects as raloxifene alone on the endometrium.
  • Trends in abdominal aortic aneurysm-related mortality in Brazil, 2000-2016: a multiple-cause-of-death study Original Article

    Santo, Augusto Hasiak; Puech-Leão, Pedro; Krutman, Mariana

    Abstract in English:

    OBJECTIVES: Remarkable changes in the epidemiology of abdominal aortic aneurysm (AAA) have occurred in many countries during last few decades, which have also affected Brazilian mortality concurrently. This study aimed to investigate mortality trends related to AAA mortality in Brazil from 2000 to 2016. METHODS: Annual AAA mortality data was extracted from the public databases of the Mortality Information System, and processed by the Multiple Cause Tabulator. RESULTS: In Brazil, 2000 through 2016, AAA occurred in 69,513 overall deaths; in 79.6% as underlying and in 20.4% as an associated cause of death, corresponding to rates respectively of 2.45, 1.95 and 0.50 deaths per 100,000 population; 65.4% male and 34.6% female; 60.6% in the Southeast region. The mean ages at death were 71.141 years overall, and 70.385 years and 72.573 years for men and women, respectively. Ruptured AAA occurred in 64.3% of the deaths where AAA was an underlying cause, and in 18.0% of the deaths where AAA was an associated cause. The standardized rates increased during 2000-2008, followed by a decrease during 2008-2016, resulting in an average annual percent change decline of -0.2 (confidence interval [CI], -0.5 to 0.2) for the entire 2000-2016 period. As associated causes, shock (39.2%), hemorrhages (33.0%), and hypertensive diseases (26.7%) prevailed with ruptured aneurysms, while hypertensive diseases (29.4%) were associated with unruptured aneurysms. A significant seasonal variation, highest during autumn and followed by in winter, was observed in the overall ruptured and unruptured AAA deaths. CONCLUSIONS: This study highlights the need to accurately document epidemiologic trends related to AAA in Brazil. We demonstrate the burden of AAA on mortality in older individuals, and our results may assist with effective planning of mortality prevention and control in patients with AAA.
  • Cognitive performance and long-latency auditory evoked potentials: a study on aging Original Article

    Oliveira, Maria de Fátima Ferreira de; Menezes, Pedro de Lemos; Carnaúba, Aline Tenório Lins; Pereira, Liliane Desgualdo; Andrade, Kelly Cristina Lira de; Frizzo, Ana Claudia Figueiredo; Soares, Ilka do Amaral

    Abstract in English:

    OBJECTIVE: To evaluate the relationship between cognitive performance and long-latency auditory evoked potentials in an elderly population. METHODS: The sample consisted of adults between 20 and 58 years of age and elderly adults between 60 and 70 years of age. The screening procedures adopted were an inspection of the external auditory canal, tonal and vocal audiometry, tympanometry, brain stem auditory evoked potential, the Montreal Cognitive Assessment test, and long-latency auditory evoked potential. RESULTS: The latency and amplitude values of cortical components by age group showed significant differences under the following conditions: (i) signals evoked by the speech stimulus /da/ and by the pure-tone stimulus at 2,000 Hz for the N2 amplitude (p=0.008 and p=0.001, respectively) , which were both higher for adults, and (ii) signals evoked by the speech stimulus /da/ for N1 latency (p=0.018) and by the pure-tone stimulus at 2,000 Hz for P2 latency (p=0.017), which were both higher in the elderly population. The cognitive component (P300) showed a significant difference when evoked by speech stimuli, with higher latency in the elderly population (p=0.013). When correlated with cognitive processes, the latency and amplitude of cortical potentials showed direct and medium-strength correlations between abnormal scores obtained on the Montreal Cognitive Assessment test and P2 amplitude (p<0.001 and r=0.452). CONCLUSION: There is a relationship between long-latency potentials and cognitive performance in the elderly, which was observed by the increase in the P2 amplitude and the impairment of the process of sound decoding.
  • Performance of mutation pathogenicity prediction tools on missense variants associated with 46,XY differences of sex development Original Article

    Montenegro, Luciana R.; Lerário, Antônio M.; Nishi, Miriam Y.; Jorge, Alexander A.L.; Mendonca, Berenice B.

    Abstract in English:

    OBJECTIVES: Single nucleotide variants (SNVs) are the most common type of genetic variation among humans. High-throughput sequencing methods have recently characterized millions of SNVs in several thousand individuals from various populations, most of which are benign polymorphisms. Identifying rare disease-causing SNVs remains challenging, and often requires functional in vitro studies. Prioritizing the most likely pathogenic SNVs is of utmost importance, and several computational methods have been developed for this purpose. However, these methods are based on different assumptions, and often produce discordant results. The aim of the present study was to evaluate the performance of 11 widely used pathogenicity prediction tools, which are freely available for identifying known pathogenic SNVs: Fathmn, Mutation Assessor, Protein Analysis Through Evolutionary Relationships (Phanter), Sorting Intolerant From Tolerant (SIFT), Mutation Taster, Polymorphism Phenotyping v2 (Polyphen-2), Align Grantham Variation Grantham Deviation (Align-GVGD), CAAD, Provean, SNPs&GO, and MutPred. METHODS: We analyzed 40 functionally proven pathogenic SNVs in four different genes associated with differences in sex development (DSD): 17β-hydroxysteroid dehydrogenase 3 (HSD17B3), steroidogenic factor 1 (NR5A1), androgen receptor (AR), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). To evaluate the false discovery rate of each tool, we analyzed 36 frequent (MAF>0.01) benign SNVs found in the same four DSD genes. The quality of the predictions was analyzed using six parameters: accuracy, precision, negative predictive value (NPV), sensitivity, specificity, and Matthews correlation coefficient (MCC). Overall performance was assessed using a receiver operating characteristic (ROC) curve. RESULTS: Our study found that none of the tools were 100% precise in identifying pathogenic SNVs. The highest specificity, precision, and accuracy were observed for Mutation Assessor, MutPred, SNP, and GO. They also presented the best statistical results based on the ROC curve statistical analysis. Of the 11 tools evaluated, 6 (Mutation Assessor, Phanter, SIFT, Mutation Taster, Polyphen-2, and CAAD) exhibited sensitivity >0.90, but they exhibited lower specificity (0.42-0.67). Performance, based on MCC, ranged from poor (Fathmn=0.04) to reasonably good (MutPred=0.66). CONCLUSION: Computational algorithms are important tools for SNV analysis, but their correlation with functional studies not consistent. In the present analysis, the best performing tools (based on accuracy, precision, and specificity) were Mutation Assessor, MutPred, and SNPs&GO, which presented the best concordance with functional studies.
  • Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats Original Article

    Chen, Danyan; Li, Li; Ren, Fang; Huang, Rongxi; Gan, Hua; Deng, Huacong; Wang, Hongman

    Abstract in English:

    OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.
  • Extracellular matrix metalloproteinase expression in endometrial tissue after arterial embolization of myomas Original Article

    Chazan, Franco Loeb; Bonetti, Tatiana C.S.; Gomes, Mariano Tamura Vieira; Fornazari, Vinicius Adami Vayego; Girão, Manoel João Batista Castello; Bonduki, Claudio Emilio

    Abstract in English:

    OBJECTIVES: Arterial embolization of myomas (AEM) is controversial because of the changes that occur in the extracellular matrix (ECM) of the endometrium and its effect on gestational success in infertile patients desiring reproductive capability. Therefore, we performed this study on the expression of genes in the ECM of the endometrium, such as those coding metalloproteinases (MMP), before and 6 months after embolization of the uterine arteries. METHODS: Seven women with leiomyomas were evaluated, and MMP3 and MMP10 levels were measured. The women underwent pelvic nuclear magnetic resonance (NMR), examination, and endometrial biopsy between the 20th and 24th day of the menstrual cycle, and pre- and post-AEM (after 6 months). For data analysis, the Cq comparative method, also known as the 2-ΔΔCT method, was used to calculate the relative quantities of MMP gene expression among the samples collected. RESULTS: There was a significant decrease by 9.52 times in the expression of MMP3 (p=0.007), and a non-significant change in the expression of MMP10 (p=0.22) in post-AEM-treated women than pre-AEM-treated women. CONCLUSIONS: The results suggest that ECM continues to undergo tissue remodeling 6 months after AEM, at least with regard to MMP3 expression, suggesting that AEM affects the ECM for at least 6 months after the procedure.
  • Polymerase chain reaction targeting 16S ribosomal RNA for the diagnosis of bacterial meningitis after neurosurgery Original Article

    Perdigão Neto, Lauro Vieira; Medeiros, Micheli; Ferreira, Suzete Cleusa; Nishiya, Anna Shoko; de Assis, Denise Brandão; Boszczowski, Ícaro; Costa, Silvia Figueiredo; Levin, Anna S.

    Abstract in English:

    OBJECTIVES: Bacterial and aseptic meningitis after neurosurgery can present similar clinical signs and symptoms. The aims of this study were to develop and test a molecular method to diagnose bacterial meningitis (BM) after neurosurgery. METHODS: A 16S ribosomal RNA gene PCR-based strategy was developed using artificially inoculated cerebrospinal fluid (CSF) followed by sequencing. The method was tested using CSF samples from 43 patients who had undergone neurosurgery and were suspected to suffer from meningitis, and from 8 patients without neurosurgery or meningitis. Patients were classified into five groups, confirmed BM, probable BM, possible BM, unlikely BM, and no meningitis. RESULTS: Among the samples from the 51 patients, 21 samples (41%) were culture-negative and PCR-positive. Of these, 3 (14%) were probable BM, 4 (19%) were possible BM, 13 (62%) were unlikely BM, and 1 (5%) was meningitis negative. Enterobacterales, non-fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii), Staphylococcus haemolyticus, Granulicatella, Variovorax, and Enterococcus cecorum could be identified. In the group of patients with meningitis, a good agreement (3 of 4) was observed with the results of cultures, including the identification of species. CONCLUSION: Molecular methods may complement the diagnosis, guide treatment, and identify non-cultivable microorganisms. We suggest the association of methods for suspected cases of BM after neurosurgery, especially for instances in which the culture is negative.
  • Efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma Original Article

    Marta, Guilherme Nader; da Fonseca, Leonardo G.; Braghiroli, Maria Ignez; Moura, Fernando; Hoff, Paulo M.; Sabbaga, Jorge

    Abstract in English:

    OBJECTIVES: To evaluate the efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma (HCC). METHODS: We analyzed data from a cohort of patients with advanced HCC treated using systemic treatment according to the local institutional protocol. Patients were divided into two groups, Group A, individuals <70 years of age, and Group B, individuals 70 years of age or older at the time of treatment initiation. Efficacy, measured based on overall survival (OS) and time to treatment failure (TTF), and toxicity were compared between groups. RESULTS: A total of 238 patients with advanced HCC who received sorafenib between 2007 and 2018 were evaluated. The median age for Group A was 59.1 years and that for Group B 73.6 years. The major prognostic characteristics were balanced between the groups. There were no significant differences in OS between Group A (8.0 months, 95%CI 6.34-9.3) and Group B (9.0 months, 95%CI 5.38-12.62), p=0.433, or in TTF between Group A (3.0 months, 95%CI 2.39-3.60) and Group B (3.0 months, 95%CI 1.68-4.32), p=0.936. There were no significant differences between Groups A and B with respect to the incidence of adverse events or treatment discontinuation because of toxicity. CONCLUSION: Efficacy and safety of sorafenib did not differ significantly between younger and older patients with HCC. Our data suggest that age alone should not restrict clinical decision-making for patients with advanced HCC.
  • Factors associated with actively working in the very long-term following acute coronary syndrome Original Article

    Nicolau, Jose C.; Furtado, Remo H.M.; Dalçóquio, Talia F.; Lara, Livia M.; Juliasz, Marcela G.; Ferrari, Aline G.; Nakashima, Carlos A.K.; Franci, Andre; Pereira, Cesar A.C.; Lima, Felipe G.; Giraldez, Roberto R.; Salsoso, Rocío; Baracioli, Luciano M.; Goodman, Shaun

    Abstract in English:

    OBJECTIVES: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS. METHODS: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed. RESULTS: The following variables were significantly and independently associated with actively working at the last contact: age>median (hazard-ratio [HR], 0.76, p<0.001); male sex (HR, 1.52, p<0.001); government health insurance (HR, 1.36, p<0.001); history of angina (HR, 0.69, p<0.001) or myocardial infarction (MI) (HR, 0.76, p=0.005); smoking (HR, 0.81, p=0.015); ST-elevation MI (HR, 0.81, p=0.021); anterior-wall MI (HR, 0.75, p=0.001); non-primary percutaneous coronary intervention (PCI) (HR, 0.77, p=0.002); fibrinolysis (HR, 0.61, p<0.001); cardiogenic shock (HR, 0.60, p=0.023); statin (HR, 3.01, p<0.001), beta-blocker (HR, 1.26, p=0.020), angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) (HR, 1.37, p=0.001) at hospital discharge; and MI at follow-up (HR, 0.72, p=0.001). The probability of not working at the last contact ranged from 24.2% for patients with no variables, up to 80% for patients with six or more variables. CONCLUSIONS: In patients discharged after ACS, prior and in-hospital clinical variables, as well as the quality of care at discharge, have a great impact on the long-term probability of actively working.
  • Mismatch negativity in older adults and its relationship with the cognitive and behavioral aspects of central auditory processing Original Article

    Brückmann, Mirtes; Pagliarin, Karina Carlesso; Garcia, Michele Vargas

    Abstract in English:

    OBJECTIVES: This study aimed to describe and compare the performance of older adults with normal hearing and hearing impairments in mismatch negativity (MMN), correlate MMN with cognitive tasks and central auditory processing (CAP), and identify normal values for MMN in older adults. METHODS: This study had 54 participants. The Montreal Cognitive Assessment (MoCA) was used to assess cognition and the random gap detection test (RGDT), dichotic digit test (DDT), and speech to noise (SN) test were used to evaluate CAP. MMN was elicited with the verbal stimulus /da/ (frequent) and /ta/ (rare), and the latency, amplitude, duration, and area were analyzed. RESULTS: When comparing the normal-hearing group to those with hearing loss, there was no significant difference in MMN. When correlating MMN with MoCA, RGDT, DDT, and the SN test, there was a weak correlation between the MMN amplitude and the RGDT and DDT. When comparing the MMN of participants with normal and altered cognitive aspects and those with normal and altered DDT, the MMN duration was found to be affected by the DDT. The mean latency value of the MMN in the normal-hearing group was 199.8 ms, the amplitude was -2.2 µV, area was 116.1 µV/ms, and duration was 81.2 ms. CONCLUSION: Mild hearing loss did not influence MMN. There was no correlation between MMN and cognitive aspects, and there were weak correlations with CAP. Alterations in CAP led to longer durations in MMN. Normal values for MMN in adults aged between 60 and 77 years were generated.
  • Positive fluid balance as an early biomarker for acute kidney injury: a prospective study in critically ill adult patients Original Article

    Ávila, Maria Olinda Nogueira; Rocha, Paulo Novis; Perez, Caio A.; Faustino, Tássia Nery; Batista, Paulo Benigno Pena; Yu, Luis; Zanetta, Dirce Maria T.; Burdmann, Emmanuel A.

    Abstract in English:

    OBJECTIVES: Positive fluid balance is frequent in critically ill patients and has been considered a potential biomarker for acute kidney injury (AKI). This study aimed to evaluate positive fluid balance as a biomarker for the early detection of AKI in critically ill patients. METHODS: This was a prospective cohort study. The sample was composed of patients ≥18 years old who stayed ≥3 days in an intensive care unit. Fluid balance, urinary output and serum creatinine were assessed daily. AKI was diagnosed by the Kidney Disease Improving Global Outcome criteria. RESULTS: The final cohort was composed of 233 patients. AKI occurred in 92 patients (40%) after a median of 3 (2-6) days following ICU admission. When fluid balance was assessed as a continuous variable, a 100-ml increase in fluid balance was independently associated with a 4% increase in the odds of AKI (OR 1.04; 95% CI 1.01-1.08). Positive fluid balance categorized using different thresholds was always significantly associated with subsequent detection of AKI. The mixed effects model showed that increased fluid balance preceded AKI by 4 to 6 days. CONCLUSION: These results suggest that a positive fluid balance might be an early biomarker for AKI development in critically ill patients.
  • Antineutrophil cytoplasmic antibody profiles differ according to type of primary sclerosing cholangitis and autoimmune hepatitis Original Article

    Crescente, Juliana Goldbaum; Dellavance, Alessandra; Diniz, Marcio Augusto; Carrilho, Flair Jose; Andrade, Luis Eduardo Coelho de; Cançado, Eduardo Luiz Rachid

    Abstract in English:

    OBJECTIVES: To determine the frequency of the antineutrophil cytoplasmic antibodies (ANCA), antiproteinase-3 and antimyeloperoxidase, in primary sclerosing cholangitis (PSC) with or without inflammatory bowel disease (IBD+ or IBD-) and in different types of autoimmune hepatitis (AIH). Additionally, to verify the agreement between ANCA patterns by indirect immunofluorescence and their antigenic specificities by ELISA. METHODS: For this study, 249 patients were enrolled (42 PSC/IBD+; 33 PSC/IBD-; 31 AIH type-1; 30 AIH type-2; 31 AIH type-3; 52 primary biliary cirrhosis; 30 healthy controls) whose serum samples were tested for ANCA autoantibodies. RESULTS: There were fewer female subjects in the PSC/IBD- group (p=0.034). Atypical perinuclear-ANCA was detected more frequently in PSC/IBD+ patients than in PSC/IBD- patients (p=0.005), and was significantly more frequent in type-1 (p<0.001) and type-3 AIH (p=0.012) than in type-2 AIH. Proteinase-3-ANCA was detected in 25 samples (only one with cytoplasmic-ANCA pattern), and more frequently in PSC/IBD+ than in PSC/IBD- patients (p=0.025). Myeloperoxidase-ANCA was identified in eight samples (none with the perinuclear-ANCA pattern). Among the 62 reactive samples for atypical perinuclear-ANCA, 13 had antigenic specific reactions for proteinase-3 and myeloperoxidase. CONCLUSIONS: PSC/IBD+ differed from PSC/IBD- in terms of sex and proteinase 3-ANCA and atypical perinuclear-ANCA reactivity, the latter of which was more frequently detected in type-1 and type-3 AIH than in type-2 AIH. There was no agreement between ANCA patterns and antigenic specificities in IBD and autoimmune liver diseases, which reinforces the need for proteinase-3 and myeloperoxidase antibody testing.
  • Endovascular correction of isolated descending thoracic aortic disease: a descriptive analysis of 1,344 procedures over 10 years in the public health system of São Paulo Original Article

    Portugal, Maria Fernanda Cassino; Teivelis, Marcelo Passos; Silva, Marcelo Fiorelli Alexandrino da; Stabellini, Nickolas; Fioranelli, Alexandre; Szlejf, Claudia; Amaro Junior, Edson; Wolosker, Nelson

    Abstract in English:

    OBJECTIVES: In Brazil, descending thoracic aorta disease (TAD), including aneurysms and dissection, are preferentially managed by endovascular treatment (TEVAR) due to the feasibility and good results of this technique. In this study, we analyzed endovascular treatment of isolated TAD (ITAD) in the public health system over a 10-year period in São Paulo, a municipality in Brazil in which more than 5 million inhabitants depend on the governmental health system. METHODS: Public data from procedures performed between 2008 and 2019 were extracted using web scraping techniques. The following types of data were analyzed: demographic data, operative technique, elective or urgent status, number of surgeries, in-hospital mortality, length of hospital stay, mean length of stay in the intensive care unit, and reimbursement values paid by the government. Trauma cases and congenital diseases were excluded. RESULTS: A total of 1,344 procedures were analyzed; most patients were male and aged ≥65 years. Most individuals had a residential address registered in the city. Approximately one-third of all surgeries were urgent cases. There were 128 in-hospital deaths (9.52%), and in-hospital mortality was lower for elective than for urgent surgeries (7.29% vs. 14.31%, p=0.031). A total of R$ 24.766.008,61 was paid; an average of R$ 17.222,98 per elective procedure and R$ 18.558,68 per urgent procedure. Urgent procedures were significantly more expensive than elective surgeries (p=0.029). CONCLUSION: Over a 10-year period, the total cost of ITAD interventions was R$ 24.766.008,61, which was paid from the governmental system. Elective procedures were associated with lower mortality and lower investment from the health system when compared to those performed in an urgent scenario.
  • Efficacy of autologous platelet-rich plasma gel in the treatment of refractory pressure injuries and its effect on wound healing time and patient quality of life Original Article

    Liu, Qian; Zhang, Ning; Li, Zhengnan; He, Hongmei

    Abstract in English:

    OBJECTIVES: To evaluate the efficacy of autologous platelet-rich plasma (PRP) gel in the treatment of refractory pressure injuries and its effect on wound healing time and quality of life of patients. METHODS: A random number table method was used to group 102 patients with refractory pressure injuries into either a control group (CG) (51 cases) receiving negative pressure wound therapy (NPWT) or a study group (SG) (51 cases) receiving NPWT+PRP gel. RESULTS: The total efficacy rate in the SG (92.16%) was higher than that in the CG (76.47%) (p<0.05). The SG exhibited lower visual analog scale (VAS) scores and pressure ulcer scale for healing (PUSH) scores, smaller wound sizes and depths, and shorter wound healing times than the CG after 21 days of treatment (p<0.05). After 6 months of treatment, the SG scored higher than the CG on the psychological, physiological, social functions, and daily activity domains on the World Health Organization Quality of Life (WHOQOL-BREF) scale (p<0.05). The incidence of postoperative complications in the SG (13.73%) was not significantly different from that of the CG (7.84%) (p>0.05). CONCLUSION: In the treatment of refractory pressure injuries, PRP gel can accelerate wound healing, reduce wound pain, shorten the treatment cycle, regulate tissue inhibitor matrix metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9) levels and the expression of specific proteins in granulation tissue, reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-8, and tumor necrosis factor-α (TNF-α), and improve the quality of life of patients without increasing complications.
  • Cost-Effective Trap qPCR Approach to Evaluate Telomerase Activity: an Important Tool for Aging, Cancer, and Chronic Disease Research Original Article

    Pinto, Thalyta Nery Carvalho; Fernandes, Juliana Ruiz; Arruda, Liã Barbara; Duarte, Alberto José da Silva; Benard, Gil

    Abstract in English:

    OBJECTIVES: Telomeres are a terminal “DNA cap” that prevent chromosomal fusion and degradation. However, aging is inherent to life, and so is the loss of terminal sequences. Telomerase is a specialized reverse transcriptase encoded by self-splicing introns that counteract chromosome erosion. Telomerase activity is observed during early embryonic development, but after the blastocyst stage, the expression of telomerase reduces. The consequences of either insufficient or unrestrained telomerase activity underscore the importance of ongoing studies aimed at elucidating the regulation of telomerase activity in humans. In the present study, we aimed to standardize a simplified telomerase repeat-amplification protocol (TRAP) assay to detect telomerase activity in unstimulated and PHA-stimulated mononuclear cells. METHODS and RESULTS: Our optimized qPCR-based can efficiently evaluate telomerase activity. Quantification of protein and DNA between unstimulated and PHA-stimulated peripheral blood mononuclear cells revealed cellular activation and cell-cycle entry. The assay also showed that relative telomerase activity is significantly different between these two conditions, supporting the applicability of the assay. Furthermore, our findings corroborated that telomerase activity decreases with age. CONCLUSIONS: Telomeres and telomerase are implicated in aging and development of chronic diseases and cancer; however, difficulty in accessing commercial kits to investigate these aspects is a critical constraint in health surveillance studies. Our optimized assay was successfully used to differentiate telomerase activity between unstimulated and stimulated cells, clearly showing the reactivation of telomerase upon cell activation. This assay is affordable, reproducible, and can be executed in resource-limited settings.
  • In vitro anti-inflammatory effects of vitamin D supplementation may be blurred in hemodialysis patients Original Article

    Gregório, Paulo C.; Bucharles, Sergio; Cunha, Regiane S. da; Braga, Tárcio; Almeida, Ana Clara; Henneberg, Railson; Stinghen, Andréa E.M.; Barreto, Fellype C.

    Abstract in English:

    OBJECTIVES: This study aimed to evaluate the potential anti-inflammatory effects of vitamin D supplementation under uremic conditions, both in vivo and in vitro, and its effects on the parameters of mineral metabolism. METHODS: Thirty-two hemodialysis patients were randomly assigned to receive placebo (N=14) or cholecalciferol (N=18) for six months. Serum levels of calcium, phosphate, total alkaline phosphatase, intact parathyroid hormone (iPTH), and vitamin D were measured at baseline and after three and six months. The levels of fibroblast growth factor-23 (FGF-23), interleukin-1β (IL-1β), and high-sensitivity C-reactive protein (hs-CRP) were also measured at baseline and at six months. Human monocytes were used for in vitro experiments and treated with cholecalciferol (150 nM) and uremic serum. Cell viability, reactive oxygen species (ROS) production, and cathelicidin (CAMP) expression were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, dichloro-dihydro-fluorescein diacetate assay, and real time-quantitative polymerase chain reaction, respectively. RESULTS: Both patient groups were clinically and biochemically similar at baseline. After six months, the levels of vitamin D and iPTH were higher and lower, respectively, in the cholecalciferol group than in the placebo group (p<0.05). There was no significant difference between the parameters of mineral metabolism, such as IL-1β and hs-CRP levels, in both groups. Treatment with uremic serum lowered the monocyte viability (p<0.0001) and increased ROS production (p<0.01) and CAMP expression (p<0.05); these effects were counterbalanced by cholecalciferol treatment (p<0.05). CONCLUSIONS: Thus, cholecalciferol supplementation is an efficient strategy to ameliorate hypovitaminosis D in hemodialysis patients, but its beneficial effects on the control of secondary hyperparathyroidism are relatively unclear. Even though cholecalciferol exhibited anti-inflammatory effects in vitro, its short-term supplementation was not effective in improving the inflammatory profile of patients on hemodialysis, as indicated by the IL-1β and hs-CRP levels.
  • Arterial stiffness in type 2 diabetes: determinants and indication of a discriminative value Original Article

    Monteiro, Clara Italiano; Simões, Rodrigo Polaquini; Goulart, Cássia Luz; Silva, Claudio Donisete da; Borghi-Silva, Audrey; Mendes, Renata Gonçalves

    Abstract in English:

    OBJECTIVES: To identify the clinical discriminative value and determinants of arterial stiffness in individuals with type 2 diabetes mellitus (T2DM). METHODS: This prospective cohort study included 51 individuals (53.57±9.35 years) diagnosed with T2DM (stage glucose≥126 mg/dL; diagnostic time: 87.4±69.8 months). All participants underwent an initial evaluation of personal habits, medications, and history; arterial stiffness assessment by carotid-femoral pulse wave velocity (cfPWV) using SphygmoCor; and blood laboratory analysis. A statistical analysis was performed using SPSS software, and values of p≤0.05 were considered significant. RESULTS: A cut-off cfPWV value of 7.9 m/s was identified for T2DM [Sensitivity (SE): 90% and Specificity (SP): 80%]. A subgroup analysis revealed higher glycated hemoglobin (Hb1Ac) (p=0.006), obesity (p=0.036), and dyslipidemia (p=0.013) than those with cfPWV ≥7.9 m/s. Multivariate analysis identified higher stage glucose (p=0.04), Hb1Ac (p=0.04), hypertension (p=0.001), and dyslipidemia (p=0.01) as determinant factors of cfPWV; positive and significant correlation between cfPWV and glucose (r=0.62; p=0.0003) and Hb1Ac (r=0.55; p=0.0031). CONCLUSIONS: In T2DM, an indicator of the discriminative value of arterial stiffness was cfPWV of 7.9 m/s. Clinical findings and comorbidities, such as hypertension, glucose, poor glycemic control, and dyslipidemia, were associated with and were determinants of arterial stiffness in T2DM. Reinforcement of monitoring risk factors, such as hypertension, dyslipidemia, and glycemic control, seems to be essential to the process of arterial stiffening. Confirmation of this discriminative value in larger populations is recommended.
  • Acellular dermal matrix in skin wound healing in rabbits - histological and histomorphometric analyses Original Article

    Carvalho-Júnior, José da Conceição; Zanata, Fabiana; Aloise, Antônio Carlos; Ferreira, Lydia Masako

    Abstract in English:

    OBJECTIVES: To analyze the histology and histomorphometry of healing associated with acellular dermal matrix in skin wounds in rabbits. METHODS: Twelve male rabbits were divided into two groups: the control group (CG) and the matrix group (MG). Three skin wounds with a total area of 20 × 20 mm were created on the dorsal region of each animal. Photographic records of the lesions taken over a 21-day period and use of the ImageJ program allowed calculation of the wound contraction rate. The lesions were biopsied on days 3, 14 and 21 for histomorphometric analysis to define the thicknesses of the dermis and epidermis (hematoxylin-eosin) and calculate the densities of type I and type III collagen (picrosirius). RESULTS: No significant difference in the healing rate was found between the groups (p>0.05). The MG presented greater epidermal thickness on day 3 (p<0.05) and on days 14 and 21 (p<0.001). The MG presented greater dermal thickness throughout the study period (p<0.05). The type I collagen density was higher in the MG throughout the study period (p<0.05), and the type III collagen density was higher in the MG on days 3 and 14 (p<0.05) and on day 21 (p<0.001). CONCLUSION: The use of acellular dermal matrix increased the thickness of the dermal and epidermal layers and the amount of type I and III collagen during skin wound healing and did not alter the rate of wound contraction.
  • Endoscopy infection control strategy during the COVID-19 pandemic: experience from a tertiary cancer center in Brazil Original Article

    Pombo, Amanda A.M.; Lenz, Luciano; Paulo, Gustavo A.; Santos, Mônica A.; Tamae, Patricia K.; Santos, Alisson L.D.R.; Rezende, Daniel T.; Martins, Bruno; Kawaguti, Fabio S.; Pennachi, Caterina M.P.S.; Gusmon-Oliveira, Carla C.; Uemura, Ricardo S.; Geiger, Sebastian; Lima, Marcelo S.; Baba, Elisa R.; Figueiredo, Viviane R.; Safatle-Ribeiro, Adriana; Maluf-Filho, Fauze; Ribeiro-Júnior, Ulysses

    Abstract in English:

    OBJECTIVES: Strategic planning for coronavirus disease (COVID-19) care has dominated the agenda of medical services, which have been further restricted by the need for minimizing viral transmission. Risk is particularly relevant in relation to endoscopy procedures. This study aimed to describe a contingency plan for a tertiary academic cancer center, define a strategy to prioritize and postpone examinations, and evaluate the infection rate among healthcare workers (HCWs) in the endoscopy unit of the Cancer Institute of the State of São Paulo (ICESP). METHODS: We created a strategy to balance the risk of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to mitigate the effects of postponing endoscopic procedures in oncological patients. A retrospective analysis of prospectively collected data on all endoscopies between March and June 2020 compared with those during the same period in 2019 was carried out. All HCWs were interviewed to obtain clinical data and SARS-CoV-2 test results. RESULTS: During the COVID-19 outbreak, there was a reduction of 55% in endoscopy cases in total. Colonoscopy was the most affected modality. The total infection rate among all HCWs was 38%. None of the senior digestive endoscopists had COVID-19. However, all bronchoscopists had been infected. One of three fellows had a serological diagnosis of COVID-19. Two-thirds of all nurses were infected, whereas half of all technicians were infected. CONCLUSIONS: In this pandemic scenario, all endoscopy services must prioritize the procedures that will be performed. It was possible to maintain some endoscopic procedures, including those meant to provide nutritional access, tissue diagnosis, and endoscopic resection. Personal protective equipment (PPE) seems effective in preventing transmission of COVID-19 from patients to digestive endoscopists. These measures can be useful in planning, even for pandemics in the future.
  • Azeliragon ameliorates Alzheimer's disease via the Janus tyrosine kinase and signal transducer and activator of transcription signaling pathway Original Article

    Yang, Lijuan; Liu, Yepei; Wang, Yuanyuan; Li, Junsheng; Liu, Na

    Abstract in English:

    OBJECTIVES: TTP488, an antagonist of the receptor for advanced glycation end-products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer’s disease (AD). However, the mechanism underlying the protective action of TTP488 against AD has not yet been fully explored. METHODS: Healthy male rats were exposed to aberrant amyloid β (Aβ) 1-42. Lipopolysaccharide (LPS) and the NOD-like receptor family pyrin domain containing 1 (NLRP1) overexpression lentivirus were injected to activate the NLRP1 inflammasome and exacerbate AD. TTP488 was administered to reverse AD injury. Finally, tofacitinib and fludarabine were used to inhibit the activity of Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) to prove the relationship between the JAK/STAT signaling pathway and TTP488. RESULTS: LPS and NLRP1 overexpression significantly increased the NLRP1 levels, reduced neurological function, and aggravated neuronal damage, as demonstrated by the impact latency time of, time spent by, and length of the platform covered by, the mice in the Morris water maze assay, Nissl staining, and immunofluorescence staining in rats with AD. CONCLUSIONS: TTP488 administration successfully reduced AD injury and reversed the aforementioned processes. Additionally, tofacitinib and fludarabine administration could further reverse AD injury after the TTP488 intervention. These results suggest a new potential mechanism underlying the TTP488-mediated alleviation of AD injury.
  • Signs of impending rupture in abdominal aortic and iliac artery aneurysms by computed tomography: Outcomes in 41 patients Original Article

    Antunes, Bruno Fabricio Feio; Tachibana, Adriano; Mendes, Cynthia de Almeida; Lembrança, Lucas; Silva, Marcela Juliano; Teivelis, Marcelo Passos; Wolosker, Nelson

    Abstract in English:

    OBJECTIVES: This study aimed to determine the prevalence of signs of impending rupture (SIR) in asymptomatic patients with abdominal aortic and iliac artery aneurysms, and to evaluate whether these signs were associated with rupture in asymptomatic patients. METHODS: This was a retrospective study of patients with abdominal aortic and iliac artery aneurysms identified on computed tomography (CT) over a 10-year period in a single center. The CT scans were reviewed by two reviewers, and patients with SIR were assigned to one of three groups: (1) early symptomatic (ES), (2) late symptomatic (LS), and (3) always asymptomatic (AA). The four main SIR described in the literature were investigated: 1) crescent sign, 2) focal wall discontinuity of circumferential calcifications, 3) aortic bulges or blebs, and 4) aortic draping. RESULTS: From a total of 759 aortic and iliac aneurysm reports on 2226 CT scans, we identified 41 patients with at least one SIR, and a prevalence of 4.14% in asymptomatic patients. Focal wall discontinuity of circumferential calcifications was the most common sign, and it was present in 46.3% of these patients (19/41); among these, 26 were repaired (ES: 9, LS: 2, AA: 15). Eleven asymptomatic patients underwent follow-up CT. The aneurysm increased in size in 6 of the 11 (54.5%) patients, and three ruptured (all with discontinuity of calcifications), one of which had no increase in diameter. CONCLUSIONS: The presence of focal wall discontinuity of circumferential calcifications was the most common SIR. There was a prevalence of all signs in less than 5% of asymptomatic patients. In unrepaired patients, the signs could be observed on follow-up CT scans with an increase in aneurysm size, indicating that the presence of SIR alone in the absence of other clinical factors or aneurysm characteristics is an insufficient indication for surgery.
  • miR-139-5p protects septic mice with acute lung injury by inhibiting Toll-like receptor 4/Myeloid differentiation factor 88/Nuclear factor-&mac_kgr;B signaling pathway Original Article

    Zhang, Xiuxiu; Liu, Xin; Chang, Rui; Li, Yue

    Abstract in English:

    OBJECTIVES: To investigate the role of miR-139-5p and the TLR4/MyD88/NF-κB signaling pathway in acute lung injury in septic mice. METHOD: A total of 140 healthy male SPF C57BL/6 mice were divided into seven groups, i.e., Normal, Control, NC, miR-139-5p mimic, miR-139-5p inhibitor, TAK-242, and miR-139-5p inhibitor+TAK-242 groups. The levels of miR-139-5p, proteins related to the TLR4/MyD88/NF-κB signaling pathway (TLR4, MyD88, and p-NF-κB p50), and MPO, SOD, GSH, and MDA in lung tissue were measured. The lung tissue wet-to-dry mass ratio (W/D), arterial oxygen partial pressure (PaO2), and carbon dioxide partial pressure (PaCO2) were measured. RESULTS: A web-based bioinformatic tool predicted that MyD88 was a target of miR-139-5p, which was verified by a dual luciferase reporter assay. Compared with those in the Normal group, the levels of miR-139-5p, PaO2, SOD, and GSH were significantly lower, while those of TLR4, MyD88, p-NF-κB p50, W/D, PaCO2, IL-1β, TNF-α, IL-6, MPO, and MDA were higher in all other groups. Moreover, compared with their levels in the Control group, these indicators exhibited contrasting results in the miR-139-5p mimic and TAK-242 groups, but were similar in the miR-139-5p inhibitor group. In the miR-139-5p inhibitor+TAK-242 group, acute lung injury, aggravated by miR-139-5p inhibitor, was partially rescued by TAK-242. CONCLUSION: miR-139-5p inhibits the TLR4/MyD88/NF-κB signaling pathway to alleviate acute lung injury in septic mice.
  • Acoustically Controlled Binaural Auditory Training with Vocal Duets: Assessment and Effectiveness Original Article

    Picinini, Taís de Azevedo; Sperança, Simone; Pereira, Liliane Desgualdo

    Abstract in English:

    OBJECTIVES: We aimed to evaluate the effectiveness of a binaural auditory training program with vocal duets by comparing skills through outcomes from behavioral and electrophysiological assessment instruments at three moments: before the intervention, moment one (M1); immediately after training, moment two (M2); and 3 months after, moment three (M3). METHODS: This interventional, longitudinal, prospective, and uncontrolled study was approved by our Research Ethics Committee. Binaural auditory training with vocal duets (ATVD) was applied in 10 adults with normal audiometric thresholds and auditory processing disorders. ATVD used four different vocals of a public domain song sung in a cappella as stimuli. Participants were asked to register any perceived difference in frequency for each syllable of the song during 30-minute sessions twice a week. The number of sessions required ranged from 12 (6 hours) to 20 (10 hours). RESULTS: Regarding behavioral tests, the dichotic consonant-vowel test showed significant evidence of an improved advantage in the left ear (LE) in the non-forced condition and a significant reduction in the number of errors at M2 and M3 in the forced left condition. The speech-in-noise test and frequency pattern test showed a significant reduction in impaired results at M2 and M3. Electrophysiological results showed a significant increase in the LE amplitude in the P3 long-latency auditory evoked potentials test, as well as a decrease in the auditory brainstem response test (III-V and I-V inter-peak latencies in the right ear and wave I and I-III inter-peak latencies in LE). CONCLUSION: The effectiveness of ATVD was evidenced, and the results were maintained after 3 months.
  • Association between ventilatory settings and pneumothorax in extremely preterm neonates Original Article

    Matsushita, Felipe Y.; Krebs, Vera L.J.; Carvalho, Werther B. de

    Abstract in English:

    OBJECTIVES: Pneumothorax is a catastrophic event associated with high morbidity and mortality, and it is relatively common in neonates. This study aimed to investigate the association between ventilatory parameters and the risk of developing pneumothorax in extremely low birth weight neonates. METHODS: This single-center retrospective cohort study analyzed 257 extremely low birth weight neonates admitted to a neonatal intensive care unit between January 2012 and December 2017. A comparison was carried out to evaluate the highest value of positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), and driving pressure (DP) in the first 7 days of life between neonates who developed pneumothorax and those who did not. The primary outcome was pneumothorax with chest drainage necessity in the first 7 days of life. A matched control group was created in order to adjust for cofounders associated with pneumothorax (CRIB II score, birth weight, and gestational age). RESULTS: There was no statistically significant difference in PEEP, PIP, and DP values in the first 7 days of life between extremely low birth weight neonates who had pneumothorax with chest drainage necessity and those who did not have pneumothorax, even after adjusting for potential cofounders. CONCLUSIONS: Pressure-related ventilatory settings in mechanically ventilated extremely low birth weight neonates are not associated with a higher risk of pneumothorax in the first 7 days of life.
  • Association of tumor mutation burden and epidermal growth factor receptor inhibitor history with survival in patients with metastatic stage III/IV non-small-cell lung cancer: A retrospective study Original Article

    Lan, Yan; Zhou, Shuo; Feng, Weihong; Qiao, Ying; Du, Xueming; Li, Fenge

    Abstract in English:

    OBJECTIVES: Lung cancer is the leading cause of cancer-related deaths worldwide. However, factors associated with the survival of patients with advanced non-small-cell lung cancer (NSCLC) who received only hospice care are largely unclear. In this study, we aimed to determine the prognostic factors correlated with survival in patients with advanced NSCLC who had undergone hospice care only. METHODS: A total of 102 patients with recurrent stage III/IV NSCLC after traditional treatment failure were investigated. Survival was measured from the date of enrollment to December 2019 or the time of death. Tumor tissues were collected, and DNA sequencing was performed to identify somatic mutations. Data on clinical factors of patients were collected and analyzed by univariate and multivariate analyses. Overall survival analysis was conducted using the Kaplan-Meier method. RESULTS: The 6-month, 1-year, and 2-year overall survival rates of the 102 patients with metastatic NSCLC were 17.65%, 3.92%, and 0.98%, respectively. The median overall survival of the 102 patients was 3.15 months. Tumor location in the peripheral lung, epidermal growth factor receptor (EGFR) inhibitor history, low tumor mutation load, adenocarcinoma, and poor performance status score were associated with prolonged survival compared with tumor location in the central lung, no EGFR inhibitor history, high tumor mutation load, squamous cell carcinoma, and good performance status score (p=0.045, p=0.003, p=0.045, p=0.021, and p=0.0003, respectively). CONCLUSIONS: EGFR inhibitor treatment history and tumor mutation load are risk factors for the overall survival of patients with stage III/IV NSCLC who have undergone only hospice care. These results provide a critical clinical basis for further study of nontraditional anti-tumor responses induced by EGFR inhibitors.
  • Multicomponent physical activity program to prevent body changes and metabolic disturbances associated with antiretroviral therapy and improve quality of life of people living with HIV: a pragmatic trial Original Article

    Santos, Elisabete Cristina Morandi dos; Florindo, Alex Antonio; Santos, Ardiles Vitor; Picone, Camila de Melo; Dias, Túlio Gamio; Segurado, Aluisio Cotrim

    Abstract in English:

    OBJECTIVES: Comprehensive care for people living with human immunodeficiency virus (HIV) (PLH) includes the promotion of healthier habits, including physical activity (PA). This study aimed to describe a multicomponent pragmatic trial protocol to assess the effect of PA in preventing body changes and metabolic disturbances, improving the quality of life of PLH starting antiretroviral therapy (ART) and present cohort characteristics. METHODS: PLH undergoing ART for ≤4 months were recruited for a randomized trial. The intervention comprised three cardiorespiratory and/or strength training sessions per week at the clinic or in public spaces for 6 months under on-site or remote supervision, and educational sessions. Participants’ PA levels, cardiorespiratory fitness, anthropometric measures, strength, flexibility, quality of life, and laboratory monitoring (blood glucose and lipids, CD4 counts) at baseline and post-intervention will be compared. The pragmatic design aims to enable the assessment of intervention effectiveness in real-life conditions. RESULTS: At baseline, our cohort of 38 recently diagnosed patients (mean time since HIV diagnosis and duration of ART were 3 and 2.58 months, respectively) were predominantly male, young, with high schooling and good immune status (median CD4 count=498 cells/mm3). Twenty-two (57.9%) patients reported a PA below the World Health Organization recommendations. We found baseline normal anthropometric measures and metabolic parameters: below-average trunk flexion and elbow extension strength, poor handgrip strength and flexibility, and high quality of life scores in all except the physical domain. CONCLUSIONS: Understanding how effective PA is in preventing body changes and metabolic disturbances, and in improving the quality of PLH starting ART may help establish guidelines to better incorporate PA in HIV care.
  • Medical students with performance difficulties need wide support: Initial results of an academic tutoring program Original Article

    Bellodi, Patrícia Lacerda; Dolhnikoff, Marisa; ,

    Abstract in English:

    BACKGROUND: Even students with previous academic success may face challenges that affect their academic performance. Many medical schools offer programs to students at the risk of academic failure, to ensure that they succeed in the course. OBJECTIVE AND METHODS: In this report we describe a pioneering academic tutoring program developed at a Brazilian medical school and discuss the initial results of the program based on the feedback from tutors and data regarding the progression of students in the medical course. RESULTS: In 2018, 33 students enrolled into the program. Students' performance difficulties were mainly associated with mental health problems and socioeconomic vulnerability. Of the 33 students, 27 (81.8%) were assisted by the Mental Health Support Service and 16 (48.5%) were assisted by the Social Assistance Service. In addition to the planning academic activity class load, tutors were able to assist students in solving socioeconomic issues, carrying out personal support interventions with the promotion of self-esteem, and presenting suggestions for behavioral changes in their routine. For most students (72%), the action plan proposed by the tutors was successful. Eight of the 14 (57%) students in the fourth year progressed to the final two years of in-hospital practical training (internship). CONCLUSIONS: The Academic Tutoring Program showed positive results for most of the students. Close monitoring and tutor intervention allowed students with poor academic performance to overcome the low performance cycle. These important tasks demand time and energy from tutors, and institutional recognition of these professionals is essential for the successful maintenance of the program.
  • Is it Safe to Perform Elective Colorectal Surgical Procedures during the COVID-19 Pandemic? A Single Institution Experience with 103 Patients Original Article

    Sobrado, Lucas Faraco; Nahas, Caio Sergio Rizkallah; Marques, Carlos Frederico Sparapan; Cotti, Guilherme Cutait de Castro; Imperiale, Antônio Rocco; Averbach, Pedro; Meira Júnior, José Donizeti de; Horvat, Natally; Ribeiro-Júnior, Ulysses; Cecconello, Ivan; Nahas, Sergio Carlos

    Abstract in English:

    OBJECTIVES: Since the outbreak of the novel coronavirus disease 2019 (COVID-19), all health services worldwide underwent profound changes, leading to the suspension of many elective surgeries. This study aimed to evaluate the safety of elective colorectal surgery during the pandemic. METHODS: This was a retrospective, cross-sectional, single-center study. Patients who underwent elective colorectal surgery during the COVID-19 pandemic between March 10 and September 9, 2020, were included. Patient data on sex, age, diagnosis, types of procedures, hospital stay, mortality, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preoperative screening tests were recorded. RESULTS: A total of 103 colorectal surgical procedures were planned, and 99 were performed. Four surgeries were postponed due to positive preoperative screening for SARS-CoV-2. Surgical procedures were performed for colorectal cancer (n=90) and inflammatory bowel disease (n=9). Laparoscopy was the approach of choice for 43 patients (43.4%), 53 (53.5%) procedures were open, and 3 (3%) procedures were robotic. Five patients developed COVID-19 in the postoperative period, and three of them died in the intensive care unit (n=3/5, 60% mortality). Two other patients died due to surgical complications unrelated to COVID-19 (n=2/94, 2.1% mortality) (p<0.01). Hospital stay was longer in patients with SARS-CoV-2 infection than in those without (38.4 versushttps://doi.org/10.3 days, respectively, p<0.01). Of the 99 patients who received surgical care during the pandemic, 94 were safely discharged (95%). CONCLUSION: Our study demonstrated that elective colorectal surgical procedures may be safely performed during the pandemic; however, preoperative testing should be performed to reduce in-hospital infection rates, since the mortality rate due to SARS-CoV-2 in this setting is particularly high.
  • Efficacy of abdominal ultrasound inspection in the diagnosis and prognosis of neonatal necrotizing enterocolitis Original Article

    Gao, Hong-Xia; Yi, Bin; Mao, Bao-Hong; Li, Wei-Yang; Bai, Xiang; Zhang, Yue; Tang, Jian-Ming; Liu, Pei-Qi; Cheng, Kun

    Abstract in English:

    OBJECTIVE: This study aimed to identify the most useful ultrasound (US) features associated with definite neonatal necrotizing enterocolitis (NEC) and their prognostic values, particularly the calculated markers combined with important features. METHODS: A total of 213 suspected NEC cases were collected from the neonatal department of our hospital from January 2015 to August 2017. Each infant received both X-ray and US examinations. RESULTS: No differences were found in sex composition and delivery modes between groups. NEC-positive neonates had poorer prognosis compared to negative ones. The NEC group showed a higher frequency of abnormal signals. US showed higher NEC-related frequencies in different parameters. A variable (named predictor in US [PUS]) with five features was constructed. For NEC diagnosis, this variable provided a much higher area under the curve Q2 (AUC) (0.965) than other parameters. In this model, PUS had a cutoff value of 0.376 with a 0.900 sensitivity and 0.922 specificity. In prognosis, the closest factors were selected to draw a receiver operating characteristic curve, as well as a novel calculated variable US prognostic (USPro) marker. USPro had a much higher AUC (0.86) than other single features and showed a cutoff value of 0.18145, with 0.75 sensitivity and 0.84 specificity. This variable had a weaker power in prognosis when compared with PUS in diagnosis. CONCLUSIONS: The application of abdominal color Doppler US can provide high accuracy and sensitivity in NEC diagnosis and also contribute to its prognosis, without induction of radiation. Suspected neonates should be examined using this technique as early as possible.
  • Hearing loss, tinnitus, and hypertension: analysis of the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Original Article

    Samelli, Alessandra Giannella; Santos, Itamar Souza; Padilha, Fernanda Yasmim Odila Maestri Miguel; Gomes, Raquel Fornaziero; Moreira, Renata Rodrigues; Rabelo, Camila Maia; Matas, Carla Gentile; Bensenor, Isabela M.; Lotufo, Paulo A.

    Abstract in English:

    OBJECTIVES: To investigate the association among hypertension, tinnitus, and sensorineural hearing loss and evaluate the influence of other covariates on this association. METHODS: Baseline data (2008-2010) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were analyzed. Altogether, 900 participants were evaluated. The baseline assessment consisted of a 7-hour examination to obtain clinical and laboratory variables. Hearing was measured using pure-tone audiometry. RESULTS: Overall, 33.3% of the participants had hypertension. Participants with hypertension were more likely to be older, male, and diabetic compared to those without hypertension. The prevalence of tinnitus was higher among hypertensive participants and the odds ratio for tinnitus was higher in participants with hypertension than in those without hypertension. However, the difference was not significant after adjusting for age. Audiometric results at 250-8,000 Hz were worse in participants with hypertension than in those without hypertension in the crude analysis; however, the differences were not significant after adjustment for age, sex, diagnosis of diabetes, and exposure to noise. No significant difference was observed in hearing thresholds among participants having hypertension for <6 years, those having hypertension for ≥6 years, and individuals without hypertension. CONCLUSION: Hearing thresholds were worse in participants with hypertension. However, after adjusting for age, sex, diagnosis of diabetes, and exposure to noise, no significant differences were observed between participants with and without hypertension. A higher prevalence of tinnitus was observed in participants with hypertension compared to those without hypertension, but without significance after adjusting for age.
  • Evaluation of the RSNA and CORADS classifications for COVID-19 on chest computed tomography in the Brazilian population Original Article

    Fonseca, Eduardo Kaiser Ururahy Nunes; Loureiro, Bruna Melo Coelho; Strabelli, Daniel Giunchetti; Farias, Lucas de Pádua Gomes de; Garcia, José Vitor Rassi; Gama, Victor Arcanjo Almeida; Ferreira, Lorena Carneiro; Chate, Rodrigo Caruso; Assunção Júnior, Antonildes Nascimento; Sawamura, Marcio Valente Yamada; Nomura, Cesar Higa

    Abstract in English:

    OBJECTIVE: To determine the correlation between the two tomographic classifications for coronavirus disease (COVID-19), COVID-19 Reporting and Data System (CORADS) and Radiological Society of North America Expert Consensus Statement on Reporting Chest Computed Tomography (CT) Findings Related to COVID-19 (RSNA), in the Brazilian population and to assess the agreement between reviewers with different experience levels. METHODS: Chest CT images of patients with reverse transcriptase-polymerase chain reaction (RT-PCR)-positive COVID-19 were categorized according to the CORADS and RSNA classifications by radiologists with different levels of experience and who were initially unaware of the RT-PCR results. The inter- and intra-observer concordances for each of the classifications were calculated, as were the concordances between classifications. RESULTS: A total of 100 patients were included in this study. The RSNA classification showed an almost perfect inter-observer agreement between reviewers with similar experience levels, with a kappa coefficient of 0.892 (95% confidence interval [CI], 0.788-0.995). CORADS showed substantial agreement among reviewers with similar experience levels, with a kappa coefficient of 0.642 (95% CI, 0.491-0.793). There was inter-observer variation when comparing less experienced reviewers with more experienced reviewers, with the highest kappa coefficient of 0.396 (95% CI, 0.255-0.588). There was a significant correlation between both classifications, with a Kendall coefficient of 0.899 (p<0.001) and substantial intra-observer agreement for both classifications. CONCLUSION: The RSNA and CORADS classifications showed excellent inter-observer agreement for reviewers with the same level of experience, although the agreement between less experience reviewers and the reviewer with the most experience was only reasonable. Combined analysis of both classifications with the first RT-PCR results did not reveal any false-negative results for detecting COVID-19 in patients.
  • Microablative fractional radiofrequency as a therapeutic option for vulvar lichen sclerosus: a pilot study Original Article

    Kamilos, Márcia Farina; Aguiar, Lana Maria; Batista, Valéria Holmo; Roa, Cristiane Lima; Aguiar, Fernando Nalesso; Soares Júnior, José Maria; Baracat, Edmund Chada

    Abstract in English:

    OBJECTIVES: To assess the clinical response to and the histomorphometric effects of microablative fractional radiofrequency (MFR) in women with symptomatic vulvar lichen sclerosus (VLS). METHODS: This was a pilot study on the use of MFR for the treatment of VLS. Upon recruitment and at each treatment session, all participants were examined and each of their symptoms were rated on a visual analog scale. After the procedure, the participants completed a satisfaction questionnaire. We compared the morphometric findings of vulvar biopsies performed at enrollment and after the last treatment session. The participants were divided into three groups according to previous treatment with corticosteroids: G1, no previous treatment; G2, treated for up to 5 years; and G3, treated for >5 years. RESULTS: This study included 26 women. After two to three sessions, most participants in all groups became either “asymptomatic” or “much better” than before treatment and were “very satisfied” or “satisfied” with the intervention. Pruritus and burning sensation were the most frequently reported symptoms. Nearly 40% of the participants in all groups reported complete remission of symptoms. The improvement was rated as moderate or higher by 80%, 76%, and 66% of the women in groups 1, 2, and 3, respectively. The improvement of symptoms persisted for 11 months (range, 7-16 months), on average, after the treatment. Type III collagen concentration significantly increased and was associated with important symptom improvement. Tissue trophism and vascularization also increased but did not reach statistical significance, probably because of the small number of cases. CONCLUSIONS: MFR may be an effective and safe treatment for symptomatic VLS.
  • Modelling the impact of contact tracing of symptomatic individuals on the COVID-19 epidemic Original Article

    Amaku, Marcos; Covas, Dimas Tadeu; Coutinho, Francisco Antonio Bezerra; Azevedo, Raymundo Soares; Massad, Eduardo

    Abstract in English:

    OBJECTIVES: With the declining numbers of coronavirus disease 2019 (COVID-19) cases in the state of São Paulo, Brazil, social distancing measures have gradually been lifted. However, the risk of a surge in the number of cases cannot be overlooked. Even with the adoption of nonpharmaceutical interventions, such as restrictions on mass gatherings, wearing of masks, and complete or partial closure of schools, other public health measures may help control the epidemic. We aimed to evaluate the impact of the contact tracing of symptomatic individuals on the COVID-19 epidemic regardless of the use of diagnostic testing. METHODS: We developed a mathematical model that includes isolation of symptomatic individuals and tracing of contacts to assess the effects of the contact tracing of symptomatic individuals on the COVID-19 epidemic in the state of São Paulo. RESULTS: For a selection efficacy (proportion of isolated contacts who are infected) of 80%, cases and deaths may be reduced by 80% after 60 days when 5000 symptomatic individuals are isolated per day, each of them together with 10 contacts. On the other hand, for a selection efficacy of 20%, the number of cases and deaths may be reduced by approximately 40% and 50%, respectively, compared with the scenario in which no contact-tracing strategy is implemented. CONCLUSION: Contact tracing of symptomatic individuals may potentially be an alternative strategy when the number of diagnostic tests available is not sufficient for massive testing.
  • COVID-19 and the teacher's voice: self-perception and contributions of speech therapy to voice and communication during the pandemic Original Article

    Nemr, Katia; Simões-Zenari, Marcia; Almeida, Vanessa Cássia de; Martins, Glauciene Amaral; Saito, Isabele Tiemi

    Abstract in English:

    OBJECTIVES: We aimed to analyze the vocal self-perception of Brazilian teachers and their communication needs, vocal signs and symptoms, and voice-related lifestyles during the coronavirus disease (COVID-19) pandemic and, based on this information, to develop guidance materials intended for dissemination to these teachers and the general community. METHODS: An online questionnaire designed for this survey was distributed via the researchers' networks and was available for completion by any teacher, except those who were not working at the time. There were 1,253 teachers from all over Brazil, of both sexes, covering a wide age range, working at different levels of education, and most with more than ten years of experience. Descriptive and inferential analyses of the data were performed. RESULTS: On comparing the prepandemic period with the current one, participants indicated voice improvements. In contrast, they presented symptoms such as dry throat, effort in addressing remote classes, hoarseness after classes, and difficulties with the use of headphones, among others. They further indicated stress, general fatigue, impact of the pandemic on mental health, and the overlapping of many home tasks with professional tasks. Some smoked, and others hydrated insufficiently. CONCLUSION: Although teachers generally noticed voice improvements during the pandemic, a proportion of them perceived worsening of voices. Many indicated several factors in which speech-language pathologists could guide them with the aim of improving performance and comfort during remote and hybrid classes, an initiative that will positively impact not only their voice and communication but also their quality of life.
  • Standardization of an experimental model of intradural injection after spinal cord injury in rats Original Article

    Letaif, Olavo B.; Tavares-Júnior, Mauro C.M.; Santos, Gustavo B. dos; Ferreira, Ricardo J.R.; Marcon, Raphael M.; Cristante, Alexandre F.; Barros-Filho, Tarcísio E.P. de

    Abstract in English:

    OBJECTIVES: The intrathecal route has not yet been thoroughly standardized and evaluated in an experimental model of spinal cord injury (SCI) in Wistar rats. The objective of this study was to standardize and evaluate the effect of intradural injection in this animal model. METHOD: The animals were divided into 6 groups: 1) laminectomy and intradural catheter; 2) laminectomy, intradural catheter and infusion; 3) only SCI; 4) SCI and intradural catheter; 5) SCI, intradural catheter and infusion; and 6) control (laminectomy only). Motor evaluations were performed using the Basso, Beattie and Bresnahan (BBB) scale and the horizontal ladder test; motor evoked potentials were measured for functional evaluation, and histological evaluation was performed as well. All experimental data underwent statistical analysis. RESULTS: Regarding motor evoked potentials, the groups with experimental SCI had worse results than those without, but neither dural puncture nor the injection of intrathecal solution aggravated the effects of isolated SCI. Regarding histology, adverse tissue effects were observed in animals with SCI. On average, the BBB scores had the same statistical behaviour as the horizontal ladder results, and at every evaluated timepoint, the groups without SCI presented scored significantly better than those with SCI (p<0.05). The difference in performance on motor tests between rats with and without experimental SCI persisted from the first to the last test. CONCLUSIONS: The present work standardizes the model of intradural injection in experimental SCI in rats. Intrathecal puncture and injection did not independently cause significant functional or histological changes.
  • Effects of the timing of laparoscopic cholecystectomy after endoscopic retrograde cholangiopancreatography on liver, bile, and inflammatory indices and cholecysto-choledocholithiasis patient prognoses Original Article

    Gao, Ming-Jun; Jiang, Zhi-Lan

    Abstract in English:

    OBJECTIVES: This study explored the effects of the timing of laparoscopic cholecystectomy (LC) after endoscopic retrograde cholangiopancreatography (ERCP) on liver function, bile biochemical indices, inflammatory reactions, and cholecysto-choledocholithiasis patient prognoses. METHODS: A total of 103 cholecysto-choledocholithiasis patients were stratified into control (CG; n=51; LC at 4-7 d after ERCP) and observation groups (OG; n=52; LC at 1-3 d after ERCP) using a random number table. RESULTS: The surgical time was shorter and intraoperative blood loss was less in OG than in CG, and the two groups were not statistically different in terms of time to the first passage of gas through anus, length of postoperative hospital stay, conversion rate to laparotomy, and stone-free rate. Four weeks after LC, alanine aminotransferase (ALT), total bilirubin (TBil), albumin (ALB), and glutamyl transpeptidase (GGT) levels declined in both groups, but the difference was not statistically significant. Three days after LC, total bile acid (TBA) levels increased, and cholesterol (CHO), unconjugated bilirubin (UCB), and TBiL levels were reduced in both groups, but were not statistically different (p>0.05). Three days after LC, interleukin (IL)-6, procalcitonin (PCT), and high-sensitivity C-reactive protein (hs-CRP) levels in the serum and bile increased in both groups and were lower in OG. The total incidence of perioperative complications was 1.92% in OG, which was lower than 15.69% in the CG. CONCLUSION: For cholecysto-choledocholithiasis patients, LC at 1-3 d after ERCP can shorten surgical times, reduce intraoperative blood loss, improve liver function and bile biochemistry, relieve inflammatory reactions, reduce complications, and improve prognoses.
  • The novel fibrosis index at diagnosis may predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis without substantial liver diseases Original Article

    Pyo, Jung Yoon; Ahn, Sung Soo; Lee, Lucy Eunju; Choi, Gwang-mu; Song, Jason Jungsik; Park, Yong-Beom; Lee, Sang-Won

    Abstract in English:

    OBJECTIVES: Antineutrophil cyto plasmic antibody-associated vasculitis (AAV) is a fatal disease. Currently, predictors of mortality due to AAV are based on the distribution of organ involvement. The novel fibrosis index (NFI) is an index composed of laboratory results that reflect the degree of liver fibrosis. This study aimed to evaluate whether NFI can predict poor outcomes in patients with AAV without substantial liver disease. METHODS: A total of 210 patients with immunosuppressive drug-naïve AAV were retrospectively reviewed. NFI was calculated as follows: NFI=(serum bilirubin × (alkaline phosphatase)2)/(platelet count×(serum albumin)2). NFI cut-off was set at 1.24 (the highest quartile). Poor outcomes were defined as all-cause mortality, relapse, and end-stage renal disease (ESRD). RESULTS: During the median 34.5 months of follow-up, 21 patients (10%) died, 72 patients (34.3%) relapsed, and 38 patients (18.1%) had ESRD due to AAV progression. The median calculated NFI was 0.61, and it was higher in AAV patients with all-cause mortality than in those without mortality, but the difference was not statistically significant (1.26 vs. 0.59). AAV patients with NFI at diagnosis ≥1.24 exhibited a significantly lower cumulative patient survival rate than those with NFI at diagnosis <1.24 (p=0.002). Multivariate Cox hazard model analysis showed that NFI at diagnosis ≥1.24 was an independent predictor of all-cause mortality in AAV (hazard ratios [HR] 2.850, 95% confidence interval [CI] 1.026, 7.910). CONCLUSIONS: NFI ≥1.24, which may be an independent predictive marker for all-cause mortality in AAV patients without substantial liver disease.
  • Vitamin D status and prevalence of hypovitaminosis D in different genders throughout life stages: A Brazilian cross-sectional study Original Article

    Leão, Lenora M. Camarate S.M.; Rodrigues, Bernardo Campos; Dias, Paulo Telles Pires; Gehrke, Bárbara; Souza, Thiago da Silva Pereira de; Hirose, Caio Kenji; Freire, Mônica Di Calafiori

    Abstract in English:

    OBJECTIVES: To evaluate the mean concentration of 25-hydroxivitamin D [25(OH) D] and prevalence of hypovitaminosis D in individuals residing in Rio de Janeiro, Brazil. METHODS: The data of 80,000 consecutive individuals who had 25(OH) D measurements performed by electrochemiluminescence between 1/2/2018 and 2/5/2018 were selected. Patients who reported the use of therapies/supplements were excluded. Levels of 25(OH) D ≥20 ng/mL (ages <60 years) and ≥30 ng/mL (ages ≥60 years) were considered adequate. RESULTS: We analyzed the data of 24,074 individuals (1-95 years old, 64.7% female). Descriptive curves showed that, in both sexes, the mean values of 25(OH) D decreased from the first years of life until adolescence, then slightly increased, and then tended to stabilize during adulthood. Levels of 25(OH) D <20 ng/mL were observed in 6% of girls versus 3.6% of boys and in 13.6% of adolescent girls versus 12.6% of adolescent boys and 11% of adults. The percentage of seniors with serum levels of 25(OH) D <20 ng/mL was 13.6% in women and 12.7% in men; 53.2% of women and 50.6% of men had levels <30 ng/mL. CONCLUSIONS: Mean 25(OH) D values were higher in children and lower in adolescents and women. Approximately 90% of non-seniors and presumably healthy residents of the urban metropolitan region of Rio de Janeiro presented satisfactory levels of 25(OH) D during the summer months; however, in over half of the elderly, the serum concentrations of 25(OH) D were inadequate. Therefore, strategies for the prevention of hypovitaminosis D should be considered in the senior population.
  • Ocular motility changes after inferomedial wall and balanced medial plus lateral wall orbital decompression in Graves’ orbitopathy: a randomized prospective comparative study Original Article

    Leite, Cristiane de Almeida; Pereira, Thaís de Sousa; Chiang, Jeane; Moritz, Rodrigo Bernal; Gonçalves, Allan Christian Pieroni; Monteiro, Mário Luiz Ribeiro

    Abstract in English:

    OBJECTIVES: To compare the surgical outcomes of inferomedial wall orbital decompression (IM-OD) and balanced medial plus lateral wall orbital decompression (ML-OD) in patients with inactive Graves’ orbitopathy (GO) with regard to exophthalmos reduction and ocular motility abnormalities. METHODS: Forty-two patients with inactive GO eligible for OD were randomly assigned to either the IM-OD or ML-OD groups. Pre and postoperative evaluations included Hertel exophthalmometry, sensory, and motor extraocular motility assessment, standardized photographs in the nine gaze positions, and computed tomography (CT) of the orbits. ClinicalTrials.gov: NCT03278964. RESULTS: Exophthalmometry reduction was statistically significant in both groups (p<0.001), but was greater in the ML-OD group (p=0.010). New-onset esotropia occurred in 11.1% and 23.5% of patients who underwent IM-OD and ML-OD, respectively, with no statistically significant difference in the frequency of pre and postoperative strabismus in either group. The mean increase in preoperative esotropia was 24±6.9 and 12±8.8 prism diopters in patients who underwent IM-OD and ML-OD, respectively. In the IM-OD group, abduction and elevation worsened at the first (p<0.05) and third (p<0.05) postoperative visits but were restored at 6 months. The versions did not change postoperatively with ML-OD. The preoperative CT-measured medial rectus muscle area predicted new-onset strabismus (p=0.023). Significant postoperative medial rectus muscle enlargement occurred in both groups (p<0.001). Restriction in elevation and abduction was significantly associated with enlarged inferior (p=0.007) and medial rectus muscle areas (p=0.002). CONCLUSIONS: IM-OD is as safe as ML-OD with regard to new-onset strabismus, and represents a good alternative for patients who do not require significant exophthalmos reduction. ML-OD offers greater exophthalmos reduction and smoother postoperative recovery. Patients with preoperative enlarged medial rectus muscle on CT are at risk for new-onset esotropia, and preoperative esotropia is likely to increase after OD.
  • The role of platelet to mean platelet volume ratio in the identification of adult-onset still’s disease from sepsis Original Article

    Ge, Suohua; Ma, Yongbin; Xie, Mengxiao; Qiao, Tengfei; Zhou, Jun

    Abstract in English:

    OBJECTIVES: Inflammatory factors exert a significant role in the development of adult-onset Still’s disease (AOSD) and sepsis. Although platelet counts and platelet parameters have long served as indicators for inflammatory diseases, their role in the differential diagnosis between adult-onset stilĺs disease and sepsis remains unclear. We designed this retrospective study to explore whether the platelet to mean platelet volume (MPV) ratio (PMR) can help to distinguish AOSD from sepsis. METHODS: A total of 110 AOSD patients and 84 sepsis patients were enrolled in the study. Seventy-three AOSD patients and 56 sepsis patients between January 2010 and June 2017 were enrolled in the test cohort to analyze PMR values, which was then validated in the validation cohort (37 AOSD patients and 28 sepsis patients between June 2017 and December 2019). RESULTS: The values of PMR were significantly higher in AOSD patients than in sepsis patients (test cohort, validation cohort, and entire cohort), In the test cohort, logistic regression analysis showed that PMR was an independent risk factor of AOSD (odds ratios [OR]: 9.22, 95% confidence interval [CI] 2.15-39.46, p=0.003). Further receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve was 0.735 (95% CI 0.631-0.839, p<0.001) for PMR alone and 0.925 (95% CI 0.869-0.980, p<0.001) for the combination of PMR and serum ferritin. Consistently, the validation cohort exhibited analogous results. CONCLUSIONS: PMR could be used as a single indicator or a complementary indicator to distinguish AOSD from sepsis.
  • Systemic Inflammation and Oxidative Stress in Adults with Bronchiectasis: Association with Clinical and Functional Features Original Article

    de Camargo, Anderson Alves; de Castro, Rejane Agnelo Silva; Vieira, Rodolfo P.; Oliveira-Júnior, Manoel Carneiro; Araujo, Amanda Aparecida de; De Angelis, Kátia; Rached, Samia Zahi; Athanazio, Rodrigo Abensur; Stelmach, Rafael; Corso, Simone Dal

    Abstract in English:

    OBJECTIVES: To compare the inflammatory and oxidative stress (OS) states of adults with bronchiectasis with those of healthy controls and correlate inflammatory and OS levels with lung function and physical capacity. METHODS: This study used a cross-sectional design. Seventy-four adults with bronchiectasis (age: 49±15 years, forced expiratory volume in 1 second [FEV1]: 52.5±25.6%) and 42 healthy controls (age: 44±17 years, FEV1: 95.9±14.0%) performed cardiopulmonary exercise tests and incremental shuttle walking tests. Their physical activity in daily life, inflammatory cytokine, and antioxidant levels in plasma were measured. RESULTS: Compared to that of the controls, the levels of interleukin (IL)-6 (p<0.001), IL-10 (p<0.001), carbonylated proteins (p=0.001), and superoxide anions (p=0.046) were significantly increased in adults with bronchiectasis. Catalase activity was also reduced in this group (p<0.001). The inflammatory markers IL-1β, IL-6, and tumor necrosis factor-α correlated negatively with aerobic capacity (r=-0.408, r=-0.308, and r=-0.207, respectively). We observed similar correlations with OS markers (thiobarbituric acid and carbonyls; r=-0.290 and r=0.379, respectively), and these markers also significantly correlated with the aerobic capacity. CONCLUSIONS: Adults with bronchiectasis presented an increased systemic inflammatory response that correlated negatively with physical capacity.
  • Core needle biopsy in fibroepithelial tumors: predicting factors for phyllodes tumors Original Article

    Reis, Yedda Nunes; Maesaka, Jonathan Yugo; Shimizu, Carlos; Soares-Júnior, José Maria; Baracat, Edmund Chada; Filassi, José Roberto

    Abstract in English:

    OBJECTIVES: This study aimed to evaluate the clinical and imaging predictive factors for the diagnosis of phyllodes tumors in patients with inconclusive results from core needle biopsy (fibroepithelial lesions). METHODS: We retrospectively analyzed data of patients who underwent surgical excision of breast lesions previously diagnosed as fibroepithelial lesions. Numeric variables were analyzed using the Shapiro-Wilk and t-tests, and categorical variables were analyzed using the chi-square and Fisher’s exact tests. Multivariate logistic regression was performed to calculate odds ratios and detect predictive factors for the diagnosis of PT. RESULTS: A total of 89 biopsy samples were obtained from 77 patients, of which 43 were confirmed as fibroadenomas, 43 as phyllodes tumors, and 3 as other benign, non-fibroepithelial breast lesions. The mean tumor size was 3.61 cm (range, 0.8-10 cm) for phyllodes tumors and 2.4 cm (range, 0.8-7.9 cm) for fibroadenomas. The predictive factor for phyllodes tumor diagnosis was lesion size >3 cm (p<0.001). CONCLUSION: Our data indicate that fibroepithelial lesions of the breast larger than 3 cm are more likely to be phyllodes tumors.
  • Long non-coding RNA KCNQ1 overlapping transcript 1 promotes the progression of esophageal squamous cell carcinoma by adsorbing microRNA-133b Original Article

    Xu, Haitao; Miao, Jing; Liu, Shuai; Liu, Hongjian; Zhang, Lianguo; Zhang, Qingguang

    Abstract in English:

    OBJECTIVE: The long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) exerts vital regulatory functions in diverse tumors. However, the biological function of KCNQ1OT1 in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: KCNQ1OT1 expression was detected in ESCC tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were detected by the CCK-8 assay, EdU assay, flow cytometry analysis, and Transwell experiments, respectively. Bioinformatics analysis, luciferase reporter experiments, and RNA immunoprecipitation assays were used to predict and validate the regulatory relationships between KCNQ1OT1, microRNA-133b (miR-133b) and epidermal growth factor receptor (EGFR). RESULTS: KCNQ1OT1 expression was remarkably upregulated in ESCC tissues and cell lines. Overexpression of KCNQ1OT1 markedly promoted ESCC cell proliferation, migration, and invasion and enhanced the expression of N-cadherin, MMP-2, and MMP-9, but inhibited apoptosis and E-cadherin expression in ESCC cell lines; KCNQ1OT1 knockdown exerted the opposite effects. KCNQ1OT1 could directly bind to miR-133b and suppress its expression, and miR-133b reversed the effects of KCNQ1OT1 overexpression in ESCC cells. MiR-133b reduced the expression of epidermal growth factor receptor (EGFR); further, KCNQ1OT1 activated the phosphatidylinositol 3-kinase/AKT serine/threonine kinase 1 (PI3K/AKT) signaling pathway by repressing miR-133b repression and indirectly upregulating EGFR. KCNQ1OT1 expression was positively correlated with EGFR mRNA expression and negatively correlated with miR-133b expression. CONCLUSION: KCNQ1OT1 facilitates ESCC progression by sponging miR-133b and activating the EGFR/PI3K/AKT pathway.
  • High serum superoxide dismutase activity improves radiation-related quality of life in patients with esophageal squamous cell carcinoma Original Article

    Xue, Nannan; Zhou, Runze; Deng, Ming; Li, Yitong; Hu, Yong; Gao, Liang; Zhang, Yunbo; Song, Xiangyu; Liu, Junqi; Fan, Ruitai

    Abstract in English:

    OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China. Intensity-modulated radiation therapy and volume-modulated arc therapy have become the main treatments for esophageal carcinoma; however, side effects caused by radiotherapy greatly impact the quality of life in these patients. This study aimed to explore the impact of serum superoxide dismutase (SOD) levels on the prognosis of patients with ESCC undergoing radiotherapy. METHODS: Patients aged between 18 and 80 years with lower-middle ESCC who underwent radiotherapy were eligible for this assessment. Adverse events, responses, treatment outcomes, and overall survival (OS) were assessed. Between 2012 and 2014, 195 patients were enrolled, of which 65 were assigned to the low- and high-SOD groups based on their serum SOD values. RESULTS: The baseline characteristics were similar between the two groups, except for the T staging. Adverse events in the low-SOD group were significantly higher than those in the high-SOD group (radiation esophagitis, p=0.007; radiation pneumonitis, p=0.032; leukopenia, p=0.023; thrombocytopenia, p=0.037; anemia, p=0.041). There were no significant differences in response, treatment outcomes, or OS. CONCLUSION: In conclusion, high serum SOD activity improved post-radiotherapy quality of life but did not impact the prognosis of patients with ESCC. To the best of our knowledge, this study is the first to report that serum SOD activity is associated with radiation-induced toxicity and moderately increased radiotherapeutic response in patients with ESCC undergoing radiotherapy.
  • Bodyweight distribution between limbs, muscle strength, and proprioception in traumatic transtibial amputees: a cross-sectional study Original Article

    Fontes Filho, Carlos Henrique da Silva; Laett, Conrado Torres; Gavilão, Ubiratã Faleiro; Campos Jr, José Carlos de; Alexandre, Dângelo José de Andrade; Cossich, Victor R.A.; Sousa, Eduardo Branco de

    Abstract in English:

    OBJECTIVES: To evaluate how transtibial amputation (TT) affects bodyweight distribution, voluntary knee joint position sense (JPS), and quadriceps (QUA) and hamstrings (HAM) strength in prosthetized patients. METHODS: Only TT patients who had been prosthetized for more than one year were included, and an age-paired able-bodied group was used as control. The participants stood on force plates with their eyes open to measure bodyweight distribution between the limbs. Knee voluntary JPS was assessed by actively reproducing a set of given arbitrary joint angles using a video analysis approach, and QUA and HAM strength were assessed isometrically with a hand-held dynamometer. RESULTS: Sixteen TT subjects (age: 39.4±4.8 years) and sixteen age-paired control subjects (age: 38.4±4.3 years) participated in the study. The amputees supported their bodyweight majorly on the sound limb (54.8±8.3%, p<0.001). The proprioceptive performance was similar between the amputated (absolute error (AE): 2.2±1.6°, variable error (VE): 1.9±1.6°, constant error (CE): -0.7±2.0°) and non-amputated limbs (AE: 2.6±0.9°, VE: 2.1±0.9°, CE: 0.02±2.3°), and was not different from that of control subjects (AE: 2.0±0.9°, VE: 1.4±0.4°, CE: -1.1±1.7°). There was a considerable weakness of the QUA and HAM in the amputated limb compared with the sound limb and control subjects (p<0.001 both). CONCLUSIONS: The asymmetric bodyweight distribution in the transtibial amputees was not accompanied by a reduction in knee proprioception. There was significant weakness in the amputated limb, which could be a potential issue when designing rehabilitation programs.
  • Role of cancer ratio and other new parameters in the differential diagnosis of malignant pleural effusion Original Article

    Ren, Zenghua; Xu, Ling

    Abstract in English:

    OBJECTIVES: We compared the diagnostic potential of cancer ratio (CR, serum lactate dehydrogenase [LDH]/pleural fluid adenosine deaminase [pfADA]), cancer ratio plus (CR plus, cancer ratio/pleural lymphocyte percentage), and age/pfADA ratio with pfADA in malignant pleural effusion. METHODS: Data from 100 patients with malignant pleural effusion (MPE) and 119 patients with tuberculous pleural effusion (TPE) were retrospectively collected. PfADA, age/pfADA ratio, CR, and CR plus were compared between patients with MPE and those with TPE in two age groups (≤50 and >50 years). The best cut-off value was determined, and the diagnostic performance was evaluated according to the receiver operating characteristic curve. RESULTS: PfADA was statistically significantly lower while age/pfADA ratio, CR, and CR plus were significantly higher in the MPE group than in the TPE group in both age groups (p<0.05). For patients aged ≤50 years, the differential diagnostic value of pfADA for MPE was better than those of age/pfADA ratio, CR, and CR plus. At a cut-off value of 13.0 U/L, the sensitivity, specificity, and accuracy were 88.9%, 100.0%, and 98.9%, respectively. For patients aged >50 years, the diagnostic performance of CR plus was superior to those of pfADA, age/pfADA ratio, and CR. At a cut-off value of 22.6, the sensitivity, specificity, and accuracy of CR plus for the diagnosis of MPE were 86.8%, 84.6%, and 86.2%, respectively. CONCLUSIONS: The best parameter for diagnosing MPE was different for patients aged ≤50 years and >50 years. For patients aged >50 years, CR plus was a good parameter for the differential diagnosis of MPE. For patients aged ≤50 years, pfADA was better.
  • Combined use of immunohistochemical markers of basal and luminal subtypes in urothelial carcinoma of the bladder: Association with clinicopathological features and outcomes Original Article

    Ravanini, Juliana Naves; Assato, Aline Kawassaki; Wakamatsu, Alda; Alves, Venâncio Avancini Ferreira

    Abstract in English:

    OBJECTIVES: Whole genome expression profiles allow the stratification of bladder urothelial carcinoma into basal and luminal subtypes which differ in histological patterns and clinical behavior. Morpho-molecular studies have resulted in the discovery of immunohistochemical markers that might enable discrimination between these two major phenotypes of urothelial carcinoma. METHODS: We used two combinations of immunohistochemical markers, i.e., cytokeratin (CK) 5 with CK20 and CK5 with GATA3, to distinguish subtypes, and investigated their association with clinicopathological features, presence of histological variants, and outcomes. Upon searching for tumor heterogeneity, we compared the findings of primary tumors with their matched lymph node metastases. We collected data from 183 patients who underwent cystectomy for high-grade muscle-invasive urothelial carcinoma, and representative areas from the tumors and from 76 lymph node metastasis were organized in tissue microarrays. RESULTS: Basal immunohistochemical subtype (CK5 positive and CK20 negative, or CK5 positive and GATA3 negative) was associated with the squamous variant. The luminal immunohistochemical subtype (CK5 negative and CK20 positive, or CK5 negative and GATA3 positive) was associated with micropapillary and plasmacytoid variants. Remarkably, only moderate agreement was found between the immunohistochemical subtypes identified in bladder tumors and their lymph node metastasis. No significant difference in survival was observed when using either combination of the markers. CONCLUSION: This study demonstrates that these three routinely used immunohistochemical markers could be used to stratify urothelial carcinomas of the bladder into basal and luminal subtypes, which are associated with several differences in clinicopathological features.
  • Estradiol prevented intestinal ischemia and reperfusion-induced changes in intestinal permeability and motility in male rats Original Article

    Ricardo-da-Silva, Fernanda Yamamoto; Fantozzi, Evelyn Thaís; Rodrigues-Garbin, Sara; Domingos, Helori Vanni; Oliveira-Filho, Ricardo Martins; Vargaftig, Bernardo Boris; Riffo-Vasquez, Yanira; Breithaupt-Faloppa, Ana Cristina; Tavares-de-Lima, Wothan

    Abstract in English:

    OBJECTIVES: Ischemia and reperfusion (I/R) in the intestine could lead to severe endothelial injury, compromising intestinal motility. Reportedly, estradiol can control local and systemic inflammation induced by I/R injury. Thus, we investigated the effects of estradiol treatment on local repercussions in an intestinal I/R model. METHODS: Rats were subjected to ischemia via the occlusion of the superior mesenteric artery (45 min) followed by reperfusion (2h). Thirty minutes after ischemia induction (E30), 17β-estradiol (E2) was administered as a single dose (280 μg/kg, intravenous). Sham-operated animals were used as controls. RESULTS: I/R injury decreased intestinal motility and increased intestinal permeability, accompanied by reduced mesenteric endothelial nitric oxide synthase (eNOS) and endothelin (ET) protein expression. Additionally, the levels of serum injury markers and inflammatory mediators were elevated. Estradiol treatment improved intestinal motility, reduced intestinal permeability, and increased eNOS and ET expression. Levels of injury markers and inflammatory mediators were also reduced following estradiol treatment. CONCLUSION: Collectively, our findings indicate that estradiol treatment can modulate the deleterious intestinal effects of I/R injury. Thus, estradiol mediates the improvement in gut barrier functions and prevents intestinal dysfunction, which may reduce the systemic inflammatory response.
  • Double-Needle Arthrocentesis with Viscosupplementation in Patients with Temporomandibular Joint Disc Displacement without Reduction Original Article

    Rossini, Rafael; Grossmann, Eduardo; Poluha, Rodrigo L.; Setogutti, Ênio T.; Dos Santos, Marcos Fabio

    Abstract in English:

    OBJECTIVES: Arthrocentesis is the simplest surgical intervention for the temporomandibular joint (TMJ). It can be performed on an outpatient basis at a low cost and with low morbidity. The objective is to release the articular disc by disrupting the adhesion formed between its surfaces and the mandibular fossa through hydraulic pressure generated by irrigation of the upper compartment of the TMJ. Viscosupplementation with hyaluronic acid during or after arthrocentesis improves clinical outcomes, increases mouth opening, and reduces pain levels. The aim of this study was to evaluate the efficiency of arthrocentesis plus hyaluronic acid viscosupplementation through clinical examination and preoperative magnetic resonance imaging in patients with unilateral disc displacement without reduction (DDwoR). METHODS: This analytical retrospective cross-sectional study clinically and radiologically evaluated 72 patients of both sexes with unilateral DDwoR. The following data were collected: sex, pain, age, duration of pain, maximum mouth opening, and patient pain perception on a visual analog scale. TMJ arthrocentesis was performed only once for each of the indicated joints. Data were collected before arthrocentesis (baseline) and at 7, 14, 30, 60, 90, and 180 days after the procedure (final evaluation). RESULTS: Between the baseline and final evaluation, there was a significant reduction in pain (p=0.001) and restoration of articular function. In addition, there was a significant increase in maximum mouth opening (p=0.001). CONCLUSION: Patients with DDwoR undergoing arthrocentesis combined with hyaluronic acid injection showed significant improvement in the perceived pain and maximum mouth opening in the mid-term follow-up periods.
  • A randomized controlled study on an integrated approach to prevent and treat re-adhesion after transcervical resection of moderate-to-severe intrauterine adhesions Original Article

    Pan, Li-Zhen; Wang, Ying; Chen, Xian

    Abstract in English:

    OBJECTIVES: This study aims to compare the clinical efficacy of an integrated approach to prevent and treat the recurrence of moderate-to-severe intrauterine adhesions (IUA) after hysteroscopic transcervical resection of adhesion (TCRA). METHODS: The study included a total of 70 patients with moderate-to-severe IUAs who underwent TCRA. Patients were randomly divided into two groups: treatment group (n=35) and control group n=35). In the treatment group, patients underwent balloon uterine stent placement and artificial cycle as well as received intrauterine perfusion of Danshen injection and oral Chinese medicine. In the control group, patients underwent balloon uterine stent placement and artificial cycle as well as received hyaluronic acid sodium and intrauterine device (IUD). Follow-up was performed after treatment of uterine cavity, menstruation and pregnancy. RESULTS: After 3 months of treatment, we observed a significantly lower rate of intrauterine re-adhesion (45.71% versus 77.14%, p=0.044) and significantly higher clinical efficiency (82.86% versus 77.14%, p=0.025) in the treatment group than those in the control group. After 6 months of treatment, we observed a significantly higher clinical efficiency in the treatment group than that in the control group (88.57% versus 68.57%, p=0.039). During the follow-up period, the pregnancy rate was 45.71% and 37.14% in the treatment group and control group, respectively, although the difference was not statistically significant (p=0.628). CONCLUSIONS: After surgical management of IUA, the integrated treatment combining a uterus stent placement and artificial cycle with Danshen injection and oral Chinese medicine can improve the condition of menstruation, and prevent and treat recurrence of IUA.
  • Overexpression of serum extracellular vesicle microRNA-215-5p is associated with early tumor recurrence and poor prognosis of gastric cancer Original Article

    Zhang, Yunfei; Huang, Fengchang; Xu, Ning; Wang, Jin; Li, Dan; Yin, Liang

    Abstract in English:

    OBJECTIVES: Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC. METHODS: Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC. CONCLUSIONS: Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.
  • A Modified Flexor Tendon Suture Technique Combining Kessler and Loop Lock Flexor Tendon Sutures Original Article

    Yang, Wenfeng; Li, Jvtao; Su, Yuewen; Liang, Wu; Ren, Yuanfei; Dong, Yvjin; Shang, Yaohua; Zhong, Sheng; Xu, Lianchun; Zhang, Tiehui

    Abstract in English:

    OBJECTIVES: In the present study, a novel single knot tenorrhaphy was developed by combining the modified Kessler flexor tendon suture (MK) with the loop lock technique. METHODS: A total of 48 porcine flexor digitorum profundus tendons were collected and randomly divided into six groups. The tendons were transversely cut and then repaired using six different techniques, the MK method, double knot Kessler-loop lock flexor tendon suture (DK), and single knot Kessler-loop lock flexor tendon suture (SK), each in combination with the epitendinous suture (P), and the same three techniques without P. Furthermore, by performing the load-to-failure tests, the biomechanical properties and the time taken to complete a repair, for each tenorrhaphy, were assessed. RESULTS: Compared to the MK+P method, DK+P was more improved, thereby enhancing the ultimate tensile strength. The SK+P method, which required fewer knots than DK+P, was easier to perform. Moreover, the SK+P repair increased the force at a 2-mm gap formation, while requiring lesser knots than DK+P. CONCLUSION: As opposed to the traditional MK+P method, the SK+P method was improved and exhibited better biomechanical properties, which may facilitate early mobilization after the repair.
  • Melatonin can be, more effective than N-acetylcysteine, protecting acute lung injury induced by intestinal ischemia-reperfusion in rat model Original Article

    Leite, Alberto Andrade; Reiter, Russel Joseph; Brandão, Julio Cezar Mendes; Sakae, Thiago Mamoru; Marinho, Marcia; Camargo, Celia Regina; Oliveira-Junior, Itamar Souza

    Abstract in English:

    OBJECTIVES: The current study compared the impact of pretreatment with melatonin and N-acetylcysteine (NAC) on the prevention of rat lung damage following intestinal ischemia-reperfusion (iIR). METHODS: Twenty-eight Wistar rats were subjected to intestinal ischemia induced by a 60 min occlusion of the superior mesenteric artery, followed by reperfusion for 120 min. Animals were divided into the following groups (n=7 per group): sham, only abdominal incision; SS+iIR, pretreated with saline solution and iIR; NAC+iIR, pretreated with NAC (20 mg/kg) and iIR; MEL+iIR, pretreated with melatonin (20 mg/kg) and iIR. Oxidative stress and inflammatory mediators were measured and histological analyses were performed in the lung tissues. RESULTS: Data showed a reduction in malondialdehyde (MDA), myeloperoxidase (MPO), and TNF-alpha in the animals pretreated with NAC or MEL when compared to those treated with SS+iIR (p<0.05). An increase in superoxide dismutase (SOD) levels in the NAC- and MEL-pretreated animals as compared to the SS+iIR group (34±8 U/g of tissue; p<0.05) was also observed. TNF-α levels were lower in the MEL+iIR group (91±5 pg/mL) than in the NAC+iIR group (101±6 pg/mL). Histological analysis demonstrated a higher lung lesion score in the SS+iIR group than in the pretreated groups. CONCLUSION: Both agents individually provided tissue protective effect against intestinal IR-induced lung injury, but melatonin was more effective in ameliorating the parameters analyzed in this study.
  • Claudin-1 and Claudin-3 as Molecular Regulators of Myelination in Leukoaraiosis Patients Original Article

    Chen, Yan; Zheng, Zheng; Mei, Ainong; Huang, Huan; Lin, Fan

    Abstract in English:

    OBJECTIVES: Leukoaraiosis is described as white matter lesions that are associated with cognitive dysfunction, neurodegenerative disorders, etc. Myelin depletion is a salient pathological feature of, and the loss of oligodendrocytes is one of the most robust alterations evident in, white matter degeneration. Recent studies have revealed that claudin proteins are aberrantly expressed in leukoaraiosis and regulate oligodendrocyte activity. However, the roles of claudin-1 and claudin-3 in oligodendrocytes and leukoaraiosis are still not well-defined. METHODS: Quantitative polymerase chain reaction was used to measure the expression of claudin-1 (CLDN1), claudin-3 (CLDN3), and myelinogenesis-related genes such as myelin basic protein (MBP), proteolipid protein (PLP), oligodendrocyte transcription factor 2 (OLIG2), and SRY-box transcription factor 10 (SOX10) in leukoaraiosis patients (n=122) and healthy controls (n=122). The expression of claudin-1 and claudin-3 was either ectopically silenced or augmented in Oli-neu oligodendrocytes, and colony formation, apoptosis, and migration assays were performed. Finally, the expression of myelin proteins was evaluated by western blotting. RESULTS: Our results revealed that in addition to SOX10, the expression levels of claudin-1, claudin-3, and myelinogenesis-related proteins were prominently downregulated in leukoaraiosis patients, compared to those in healthy controls. Furthermore, the growth and migration of Oli-neu cells were downregulated upon silencing claudin-1 or claudin-3. However, the overexpression of claudin-1 or claudin-3 resulted in the reduction of the degree of apoptosis in Oli-neu cells. In addition, claudin-1 and claudin-3 promoted the expression of MBP, OLIG2, PLP, and SOX10 at the translational level. CONCLUSION: Our data has demonstrated that the abnormal expression of claudin-1 and claudin-3 regulates the pathological progression of leukoaraiosis by governing the viability and myelination of oligodendrocytes. These findings provide novel insights into the regulatory mechanisms underlying the roles of claudin-1 and claudin-3 in leukoaraiosis.
  • Efficacy and safety of umbilical cord mesenchymal stem cells for the treatment of patients with COVID-19 Original Article

    Wei, Fengtao; Kong, Dexiao; Li, Tao; Li, Ai; Tan, Yi; Fang, Jinfeng; Zhuang, Xianghua; Lai, Chao; Xu, Weihua; Dong, Hong; Ma, Chengen; Hong, Ke; Cui, Yuqin; Tang, Shengbin; Yu, Fenggang; Zheng, Chengyun

    Abstract in English:

    OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.
  • Risk Factors Associated with Postoperative Infection in Cancer Patients Undergoing Spine Surgery Original Article

    Tavares-Júnior, Mauro Costa Morais; Cabrera, Gabriela Estefania Delgado; Teixeira, William Gemio Jacobsen; Narazaki, Douglas Kenji; Ghilardi, Cesar Salge; Marcon, Raphael Martus; Cristante, Alexandre Fogaça; Barros-Filho, Tarcisio Eloy Pessoa de

    Abstract in English:

    OBJECTIVES: To determine the rate of and main risk factors for postoperative infection in cancer patients who underwent spine surgery in the last 5 years in order to determine whether there is an association between postoperative infection and increased mortality during hospitalization. METHODS: All cancer patients who underwent surgical procedures between January 2015 and December 2019 at a single hospital specializing in spine cancer surgery were analyzed. The primary outcome of interest was postoperative infection. Bivariate logistic regression was used to estimate the odds ratio and 95% confidence interval for each variable in relation to the occurrence of infection. RESULTS: We evaluated 324 patients, including 176 men (54.3%) and 148 women (45.7%) with a mean age of 56 years. The incidence of postoperative infection was 20.37%. Of the 324 patients, 39 died during hospitalization (12%). CONCLUSIONS: Surgical time greater than 4 hours, surgical instrumented levels greater than 6, and an Eastern Cooperative Oncology Group of 3 or 4 were associated with an increased risk of postoperative infection, but these factors did not lead to an increase in mortality during hospitalization.
  • Multilayer stents affect the final diameter of aortic aneurysms and maintain renal artery patency for a short time in a swine experimental model Original Article

    Baptista-Strazzi, Anna Paula Weinhardt; Aun, Ricardo; Sincos, Igor Rafael; Tobita, Allana M.; Portugal, Maria Fernanda Cassino; Paula, Vitória Penido de; Kaufmann, Oskar; Wolosker, Nelson

    Abstract in English:

    OBJECTIVES: We sought to analyze the hemodynamic effects of the multilayer flow-modulated stent (MFMS) in Thoracoabdominal aortic aneurysms (TAAAs). METHODS: The hemodynamic effects of MFMS were analyzed in aortic thoracoabdominal aneurysms in experimental swine models. We randomly assigned 18 pigs to the stent or control groups and underwent the creation of an artificial bovine pericardium transrenal aneurysm. In the stent group, an MFMS (Cardiatis, Isnes, Belgium) was immediately implanted. After 4 weeks, we evaluated aneurysm sac thrombosis and renal branch patency by angiography, duplex scan, and morphological analysis. RESULTS: All the renal arteries remained patent after re-evaluation in both groups. Aneurysmal sac thrombosis was absent in the control group, whereas in the stent group it was present in 66.7% of aneurysmal sacs (p=0.061). The mean final aneurysm sac diameter was significantly lower in the stent group (mean estimated reduction, 6.90 mm; p=0.021). The proximal neck diameter decreased significantly in the stent group (mean difference, 2.51 mm; p=0.022) and grew significantly in the control group (mean difference, 3.02 mm; p=0.007). The distal neck diameter increased significantly in the control group (mean difference, 3.24 mm; p=0.017). There were no significant findings regarding distal neck measurements in the stent group. CONCLUSION: The MFMSs remained patent and did not obstruct the renal arteries within 4 weeks. In the stent group, the device was also associated with a significant decrease in aneurysmal sac diameter and a large proportion (albeit non-significant) of aneurysmal sac thrombosis.
  • Short-term survival in extensive craniofacial resections Original Article

    Leite, Ana Kober N.; Alvarenga, Gustavo Fernandes de; Gonçalves, Sérgio; Santos, Alexandre Bezerra dos; Sterman Neto, Hugo; Cernea, Claudio R.; Kulcsar, Marco Aurélio V.; Kowalski, Luiz Paulo; Matos, Leandro Luongo

    Abstract in English:

    OBJECTIVES: Craniofacial resection (CFR) procedures for craniofacial tumors with cranial extension are often extensive. Although CFRs may yield good oncological results, there are concerns about high perioperative morbidity and mortality. This study aimed to determine risk factors for perioperative mortality after open CFR in terms of deaths occurring during index hospitalizations. METHODS: We conducted a retrospective analysis of CFRs conducted at a tertiary oncology hospital from May 2009 through December 2018. RESULTS: Our analysis included data from the medical records of 102 patients, the majority of whom were male (n=74, 72.5%). The mean age was 61 years (±18.3 years). Skin malignancies (n=64, 63.4%) accounted for nearly two-thirds of the treated tumors, and most of these were squamous cell carcinoma. Postoperative medical complications occurred in 33 patients (33%), and surgical complications occurred in 48 (47%). Multivariate analysis revealed the only independent risk factors for perioperative deaths to be the presence of intracranial tumor extension on preoperative imaging (hazard ratio [HR]=4.56; 95% confidence interval [CI]: 1.74-11.97; p=0.002) and the unexpected emergence of postoperative neurological dysfunction (HR=10.9; 95% CI: 2.21-54.3; p=0.003). CONCLUSIONS: In our study, factors related to tumor extension were associated with a higher risk of perioperative death.
  • Continuous peripheral nerve block for in-patients with lower limb ischemic pain Original Articles

    Fernandes, Hermann dos Santos; Ximenes, Jorge Luiz Saraiva; Taguchi, Paloma Kiyomi; Espada, Eloisa Bonetti; Gouvêa, Áquila Lopes; Vieira, Joaquim Edson; Ashmawi, Hazem Adel

    Abstract in English:

    OBJECTIVES: Demonstrate that continuous peripheral nerve block (CPNB) may be an alternative with adequate analgesia and a lower incidence of side effects for ischemic pain due peripheral obstructive arterial disease (POAD). METHODS: Retrospective cohort study with 21 patients with POAD, Fontaine IV graded, with foot pain. Patients were submitted to continuous sciatic nerve block (CSNB), through a perineural catheter. Primary outcomes were pain intensity (by numerical rating scale) and opioid consumption (in oral morphine equivalents). RESULTS: During CSNB, pain scores markedly decreased in comparison to the pre-block period. CONCLUSIONS: CPNB may be a good option for ischemic pain treatment in in-patients, as it provides effective pain control with fewer adverse effects.
  • Home-based training program in patients with chronic heart failure and reduced ejection fraction: a randomized pilot study Original Article

    Andrade, Geisa Nascimento de; Umeda, Iracema Ioco Kikuchi; Fuchs, Angela Rubia Cavalcanti Neves; Mastrocola, Luiz Eduardo; Rossi-Neto, João Manoel; Moreira, Dalmo Antonio Ribeiro; Oliveira, Patricia Alves de; André, Carmen Diva Saldiva de; Cahalin, Lawrence Patrick; Nakagawa, Naomi Kondo

    Abstract in English:

    OBJECTIVES: We aimed to compare the effects of home-and center-based exercise training programs on functional capacity, inspiratory muscle strength, daily physical activity level, and quality of life (QoL) in patients with chronic heart failure (CHF) over a 12-week period. METHODS: This study included 23 patients with CHF (left ventricular ejection fraction 31±6%) randomized to a home-based (n=11) or center-based (n=12) program. Patients underwent 12 weeks of aerobic training (60%-70% heart rate reserve): walking for the home-based and supervised cycling for the center-based group, both combined with resistance training (50% of 1 maximum repetition). At baseline and after 12 weeks of training, we assessed cardiopulmonary test variables, 6-min walk test distance (6 MWD), steps/day with accelerometry, and QoL (Minnesota Living with Heart Failure questionnaire). Maximal inspiratory pressure and handgrip strength were measured at baseline and after 4, 8, and 12 weeks of training. ClinicalTrials.gov: NCT03615157. RESULTS: There were no adverse events during training in either group. The home- and center-based training groups obtained similar improvements in peak oxygen uptake, maximal ventilation, and 6 MWD. However, there were significant between-group differences: center-based training was more effective in improving maximal inspiratory pressure (p=0.042), number of steps/day (p=0.001), and QoL (p=0.039). CONCLUSIONS: Home-based training is safe and can be an alternative to improve the exercise capacity of patients with stable CHF. However, center-based training was superior in improving inspiratory muscle strength, QoL, and daily physical activity.
  • Predictive performance of critical illness scores and procalcitonin in sepsis caused by different gram-stain bacteria Original Article

    Yan, ShengTao; Zhang, GuoQiang

    Abstract in English:

    OBJECTIVES: To compare the early and late predictive values of several critical illness scores (CISs) and biomarkers in sepsis-3 patients with bloodstream infections (BSIs) and to identify the prognostic value of procalcitonin (PCT) for different gram-stain bacteria infections. METHODS: Patients with at least one positive blood culture within 24h of emergency department admission and with a final diagnosis of sepsis/septic shock were enrolled. CISs were calculated based on the first parameters on the day of admission. The receiver operating characteristics curve was used to analyze the predictive value of CISs and biomarkers for early and late mortality. RESULTS: Of 834 enrolled patients with sepsis-3, death occurred in 214 patients within 28 days and in 273 patients within 60 days. Compared with biomarkers, CISs showed a significantly higher area under the curve (AUC) in the prediction of early and late mortality (p<0.01), especially for patients with GNB infection. The Sequential Organ Failure Assessment score showed a higher AUC for predicting early mortality than the Mortality in Emergency Department Sepsis score (p=0.036). Compared with GNB infections, the AUC values of the PCT for gram-positive bacteria (GPB) infections were higher for predicting early or late mortality; PCT showed higher AUC than high-sensitivity C-reactive protein and white blood cells for predicting early mortality (p<0.05). CONCLUSIONS: CISs were more advantageous in the assessment of early and late prognosis, especially for patients with GNB infections; however, for sepsis with GPB infection, PCT can be used for the prediction of early mortality.
  • Clinical and echocardiographic predictors of left ventricular remodeling following anterior acute myocardial infarction Original Article

    Silveira, Caroline Ferreira da Silva Mazeto Pupo da; Malagutte, Karina Nogueira Dias Secco; Nogueira, Bruna Franco; Reis, Fabrício Moreira; Rodrigues, Cássia da Silva Antico; Rossi, Daniele Andreza Antonelli; Okoshi, Katashi; Bazan, Rodrigo; Martin, Luis Cuadrado; Minicucci, Marcos Ferreira; Bazan, Silméia Garcia Zanati

    Abstract in English:

    OBJECTIVES: Coronary artery disease is the primary cause of death and is responsible for a high number of hospitalizations worldwide. Ventricular remodeling is associated with worse prognosis following ST-segment elevation myocardial infarction (STEMI) and is a risk factor for ventricular dysfunction and heart failure. This study aimed to identify the predictors of ventricular remodeling following STEMI. Additionally, we evaluated the clinical, laboratory, and echocardiographic characteristics of patients with anterior wall STEMI who underwent primary percutaneous intervention in the acute phase and at 6 months after the infarction. METHODS: This prospective, observational, and longitudinal study included 50 patients with anterior wall STEMI who were admitted to the coronary care unit (CCU) of a tertiary hospital in Brazil between July 2017 and August 2018. During the CCU stay, patients were evaluated daily and underwent echocardiogram within the first three days following STEMI. After six months, the patients underwent clinical evaluation and echocardiogram according to the local protocol. RESULTS: Differences were noted between those who developed ventricular remodeling and those who did not in the mean±standard deviation levels of creatine phosphokinase MB isoenzyme (CKMB) peak (no remodeling group: 323.7±228.2 U/L; remodeling group: 522.4±201.6 U/L; p=0.008) and the median and interquartile range of E/E’ ratio (no remodeling group: 9.20 [8.50-11.25] and remodeling group: 12.60 [10.74-14.40]; p=0.004). This difference was also observed in multivariate logistic regression. CONCLUSIONS: Diastolic dysfunction and CKMB peak in the acute phase of STEMI can be predictors of ventricular remodeling following STEMI.
  • Biomechanical evaluation in runners with Achilles tendinopathy Original Article

    Andere, Nathalie Ferrari Bechara; Godoy-Santos, Alexandre Leme; Mochizuki, Luis; Rodrigues, Marcelo Bordalo; Fernandes, Túlio Diniz; Soares-Júnior, José Maria; Alonso, Angélica Castilho; Luna, Natália Mariana Silva; Brech, Guilherme Carlos; Greve, Júlia Maria D’Andréa

    Abstract in English:

    OBJECTIVES: To evaluate the clinical characteristics, ground reaction force (GRF), and function of the plantar muscles and dorsiflexors of the ankle in runners with and without Achilles tendinopathy (AT) and in non-runners. METHODS: Seventy-two participants (42 men, 30 women; mean age: 37.3±9.9 years) were enrolled in this cross-sectional study and divided into three groups: AT group (ATG, n=24), healthy runners’ group (HRG, n=24), and non-runners’ group (NRG, n=24). Both ankles were evaluated in each group. The American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale was used for clinical and functional evaluation. GRF was evaluated using force plates and muscle strength was evaluated using an isokinetic dynamometer. RESULTS: The AOFAS scores were lower in the ATG. The strike impulse was higher in the ATG than in the HRG and NRG. However, GRF was similar among the groups. The ATG exhibited lower total work at 120°/s speed than the HRG. The peak torque in concentric dorsiflexion was lower in the NRG than in the ATG and HRG. The peak torque and total work in concentric plantar flexion were lower in the NRG than in the ATG. The peak torque and total work in eccentric plantar flexion were lower in the NRG than in the ATG and HRG. CONCLUSION: Runners with AT showed higher strike impulse, lower muscle strength of the plantar flexors, and higher clinical and functional damage.
  • Brazilian version of Calgary-Cambridge Observation Guide 28-item version: cross-cultural adaptation and psychometric properties Original Article

    Dohms, Marcela C.; Collares, Carlos Fernando; Tiberio, Iolanda Calvo

    Abstract in English:

    OBJECTIVES: The search for appropriate tools to assess communicational skills remains an ongoing challenge. The Calgary-Cambridge Observation Guide (CCOG) 28-item version can measure and compare performance in communication skills training. Our goal was to adapt this version of the CCOG for the Brazilian cultural context and perform a psychometric quality analysis of the instrument. METHODS: Experienced preceptors (35) assessed videos of five medical residents with a simulated patient using the translated guide. For the cultural adaptation, we followed the methodological norms on synthesis, retro-translation, committee review, and testing. We obtained validity evidence for the CCOG 28-item version using confirmatory factor analysis and the Many-Facet Rasch Model (MFRM). RESULTS: Confirmatory factor analysis indicated an adequate level of goodness-of-fit. The MFRM reliability coefficient was high in all facets, namely assessors (0.90), stations (0.99), and items (0.98). The assessors had greater difficulty with attitudinal items, such as demonstration of respect, confidence, and empathy. CONCLUSIONS: The psychometric indicators of the tool were adequate, a good potential for reproducing its Brazilian version as well as acceptable reliability for its use.
  • Statistical analysis for efficacy of tirofiban combined with ozagrel in the treatment of progressive cerebral infarction patients out of thrombolytic therapy time window Original Article

    Zhang, Huiying; Zheng, Lei

    Abstract in English:

    OBJECTIVES: To investigate the safety and efficacy of combined tirofiban-ozagrel therapy for treating progressive stroke patients out of thrombolytic therapy time window. METHODS: This prospective, double-blind, randomized controlled study included 337 patients who had experienced an acute ischemic stroke between November 2017 and December 2018. All patients were randomized into three groups: 1) the tirofiban/ozagrel group (n=113), 2) the tirofiban group (n=110), and 3) the ozagrel group (n=114). The platelet aggregation (PAG), thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) levels in the patients from these groups were evaluated before starting treatment and then, at 24h, 7 days, and 14 days after treatment. The National Institutes of Health Stroke Scale (NIHSS) scores were evaluated before treatment and then, 24h, 1 week, 2 weeks, and 4 weeks after treatment. The Barthel Index (BI) score was used to measure safety, and the modified Rankin scale (mRS) was used to evaluate disability following 3 months of treatment. The risk factors affecting clinical outcomes were analyzed using logistic multivariate regression. RESULTS: The mean NIHSS score for all the patients was 13.17±3.13 before treatment, and no significant difference between the basic clinical parameters of the three patient groups was found. Following treatment, both PAG and FIB were significantly reduced compared with the baseline (p<0.05). The levels of PAG and FIB in the tirofiban/ozagrel group were significantly lower than those in the tirofiban and ozagrel groups at 24h and 7 days after treatment (p<0.05). The NIHSS score decreased significantly in all treatment groups (p<0.05). The tirofiban/ozagrel NIHSS scores were significantly lower than that of the tirofiban and ozagrel groups at 24h, 1 week, and 2 weeks post initiation (p<0.05 for all). There were no significant differences in the BI and mRS scores or the intracranial hemorrhage rates; further, age, sex, Trial of ORG 10172 in acute stroke treatment (TOAST) type, baseline NIHSS and 24-h NIHSS scores, baseline thrombus-related factors, and treatment methods were shown to not be independent risk factors for clinical outcomes. CONCLUSION: The combination of tirofiban and ozagrel, as well as monotherapy with either tirofiban or ozagrel, transiently improves the neural function of patients and reduces platelet aggregation and fibrinogen formation in the first 4 weeks following a stroke event; additionally, none of these treatments increased the risk for hemorrhage in these progressive stroke patients over a 3-month period.
  • Building an outpatient telemedicine care pilot using Scrum-like framework within a medical residency program Original Article

    Bin, Kaio Jia; Higa, Natalia; da Silva, Jéssica Helena; Quagliano, Daniele Abud; Hangai, Rosemeire Keiko; Cobello-Júnior, Vilson; Pereira, Antonio José Rodrigues; Carneiro-D'Albuquerque, Luiz Augusto; Carrilho, Flair José; Wen, Chao Lung; Ono, Suzane Kioko

    Abstract in English:

    OBJECTIVES: A good health care does not only depend on good medical practice, but also needs great management of its resources, which are generally short. In this sense, PROAHSA has been training new health managers since 1972. With the arrival of the COVID-19 pandemic, it was clear that medicine will go through a new phase, where telehealth will be present in this “Improved Normal”. This report is about how a pilot teleconsultation study was carried out for HCFMUSP patients through the Scrum-like framework. It is to deploy a pilot of remote assistance involving a doctor and a patient in the Ambulatory of Hepatology and Liver Transplantation of HCFMUSP. METHODS: We applied the Scrum-like framework to carry out this work with an interdisciplinary multifunctionality team. RESULTS: A full telemedicine service flow was implemented within eight weeks using existing infrastructure and resources implementing the Scrum methodology. Twenty-three teleconsultations were scheduled and eight guides built. CONCLUSION: Scrum framework has a great potential to improve the training of students and to conclude pilot projects.
  • Rehabilitation of patients after COVID-19 recovery: An experience at the Physical and Rehabilitation Medicine Institute and Lucy Montoro Rehabilitation Institute Original Article

    Imamura, Marta; Mirisola, Aline Rossetti; Ribeiro, Fernando de Quadros; De Pretto, Lucas Ramos; Alfieri, Fábio Marcon; Delgado, Vinicius Ramos; Battistella, Linamara Rizzo

    Abstract in English:

    OBJECTIVES: As patients recovering from the novel coronavirus disease 2019 (COVID-19) present with physical, respiratory, cognitive, nutritional, and swallowing-related impairments and mental health complications, their rehabilitation needs are complex. This study aimed to describe the demographic, clinical, and functional status after the discharge of COVID-19 survivors who underwent intensive multidisciplinary inpatient rehabilitation at the Physical and Rehabilitation Medicine Institute of the University of Sao Paulo Medical School General Hospital and Lucy Montoro Rehabilitation Institute. We determined the most important factors related to the length of inpatient rehabilitation treatment and present the functional outcomes. METHODS: This was a retrospective study based on electronic medical records. In addition to the severity of COVID-19 and length of hospital stay for the management of COVID-19 and comorbidities, we collected sociodemographic data including age, sex, height, and weight. Functional assessments were performed using the Functional Independence Measure (FIM); Short Physical Performance Battery; Montreal Cognitive Assessment; Depression, Anxiety and Stress Scale; Revised Impact of Events Scale; bioelectrical impedance; Functional Oral Intake Scale; oropharyngeal dysphagia classification; and nutritional assessment. RESULTS: There was a significant improvement in FIM before and after inpatient rehabilitation treatment (p<0.0001). Muscle strength and walking capacity were significantly improved (p<0.01). The most important factors related to the length of inpatient rehabilitation treatment were improvement in FIM scores (Spearman’s r=0.71) and gain in lean mass (Spearman’s r=0.79). CONCLUSIONS: Rehabilitation of patients after COVID-19 recovery improves their functional status and should be considered in the post-acute phase for selected patients with COVID-19.
  • Pulmonary function evaluation after hospital discharge of patients with severe COVID-19 Original Article

    Polese, Jessica; Sant’Ana, Larissa; Moulaz, Isac Ribeiro; Lara, Izabella Cardoso; Bernardi, Julia Muniz; Lima, Marina Deorce de; Turini, Elaína Aparecida Silva; Silveira, Gabriel Carnieli; Duarte, Silvana; Mill, José Geraldo

    Abstract in English:

    OBJECTIVES: Coronavirus disease 2019 (COVID-19) may be associated with prolonged symptoms and post-recovery health impairment. This study aimed to evaluate the persistence of symptoms, lung function, and pulmonary diffusion for carbon monoxide (DLCO) in patients between 15 and 30 days after hospital discharge after admission for severe COVID-19. METHODS: The evaluation consisted of 1) comparative analysis between the initial symptoms and symptoms still present at the post-discharge evaluation 2) analysis of the chest images obtained during hospitalization, and 3) conducting spirometry, plethysmography, and DLCO assessment. RESULTS: Forty-one patients who were hospitalized for 16±8 days with severe COVID-19 were included. Patients were predominantly men (73%) and had a mean age of 51±14 years. The most frequent comorbidities were arterial hypertension (51%) and diabetes mellitus (37%). Pulmonary evaluation was performed a mean of 36 days after the onset of symptoms, with the most frequent persistent symptoms being dyspnea (83%) and coughing (54%). Approximately 93% of patients still had at least one symptom, and 20% had more than five symptoms. Chest imaging revealed a typical pattern of COVID-19 on X-ray (93%) and computer tomography (95%). Lung function test results showed a restrictive pattern with a reduction in forced vital capacity (FVC) in 54% of individuals, with an average FVC of 78±14%. A reduction in DLCO was observed in 79% of patients. CONCLUSIONS: We observed a high prevalence of symptoms, in addition to a significant change in lung function and DLCO, in the post-discharge assessment of patients requiring hospitalization after admission for COVID-19.
  • Current Status of Antimicrobial Stewardship Programs in São Paulo Hospitals Original Article

    Sato, Silvia Akemi; Brandão, Denise Assis; Madalosso, Geraldine; Levin, Anna S.; Perdigão Neto, Lauro Vieira; Oliveira, Maura Salaroli

    Abstract in English:

    OBJECTIVES: Antimicrobial stewardship programs (ASPs) comprise coordinated interventions designed to improve antimicrobial use. Understanding the current structure of ASP hospitals will support interventions for the improvement of these programs. This study aimed to describe the status of ASPs in hospitals in São Paulo, Brazil. METHODS: A cross-sectional survey was conducted on the ASPs of hospitals in the state of São Paulo from March to July 2018. Through interviews by telephone or e-mail, we queried which components of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and Centers for Disease Control and Prevention guidelines were implemented. RESULTS: The response rate was 30% (28/93 hospitals), and 26 hospitals (85%) reported having a formal ASP. The most frequently implemented strategies were antimicrobial surgical prophylaxis guidelines (100%), empiric sepsis guidelines (93%), and the presence of ASP team members during bedside rounds (96%). The least commonly implemented strategies included prior authorization for all antimicrobials (11%), pharmacokinetic monitoring, and an adjustment program for patients on IV aminoglycosides (3%). Regarding the metrics of the ASP, the most common indicator was the rate of antimicrobial resistance (77%). Eighteen hospitals evaluated antimicrobial consumption using defined daily dose, and only 29% evaluated the days of therapy; 61% of hospitals reported their results to the hospital administration and 39% to the prescribers. CONCLUSIONS: Most hospitals have a formal and active ASP, but with timely actions. We observed inconsistencies between what program leaders understand as the main objective of ASP and the metrics used to evaluate it. Part of the effort for the next few years should be to improve program evaluation metrics and to provide feedback to physicians and hospital leadership.
  • Symptoms of anxiety and depression in patients with primary hyperhidrosis and its association with the result of clinical treatment with oxybutynin Original Article

    Kamikava, Débora Yumi Ferreira; Wolosker, Nelson; Silva, Marcelo Fiorelli Alexandrino da; Campos, José Ribas Milanez de; Puech-Leão, Pedro

    Abstract in English:

    OBJECTIVES: Studies have identified correlations between the psychological characteristics of individuals with primary hyperhidrosis (HH), the degree of sweating, and the quality of life (QoL). This study aimed to evaluate the prevalence of anxiety and depression symptoms in patients with HH before and after oxybutynin treatment. METHODS: Data were collected from 81 patients. Palmar or axillary HH was the most frequent complaint (84.0%). All patients were evaluated before the medication was prescribed and after five weeks of treatment. The Beck Depression Inventory and Beck Anxiety Inventory were used to evaluate depression and anxiety. RESULTS: Improvement in HH occurred in 58 patients (71.6%), but there was no improvement in 23 patients (28.4%). The QoL before treatment in all patients was either “poor” or “very poor.” Patients who experienced improvement in sweating rates also experienced a greater improvement in QoL than patients who did not experience improvement in sweating at the main site (87.9% vs. 34.7%) (p<0.001). A total of 19.7% of patients showed an improvement in their level of depression, and a total of 46.9% of patients exhibited improvements in their level of anxiety. A significant correlation was observed between sweating and anxiety (p=0.015). CONCLUSION: Patients with HH who experienced improvements in sweating immediately after treatment with oxybutynin exhibited small improvements in their levels of depression and significant improvements in their levels of anxiety and QoL.
  • Mental health and the COVID-19 pandemic: a study of medical residency training over the years Original Article

    Mendonça, Vitor S.; Steil, Amanda; Góis, Aécio F.T.

    Abstract in English:

    OBJECTIVES: This study aims to assess the symptoms of burnout, depression, and anxiety in Brazilian medical residents during the COVID-19 pandemic and to compare residents’ beliefs and clinical practices related to COVID-19 patients among all six years of medical residency training in Brazil. METHODS: A quantitative study was conducted in April 2020 with a convenience sample of medical resident volunteers from an anonymous online survey. This investigation collected sociodemographic information and used the Oldenburg Burnout Inventory (OLBI) to measure burnout, the Patient Health Questionnaire (PHQ-9) to measure depression, and the General Anxiety Disorders (GAD-7) to measure generalized anxiety disorder. This study also developed a COVID-19 Impact Questionnaire (CIQ-19) to assess the residents’ beliefs and clinical practices related to COVID-19 patients. RESULTS: Our sample comprised 3071 respondents. Depressive symptoms were the most common among second-year residents (70.5%), followed by anxiety symptoms (56.0%) and burnout (55.2%) among fourth-year residents. We also observed burnout symptoms (55.1%) among second-year residents. CONCLUSION: The COVID-19 pandemic increased the risk of mental illnesses in some years of residency. Our study could not conclude the reasons why the incidence varies among levels of physician training. Final year medical residents have avoided seeing COVID-19 patients.
  • Risk stratification in acute variceal bleeding: Far from an ideal score Original Article

    Aluizio, Carla Luiza de Souza; Montes, Ciro Garcia; Reis, Glaucia Fernanda Soares Ruppert; Nagasako, Cristiane Kibune

    Abstract in English:

    OBJECTIVES: Acute variceal bleeding (AVB) results from rupture of esophageal or gastric varices. It is a life-threatening complication of portal hypertension. Nevertheless, it remains unclear how to predict adverse outcomes and identify high-risk patients. In variceal hemorrhage, high Child-Turcotte-Pugh (Child) and Model for End-stage Liver Disease (MELD) scores are associated with a worse prognosis. The Rockall system (Rockall), Glasgow-Blatchford (Blatchford), and AIMS65 scores have been validated for risk stratification for nonvariceal upper gastrointestinal bleeding; however, their use is controversial in AVB. The aim of this study was to compare the performance of Child, MELD, Rockall, Blatchford, and AIMS65 scores in risk stratification for rebleeding and/or mortality associated with AVB. METHODS: This retrospective study was conducted at a tertiary care hospital over 42 months. The outcomes were 6-week rebleeding and mortality. The AUROC was calculated for each score (1-0.9, 0.9-0.8, and 0.8-0.7, indicating excellent, good, and acceptable predictive power, respectively). RESULTS: In total, 222 patients were included. Six-week rebleeding and mortality rates were 14% and 18.5%, respectively. No score was useful for discriminating patients at a higher risk of rebleeding. The AUROCs were 0.59, 0.57, 0.61, 0.63, and 0.56 for Rockall, Blatchford, AIMS65, Child, and MELD scores, respectively. Prediction of 6-week mortality based on Rockall (AUROC 0.65), Blatchford (AUROC=0.60), and AIMS65 (AUROC=0.67) scores were also not considered acceptable. The AUROCs for predicting mortality were acceptable for Child and MELD scores (0.72 and 0.74, respectively). CONCLUSION: Rockall, Blatchford, and AIMS65 scores are not useful for predicting 6-week rebleeding or mortality in patients with AVB. Child and MELD scores can identify patients at higher risk for 6-week mortality but not for 6-week rebleeding.
  • Combination of Dendrobium Mixture and Metformin Curbs the Development and Progression of Diabetic Cardiomyopathy by Targeting the lncRNA NEAT1 Original Article

    Qin, Wenmin; Zhao, Xing; Tai, Jie; Qin, Guoyun; Yu, Shanshan

    Abstract in English:

    OBJECTIVES: This study aimed to explore the efficacy of combination treatment with dendrobium mixture and metformin (Met) in diabetic cardiomyopathy (DCM) and its effects on NEAT1 and the Nrf2 signaling pathway. METHODS: H9c2 cells were maintained in medium supplemented with either low (5.5 mmol/L) or high (50 mmol/L) glucose. Male Sprague-Dawley rats were fed a high-glucose diet and administered a single, low dose of streptozotocin (35 mg/kg) via intraperitoneal injection to induce the development of DM. After induction of DM, the rats were treated with dendrobium mixture (10 g/kg) and Met (0.18 g/kg) daily for 4 weeks. Next, quantitative reverse transcription (qRT)-PCR and western blotting were performed to evaluate the expression levels of target genes and proteins. Flow cytometry was performed to assess apoptosis, and hematoxylin and eosin staining was performed to evaluate the morphological changes in rat cardiac tissue. RESULTS: In patients with diabetes mellitus (DM) and myocardial cells and heart tissues from rats with high glucose-induced DM, NEAT1 was downregulated, and the expression levels of Nrf2 were decreased (p<0.01, p<0.001). The combination of dendrobium mixture and Met upregulated the expression of NEAT1 which upregulated Nrf2 by targeting miR-23a-3p, resulting in reduced apoptosis and improved cardiac tissue morphology (p<0.01, p<0.001). CONCLUSION: Dendrobium mixture and Met upregulated the expression of NEAT1 in DCM, thereby inhibiting apoptosis of myocardial cells.
  • Effect of tumor and normal lung volumes on the lung volume–dose parameters of IMRT in non–small-cell lung cancer Original Article

    Zou, Xi; Lan, Linzhen; Zheng, Lijing; Chen, Jinmei; Guo, Feibao; Cai, Chuanshu; Hong, Jinsheng; Zhang, Weijian

    Abstract in English:

    OBJECTIVES: To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT). METHODS: The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20). RESULTS: The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001). CONCLUSION: The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).
  • Mental health in medical students during COVID-19 quarantine: a comprehensive analysis across year-classes Original Article

    Perissotto, Thais; Silva, Thamires Clair Rodrigues Pereira da; Miskulin, Fabricio Petermann Choueiri; Pereira, Mariana Berwerth; Neves, Beatriz Astolfi; Almeida, Beatriz Cantieri; Casagrande, Amanda Victoria; Ribeiz, Salma Rose Imanari; Nunes, Paula Villela

    Abstract in English:

    OBJECTIVES: The COVID-19 pandemic brought abrupt changes when quarantine measures were implemented. Most medical students had distance learning as their main content delivery mode, but in clerkship (fifth and sixth years), in-person activities were maintained under new protocols. These different modes may have affected student mental health. This study examines mental burden and empathy in medical students during the beginning of the COVID-19 pandemic according to the year of attendance. METHODS: All students attending first to the sixth year in the same medical school were invited to participate. The Hospital Anxiety and Depression Scale (HADS), the Self-Reporting Questionnaire (SRQ-20), the Interpersonal Reactivity Index (IRI), and the Mindful Attention Awareness Scale (MAAS) were provided. RESULTS: HADS scores for Anxiety and Depression (n=347) were 9.8±4.3 and 7.1±3.6, respectively; the SRQ-20 (n=373) score was 8.1±4.5; all scores were negatively correlated with the year of attendance. IRI (n=373) scores were: 2.6±0.5 (Empathic Concern), 2.7±0.7 (Perspective Taking), 2.5±0.9 (Fantasy), and 1.7±0.7 (Personal Distress). Fantasy was negatively correlated with the year of attendance. MAAS scores were positively correlated with the year of attendance. Worse mental health scores were found for first-year students across all scales. CONCLUSIONS: We found high levels of mental burden in medical students in the early period of the COVID-19 pandemic, especially in first-year students, who may have fewer resources to deal with stress. Moreover, as they entered college a short time before the pandemic, they were unable to experience academic life fully or create important new social support networks to deal with adversities.
  • Increased Serum Interleukin-6 and Tumor Necrosis Factor Alpha Levels in Fabry Disease: Correlation with Disease Burden Original Article

    Rosa Neto, Nilton Salles; Bento, Judith Campos de Barros; Caparbo, Valéria de Falco; Pereira, Rosa Maria Rodrigues

    Abstract in English:

    OBJECTIVES: Fabry disease (FD) is an X-linked lysosomal disease caused by variants of the GLA gene; the formation of defective alpha-galactosidase A contributes to the accumulation of substrates in several organs. Chronic inflammation is thought to contribute to organ damage in FD patients. METHODS: In total, 36 classic FD patients (15 men/21 women) and 25 healthy controls (20 men/8 women) were assessed. The Mainz Severity Score Index (MSSI) was established after conducting interviews with the patients and chart review. Serum IL-6, IL-1β, and TNF-α levels were evaluated in both groups. RESULTS: The mean age (years) for FD patients was 43.1±15.4 and that for the controls was 47.4±12.2 (p>0.05). Twenty-two patients (59.5%) were treated with enzyme replacement therapy (ERT). Serum IL-6 and TNF-α levels were significantly higher in FD patients than in the controls. Patients treated with ERT had higher serum IL-6 and TNF-α levels than those not treated with ERT. There was no difference in the serum IL-1β levels between patients treated with ERT and those who were not. The MSSI scores in the patients were correlated with serum levels of IL-6 (r=0.60, p<0.001) and TNF-α (r=0.45, p<0.001). CONCLUSION: FD was associated with elevated serum levels of IL-6 and TNF-α in this cohort. The FD patients treated with ERT, particularly, women, exhibited higher levels of serum IL-6 and TNF-α than those not treated with ERT; the serum IL-6 and TNF-α levels were correlated with the MSSI scores reflecting greater disease burden.
  • Use of medicines in São Paulo, Brazil, and State Health Care Coverage, 2003 and 2015 Original Article

    Monteiro, Camila Nascimento; Santos, Felipe Tadeu Carvalho; Costa, Karen Sarmento; Barros, Marilisa Berti de Azevedo; Cesar, Chester Luiz Galvão; Goldbaum, Moisés

    Abstract in English:

    OBJECTIVES: To analyze the use and acquisition of medicines in São Paulo, Brazil, in 2003 and 2015, according to sociodemographic factors, socioeconomic status, and health conditions of the population. METHODS: Data were obtained from population health surveys “ISA-Capital”. Descriptive analysis, bivariate analysis, and logistic regression models were used to evaluate the use of medicines and coverage by the Brazilian Unified Health System (SUS) according to socioeconomic status and health conditions in two periods: 2003 and 2015. RESULTS: From 2003 to 2015, the surveys showed an increase in the income and education level of the study population. There was no increase in the prevalence of chronic diseases and use of medicines from 2003 to 2015. The provision of medicines by SUS was higher in 2015 than in 2003, and the coverage by SUS was higher in the population with lower education level and income in both 2003 and 2015. CONCLUSIONS: The use of medicines, mainly for chronic disease control, did not change over the years, and there was an increase in SUS coverage for medicines during 2003-2015 in all population groups, with a greater impact on the lower socioeconomic status population. The programs of the provision of medicines implanted since 2003 had influenced the greater SUS coverage for medicines and in the reduction of inequalities in access to medicines.
  • Germline and Somatic mutations in postmenopausal breast cancer patients Original Article

    Nagy, Tauana Rodrigues; Maistro, Simone; Encinas, Giselly; Katayama, Maria Lucia Hirata; Pereira, Glaucia Fernanda de Lima; Gaburo-Júnior, Nelson; Franco, Lucas Augusto Moyses; Gouvêa, Ana Carolina Ribeiro Chaves de; Diz, Maria del Pilar Estevez; Leite, Luiz Antonio Senna; Folgueira, Maria Aparecida Azevedo Koike

    Abstract in English:

    OBJECTIVES: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. METHODS: Forty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated. RESULTS: The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations. CONCLUSIONS: Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.
  • Radiomic analysis of MRI to Predict Sustained Complete Response after Radiofrequency Ablation in Patients with Hepatocellular Carcinoma - A Pilot Study Original Article

    Horvat, Natally; Araujo-Filho, Jose de Arimateia B.; Assuncao-Jr, Antonildes N.; Machado, Felipe Augusto de M.; Sims, John A.; Rocha, Camila Carlos Tavares; Oliveira, Brunna Clemente; Horvat, Joao Vicente; Maccali, Claudia; Puga, Anna Luísa Boschiroli Lamanna; Chagas, Aline Lopes; Menezes, Marcos Roberto; Cerri, Giovanni Guido

    Abstract in English:

    OBJECTIVES: To investigate whether quantitative textural features, extracted from pretreatment MRI, can predict sustained complete response to radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC). METHODS: In this IRB-approved study, patients were selected from a maintained six-year database of consecutive patients who underwent both pretreatment MRI imaging with a probable or definitive imaging diagnosis of HCC (LI-RADS 4 or 5) and loco-regional treatment with RFA. An experienced radiologist manually segmented the hepatic nodules in MRI arterial and equilibrium phases to obtain the volume of interest (VOI) for extraction of 107 quantitative textural features, including shape and first- and second-order features. Statistical analysis was performed to evaluate associations between textural features and complete response. RESULTS: The study consisted of 34 patients with 51 treated hepatic nodules. Sustained complete response was achieved by 6 patients (4 with single nodule and 2 with multiple nodules). Of the 107 features from the arterial and equilibrium phases, 20 (18%) and 25 (23%) achieved AUC >0.7, respectively. The three best performing features were found in the equilibrium phase: Dependence Non-Uniformity Normalized and Dependence Variance (both GLDM class, with AUC of 0.78 and 0.76, respectively) and Maximum Probability (GLCM class, AUC of 0.76). CONCLUSIONS: This pilot study demonstrates that a radiomic analysis of pre-treatment MRI might be useful in identifying patients with HCC who are most likely to have a sustained complete response to RFA. Second-order features (GLDM and GLCM) extracted from equilibrium phase obtained highest discriminatory performance.
  • Epidemiological Analysis of 5,595 Procedures of Endovascular Correction of Isolated Descending Thoracic Aortic Disease Over 12 Years in the Public Health System in Brazil Original Article

    Portugal, Maria Fernanda Cassino; Teivelis, Marcelo Passos; Silva, Marcelo Fiorelli Alexandrino da; Fioranelli, Alexandre; Szlejf, Claudia; Amaro-Júnior, Edson; Wolosker, Nelson

    Abstract in English:

    OBJECTIVES: In Brazil, descending thoracic aorta disease, including aneurysms and dissections, is managed preferentially by endovascular treatment, owing to its feasibility and good results. In this study, we analyzed endovascular treatment of isolated descending thoracic aortic disease cases in the Brazilian public health system over a 12-year period. METHODS: Public data from procedures performed from 2008 to 2019 were extracted using web scraping techniques to assess procedure type frequency (elective or urgency), mortality, and governmental costs. RESULTS: A total of 5,595 procedures were analyzed, the vast majority of which were urgent procedures (61.82% vs. 38.18%). In-hospital mortality was lower for elective than for urgent surgeries (4.96 vs.10.32% p=0.008). An average of R$16,845.86 and R$20,012.04 was paid per elective and emergency procedure, respectively, with no statistical difference (p=0.095). CONCLUSION: Elective procedures were associated with lower mortality than urgent procedures. There was no statistically significant difference between elective and urgent procedures regarding costs.
  • Detection of coronavirus-2 by real-time reverse transcription polymerase chain reaction in conjunctival swabs from patients with severe form of Coronavirus disease 2019 in São Paulo, Brazil Original Article

    Misawa, Mariana Akemi Matsura; Tanaka, Tatiana; Minelli, Tomás; Braga, Pedro Gomes Oliveira; Kato, Juliana Mika; Gouvêa, Michele Soares Gomes; Pinho, João Renato Rebello; Yamamoto, Joyce Hisae

    Abstract in English:

    OBJECTIVES: To test conjunctival swabs from patients with laboratory-confirmed severe forms of coronavirus disease 2019 (COVID-19) for the presence of SARS-CoV-2 on real-time reverse-transcription polymerase chain reaction (rRT-PCR). METHODS: Fifty conjunctival swabs were collected from 50 in-patients with laboratory-confirmed severe forms of COVID-19 at the largest teaching hospital and referral center in Brazil (HCFMUSP, São Paulo, SP). The samples were tested for SARS-CoV-2 on rRT-PCR with the primers and probes described in the CDC protocol which amplify the region of the nucleocapsid N gene (2019_nCoV_N1 and 2019_nCoV_N2) of SARS-CoV-2 RNA and compared with naso/oropharyngeal swabs collected within 24 hours of the conjunctival swabs. RESULTS: Five conjunctival samples (10%) tested positive (amplification of the N1 and N2 primer/probe sets) while two conjunctival samples (4%) yielded inconclusive results (amplification of the N1 primer/probe set only). The naso/oropharyngeal swabs were positive for SARS-CoV-2 on rRT-PCR in 34 patients (68%), negative in 14 (28%) and inconclusive in 2 (4%). The 5 patients with positive conjunctival swabs had positive (n=2), negative (n=2) or inconclusive (n=1) naso/oropharyngeal swabs on rRT-PCR. Patients with negative or inconclusive naso/oropharyngeal swabs had the diagnosis of COVID-19 confirmed by previous positive rRT-PCR results or by serology. CONCLUSION: This is the first study to present conjunctival swab rRT-PCR results for SARS-CoV-2 in a Brazilian population. In our sample of 50 patients with severe forms of COVID-19, 10% had positive conjunctival swabs, most of which were correlated with positive naso/oropharyngeal rRT-PCR results.
  • Changes in the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios before and after percutaneous coronary intervention and their impact on the prognosis of patients with acute coronary syndrome Original Article

    Sheng, Jianlong; Liu, Nina; He, Fei; Cheng, Cheng; Shen, Shichun; Sun, Yuting

    Abstract in English:

    OBJECTIVES: This study aimed to prospectively observe the changes in the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) before and after percutaneous coronary intervention (PCI) and their impact on the prognosis of patients with acute coronary syndrome (ACS). METHODS: Blood samples from 205 patients with ACS were collected at admission and at 24h and 30 days post-PCI to observe changes in the complete blood count. The Cox multivariate regression model was used to analyze the factors influencing major adverse cardiac events (MACE) after PCI in patients with ACS. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of inflammation indicators for MACE after PCI. RESULTS: Following PCI, NLR and PLR first increased postoperatively and then decreased within 30 days after PCI. Cox multivariate regression analysis showed that NLR and PLR at 24h post-PCI and acute ST-segment elevation myocardial infarction were independent influencing factors for the incidence of MACE after PCI. The ROC curve analysis showed that the NLR at 24h post-PCI was a better predictor of the incidence of MACE. The NLR at 24h post-PCI was significantly correlated with the number and length of implanted stents and operation duration. CONCLUSIONS: After PCI, patients with ACS had an increased neutrophil proportion and NLR. The NLR at 24h post-PCI was a better predictor of the incidence of postoperative MACE.
  • Efficacy and safety of endoscopic ultrasound-guided drainage of pancreatic pseudocysts using double-pigtail plastic stents: A single tertiary center experience Original Article

    Sousa, Giovana Biasia de; Machado, Rodrigo Strehl; Nakao, Frank Shigueo; Libera, Ermelindo Della

    Abstract in English:

    OBJECTIVES: Pancreatic pseudocysts (PPC) are fluid collections with a well-defined wall that persist for more than 4 weeks inside or around the pancreas as a result of pancreatic inflammation and/or a ductal lesion. PPC have been successfully treated with endoscopic ultrasound (EUS)-guided drainage using different stents. This study aimed to evaluate the safety and efficacy of EUS-guided drainage of PPC using double-pigtail plastic stents in a tertiary hospital. METHODS: Patients with PPC referred for EUS-guided drainage between May 2015 and December 2019 were included in this case series. The primary endpoint was to evaluate the efficacy (clinical success) and safety (adverse events and mortality) of EUS-guided drainage of PPC. Secondary endpoints included technical success and pseudocyst recurrence. RESULTS: Eleven patients (mean age, 44.5±18.98 years) were included in this study. The etiologies for PPC were acute biliary pancreatitis, chronic alcoholic pancreatitis, and blunt abdominal trauma. The mean pseudocyst size was 9.4±2.69 cm. The clinical success rate was 91% (10/11). Adverse events occurred in three of 11 patients (27%). There were no cases of mortality. The technical success rate was 100%. Pseudocyst recurrence was identified in one of 11 patients (9%) at 12 weeks after successful clinical drainage and complete pseudocyst resolution. CONCLUSION: EUS-guided transmural drainage of PPC using double-pigtail plastic stents is safe and effective with high technical and clinical success rates.
  • C-peptide level as predictor of type 2 diabetes remission and body composition changes in non-diabetic and diabetic patients after Roux-en-Y gastric bypass Original Article

    de Cleva, Roberto; Kawamoto, Flavio; Borges, Georgia; Caproni, Priscila; Cassenote, Alex Jones Flores; Santo, Marco Aurelio

    Abstract in English:

    OBJECTIVES: Several predictors of type 2 diabetes mellitus (T2DM) remission after metabolic surgery have been proposed and used to develop predictive scores. These scores may not be reproducible in diverse geographic regions with different baseline characteristics. This study aimed to identify predictive factors associated with T2DM remission after Roux-en-Y gastric bypass (RYGB) in patients with severe obesity. We hypothesized that the body composition alterations induced by bariatric surgery could also contribute to diabetes remission. METHODS: We retrospectively evaluated 100 patients with severe obesity and T2DM who underwent RYGB between 2014 and 2016 for preoperative factors (age, diabetes duration, insulin use, HbA1c, C-peptide plasma level, and basal insulinemia) to identify predictors of T2DM remission (glycemia<126 mg/dL and/or HbA1c<6.5%) at 3 years postoperatively. The potential preoperative predictors were prospectively applied to 20 other patients with obesity and T2DM who underwent RYGB for validation. In addition, 81 patients with severe obesity (33 with T2DM) underwent body composition evaluations by bioelectrical impedance analysis (InBody 770®) 1 year after RYGB for comparison of body composition changes between patients with and those without T2DM. RESULTS: The retrospective analysis identified only a C-peptide level >3 ng/dL as a positive predictor of 3-year postoperative diabetes remission, which was validated in the prospective phase. There was a significant difference in the postoperative body composition changes between non-diabetic and diabetic patients only in trunk mass. CONCLUSION: Preoperative C-peptide levels can be useful for predicting T2DM remission after RYGB. Trunk mass is the most important difference in postoperative body composition changes between non-diabetic and diabetic patients.
  • Association of 2D and 3D transvaginal ultrasound findings with adenomyosis in symptomatic women of reproductive age: a prospective study Original Article

    Marques, Ana Luiza Santos; Andres, Marina Paula; Mattos, Leandro A.; Gonçalves, Manoel O.; Baracat, Edmund Chada; Abrão, Mauricio Simões

    Abstract in English:

    OBJECTIVE: To evaluate the association of two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasound (TVUS) findings with adenomyosis symptoms. METHODS: This prospective study conducted between January and December 2018 enrolled 78 women aged 18 to 40 years with abnormal uterine bleeding (AUB), infertility, and/or pelvic pain. All patients underwent 2D and 3D TVUS. Signs of adenomyosis on TVUS were identified according to the consensus of the Morphological Uterus Sonographic Assessment group. RESULTS: The prevalence of adenomyosis on TVUS was 55.12%. Patients with adenomyosis were older (p=0.002) and had more dysmenorrhea, AUB, and endometriosis than those without adenomyosis. When comparing the presence of symptoms with each adenomyosis feature, on 2D TVUS, severe dyspareunia was significantly associated with the presence of a poorly defined junctional zone (JZ) (p=0.023) and on 3D TVUS, patients with AUB had a more irregular (p=0.003), poorly defined (p=0.028), and interrupted JZ (p=0.011). After logistic regression analysis, signs of adenomyosis on TVUS remained significantly associated only with age over 30 years (OR: 1.2; 95% CI: 1.0-1.2) and AUB (OR: 7.65; 95% CI: 2-29). Patients with diffuse adenomyosis were older and presented with more infertility and AUB than patients with focal or no adenomyosis. CONCLUSION: The findings of adenomyosis by 2D and 3D TVUS showed association with age and AUB. 3D TVUS alterations in the JZ were associated with AUB and dyspareunia. Diffuse adenomyosis was associated with older age, a greater prevalence of infertility, and AUB.
  • Usefulness of pre-thyroidectomy neutrophil–lymphocyte, platelet–lymphocyte, and monocyte–lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer Original Article

    Riguetto, Cínthia Minatel; Barreto, Icléia Siqueira; Maia, Frederico Fernandes Ribeiro; Assumpção, Lígia Vera Montali da; Zantut-Wittmann, Denise Engelbrecht

    Abstract in English:

    OBJECTIVE: This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). METHODS: This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. RESULTS: PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). CONCLUSION: Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.
  • Comparison of transcutaneous electrical tibial nerve stimulation for the treatment of overactive bladder: a multi-arm randomized controlled trial with blinded assessment Original Article

    Pierre, Munick Linhares; Friso, Beatriz; Casarotto, Raquel Aparecida; Haddad, Jorge Milhem; Baracat, Edmund Chada; Ferreira, Elizabeth Alves Gonçalves

    Abstract in English:

    OBJECTIVE: To compare the effectiveness of tibial nerve transcutaneous electrical nerve stimulation (TENS) for an overactive bladder, considering the sites of application and frequency of attendance. METHODS: This multi-arm randomized controlled trial enrolled 137 adult women (61.0±9.0 years) with overactive bladder from a university hospital. They underwent 12 sessions of 30-min TENS application and were assigned to five groups: one leg, once a week (n=26); one leg, twice a week (n=27); two legs, once a week (n=26); two legs, twice a week (n=28); and placebo (n=30). Symptoms of overactive bladder and its impact on quality of life were evaluated before and after 6 or 12 weeks of treatment using the Overactive Bladder Questionnaire-V8 and voiding diary. ClinicalTrials.gov: NCT01912885. RESULTS: The use of one leg, once a week TENS application reduced the frequency of urgency episodes compared with the placebo (1.0±1.6 vs. 1.4±1.9; p=0.046) and frequency of incontinence episodes compared with the placebo (0.7±1.4 vs.1.4±2.2; p<0.0001). The one-leg, twice a week protocol decreased the urinary frequency compared with the two legs, once a week protocol (8.2±3.5 vs. 9.0±5.1; p=0.026) and placebo (8.2±3.5 vs. 7.9±2.7; p=0.02). Nocturia improved using the two legs, once a week protocol (1.5±1.8) when compared with the one leg, twice a week protocol (1.9±2.0) and placebo (1.7±1.6) (p=0.005 and p=0.027, respectively). Nocturia also improved using the two legs, twice a week protocol when compared with the one leg, twice a week protocol (1.3±1.2 vs.1.9±2.0; p=0.011). CONCLUSION: One-leg stimulation improved the daily urinary frequency, urgency, and incontinence, and the two-leg stimulation once and twice weekly improved nocturia.
  • Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats Original Article

    Ricardo-da-Silva, Fernanda Yamamoto; Armstrong-Jr, Roberto; Vidal-dos-Santos, Marina; Correia, Cristiano de Jesus; Coutinho e Silva, Raphael dos Santos; Anunciação, Lucas Ferreira da; Moreira, Luiz Felipe Pinho; Leuvenink, Henri Gerrit Derk; Breithaupt-Faloppa, Ana Cristina

    Abstract in English:

    OBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17β-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD. METHODS: Female Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17β-estradiol (50 μg/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17β-estradiol (50 μg/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-α, IL-1β, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed. RESULTS: Estradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-α and IL-1β gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group. CONCLUSIONS: Brain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes.
  • Antibody indexes in COVID-19 convalescent plasma donors: Unanswered questions Original Article

    Bonetti, Tatiana Carvalho de Souza; Latini, Flavia Roche Moreira; Invitti, Adriana Lukow; Fonseca, Marcelo Cunio Machado; Scorza, Fulvio Alexandre; Saldanha, Maira Garcia; Bellucco, Fernanda T.; Bacarov, Natalia B.S.; Soane, Michel M.; Girão, Manoel João Batista Castelo

    Abstract in English:

    OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by high contagiousness, as well as variable clinical manifestations and immune responses. The antibody response to SARS-CoV-2 is directly related to viral clearance and the antibodies' ability to neutralize the virus and confer long-term immunity. Nevertheless, the response can also be associated with disease severity and evolution. This study correlated the clinical characteristics of convalescent COVID-19 patients with immunoglobulin A (IgA) and IgG anti-SARS-CoV-2 antibodies. METHODS: This study included 51 COVID-19 health care professionals who were candidates for convalescent plasma donation from April to June 2020. The subjects had symptomatic COVID-19 with a polymerase chain reaction-confirmed diagnosis. We measured anti-SARS-CoV-2 IgA and IgG antibodies after symptom recovery, and the subjects were classified as having mild, moderate, or severe symptoms. RESULTS: Anti-SARS-CoV-2 antibodies were positive in most patients (90.2%). The antibody indexes for IgA and IgG did not differ significantly between patients presenting with mild or moderate symptoms. However, they were significantly higher in patients with severe symptoms. CONCLUSIONS: Our study showed an association between higher antibody indexes and severe COVID-19 cases, and several hypotheses regarding the association of the antibody dynamics and severity of the disease in SARS-CoV-2 infection have been raised, although many questions remain unanswered.
  • Impact of clinical characteristics on human chorionic gonadotropin regression after molar pregnancy Original Article

    Gockley, Allison A.; Lin, Lawrence H.; Davis, Michelle; Melamed, Alexander; Rizzo, Anthony; Sun, Sue Yazaki; Elias, Kevin; Goldstein, Donald P.; Berkowitz, Ross S.; Horowitz, Neil S.

    Abstract in English:

    OBJECTIVES: This study aimed to determine the effects of age, race/ethnicity, body mass index, and contraception on human chorionic gonadotropin (hCG) regression following the evacuation of a molar pregnancy. METHODS: This was a retrospective cohort study of 277 patients with molar pregnancies between January 1, 1994 and December 31, 2015. The rate of hCG regression was estimated using mixed-effects linear regression models on daily log-transformed serum hCG levels after evacuation. RESULTS: There were no differences in hCG half-lives among age (p=0.13) or race/ethnicity (p=0.16) groups. Women with obesity and hormonal contraceptive use demonstrated faster hCG regression than their counterparts (3.2 versus. 3.7 days, p=0.02 and 3.4 versus. 4.0 days, p=0.002, respectively). CONCLUSION: Age and race/ethnicity were not associated with hCG regression rates. Hormonal contraceptive use and obesity were associated with shorter hCG half-lives, but with unlikely clinical significance. It is important to understand whether the clinical characteristics of patients may influence the hCG regression curve, as it has been proposed as a way to predict the risk of gestational trophoblastic neoplasia.
  • Expression of Amphiregulin in Enchondromas and Central Chondrosarcomas Original Article

    Losada, Daniele Moraes; Ribeiro, André Luiz da Cruz; Cintra, Francisco Fontes; Mendonça, Guilherme Rossi Assis de; Etchebehere, Maurício; Amstalden, Eliane Maria Ingrid

    Abstract in English:

    OBJECTIVES: The aim of this study was to evaluate the role of amphiregulin protein, an epidermal growth factor receptor ligand, in cartilaginous tumors. METHODS: Amphiregulin expression was examined in 31 enchondromas and 67 chondrosarcomas using immunohistochemistry analysis. RESULTS: Overall, 15 enchondromas (48.40%) and 24 chondrosarcomas (35.82%) were positive for amphiregulin. According to the receiver operating characteristic curve test, no difference in amphiregulin expression was observed between enchondromas and low-grade chondrosarcomas (p=0.0880). Additionally, 39 lesions (16 in short bones, 13 in long bones, and 10 in flat bones) were positive for amphiregulin, exhibiting a higher percentage of positive cells (p=0.0030) and intensity of immunohistochemical expression (p=0.0055) in short bone lesions than in others. Among 25 enchondromas localized in short bones, 15 expressed amphiregulin; however, all 6 cases localized in long bones were negative for this marker (p=0.0177). CONCLUSIONS: Amphiregulin did not help in distinguishing enchondromas from low-grade chondrosarcomas. The present study is the first to document the expression of this immunohistochemical marker in enchondromas. Furthermore, amphiregulin expression in enchondromas was localized in short bones, indicating a phenotypic distinction from that in long bones. This distinction may contribute to an improved understanding of the pathogenesis of these lesions.
  • Serum miR-195-5p Exhibits Clinical Significance in the Diagnosis of Essential Hypertension with Type 2 Diabetes Mellitus by Targeting DRD1 Original Article

    Hu, Yueyan; Li, Qian; Zhang, Leisheng; Zhong, Lianmei; Gu, Man; He, Bo; Qu, Qiu; Lao, Yaling; Gu, Kunli; Zheng, Bingrong; Yang, Hongju

    Abstract in English:

    OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM.
  • Exercise training reduces sympathetic nerve activity and improves executive performance in individuals with obstructive sleep apnea Original Article

    Goya, Thiago Tanaka; Ferreira-Silva, Rosyvaldo; Gara, Elisangela Macedo; Guerra, Renan Segalla; Barbosa, Eline Rozária Ferreira; Toschi-Dias, Edgar; Cunha, Paulo Jannuzzi; Negrão, Carlos Eduardo; Lorenzi-Filho, Geraldo; Ueno-Pardi, Linda Massako

    Abstract in English:

    OBJECTIVE: To investigate the effects of exercise training (ET) on muscle sympathetic nerve activity (MSNA) and executive performance during Stroop Color Word Test (SCWT) also referred to as mental stress test. METHODS: Forty-four individuals with obstructive sleep apnea (OSA) and no significant co-morbidities were randomized into 2 groups; 15 individuals completed the control period, and 18 individuals completed the ET. Mini-mental state of examination and intelligence quotient were also assessed. MSNA assessed by microneurography, heart rate by electrocardiography, blood pressure (automated oscillometric device) were measured at baseline and during 3 min of the SCWT. Peak oxygen uptake (VO2 peak) was evaluated using cardiopulmonary exercise testing. Executive performance was assessed by the total correct responses during 3 min of the SCWT. ET consisted of 3 weekly sessions of aerobic exercise, resistance exercises, and flexibility (72 sessions, achieved in 40±3.9 weeks). RESULTS: Baseline parameters were similar between groups. Heart rate, blood pressure, and MSNA responses during SCWT were similar between groups (p>0.05). The comparisons between groups showed that the changes in VO2 (4.7±0.8 vs -1.2±0.4) and apnea-hypopnea index (-7.4±3.1 vs 5.5±3.3) in the exercise-trained group were significantly greater than those observed in the control group respectively (p<0.05) after intervention. ET reduced MSNA responses (p<0.05) and significantly increased the number of correct answers (12.4%) during SCWT. The number of correct answers was unchanged in the control group (p>0.05). CONCLUSIONS: ET improves sympathetic response and executive performance during SCWT, suggesting a prominent positive impact of ET on prefrontal functioning in individuals with OSA. ClinicalTrials.gov: NCT002289625.
  • The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic Original Article

    Cruz, Fernanda C.S.G.; Drager, Luciano F.; Queiróz, Daniel B.C.; Souza, Gabriela A.; Pedrosa, Rodrigo P.; Patriota, Tarcya L.G Couto; Dórea, Egidio L.; Vieira, Marcelo Luiz C.; Righi, Camila G.; Martinez, Denis; Silva, Geruza A. da; Silva, Giovanio V.; Pio-Abreu, Andrea; Lotufo, Paulo A.; Benseãor, Isabela M.; Bortolotto, Luiz A.; Fuchs, Flávio D.; Lorenzi-Filho, Geraldo

    Abstract in English:

    OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.
  • Spontaneous pneumomediastinum incidence and clinical features in non-intubated patients with COVID-19 Original Article

    Haberal, Miktat Arif; Akar, Erkan; Dikis, Ozlem Sengoren; Ay, Mehmet Oguzhan; Demirci, Hakan

    Abstract in English:

    OBJECTIVES: To evaluate the presentation characteristics and disease course of seven patients with COVID-19 who spontaneously developed pneumomediastinum without a history of mechanical ventilation. METHODS: A total of seven non-intubated patients with COVID-19, of age ranging from 18-67 years, who developed spontaneous pneumomediastinum between 01 April and 01 October 2020 were included in the study. Patients' demographic data, clinical variables, and laboratory values were examined. Spontaneous pneumomediastinum was evaluated using posteroanterior chest radiography and thorax computed tomography. RESULTS: During the research period, 38,492 patients reported to the emergency department of our hospital with COVID-19 symptoms. Of these, spontaneous pneumomediastinum was detected in seven patients who had no previous history of intubation. Chronic obstructive pulmonary disease (2/7) and asthma bronchiale (2/7) were determined as the most common causes of comorbidity. CONCLUSIONS: In our study, the frequency of spontaneous pneumomediastinum developing without pneumothorax was found to be high in non-intubated patients. Whether this is related to the nature of the disease or it is a result of the increase in cases diagnosed incidentally owing to the increasing use of low-dose computed tomography should be explored in further studies.
  • Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents Original Article

    Silva, Giselle P.; Pereira-Manfro, Wania F.; Costa, Priscilla R.; Costa, Dayane A.; Ferreira, Bianca; Barreto, Daniela M.; Frota, Ana Cristina C.; Hofer, Cristina B.; Figueredo, Carlos M.; Coelho, Barbara; Kallas, Esper G.; Milagres, Lucimar G.

    Abstract in English:

    OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.
  • Diagnostic accuracy of oximetry for obstructive sleep apnea: a study on older adults in a home setting Original Article

    Rosa, João Carlos Fraga da; Peres, Alessandra; Gasperin Júnior, Luciano; Martinez, Denis; Fontanella, Vania

    Abstract in English:

    OBJECTIVES: Owing to the fact that obstructive sleep apnea (OSA) is an underreported disease, the strategy used for the diagnosis of OSA has been extensively dissected to devise a simplified process that can be accessed by the public health services. Polysomnography (PSG) type I, the gold standard for the diagnosis of OSA, is expensive and difficult to access by low-income populations. In this study, we aimed to verify the accuracy of the oxyhemoglobin desaturation index (ODI) in comparison to the apnea-hypopnea index (AHI) using a portable monitor. METHODS: We evaluated 94 type III PSG home test results of 65 elderly patients (69.21±6.94 years old), along with information, such as the body mass index (BMI) and sex, using data obtained from a clinical trial database. RESULTS: A significant linear positive correlation (r=0.93, p<0.05) was observed between ODI and AHI, without any interference from sex, BMI, and positional component. The sensitivity of ODI compared to that of AHI increased with an increase in the severity of OSA, while the specificity of ODI in comparison to that of AHI was high for all degrees of severity. The accuracy of ODI was 80.7% for distinguishing between patients with mild and moderate apnea and 84.4% for distinguishing between patients with moderate and severe apnea. CONCLUSION: The ODI values obtained in uncontrolled conditions exhibited high sensitivity for identifying severe apnea compared to the AHI values, and correctly identified the severity of OSA in more than 80% of the cases. Thus, oximetry is promising strategy for diagnosing OSA.
  • Vision for the Future Project: Screening impact on the prevention and treatment of visual impairments in public school children in São Paulo City, Brazil Original Article

    Costa, Douglas Rodrigues da; Debert, Iara; Susanna, Fernanda Nicolela; Falabreti, Janaina Guerra; Polati, Mariza; Susanna Júnior, Remo

    Abstract in English:

    OBJECTIVES: Uncorrected refractive errors are the leading cause of visual impairment in children. In this cross-sectional retrospective study, we analyzed a social visual screening program for school children in São Paulo, Brazil, evaluated its impact on the prevention and treatment of children’s visual disabilities, and assessed its epidemiological outcomes to outline suggestions for its improvement. METHODS: First-grade children from public schools were submitted to prior visual screening by their teachers. Selected children were forwarded to the hospital’s campaigns for a second screening by ophthalmologists and treatment if needed. Data were analyzed for age, sex, visual acuity, biomicroscopy, refractive errors, ocular movement disorders, amblyopia, number of donated spectacles, and number of children forwarded to specialized care. RESULTS: A total of 1080 children were included with mean age of 6.24±0.45 years. Children with normal ophthalmological exam, 591 (54.7%; 95% confidence interval [CI]: 51.7%-57.7%) were dismissed and considered false-positives. Myopia, hyperopia, and astigmatism components were found in 164 (15.2%; CI: 13.1%-17.4%), 190 (17.6%; CI: 15.3%-20.0%), and 330 (30.5%; CI: 27.8%-33.4%) children, respectively. Amblyopia was diagnosed in 54 (5%; CI: 3.5%-6.4%) children, and 117 (10.8%; CI: 9.8%-12.8%) presented ocular movement disorders. A total of 420 glasses were donated. CONCLUSION: Epidemiological findings for amblyopia and refractive errors are consistent with those of similar studies. The expressive number of diagnoses performed and number of glasses donated to underprivileged children depict the importance of such projects. New guidelines to improve their cost-effectiveness, such as professional training and community sensitization, are imperative.
  • Long non-coding ribonucleic acid H19 and ten-eleven translocation enzyme 1 messenger RNA expression levels in uterine fibroids may predict their postoperative recurrence Original Article

    Zhan, Xiangjuan; Zhou, Hui; Sun, Yuhong; Shen, Baomei; Chou, Di

    Abstract in English:

    OBJECTIVES: To investigate the predictive value of long non-coding RNA (lncRNA) H19 and the ten-eleven translocation enzyme 1 (TET1) transcriptional expression in postoperative recurrence of uterine fibroids (UFs). METHODS: Seventy-five patients with UF, who underwent surgical treatment, were enrolled in the treatment group, and 60 healthy individuals were enrolled in the control group. The relative expression levels of lncRNA H19 and TET1 mRNA in the serum and UF tissues were analyzed. The patients were further divided into a better curative (BC) group and a poor efficacy (PE) group to analyze the predictive value of lncRNA H19 and TET1 and the independent risk factors affecting the recurrence of UF. RESULTS: Compared with the control group, lncRNA H19 expression levels were significantly higher, while TET1 expression levels were significantly lower in the treatment group (p<0.001). The area under the receiver operating characteristic (ROC) curve (AUC) values of the two indicators for diagnostic importance were found to be 0.872 and 0.826, respectively. Compared with the PE group, lncRNA H19 expression levels were significantly lower, while TET1 expression levels were significantly higher in the BC group (p<0.001). The AUC values of the two indicators for their predictive efficacy were 0.788 and 0.812, respectively. Logistic regression analysis showed that age, menarche age, maximum diameter of UFs, number of UFs, lncRNA H19 levels, and TET1 levels were independent risk factors affecting UF recurrence. The AUC values of lncRNA H19 and TET1 for their predictive value for postoperative recurrence were 0.814 and 0.765, respectively. CONCLUSIONS: The lncRNA H19 and TET1 have high diagnostic and predictive efficacy for determining the postoperative recurrence of UFs.
  • Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) Original Article

    Carvalho, Sylene C.R.; Vasconcelos, Luydson R.S.; Fonseca, Leonardo da; Carmo, Rodrigo F.; Tomitão, Michele T.; Aroucha, Dayse C.B.L.; Pereira, Leila M.M.B.; Stefano, José Tadeu; Ribeiro-Júnior, Ulysses; Oliveira, Claudia P.; Carrilho, Flair J.

    Abstract in English:

    OBJECTIVE: The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC. METHODS: A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated. RESULTS: The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)]. CONCLUSION: Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.
  • Comparison of hormonal receptor expression and HER2 status between circulating tumor cells and breast cancer metastases Original Article

    Sanches, Solange Moraes; Braun, Alexcia Camila; Calsavara, Vinicius Fernando; Barbosa, Paula Nicole Vieira Pinto; Chinen, Ludmilla Thome Domingos

    Abstract in English:

    OBJECTIVES: Breast cancer (BC) is the most common neoplasm in women. Biopsy of metastatic lesions is recommended to confirm estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as there are discrepancies in these patterns between primary tumors and metastases in up to 40% of the cases. Circulating tumor cells (CTCs) are related to BC outcomes and could potentially be an alternative to the invasive procedures of metastasis rebiopsy. ISET® technology is not currently employed to detect CTCs in patients with BC. Emerging data support that the characterization of CTC protein expression can refine its prognostic value. Transforming growth factor (TGF)-β plays a role in BC progression and invasiveness. Thus, in this study, we aimed to compare ER, PR, and HER2 expression in primary tumors, CTCs, and metastases and evaluate TGF-β type 1 receptor (TGF-β RI) expression in CTCs as prognostic factor for progression free survival (PFS) and overall survival (OS). METHODS: This prospective study was conducted at the A.C. Camargo Cancer Center, Brazil. Blood samples were processed in ISET® (Isolation by SizE of Tumors, Rarecells, France) before computed tomography-guided biopsy of suspected metastatic lesions. Protein expression levels in CTCs were compared to those in primary tumors/metastases (medical records). RESULTS: Of the 39 patients initially included, 27 underwent both biopsies of metastases and blood collection and were considered for analysis. The concordance rates for ER, PR, and HER2 expression between primary tumors and metastases were high. No loss of HER2 expression at any metastasis site and retention of the same pattern of protein expression in all triple-negative (TN) tumors (92.5%, 81.5% and 96.2% respectively) (p<0.0001) was observed. When metastases/CTCs were classified as TN/non-TN, CTCs showed high specificity (93%), accuracy (84.2%), and negative predictive value (88%). The median OS of patients without TGF-β RI expression in CTCs was 42.6 versus 20.8 months for TGF-β RI expression-positive ones (p>0.05). CONCLUSION: The role of CTCs detected by ISET has not yet been established in BC. Here, we suggest that this methodology may be useful to evaluate metastasis in non-TN cases as well as TGF-β RI expression in CTCs, which may impact patient survival. Due to sample limitations, future studies must focus on specific BC subtypes and an expansion of the cohort.
  • CircularRNA_0119872 regulates the microRNA-582-3p/E2F transcription factor 3 pathway to promote the progression of malignant melanoma Original Article

    Qu, Jinlong; Yuan, Chunying; Jia, Qi; Sun, Mengwei; Jiang, Min; Zuo, Fuguang

    Abstract in English:

    OBJECTIVES: Malignant melanoma (MM) is an invasive tumor that poses a threat to patient health. Circular RNAs (circRNAs) are important regulators of MM carcinogenesis. In this study, we investigated the expression characteristics and biological functions of, and mechanism underlying, circ_0119872 expression in MM. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to examine the circ_0119872, microRNA (miR)-582-3p, and E2F transcription factor 3 (E2F3) mRNA expression levels in MM tissues and cell lines. Western blotting was performed to quantify E2F3 protein expression. MM cells with circ_0119872 knockdown were established, and cell counting kit 8 (CCK-8) and transwell assays were utilized to examine the function of circ_0119872 and its effects on the malignant characteristics of MM cells. The MiRDB and TargetScan databases were used to predict the target genes of miR-582-3p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to explore the biological functions of the target genes of miR-582-3p. Additionally, a dual-luciferase reporter gene experiment was performed to verify the targeting relationship between circ_0119872 and miR-582-3p as well as that between miR-582-3p and E2F3. RESULTS: Circ_0119872 was remarkably upregulated in MM tissues and cell lines. Circ_0119872 knockdown suppressed the cell proliferation and metastasis In addition, miR-582-3p was identified as a downstream target of circ_0119872. The target genes of miR-193a-3p are involved in melanogenesis and cancer-related signaling pathways. Mechanistically, circ_0119872 facilitated MM progression by adsorbing miR-582-3p and upregulating E2F3 expression. CONCLUSION: Circ_0119872 is an oncogenic circRNA that participates in the promotion of MM progression by regulating the miR-582-3p/E2F3 axis.
  • Phase II trial of humanized anti-Lewis Y monoclonal antibody for advanced hormone receptor-positive breast cancer that progressed following endocrine therapy Original Article

    Testa, Laura; Mano, Max; Arai, Roberto Jun; Bonadio, Renata Colombo; Serrano, Sergio V.; Zorzetto, Marina M Costa; Crocamo, Susanne; Smaletz, Oren; Freitas-Junior, Ruffo; Hoff, Paulo M.

    Abstract in English:

    OBJECTIVES: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET). METHODS: A single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239. RESULTS: The study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively. CONCLUSIONS: The humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked.
  • 6-hydroxydopamine and ovariectomy has no effect on heart rate variability parameters of females Original Article

    de la Rosa, Tomás; Calvo, Viviam Sanabria; Gonçalves, Valeria Cassia; Scerni, Débora Amado; Scorza, Fúlvio Alexandre

    Abstract in English:

    OBJECTIVES: In addition to the classic motor symptoms of Parkinson’s disease (PD), patients also present with non-motor symptoms, such as autonomic dysfunction, which is present in almost 90% of patients with PD, affecting the quality of life and mortality. Regarding sex differences in prevalence and presentation, there is increasing concern about how sex affects autonomic dysfunction. However, there are no previous data on autonomic cardiac function in females after 6-hydroxydopamine (6-OHDA) striatal injection. METHODS: Wistar female rats were ovariectomized. After 20 days, the animals received bilateral injections of 6-OHDA (total dose per animal: 48 µg) or a vehicle solution in the striatum. Thirty days after 6-OHDA injection, subcutaneous electrodes were implanted for electrocardiogram (ECG) recording. Ten days after electrode implantation, ECG signals were recorded. Analyses of heart rate variability (HRV) parameters were performed, and the 6-OHDA lesion was confirmed by analyzing the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta (SNpc). RESULTS: A high dose of 6-OHDA did not affect HRV of females, independent of ovariectomy. As expected, ovariectomy did not affect HRV or lesions in the SNpc after 6-OHDA injection. CONCLUSIONS: We suggest that females with 6-OHDA present with cardioprotection, independent of ovarian hormones, which could be related to female vagal predominance.
  • Statewide evaluation of infection control measures for preventing coronavirus disease 2019 in hemodialysis facilities Original Article

    Guedes, Ana Rubia; Tavares, Bruno de Melo; Assis, Denise Brandão de; Freire, Maristela Pinheiro; Madalosso, Geraldine; Levin, Anna S.; Perdigão Neto, Lauro Vieira; Oliveira, Maura Salaroli de

    Abstract in English:

    OBJECTIVE: This study aimed to evaluate the occurrence of coronavirus disease 2019 (COVID-19) in hemodialysis facilities and the occurrence of and risk factors for clustering of COVID-19 cases. METHODS: We conducted a cross-sectional online survey between March and July 2020, in all dialysis facilities in São Paulo state, using Google Forms. The online questionnaire contained questions addressing specific components of infection prevention and control practices and the number of cases during the COVID-19 pandemic. RESULTS: A total of 1,093 (5%) COVID-19 cases were reported among 20,984 patients; approximately 56% of the facilities had ≥1 cluster. Most facilities implemented various measures (such as allocation of dedicated COVID-19 areas/shifts, symptom screening, environmental disinfection, and maintenance of adequate ventilation) to prevent the transmission of severe acute respiratory syndrome coronavirus 2. Clustering of COVID-19 cases was suspected in only 7% of dialysis facilities. The only variable associated with this event was the performance of aerosol-generating procedures (odds ratio: 4.74; 95% confidence interval: 1.75-12.86). CONCLUSION: Attention should be paid to avoiding the performance of aerosol-generating procedures in dialysis facilities and monitoring the clustering of cases.
  • Effect of Calcium Dobesilate in Preventing Contrast-Induced Nephropathy in Patients with Diabetes and Chronic Kidney Disease Original Article

    Zhang, Hao; Guo, Shao-Hua; Xue, Zheng-Kai; Zhang, Ya-Ru; Wang, Jia-Rui; Che, Jing-Jin; Liu, Tong; Tao, Hua-Yue; Li, Guang-Ping; Rha, Seung-Woon; Ashraful-Haque, Swapnil-Zaman; Chen, Kang-Yin

    Abstract in English:

    OBJECTIVES: This study assessed the protective effect of calcium dobesilate against contrast-induced nephropathy (CIN) after coronary angiography (CAG) or percutaneous coronary intervention (PCI) in patients with diabetes and chronic kidney disease (CKD). METHODS: A total of 130 patients with diabetes and CKD estimated glomerular filtration rate: 30-90 mL/min/1.73m2 were enrolled and included in the analysis. They were divided into experimental (n=65) and control groups (n=65). Patients in the experimental group were administered oral calcium dobesilate (500 mg) three times daily for 2 days before and 3 days after the procedure. The serum creatinine (SCr), cystatin C (Cys C), and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured before and after the procedure. RESULTS: The mean SCr level at 24h after the procedure was found to be significantly lower in the experimental group than in the control group (79.1±19.6 μmol/L vs. 87.0±19.3 μmol/L, p=0.023). However, the Cys C and NGAL levels were not significantly different between the two groups at all measurement time points (all p>0.05). The incidence of CIN defined by the SCr level was significantly lower in the experimental group than in the control group (3 [4.6%] vs. 13 [20.0%], p=0.017). However, the incidence of CIN defined by the Cys C level was not statistically different between the two groups (7 [10.8%] vs. 7 [10.8%], p=1.000). CONCLUSIONS: This study revealed that calcium dobesilate has no preventive effect against CIN in patients with diabetes and CKD.
  • Cortical auditory-evoked potential as a biomarker of central auditory maturation in term and preterm infants during the first 3 months Original Article

    Didoné, Dayane Domeneghini; Oliveira, Lilian Sanches; Durante, Alessandra Spada; Almeida, Kátia de; Garcia, Michele Vargas; Riesgo, Rudimar dos Santos; Sleifer, Pricila

    Abstract in English:

    OBJECTIVES: To analyze central auditory maturation in term and preterm infants during the first 3 months of life by comparing the latency and amplitude of cortical auditory-evoked potential at different frequencies. METHODS: In this study, 17 term and 18 preterm infants were examined; all had tested positive on the neonatal hearing screening test. Cortical auditory potential was investigated during the first and third months of life. The response of the cortical auditory-evoked potential was investigated at frequencies of 500, 1000, 2000, and 4000 Hz. The latency and amplitude of the cortical response were automatically detected and manually analyzed by three researchers with experience in electrophysiology. The results were compared using analysis of variance and the Bonferroni test. A significance level of 5% was used for all analyses. RESULTS: Latency values of cortical auditory-evoked potential in the first month of birth were significantly higher than those in the third month, and latency values of the preterm group were higher than those of the term group, regardless of the frequency and time of evaluation. In general, the latency of the cortical auditory-evoked potential was higher at high frequencies. Amplitude values in the third month of life were significantly higher than those in the first month for term and preterm infants. CONCLUSION: Central auditory maturation was observed in both groups but with different results between those born at term and preterm, with latencies of cortical auditory-evoked potential higher for the preterm group and at high frequencies.
  • The renoprotective effects of Heme Oxygenase-1 during contrast-induced acute kidney injury in preclinical diabetic models Original Article

    Fonseca, Cassiane Dezoti da; Watanabe, Mirian; Couto, Sheila Marques Fernandes; Santos, Alef Aragão Carneiro dos; Borges, Fernanda Teixeira; Vattimo, Maria de Fatima Fernandes

    Abstract in English:

    OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is an important clinical problem that can be aggravated by diabetes mellitus, a major risk factor. However, heme oxygenase-1 (HO-1), a promising therapeutic target, can exert antioxidant effects against CI-AKI. Thus, we investigated the role of HO-1 in CI-AKI in the presence of diabetes mellitus. METHODS: Twenty-eight male Wistar rats weighing 250-300g were subjected to left uninephrectomy, and concomitantly, diabetes induced by streptozotocin (65 mg/kg). After 12 weeks, iodinated contrast (meglumine ioxithalamate, 6 mL/kg) and hemin (HO-1 inducer-10 mg/k) were administered 60 min before iodinated contrast treatment. The rats were randomly divided into four groups: control, diabetes mellitus (DM), DM iodinated contrast (DMIC), and DMIC hemin (DMICH). Kidney function, albuminuria, oxidative profile, and histology were assessed. All experimental data were subjected to statistical analyses. RESULTS: CI-AKI in preclinical diabetic models decreased creatinine clearance and increased urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and the degree of albuminuria. Additionally, the levels of oxidative and nitrosative stress metabolites (urinary peroxides, thiobarbituric acid-reactive substances, and NO) were elevated, while thiol levels in kidney tissue were reduced. Kidney histology showed tubular cell vacuolization and edema. HO-1 inducer treatment improved kidney function and reduced urinary the NGAL levels. The oxidative profile showed an increase in the endogenous thiol-based antioxidant levels. Additionally, the tubular injury score was reduced following HO-1 treatment. CONCLUSIONS: Our findings highlight the renoprotective effects of HO-1 in CI-AKI and preclinical diabetic models. Therefore, HO-1 ameliorates kidney dysfunction, reduces oxidative stress, and prevents cell necrosis.
  • Structured evaluation of a comprehensive microsurgical training program Original Article

    Mattar, Tiago Guedes da Motta; Santos, Gustavo Bispo dos; Telles, João Paulo Mota; Rezende, Marcelo Rosa de; Wei, Teng Hsiang; Mattar Júnior, Rames

    Abstract in English:

    OBJECTIVES: This study proposed a structured microsurgical training program and evaluated it with the assistance of a large sample of surgeons. METHODS: The practical course comprised 16 sessions of approximately 4 hours each. This included two sessions for suturing rubber gloves and two sessions for suturing arteries, veins, and nerves in chicken thighs. The other sessions were performed on the femoral vessels of rats: 5 sessions for end-to-end arterial anastomosis, 5 for end-to-end venous anastomosis, 1 for arterial grafting, and 1 for end-to-side anastomosis. We conducted a structured assessment of the microsurgical skills in each training session. RESULTS: In this study, 89 surgeons were evaluated. The mean scores for the different procedures were as follows: glove suturing, 33.3±0.59; chicken nerve end-to-end anastomosis, 40.3±0.49; chicken artery suturing, 40.9±0.36; chicken vein suturing, 42.3±0.36; graft interposition, 44.8±0.7; and end-to-side anastomosis, 43.7±0.63 (p<0.05 for all). The chicken thigh suturing scores were significantly higher than the rubber gloves suturing scores (p<0.01). There were no differences between scores of the rat artery and chicken thigh suturing procedures (p=0.24). The rat venous anastomosis scores were higher than the rat arterial anastomosis scores (p=0.02), as were graft interposition scores when compared with end-to-end venous anastomosis scores. The end-to-side anastomosis scores did not differ significantly from the grafting scores (p=0.85). The most common errors were inadequate knotting technique and suture rupture due to inadequate technique (both n=88 [98.9%]). CONCLUSION: We propose a 16-step, progressive microsurgical training program to learn the basic microsurgical techniques comprehensively and reliably. The program was evaluated in a large sample of trainees, and it demonstrated the adequacy of the training sequence and results.
  • Diagnostic and prognostic value of serum miR-9-5p and miR-128-3p levels in early-stage acute ischemic stroke Original Article

    Wang, Qi; Wang, Fei; Fu, Fengwei; Liu, Jinlin; Sun, Weilu; Chen, Yongqing

    Abstract in English:

    OBJECTIVES: To investigate the clinical utility of serum microRNA levels (miR-9-5p and miR-128-3p) in the diagnosis and prognosis of early-stage acute ischemic stroke (AIS). METHODS: We compared the differences in serum miR-9-5p and miR-128-3p levels between patients with AIS and healthy individuals (controls). The serum levels of miR-9-5p and miR-128-3p were quantified using quantitative real-time PCR, and the association of each miRNA with AIS was determined using receiver operator characteristic curve analysis. The predictive value of these indices in the diagnosis of early-stage AIS was evaluated in conjunction with that of computed tomography findings and neuron-specific enolase levels. The prognosis of patients with AIS was evaluated three months after their discharge from hospital using the modified Rankin scale, which classifies the prognosis as either favorable or poor. Logistic regression analysis was used to analyze the correlation between miR-9-5p and miR-128-3p levels and patient prognosis. RESULTS: The serum levels of miR-9-5p and miR-128-3p were upregulated in patients with AIS relative to those in healthy individuals. A pronounced correlation was identified between serum miR-9-5p and miR-128-3p levels and patient prognosis, with high levels of both miRNAs being associated with poor patient outcomes. CONCLUSION: Assessment of serum miR-9-5p and miR-128-3p levels is important for the early diagnosis and prognosis of AIS.
  • Detecting and grading prostate cancer in radical prostatectomy specimens through deep learning techniques Original Article

    Melo, Petronio Augusto de Souza; Estivallet, Carmen Liane Neubarth; Srougi, Miguel; Nahas, William Carlos; Leite, Katia Ramos Moreira

    Abstract in English:

    OBJECTIVES: This study aims to evaluate the ability of deep learning algorithms to detect and grade prostate cancer (PCa) in radical prostatectomy specimens. METHODS: We selected 12 whole-slide images of radical prostatectomy specimens. These images were divided into patches, and then, analyzed and annotated. The annotated areas were categorized as follows: stroma, normal glands, and Gleason patterns 3, 4, and 5. Two analyses were performed: i) a categorical image classification method that labels each image as benign or as Gleason 3, Gleason 4, or Gleason 5, and ii) a scanning method in which distinct areas representative of benign and different Gleason patterns are delineated and labeled separately by a pathologist. The Inception v3 Convolutional Neural Network architecture was used in categorical model training, and a Mask Region-based Convolutional Neural Network was used to train the scanning method. After training, we selected three new whole-slide images that were not used during the training to evaluate the model as our test dataset. The analysis results of the images using deep learning algorithms were compared with those obtained by the pathologists. RESULTS: In the categorical classification method, the trained model obtained a validation accuracy of 94.1% during training; however, the concordance with our expert uropathologists in the test dataset was only 44%. With the image-scanning method, our model demonstrated a validation accuracy of 91.2%. When the test images were used, the concordance between the deep learning method and uropathologists was 89%. CONCLUSION: Deep learning algorithms have a high potential for use in the diagnosis and grading of PCa. Scanning methods are likely to be superior to simple classification methods.
  • Evaluating the Efficacy of VitalStim Electrical Stimulation Combined with Swallowing Function Training for Treating Dysphagia following an Acute Stroke Original Article

    Liang, Yu; Lin, Jing; Wang, Hui; Li, Shufen; Chen, Fang; Chen, Lili; Li, Ling

    Abstract in English:

    OBJECTIVES: This study explored the clinical efficacy of VitalStim electrical stimulation combined with swallowing function training for patients with dysphagia following an acute stroke. METHODS: Seventy-two patients with dysphagia following an acute stroke were admitted to our hospital and were further divided into two groups using prospective research methods. There were 36 cases in each group according to the random number table method. The control group received conventional medical treatment and swallowing function training while the experimental group received conventional medical treatment and VitalStim electrical stimulation combined with swallowing function training. RESULTS: The overall response rate of the experimental group (94.44%) was higher than that of the control group (77.78%), and the difference was statistically significant (p<0.05). Compared with before treatment, the upward and forward movement speeds of the hyoid bone, anterior movement speed, the grading score of the Kubota drinking water test, Caiteng’s grading score, serum superoxide dismutase, 5-hydroxytryptamine, and norepinephrine levels, Fugl-Meyer Assessment score, and multiple quality of life scores of the two groups showed improvement after treatment. While the standard swallowing assessment score, serum malondialdehyde level, and National Institutes of Health Stroke Scale score decreased, the aforementioned indices showed a significant improvement in the experimental group (p<0.05). CONCLUSION: The results of this study indicate that VitalStim electrical stimulation combined with swallowing function is effective for treating dysphagia following an acute stroke. It can effectively improve swallowing, neurological, and limb motor functions, reduce complications, promote physical recovery, and improve overall quality of life of patients.
  • Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial Original Article

    Lucena, Lucas Siqueira de; Rodrigues, Roseny dos Reis; Carmona, Maria José Carvalho; Noronha, Francisco José Diniz; Oliveira, Heleno de Paiva; Lima, Natalia Martins; Pinheiro, Rodrigo Brandão; Silva, Wallace Andrino da; Cavalcanti, Alexandre Biasi

    Abstract in English:

    OBJECTIVE: To evaluate the clinical effects of early administration of fibrinogen concentrate in patients with severe trauma and hypofibrinogenemia. METHODS: We conducted an open randomized feasibility trial between December 2015 and January 2017 in patients with severe trauma admitted to the emergency department of a large trauma center. Patients presented with hypotension, tachycardia, and FIBTEM findings suggestive of hypofibrinogenemia. The intervention group received fibrinogen concentrate (50 mg/kg), and the control group did not receive early fibrinogen replacement. The primary outcome was feasibility assessed as the proportion of patients receiving the allocated treatment within 60 min after randomization. The secondary outcomes were transfusion requirements and other exploratory outcomes. Randomization was performed using sequentially numbered and sealed opaque envelopes. ClinicalTrials.gov: NCT02864875. RESULTS: Thirty-two patients were randomized (16 in each group). All patients received the allocated treatment within 60 min after randomization (100%, 95% confidence interval, 86.7%-100%). The median length of intensive care unit stay was shorter in the intervention group (8 days, interquartile range [IQR] 5.75-10.0 vs. 11 days, IQR 8.5-16.0; p=0.02). There was no difference between the groups in other clinical outcomes. No adverse effects related to treatment were recorded in either group. CONCLUSION: Early fibrinogen replacement with fibrinogen concentrate was feasible. Larger trials are required to properly evaluate clinical outcomes.
  • Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study Original Article

    Pontual, Daniela Malta; Nabuco, Leticia Cancella; Luiz, Ronir Raggio; Cardoso, Ana Carolina; Perez, Renata M.; Villela-Nogueira, Cristiane A.

    Abstract in English:

    OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.
  • COMVC-19: A Program to protect healthcare workers’ mental health during the COVID-19 Pandemic. What we have learned Original Article

    Fukuti, Pedro; Uchôa, Caroline Louise Mesquita; Mazzoco, Marina Flaborea; Cruz, Isabella D'Andrea Garcia da; Echegaray, Mariana V.F.; Humes, Eduardo de Castro; Silveira, Júlia Belizário; Santi, Talita Di; Miguel, Euripedes Constantino; Corchs, Felipe; ,

    Abstract in English:

    OBJECTIVE: In 2020, the COVID-19 pandemic brought a work and stress overload to healthcare workers, increasing their vulnerability to mental health impairments. In response, the authors created the COMVC-19 program. The program offered preventive actions and mental health treatment for the 22,000 workers of The Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). This paper aims to describe its implementation and share what we have learned from this experience. METHODS: Workers were able to easily access the program through a 24/7 hotline. Additionally, a mobile phone app that screened for signs and symptoms of emotional distress and offered psychoeducation and/or referral to treatment was made available. Data from both these sources as well as any subsequent psychiatric evaluations were collected. RESULTS: The first 20 weeks of our project revealed that most participants were female, and part of the nursing staff working directly with COVID-19 patients. The most frequently reported symptoms were: anxiety, depression and sleep disturbances. The most common diagnoses were Adjustment, Anxiety, and Mood disorders. CONCLUSIONS: Implementing a mental health program in a multimodal intervention was feasible in a major quaternary public hospital. Our data also suggests that preventive actions should primarily be aimed at anxiety and depression symptoms, with a particular focus on the nursing staff.
  • Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study Original Article

    Lourenço, Mariana Sandoval; Zitelli, Patricia Momoyo Y.; Cunha-Silva, Marlone; Oliveira, Arthur Ivan N.; Lima, Roque Gabriel Rezende de; Souza, Evandro de Oliveira; Oliveira, Claudia P.; Sevá-Pereira, Tiago; Carrilho, Flair J.; Pessoa, Mario G.; Mazo, Daniel F.

    Abstract in English:

    OBJECTIVES:Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil.METHODS:We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil.RESULTS:Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832).CONCLUSIONS:Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.
  • RNA-binding protein with serine-rich domain 1 regulates microsatellite instability of uterine corpus endometrial adenocarcinoma Original Article

    Liu, Xiaojuan; Ma, Hui; Ma, Lisha; Li, Kun; Kang, Yanhua

    Abstract in English:

    OBJECTIVE: To determine the role of RNA-binding protein with serine-rich domain 1 (RNPS1) in uterine corpus endometrial carcinoma (UCEC), the role of RNPS1 knockdown in UCEC development in vitro and in vivo, and the relationship between RNPS1 and mismatch repair (MMR) in UCEC. METHODS: We predicted the potential function of RNPS1 using bioinformatics systems. The expression of RNPS1 in tissues and cell lines was analyzed by western blotting and immunohistochemistry. The expression of RNPS1 in MMR was assessed using bioinformatics and western blotting. The proliferation and apoptosis of UCEC cells were assessed under RNPS1 knockdown conditions, and RNPS1 regulation in MMR was detected by suppressing Notch signaling. Associations between RNPS1 and gene mutations in UCEC and prognosis were analyzed. RESULTS: The RNPS1 level was higher in UCEC tumors than in normal tissues and tumors or RL952 cells. Prognostic outcomes were worse when UCEC showed abundant RNPS1 expression. Lentiviral RNPS1 knockdown weakened tumor cell proliferation and suppressed biomarker expression, reduced the tumor volume, promoted apoptosis in vitro and in vivo, and inhibited UCEC development. Increased MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) levels in MMR after RNPS1 knockdown were reversed by inhibiting Notch signaling. Furthermore, RNPS1 was associated with mutations in NAA11, C2orf57, NUPR1, and other genes involved in UCEC prognosis. CONCLUSION: RNPS1 may regulate the expression levels of MSH2 and MSH6 in MMR, enhancing the proliferation, development, and prognosis of UCEC through a Notch signaling pathway in UCEC. Our study offers a new method and strategy for delaying UCEC development through modulating MMR.
  • Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine Original Article

    Helito, Alberto C.; Lindoso, Livia; Sieczkowska, Sofia M.; Astley, Camilla; Queiroz, Ligia B.; Rose, Natalia; Santos, Claudia Renata P.; Bolzan, Thalis; Peralta, Rita María I.A.; Franco, Ruth R.; Cominato, Louise; Pereira, Rosa Maria R.; Tannuri, Uenis; Campos, Lucia Maria A.; Lourenço, Benito; Toma, Ricardo K.; Medeiros, Karina; Watanabe, Andréia; Grangeiro, Patricia Moreno; Farhat, Sylvia C.; Casella, Caio B.; Polanczyk, Guilherme V.; Gualano, Bruno; Silva, Clovis A.; ,

    Abstract in English:

    OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.
  • Hepatitis E virus infection increases the risk of diabetes and severity of liver disease in patients with chronic hepatitis C virus infection Original Article

    Zitelli, Patricia Momoyo Yoshimura; Gomes-Gouvêa, Michele; Mazo, Daniel F.; Singer, Julio da Motta; Oliveira, Claudia P.M.S.; Farias, Alberto Queiroz; Pinho, João Renato; Tanigawa, Ryan Yukimatsu; Alves, Venâncio Avancini Ferreira; Carrilho, Flair José; Pessoa, Mário Guimarães

    Abstract in English:

    OBJECTIVES: Co-infection with hepatitis A or B viruses may aggravate liver injury in patients infected with hepatitis C virus (HCV). However, few studies have assessed co-infection with hepatitis E virus (HEV) and HCV. Therefore, this study aimed to assess the prevalence and impact of HEV infection among Brazilian patients with chronic HCV infection. METHODS: This observational study included adult patients with chronic HCV infection who were naive to antiviral therapy from January 2013 to March 2016. A total of 181 patients were enrolled, and HEV serology and PCR were performed for all patients. RESULTS: Seropositivity for anti-HEV IgG was detected in 22 (12.0%) patients and anti-HEV immunoglobulin M in 3 (1.6%). HEV RNA showed inconclusive results in nine (4.9%) patients and was undetectable in the remaining patients. HEV serology positive patients had more severe liver disease, characterized by liver fibrosis ≥3 versus ≤2 (p<0.001), Aspartate Aminotransferase-to-Platelet Ratio Index of ≥1.45 (p=0.003), and Fibrosis-4 score of ≥3.25 (p=0.001). Additionally, the odds of HEV-positive patients developing diabetes mellitus were 3.65 (95% CI 1.40-9.52) times the corresponding odds of HEV-negative patients. A case-control-based histological analysis (n=11 HEV-HCV-positive patients and n=22 HCV-positive patients) showed no significant differences between the groups. CONCLUSIONS: This prevalence is higher than that reported in previous studies of the general population in Brazil. Thus, HEV infection may influence the severity of liver disease and may represent an additional risk of developing diabetes mellitus in patients with HCV infection.
  • Relationship of the Pelvic-Trochanteric Index with greater trochanteric pain syndrome Original Article

    Santos, Leandro Emílio Nascimento; Navarro, Túlio Pinho; Machado, Carla Jorge; Cabrita, Henrique Antônio Berwanger de Amorim; Pires, Robinson Esteves; Figueiredo, Leonardo Brandão; Gurgel, Henrique Melo Campos; Pfeilsticker, Rudolf Moreira; Grandinetti, Helvécio; Souza, Amanda Damasceno de; Andrade, Marco Antônio Percope de

    Abstract in English:

    OBJECTIVES: This study aimed to correlate a higher Pelvic-Trochanteric Index (PTI) with an increased varus of the femoral neck with greater trochanteric pain syndrome (GTPS). The secondary objective was to check whether the pelvic width changes with age. METHODS: A prospective study was conducted to compare female patients diagnosed with GTPS (case group) with asymptomatic female participants (control group) from March 2011 to June 2017. On an anteroposterior pelvic radiograph, lines were drawn by two radiologists, and the PTI (ratio of the distance between the greater trochanters and distance between the iliac crests) was defined and the femoral neck-shaft angle was measured. RESULTS: Data collected based on radiographs of 182 female patients (cases) and 150 female participants (controls) showed that the mean PTI was 1.09 (SD=0.01) in the case group and 1.07 (SD=0.01) in the control group (p<0.05), regardless of age. The distance between iliac crests increased with age (p<0.05) in symptomatic and asymptomatic individuals. It was also found that the mean femoral neck-shaft angle was 130.6° (SD=0.59) and progression of the varus angulation occurred with age in both groups, with a significance level of 5%. CONCLUSIONS: The PTI was higher in patients with GTPS. The femoral neck-shaft angle does not differ between individuals with and without GTPS; however, it does decrease with age. The pelvic width tends to increase with aging in symptomatic or asymptomatic individuals; therefore, the increase in the pelvic width and decrease in the femoral neck-shaft angle can be interpreted as normal in aging women, which could alter the biomechanics of the hips and pelvis.
  • Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital Original Article

    Marques, Heloisa Helena de Sousa; Pereira, Maria Fernanda Badue; Santos, Angélica Carreira dos; Fink, Thais Toledo; Paula, Camila Sanson Yoshino de; Litvinov, Nadia; Schvartsman, Claudio; Delgado, Artur Figueiredo; Gibelli, Maria Augusta Bento Cicaroni; Carvalho, Werther Brunow de; Odone Filho, Vicente; Tannuri, Uenis; Carneiro-Sampaio, Magda; Grisi, Sandra; Duarte, Alberto José da Silva; Antonangelo, Leila; Francisco, Rossana Pucineli Vieira; Okay, Thelma Suely; Batisttella, Linamara Rizzo; Carvalho, Carlos Roberto Ribeiro de; Brentani, Alexandra Valéria Maria; Silva, Clovis Artur; ,

    Abstract in English:

    OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.
  • Impact of COVID-19 pandemic on the surgical treatment of gastric cancer Original Article

    Arneiro, Amanda Juliani; Ramos, Marcus Fernando Kodama Pertille; Pereira, Marina Alessandra; Dias, André Roncon; Zilberstein, Bruno; Ribeiro Junior, Ulysses; Nahas, Sergio Carlos

    Abstract in English:

    OBJECTIVE: The Coronavirus Disease 2019 (COVID-19) pandemic has been recognized as one of the most serious public health crises. This study aimed to evaluate the short-term impact of the pandemic on the surgical treatment of patients with gastric cancer (GC) in addition to their clinicopathological characteristics. We also verified adherence to the COVID-19 screening protocol adopted in the institution. METHODS: All patients with GC who underwent surgical treatment between 2015 and 2021 were retrospectively evaluated and divided into two groups according to the time period: control group (2015-2019) and COVID group (2020-2021). The institutional protocol recommends that patients referred for surgery undergo RT-PCR for severe acute respiratory syndrome coronavirus 2 infection. RESULTS: A total of 83 patients were classified into the COVID group and 535 into the control group. The number of surgical procedures performed in the control group was 107 (SD±23.8) per year. Diagnostic procedures (p=0.005), preoperative chemotherapy (p<0.001), and adenocarcinomas without Lauren's subtype (p=0.009) were more frequent in the COVID group than in the control group. No significant difference was observed in the pathological characteristics and surgical outcomes of curative GC between the two groups. Evaluation of protocol compliance showed that of 83 patients with GC in the COVID group, 19 (22.9%) were not tested for COVID-19 before surgery. Two patients tested positive for COVID-19 (one preoperative and one postoperative). CONCLUSION: A decrease in the average number of surgeries and a higher frequency of diagnostic procedures occurred during the pandemic than in the previous time period. Tumor/node/metastasis classification, morbidity rates, and mortality rates in patients with GC during the pandemic did not differ from those in the previous time period. Accordingly, GC surgical treatment with acceptable screening protocol compliance could be safely performed during the COVID-19 pandemic.
  • Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital Original Article

    Fink, Thais T.; Marques, Heloisa H.S.; Gualano, Bruno; Lindoso, Livia; Bain, Vera; Astley, Camilla; Martins, Fernanda; Matheus, Denise; Matsuo, Olivia M.; Suguita, Priscila; Trindade, Vitor; Paula, Camila S.Y.; Farhat, Sylvia C.L.; Palmeira, Patricia; Leal, Gabriela N.; Suzuki, Lisa; Odone Filho, Vicente; Carneiro-Sampaio, Magda; Duarte, Alberto José S.; Antonangelo, Leila; Batisttella, Linamara R.; Polanczyk, Guilherme V.; Pereira, Rosa Maria R.; Carvalho, Carlos Roberto R.; Buchpiguel, Carlos A.; Latronico, Ana Claudia; Seelaender, Marilia; Silva, Clovis Artur; Pereira, Maria Fernanda B.; ,

    Abstract in English:

    OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.
  • Physical and pulmonary capacities of individuals with severe coronavirus disease after hospital discharge: A preliminary cross-sectional study based on cluster analysis Original Article

    Alonso, Angelica Castilho; Silva-Santos, Paulo Roberto; Quintana, Marília Simões Lopes; Silva, Vanderlei Carneiro da; Brech, Guilherme Carlos; Barbosa, Lorena Gonçalves; Pompeu, José Eduardo; Silva, Erika Christina Gouveia e; Silva, Elizabeth Mendes da; Godoy, Caroline Gil de; Greve, Julia Maria D’Andréa

    Abstract in English:

    OBJECTIVE: This study aimed to analyze the physical and pulmonary capacities of hospitalized patients with severe coronavirus disease and its correlation with the time of hospitalization and complications involved. METHODS: A total of 54 patients, aged ≥18 years of both sexes, were evaluated 2-4 months after hospital discharge in São Paulo, Brazil. The physical characteristics analyzed were muscle strength, balance, flexibility, and pulmonary function. The K-means cluster algorithm was used to identify patients with similar physical and pulmonary capacities, related to the time of hospitalization. RESULTS: Two clusters were derived using the K-means algorithm. Patients allocated in cluster 1 had fewer days of hospitalization, intensive care, and intubation than those in cluster 2, which reflected a better physical performance, strength, balance, and pulmonary condition, even 2-4 months after discharge. Days of hospitalization were inversely related to muscle strength, physical performance, and lung function: hand grip D (r=−0.28, p=0.04), Short Physical Performance Battery score (r=−0.28, p=0.03), and forced vital capacity (r=−0.29, p=0.03). CONCLUSION: Patients with a longer hospitalization time and complications progressed with greater loss of physical and pulmonary capacities.
  • Extended minimally invasive autopsy: Technical improvements for the investigation of cardiopulmonary events in COVID-19 Original Article

    Theodoro-Filho, Jair; Monteiro, Renata Aparecida de Almeida; Duarte-Neto, Amaro Nunes; Mauad, Thais; Silva, Luiz Fernando Ferraz da; Saldiva, Paulo Hilário Nascimento; Dolhnikoff, Marisa

    Abstract in English:

    OBJECTIVES: Ultrasound-guided minimally invasive autopsies (MIA-US) are an alternative to conventional autopsies and have been used in our institution to investigate the pathophysiology of COVID-19 since the beginning of the pandemic. Owing to the limitations of post-mortem biopsies for evaluating cardiopulmonary events involving large vessels, we continuously improved the technique during this period. Objectives: To demonstrate the usefulness of an extended MIA-US technique (EMIA-US) for the study of thoracic involvement in COVID-19. METHOD: US-guided percutaneous tissue sampling was combined with a small thoracic incision (≤5 cm), allowing for the sampling of larger tissue samples or even the entire organ (lungs and heart). RESULTS: EMIA-US was performed for eight patients who died of COVID-19 in 2021. We demonstrate cardiopulmonary events, mainly thromboembolism and myocardial infarction, that could be evaluated using EMIA-US. CONCLUSIONS: Minimally invasive image-guided post-mortem tissue sampling is a flexible and practical method to conduct post-mortem studies of human diseases, mainly in areas that do not have autopsy facilities or, alternatively, when autopsy is not possible owing to financial constraints, cultural and religious values, or for safety reasons, such as in the case of highly contagious infectious diseases. We present evidence that EMIA-US is feasible and can be used as an alternative to increase the accuracy of MIA-US in detecting cardiopulmonary events involving large vessels, which may not be assessed through post-mortem biopsies.
  • Effect of a Single High-Dose Vitamin D3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19 Original Article

    Murai, Igor H.; Fernandes, Alan L.; Antonangelo, Leila; Gualano, Bruno; Pereira, Rosa Maria Rodrigues

    Abstract in English:

    OBJECTIVES: In this ancillary analysis of a multicenter, double-blinded, randomized, placebo-controlled trial, we investigated the effect of a single high dose of vitamin D3 on the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19. METHODS: The primary outcome was length of hospital stay, defined as the total number of days that patients remained hospitalized from the date of randomization until the date of hospital discharge. Secondary outcomes included serum levels of 25-hydroxyvitamin D, mortality during hospitalization, number of patients admitted to the intensive care unit, and number of patients who required mechanical ventilation. ClinicalTrials.gov: NCT04449718. RESULTS: Thirty-two patients were included in the study. The mean (SD) age was 58.5 (15.6) years, body mass index was 30.8 (8.6) kg/m2, and 25-hydroxyvitamin D level was 7.8 (1.6) ng/mL. No significant difference was observed in the median interquartile range of length of hospital stay between the vitamin D3 group (6.0 [4.0-18.0] days) versus placebo (9.5 [6.3-15.5] days) (log-rank p=0.74; hazard ratio, 1.13 [95% confidence interval (CI), 0.53-2.40]; p=0.76). Vitamin D3 significantly increased serum 25-hydroxyvitamin D levels in the vitamin D3 group compared with that in the placebo group (between-group difference, 23.9 ng/mL [95% CI, 17.7-30.1]; p<0.001). CONCLUSIONS: A dose of 200.000 IU of vitamin D3 did not significantly reduce the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19.
  • C-Reactive protein level and left ventricular mass are associated with acute cellular rejection after heart transplant Original Article

    Bacal, Débora Cestari; Fernandes-Silva, Miguel Morita; Mangini, Sandrigo; Jesus, Marcia Santos de; Bacal, Fernando

    Abstract in English:

    OBJECTIVES: Acute cellular rejection (ACR) remains a major complication of heart transplant (HT). The gold standard for its diagnosis is endomyocardial biopsy (EMB), whereas the role of non-invasive biomarkers for detecting ACR is unclear. This study aimed to identify non-invasive biomarkers for the diagnosis of ACR in patients undergoing HT and presenting with normal left ventricular function. METHODS: We evaluated patients who underwent HT at a single center between January 2010 and June 2019. Patients were enrolled after HT, and those with left ventricular (LV) systolic dysfunction before EMB were excluded. We included only the results of the first EMB performed at least 30 days after HT (median, 90 days). Troponin, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) levels were measured and echocardiography was performed up to 7 days before EMB. ACR was defined as International Society for Heart and Lung Transplantation grade 2R or 3R on EMB. We performed logistic regression analysis to identify the non-invasive predictors of ACR (2R or 3R) and evaluated the accuracy of each using area under the receiver operator characteristic curve analysis. RESULTS: We analyzed 72 patients after HT (51.31±13.63 years; 25 [34.7%] women); of them, 9 (12.5%) developed ACR. Based on multivariate logistic regression analysis, we performed forward stepwise selection (entry criteria, p<0.05). The only independent predictors that remained in the model were CRP level and LV mass index. The optimal cut-off point for CRP level was ≥15.9 mg/L (odds ratio [OR], 11.7; p=0.007) and that for LV mass index was ≥111 g/m2 (OR, 13.6; p=0.003). The area under the receiver operating characteristic curve derived from this model was 0.87 (95% confidence interval [CI], 0.75-0.99), with sensitivity of 85.7% (95% CI, 42.1%-99.6%), specificity of 78.4% (95% CI, 64.7%-88.7%), positive predictive value of 35.3% (95% CI, 14.3%-61.7%), and negative predictive value of 97.6% (95% CI, 87.1%-99.9%). CONCLUSIONS: Among patients undergoing HT, CRP level and LV mass were directly associated with ACR, but troponin and BNP levels were not.
  • Edaravone Improves the Post-traumatic Brain Injury Dysfunction in Learning and Memory by Modulating Nrf2/ARE Signal Pathway Original Article

    Li, Xiushan; Yu, Jing; Ma, Dongzhou; Weng, Xuehui

    Abstract in English:

    OBJECTIVES: To investigate the molecular mechanism of edaravone (EDA) in improving the post-traumatic brain injury (TBI) dysfunction in learning and memory. METHODS: In vitro and in vivo TBI models were established using hydrogen peroxide (H2O2) treatment for hippocampal nerve stem cells (NSCs) and surgery for rats, followed by EDA treatment. WST 1 measurement, methylthiazol tetrazolium assay, and flow cytometry were performed to determine the activity, proliferation, and apoptosis of NSCs, and malondialdehyde (MDA), lactic dehydrogenase (LDH), and reactive oxygen species (ROS) detection kits were used to analyze the oxides in NSCs. RESULTS: Following EDA pretreatment, NSCs presented with promising resistance to H2O2-induced oxidative stress, whereas NSCs manifested significant increases in activity and proliferation and a decrease in apoptosis. Meanwhile, for NSCs, EDA pretreatment reduced the levels of MDA, LDH, and ROS, with a significant upregulation of Nrf2/antioxidant response element (ARE) signaling pathway, whereas for EDA-treated TBI rats, a significant reduction was observed in the trauma area and injury to the hippocampus, with improvement in memory and learning performance and upregulation of Nrf2/ARE signaling pathway. CONCLUSIONS: EDA, by regulating the activity of Nrf2/ARE signal pathway, can improve the TBI-induced injury to NSCs and learning and memory dysfunction in rats.
  • The importance of viral load in the severity of acute bronchiolitis in hospitalized infants Original Article

    De Paulis, Milena; Oliveira, Danielle Bruna Leal; Thomazelli, Luciano Matsumiya; Ferraro, Alexandre Archanjo; Durigon, Edison Luiz; Vieira, Sandra E.

    Abstract in English:

    OBJECTIVE: The relationship between viral load and the clinical evolution of bronchiolitis is controversial. Therefore, we aimed to analyze viral loads in infants hospitalized for bronchiolitis. METHODS: We tested for the presence of human respiratory syncytial virus (HRSV) or human rhinovirus (HRV) using quantitative molecular tests of nasopharyngeal secretions and recorded severity outcomes. RESULTS: We included 70 infants [49 (70%) HRSV, 9 (13%) HRV and 12 (17%) HRSV+HRV]. There were no differences among the groups according to the outcomes analyzed individually. Clinical scores showed greater severity in the isolated HRSV infection group. A higher isolated HRSV viral load was associated with more prolonged ventilatory support, oxygen therapy, and hospitalization days, even after adjustment for the age and period of nasopharyngeal secretion collection. In the co-infection groups, there was a longer duration of oxygen therapy when the HRSV viral load was predominant. Isolated HRV infection and co-infection with a predominance of HRV were not associated with severity. CONCLUSION: Higher HRSV viral load in isolated infections and the predominance of HRSV in co-infections, independent of viral load, were associated with greater severity. These results contribute to the development of therapeutic and prophylactic approaches and a greater understanding of the pathophysiology of bronchiolitis.
  • Association of health vulnerability with adverse outcomes in older people with COVID-19: a prospective cohort study Original Article

    Assis, Fábio Cavalcante de; Silva, Michelle Cristina-Oliveira da; Geber-Júnior, João Carlos; Roschel, Hamilton; Peçanha, Tiago; Drager, Luciano Ferreira; Santana, Alfredo Nicodemos Cruz

    Abstract in English:

    OBJECTIVES: Health vulnerability is associated with a higher risk of mortality and functional decline in older people in the community. However, few studies have evaluated the role of the Vulnerable Elders Survey (VES-13) in predicting clinical outcomes of hospitalized patients. In the present study, we tested the ability of the VES-13 to predict mortality and the need for invasive mechanical ventilation in older people hospitalized with coronavirus disease 2019 (COVID-19). METHODS: This prospective cohort included 91 participants aged ≥60 years who were confirmed to have COVID-19. VES-13 was applied, and the demographic, clinical, and laboratory variables were collected within 72h of hospitalization. A Poisson generalized linear regression model with robust variance was used to estimate the relative risk of death and invasive mechanical ventilation. RESULTS: Of the total number of patients, 19 (21%) died and 15 (16%) required invasive mechanical ventilation. Regarding health vulnerability, 54 (59.4%) participants were classified as non-vulnerable, 30 (33%) as vulnerable, and 7 (7.6%) as extremely vulnerable. Patients classified as extremely vulnerable and male sex were strongly and independently associated with a higher relative risk of in-hospital mortality (p<0.05) and need for invasive mechanical ventilation (p<0.05). CONCLUSION: Elderly patients classified as extremely vulnerable had more unfavorable outcomes after hospitalization for COVID-19. These data highlight the importance of identifying health vulnerabilities in this population.
  • Lung Lesion Burden found on Chest CT as a Prognostic Marker in Hospitalized Patients with High Clinical Suspicion of COVID-19 Pneumonia: a Brazilian experience Original Article

    Fonseca, Eduardo Kaiser Ururahy Nunes; Assunção Júnior, Antonildes Nascimento; Araujo-Filho, Jose de Arimateia Batista; Ferreira, Lorena Carneiro; Loureiro, Bruna Melo Coelho; Strabelli, Daniel Giunchetti; Farias, Lucas de Pádua Gomes de; Chate, Rodrigo Caruso; Cerri, Giovanni Guido; Sawamura, Marcio Valente Yamada; Nomura, Cesar Higa

    Abstract in English:

    OBJECTIVE: To investigate the relationship between lung lesion burden (LLB) found on chest computed tomography (CT) and 30-day mortality in hospitalized patients with high clinical suspicion of coronavirus disease 2019 (COVID-19), accounting for tomographic dynamic changes. METHODS: Patients hospitalized with high clinical suspicion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a dedicated and reference hospital for COVID-19, having undergone at least one RT-PCR test, regardless of the result, and with one CT compatible with COVID-19, were retrospectively studied. Clinical and laboratory data upon admission were assessed, and LLB found on CT was semi-quantitatively evaluated through visual analysis. The primary outcome was 30-day mortality after admission. Secondary outcomes, including the intensive care unit (ICU) admission, mechanical ventilation used, and length of stay (LOS), were assessed. RESULTS: A total of 457 patients with a mean age of 57±15 years were included. Among these, 58% presented with positive RT-PCR result for COVID-19. The median time from symptom onset to RT-PCR was 8 days [interquartile range 6-11 days]. An initial LLB of ≥50% using CT was found in 201 patients (44%), which was associated with an increased crude at 30-day mortality (31% vs. 15% in patients with LLB of <50%, p<0.001). An LLB of ≥50% was also associated with an increase in the ICU admission, the need for mechanical ventilation, and a prolonged LOS after adjusting for baseline covariates and accounting for the CT findings as a time-varying covariate; hence, patients with an LLB of ≥50% remained at a higher risk at 30-day mortality (adjusted hazard ratio 2.17, 95% confidence interval 1.47-3.18, p<0.001). CONCLUSION: Even after accounting for dynamic CT changes in patients with both clinical and imaging findings consistent with COVID-19, an LLB of ≥50% might be associated with a higher risk of mortality.
  • Cardiology referral during the COVID-19 pandemic Original Article

    Santorio, Nathalia Conci; Cardozo, Francisco Akira Malta; Miada, Rodrigo Freddi; Pitta, Fabio Grunspun; Tavares, Caio de Assis Moura; Habrum, Fabio Cetinic; Pinesi, Henrique Trombini; Magalhães, Iuri Resedá; Menezes, Maria Clara Saad; Caramelli, Bruno; Calderaro, Daniela

    Abstract in English:

    OBJECTIVES: This study presents the cardiology referral model adopted at the University of São Paulo-Hospital das Clínicas complex during the initial period of the coronavirus disease (COVID-19) pandemic, main reasons for requesting a cardiologic evaluation, and clinical profile of and prognostic predictors in patients with COVID-19. METHODS: In this observational study, data of all cardiology referral requests between March 30, 2020 and July 6, 2020 were collected prospectively. A descriptive analysis of the reasons for cardiologic evaluation requests and the most common cardiologic diagnoses was performed. A multivariable model was used to identify independent predictors of in-hospital mortality among patients with COVID-19. RESULTS: Cardiologic evaluation was requested for 206 patients admitted to the ICHC-COVID. A diagnosis of COVID-19 was confirmed for 180 patients. Cardiologic complications occurred in 77.7% of the patients. Among these, decompensated heart failure was the most common complication (38.8%), followed by myocardial injury (35%), and arrhythmias, especially high ventricular response atrial fibrillation (17.7%). Advanced age, greater need of ventilatory support on admission, and pre-existing heart failure were independently associated with in-hospital mortality. CONCLUSIONS: A hybrid model combining in-person referral with remote discussion and teaching is a viable alternative to overcome COVID-19 limitations. Cardiologic evaluation remains important during the pandemic, as patients with COVID-19 frequently develop cardiovascular complications or decompensation of the underlying heart disease.
  • SARS-CoV-2 recombinant proteins stimulate distinct cellular and humoral immune response profiles in samples from COVID-19 convalescent patients Original Article

    Silva, Laís Teodoro da; Ortega, Marina Mazzilli; Tiyo, Bruna Tiaki; Viana, Isabelle Freire Tabosa; Lima, Tayná Evily de; Tozetto-Mendoza, Tania Regina; Oliveira, Luanda Mara da Silva; Teixeira, Franciane Mouradian Emidio; Lins, Roberto Dias; Almeida, Alexandre de; Mendes-Correa, Maria Cassia; Duarte, Alberto Jose da Silva; Oshiro, Telma Miyuki

    Abstract in English:

    OBJECTIVES: In this preliminary study we investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood samples from 14 recovered coronavirus disease 2019 (COVID-19) patients and compared them to those in samples from 12 uninfected/unvaccinated volunteers. METHODS: Cellular immunity was assessed by intracellular detection of IFN-γ in CD3+ T lymphocytes after stimulation with SARS-CoV-2 spike (S1), nucleocapsid (NC), or receptor-binding domain (RBD) recombinant proteins or overlapping peptide pools covering the sequence of SARS-CoV-2 spike, membrane and nucleocapsid regions. The humoral response was examined by ELISAs and/or chemiluminescence assays for the presence of serum IgG antibodies directed to SARS-CoV-2 proteins. RESULTS: We observed differences between humoral and cellular immune profiles in response to stimulation with the same proteins. Assays of IgG antibodies directed to SARS-CoV-2 NC, RBD and S1/S2 recombinant proteins were able to differentiate convalescent from uninfected/unvaccinated groups. Cellular immune responses to SARS-CoV-2 protein stimuli did not exhibit a specific response, as T cells from both individuals with no history of contact with SARS-CoV-2 and from recovered donors were able to produce IFN-γ. CONCLUSIONS: Determination of the cellular immune response to stimulation with a pool of SARS-CoV-2 peptides but not with SARS-CoV-2 proteins is able to distinguish convalescent individuals from unexposed individuals. Regarding the humoral immune response, the screening for serum IgG antibodies directed to SARS-CoV-2 proteins has been shown to be specific for the response of recovered individuals.
  • Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study Original Article

    Gonçalves, Fabio Augusto Rodrigues; Besen, Bruno Adler Maccagnan Pinheiro; Lima, Clarice Antunes de; Corá, Aline Pivetta; Pereira, Antônio José Rodrigues; Perazzio, Sandro Félix; Gouvea, Christiane Pereira; Fonseca, Luiz Augusto Marcondes; Trindade, Evelinda Marramon; Sumita, Nairo Massakazu; Duarte, Alberto José da Silva; Lichtenstein, Arnaldo; ,

    Abstract in English:

    OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.
  • Huangkui Capsule in Combination with Leflunomide Improves Immunoglobulin A Nephropathy by Inhibiting the TGF-β1/Smad3 Signaling Pathway Original Article

    Pei, Shuwen; Li, Yan

    Abstract in English:

    OBJECTIVES: To investigate the efficacy and potential molecular mechanism of Huangkui capsule in combination with leflunomide (HKL) for the treatment of immunoglobulin A nephropathy (IgAN) METHODS: IgAN rat models were constructed by treating rats with bovine serum albumin, lipopolysaccharide, and tetrachloromethane. Th22 cells were isolated from the blood samples of patients with IgAN using a CD4+ T cell isolation kit. The expression levels of the components of the TGF-β1/Smad3 signaling pathway, namely, TGF-β1, Smad2, Smad3, Smad4, and Smad7, were detected using quantitative reverse transcription polymerase chain reaction. Cell proliferation was determined using the MTT assay, cell viability was determined using the WST 1 method, and the chemotaxis of Th22 cells was observed using the wound healing assay. Changes in the histology of the kidney tissues were analyzed using hematoxylin and eosin staining. RESULTS: Compared with IgAN rats, the rats subjected to HKL treatment showed good improvement in kidney injuries, and the combined drug treatment performed much better than the single-drug treatment. In addition, following HKL treatment, the viability, proliferation, and chemotaxis of Th22 cells dramatically decreased (*p<0.05, **p<0.01, and ***p<0.001). In addition, CCL20, CCL22, and CCL27 levels decreased and the expression of the key components of the TGF-β1/Smad3 signaling pathway was downregulated in IgAN rats and Th22 cells (*p<0.05, ***p<0.001). CONCLUSIONS: By targeting the TGF-β1/Smad3 signaling pathway, HKL treatment can improve kidney injury in IgAN rats as well as the excessive proliferation and metastasis of Th22 cells.
  • Response of patients with acute respiratory failure caused by COVID-19 to awake-prone position outside the intensive care unit based on pulmonary involvement Original Article

    Silva Junior, João Manoel; Treml, Ricardo Esper; Golinelli, Pamela Cristina; Segundo, Miguel Rogério de Melo Gurgel; Menezes, Pedro Ferro L.; Umada, Julilane Daniele de Almeida; Alves, Ana Paula Santana; Nabeshima, Renata Peres; Carvalho, André dos Santos; Pereira, Talison Silas; Sponton, Elaine Serafim

    Abstract in English:

    OBJECTIVES: Since there are difficulties in establishing effective treatments for COVID-19, a vital way to reduce mortality is an early intervention to prevent disease progression. This study aimed to evaluate the performance of patients with COVID-19 with acute hypoxic respiratory failure according to pulmonary impairment in the awake-prone position, outside of the intensive care unit (ICU). METHODS: A prospective observational cohort study was conducted on COVID-19 patients under noninvasive respiratory support. Clinical and laboratory data were obtained for each patient before the treatment and after they were placed in the awake-prone position. To identify responders and non-responders after the first prone maneuver, receiver operating characteristic curves with sensitivity and specificity of the PaO2/FiO2 and SpO2/FiO2 indices were analyzed. The maneuver was considered positive if the patient did not require endotracheal intubation for ventilatory assistance. RESULTS: Forty-eight patients were included, and 64.6% were categorized as responders. The SpO2/FiO2 index was effective for predicting endotracheal intubation in COVID-19 patients regardless of lung parenchymal damage (area under the curve 0.84, cutoff point 165, sensitivity 85%, specificity 75%). Responders had better outcomes with lower hospital mortality (hazard ratio [HR]=0.107, 95% confidence interval [CI]: 0.012-0.93) and a shorter length of stay (median difference 6 days, HR=0.30, 95% CI: 0.13-0.66) after adjusting for age, body mass index, sex, and comorbidities. CONCLUSIONS: The awake-prone position for COVID-19 patients outside the ICU can improve oxygenation and clinical outcomes regardless of the extent of pulmonary impairment. Furthermore, the SpO2/FiO2 index discriminates responders from non-responders to the prone maneuver predicting endotracheal intubation with a cutoff under or below 165.
  • Effect of hip fracture on prognosis of acute cerebral infarction Original Article

    Yuan, Jiawen; Zhu, Gang; Zhao, Yuwu; Huang, Jiankang

    Abstract in English:

    OBJECTIVES: Hip fractures are a worldwide public health problem. The incidence of hip fracture is high among the elderly, and it is an important cause of death and disability in this population. This observational study aimed to investigate the effect of acute hip fracture on the recovery of neurological function and the prognosis of patients with acute cerebral infarction, as well as whether surgical treatment of combined acute fracture can improve the prognosis of patients. METHODS: Thirty patients with acute cerebral infarction combined with acute hip fracture, who were hospitalized in two hospitals between January 1, 2013 and December 31, 2019, were included. The patients did not undergo surgical treatment. The control group included patients with common acute cerebral infarction without hip fracture admitted in the same period. The neurological function recovery, hospitalization period, half a year recovery rate, incidence of complications, and one-year mortality rate between the two groups were compared. Eleven patients with acute cerebral infarction combined with hip fracture, who underwent surgical treatment, were selected and compared with those in the non-surgery group. RESULTS: Compared with patients with common acute cerebral infarction, the National Institutes of Health Stroke Scale score of those with acute cerebral infarction combined with hip fracture was higher (7.2±5.4 vs. 5.6%±4.3, p=0.034), the hospitalization period was prolonged (16.1±8.9% vs. 12.2±5.3, p=0.041), and the half a year recovery rate was lower (26.7% vs. 53.3%, p=0.016). Additionally, the incidence of pulmonary infection and lower extremity deep vein thrombosis was increased (30% vs. 11.7%, p=0.03; 6.7% vs. 0, p=0.043). The one-year mortality rate of patients with hip fracture was higher than that of patients with common cerebral infarction (23.3% vs. 6.7%, p=0.027). Compared with the non-surgical group, the good recovery rate after half a year of surgical treatment of the group with cerebral infarction and acute hip fracture had an increasing trend, while the hospitalization cycle, incidence of complications, and one-year mortality rate were all decreased, although this was not statistically significant. CONCLUSIONS: Acute cerebral infarction combined with hip fracture leads to worse neurological recovery, prolonged hospitalization period, increased complications, decreased patient prognosis, and increased one-year mortality. Surgical treatment improves the prognosis of patients with acute cerebral infarction. These findings may provide insights into the management of acute cerebral infarction.
  • Previous preeclampsia and its association with the future development of cardiovascular diseases: a systematic review and meta-analysis Review Article

    Veiga, Eduardo Carvalho de Arruda; Rocha, Paulo Ricardo Higassiaraguti; Caviola, Leonardo L.; Cardoso, Viviane Cunha; Costa, Fabricio da Silva; Saraiva, Maria da Conceição Pereira; Barbieri, Marco Antonio; Bettiol, Heloisa; Cavalli, Ricardo Carvalho

    Abstract in English:

    Preeclampsia is a multifactorial disease. Among these factors, untreated hypertension during pregnancy can result in high morbidity and mortality rates and may also be related to the future development of cardiovascular diseases.Therefore, this systematic review aimed to determine the association of previous preeclampsia with the future development of cardiovascular diseases. Studies on the association between preeclampsia and future cardiovascular diseases published in the last 10 years (2009-2019) were identified from the PubMed/Medline (207 articles), Embase (nine articles), and Cochrane (three articles) databases using the keywords “preeclampsia” and “future cardiovascular diseases”, “preeclampsia” and “future heart attack”, and “preeclampsia” and “future cardiac disease”. After applying the inclusion and exclusion criteria, 15 articles were analyzed by systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The meta-analysis and the determination of the quality of the articles were conducted using RevMan software, version 5.3. Statistically significant differences were observed between the control and previous preeclampsia groups with respect to systolic blood pressure (mean difference [MD] 4.32; 95% confidence interval [95%CI] 3.65, 4.99; p<0.001), diastolic blood pressure (MD): 2.11; 95%CI: 1.68, 2.55; p<0.0001), and insulin level (MD: 2.80; 95% CI: 0.50, 5.11; p<0.001). Body mass index (MD: 2.57, 95%CI: 2.06, 3.07; p=0.0001), total cholesterol (MD: 10.39; 95%CI: 8.91, 11.87; p=0.0001), HDL (MD: 2.83; 95%CI: 2.20, 3.46; p=0.0001), and LDL (MD: 1.77; 95%CI: 0.42, 3.13; p=0.0001) also differed significantly between groups. Thus, the results of the present study showed that women with a history of preeclampsia were more likely to develop cardiovascular disease.
  • Ultrasound-guided peripheral abdominal wall blocks Review Article

    Fernandes, Hermann dos Santos; Azevedo, Artur Salgado de; Ferreira, Thiago Camargo; Santos, Shirley Andrade; Rocha-Filho, Joel Avancini; Vieira, Joaquim Edson

    Abstract in English:

    The practice of regional anesthesia is in a state of progressive evolution, mainly due to the advent of ultrasound as an anesthesiologist's instrument. Alternative techniques for postoperative analgesia of abdominal surgeries, such as transversus abdominis plane block, oblique subcostal transversus abdominis plane block, rectus abdominis muscle sheath block, ilioinguinal and iliohypogastric nerve block, and quadratus lumborum plane block, have proven useful, with good analgesic efficacy, especially when neuroaxial techniques (spinal anesthesia or epidural anesthesia) are not possible. This review discusses such blockades in detail, including the anatomical principles, indications, techniques, and potential complications.
  • Portal vein surgical treatment on non-tumoral portal vein thrombosis in liver transplantation: Systematic Review and Meta-Analysis Review Article

    Nacif, Lucas S.; Zanini, Leonardo Y.; Pinheiro, Rafael S.; Waisberg, Daniel R.; Rocha-Santos, Vinicius; Andraus, Wellington; Carrilho, Flair J.; Carneiro-D'Albuquerque, Luiz

    Abstract in English:

    Non-tumoral portal vein thrombosis (PVT) is associated with higher morbidity and mortality in liver transplantation (LT). In this study, we aimed to evaluate the impact of PVT in LT outcomes and analyze the types of surgical techniques used for dealing with PVT during LT. A systematic review was conducted in Cochrane, MEDLINE, and EMBASE databases, selecting articles from January 1990 to December 2019. The MESH-terms used were (“Portal Vein”[Mesh] AND “Thrombosis”[Mesh] NOT “Neoplasms”[Mesh]) AND (“Liver Transplantation”[Mesh]). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendation was used, and meta-analysis was performed with Review Manager Version 5.3 software. A total of 1,638 articles were initially found: 488 in PubMed, 289 in Cochrane Library, and 861 in EMBASE, from which 27 were eventually selected for the meta-analysis. Surgery time of LT in patients with PVT was longer than in patients without LT (p<0.0001). Intraoperative red blood cell (p<0.00001), fresh frozen plasma (p=0.01), and platelets (p=0.03) transfusions during LT were higher in patients with PVT. One-year (odds ratio [OR] 1.17; p=0.002) and 5-year (OR 1.12; p=0.01) patient survival after LT was worse in the PVT group. Total occlusive PVT presented higher mortality (OR 3.70; p=0.00009) and rethrombosis rates (OR 3.47 [1.18-10.21]; p=0.02). PVT Yerdel III/IV classification exhibited worse 1-year [2.04 (1.21-3.42); p=0.007] and 5-year [0.98 (0.59-1.62); p=0.93] patient survival. Thrombectomy with primary anastomosis was associated with better outcomes. LT in patients with non-tumoral PVT demands more surgical time, needs more intraoperative transfusion, and presents worse 1- and 5-year patient survival. Total occlusive PVT and Yerdel III/IV PVT classification were associated with higher mortality. (PROSPERO, registration number: CRD42020132915).
  • Fatty Pancreas: Disease or Finding? Review Article

    Silva, Lucas de Lucena Simões e; Fernandes, Matheus Santos de Sousa; Lima, Eline Autran de; Stefano, José Tadeu; Oliveira, Claudia P.; Jukemura, José

    Abstract in English:

    Despite a growing number of investigative studies on pancreatic fat deposition, there remains no clear indication regarding the clinical relevance of fat infiltration in the pancreas, also called fatty pancreas (FP). An individual’s body weight is correlated with their pancreatic weight. Moreover, lipid infiltration causes disorders that compromise not only morphology but also metabolic functions. Fat infiltration leads to insulin resistance, type II diabetes mellitus, and pancreatic cancer; however, knowledge about pancreatic fat content and aspects related to the clinical profile remains unclear in the literature. The present review describes the current knowledge of FP, including its pathophysiology and clinical implications, as well as lifestyle changes in FP.
  • Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials Review Article

    Tustumi, Francisco; Miranda Neto, Antonio Afonso de; Silveira Júnior, Sérgio; Fernandes, Felipe Alexandre; Silva, Miller Barreto de Brito e; Ernani, Lucas; Nacif, Lucas Souto; Coelho, Fabricio Ferreira; Andraus, Wellington; Bernardo, Wanderley Marques; Herman, Paulo; Carneiro-D’Albuquerque, Luiz Augusto

    Abstract in English:

    A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.
  • Efficacy of short-term moderate or high-dose statin therapy for the prevention of contrast-induced nephropathy in high-risk patients with chronic kidney disease: systematic review and meta-analysis Review Article

    Zhou, Yan-Lin; Chen, Li-Qun; Du, Xiao-Gang

    Abstract in English:

    Although previous studies have indicated that statin therapy can effectively prevent the development of CIN, this observation remains controversial, especially in high-risk patients. A meta-analysis was performed to evaluate the efficacy of statin pretreatment for preventing the development of CIN in patients with chronic kidney disease (CKD) and to determine its effectiveness in various subgroups. We searched the online databases PubMed, EMBASE, and the Cochrane Library. RCTs that involved the comparison of the short-term moderate or high-dose statin pretreatment with placebo for CIN prevention in CKD patients undergoing angiography were included. The primary outcome was CIN prevalence. Seven RCTs comprising 4256 participants were investigated in this analysis. The risk of developing CIN in patients pretreated with statins was significantly lower than that in patients pretreated with placebo (RR=0.57, 95%CI=0.43-0.76, p=0.000). The SCr values of the statin group, when analyzed 48h after angiography were lower than those of the placebo group ((SMD=-0.15, 95% CI=-0.27 to -0.04, p=0.011). In the subgroup analysis, statin pretreatment could decrease the risk of CIN in CKD patients with DM (RR=0.54, 95% CI=0.39-0.76, p=0.000), but not in CKD patients without DM (RR=0.84, 95% CI=0.44-1.60, p=0.606). The efficacy of atorvastatin for preventing CIN was consistent with that observed with the use of rosuvastatin. The risk ratios (RR) were 0.51 (95% CI=0.32-0.81, p=0.004) and 0.60 (95% CI=0.41-0.88, p=0.009), respectively. Our study demonstrated that statin pretreatment could prevent the development of CIN in CKD patients. However, subgroup analysis demonstrated that statin pretreatment, despite being effective in preventing CIN in patients with CKD and DM, was not helpful for CKD patients without DM. Rosuvastatin and atorvastatin exhibited similar preventive effects with respect to CIN.
  • Geriatric nutritional risk index predicts all-cause mortality in patients with heart failure: A systematic review and meta-analysis Review Article

    Dong, Chao-hui; Chen, Si-yu; Zeng, Hong-lian; Yang, Bo; Pan, Jia

    Abstract in English:

    OBJECTIVES: Geriatric nutritional risk index (GNRI) might predict the all-cause mortality in patients with heart failure (HF). We performed a meta-analysis to evaluate the correlation between GNRI and all-cause mortality in patients with HF. METHODS: We searched the PubMed, Medline, Cochrane Library, and Embase databases for clinical trials investigating the association between GNRI and all-cause mortality in patients with HF, having the primary endpoint as all-cause mortality. RESULTS: In total, nine studies involving 7,659 subjects were included in the systematic review and meta-analysis. The results indicated that major risk and moderate risk GNRI (GNRI<92) was associated with an increased risk of all-cause mortality in elderly patients with HF (hazard ratios [HR] 1.59, 95% confidence intervals [CI] 1.37-1.85). Low risk GNRI (GNRI<98) group predicted all-cause mortality in elderly HF patients (HR 1.56, 95%CI 1.12-2.18) when compared with the high GNRI value group. A subgroup analysis indicated that the relationship between GNRI and HF might differ based on the subtype of heart failure. CONCLUSIONS: GNRI is a simple and well-established nutritional assessment tool to predict all-cause mortality in patients with HF.
  • COVID-19 and Thromboinflammation: Is There a Role for Statins? Review Article

    Ferrari, Filipe; Martins, Vítor M.; Teixeira, Marcelo; Santos, Raul D.; Stein, Ricardo

    Abstract in English:

    The novel coronavirus disease (COVID-19) showed increased morbidity and mortality rates and worse prognosis in individuals with underlying chronic diseases, especially cardiovascular disease and its risk factors, such as hypertension, diabetes, and obesity. There is also evidence of possible links among COVID-19, myocardial infarction, and stroke. Emerging evidence suggests a pro-inflammatory milieu and hypercoagulable state in patients with this infection. Despite anticoagulation, a large proportion of patients requiring intensive care may develop life-threatening thrombotic complications. Indeed, the levels of some markers of hemostatic activation, such as D-dimer, are commonly elevated in COVID-19, indicating potential risk of deep vein thrombosis and pulmonary thromboembolism. In this review, we critically examine and discuss aspects of hypercoagulability and inflammation in COVID-19 and the possible benefits of statins in this scenario, with emphasis on their underlying molecular mechanisms. Moreover, we present recommendations on the use of antiviral drugs in combination with statins.
  • Renin-Angiotensin-Aldosterone System Inhibitors in COVID-19: A Review Review Article

    Ferrari, Filipe; Martins, Vítor Magnus; Fuchs, Flávio Danni; Stein, Ricardo

    Abstract in English:

    Among the multiple uncertainties surrounding the novel coronavirus disease (COVID-19) pandemic, a research letter published in The Lancet implicated drugs that antagonize the renin-angiotensin-aldosterone system (RAAS) in an unfavorable prognosis of COVID-19. This report prompted investigations to identify mechanisms by which blocking angiotensin-converting enzyme 2 (ACE2) could lead to serious consequences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The possible association between RAAS inhibitors use and unfavorable prognosis in this disease may have been biased by the presence of underlying cardiovascular diseases. As the number of COVID-19 cases has increased worldwide, it has now become possible to investigate the association between RAAS inhibitors and unfavorable prognosis in larger cohorts. Observational studies and one randomized clinical trial failed to identify any consistent association between the use of these drugs and unfavorable prognosis in COVID-19. In view of the accumulated clinical evidence, several scientific societies recommend that treatment with RAAS inhibitors should not be discontinued in patients diagnosed with COVID-19 (unless contraindicated). This recommendation should be followed by clinicians and patients.
  • Corona Mortis: A Systematic Review of Literature Review Article

    Cardoso, Giovana Irikura; Chinelatto, Lucas Albuquerque; Hojaij, Flavio; Akamatsu, Flávia Emi; Jacomo, Alfredo Luiz

    Abstract in English:

    Our systematic review evaluates surgically relevant information about corona mortis (CM), such as anatomical structure, size, laterality, incidence, and anthropometric correlations. This study aimed to provide data about anastomosis in an attempt to avoid iatrogenic damage during surgery. Articles were searched online using the descriptor “Corona Mortis” in PubMed, Biblioteca Virtual em Saúde (BVS) (Literatura Latino-Americana e do Caribe em Saúde [LILACS], MEDLINE, indice bibliografico espaãol en ciencias de la salud [IBECS]), and SciELO database. The time range was set between 1995 and 2020. The articles were selected according to their titles and later the abstracts' relation to our research purpose. All the selected articles were read entirely. A manual search based of the references cited in these articles was also conducted to identify other articles or books of interest. Forty references fulfilled the criteria for this review. The mean incidence of CM was 63% (the majority venous) among 3,107 hemipelvises. The incidence of bilateral CM was lower than that of unilateral variations based on the analysis of 831 pelvises. The mean caliber of the anastomosis was 2.8 mm among 1,608 hemipelvises. There is no consensus concerning the anthropometric influences in CM. Finally, we concluded that CM is not an unusual anatomical variation and that we must not underestimate the risk of encountering the anastomosis during surgery. Anatomical knowledge of CM is, therefore, essential in preventing accidents for surgeons who approach the inguinal and retropubic regions.
  • Risk factors for bronchiectasis in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis Review Article

    Zhang, XinXin; Pang, LiJian; Lv, XiaoDong; Zhang, HaoYang

    Abstract in English:

    The risk factors of bronchiectasis in patients with chronic obstructive pulmonary disease have not yet been established. This systematic review and meta-analysis aimed to investigate and identify potential risk factors for patients with chronic obstructive pulmonary disease accompanied by bronchiectasis. We reviewed eight electronic journal databases from their inception to November 2019 for observational studies with no language restrictions. The Newcastle-Ottawa Scale was applied to evaluate the quality of the literature. Binary variables were pooled using odds ratios and continuous variables using the standardized mean difference with 95% confidence intervals. The confidence of evidence was assessed according to the grading of the recommendations assessment, development, and evaluation method. Eight case-control studies met the inclusion criteria. Tuberculosis history, smoking history, hospitalization stays, admissions in the past year, and duration of symptoms were considered risk factors. In addition, the ratio between the forced expiratory volume in 1s and forced vital capacity, the percentage of forced expiratory volume in 1s, the forced expiratory volume in 1s as a percentage of the predicted value, purulent sputum, purulent mucus sputum, positive sputum culture, Pseudomonas aeruginosa infection, arterial oxygen pressure, daily dyspnea, C-reactive protein, leukocytes, and the percentage of neutrophils were found to be closely related to bronchiectasis. However, these were not considered risk factors. The evidence of all outcomes was judged as “low” or “very low.” Additional prospective studies are required to elucidate the underlying risk factors and identify effective preventive interventions.
  • Combination of toothbrushing and chlorhexidine compared with exclusive use of chlorhexidine to reduce the risk of ventilator-associated pneumonia: A systematic review with meta-analysis Review Article

    Silva, Pedro Urquiza Jayme; Paranhos, Luiz Renato; Meneses-Santos, Daniela; Blumenberg, Cauane; Macedo, Dhiancarlo Rocha; Cardoso, Sérgio Vitorino

    Abstract in English:

    This study aimed to compare the effectiveness of 0.12% chlorhexidine alone and 0.12% chlorhexidine in combination with toothbrushing to prevent ventilator-associated pneumonia (VAP) in mechanically ventilated patients. The Embase, Latin American and Caribbean Health Science Literature, PubMed, Scientific Electronic Library Online, Scopus, LIVIVO, Web of Science, Cochrane Library, OpenThesis, and Open Access Thesis and Dissertations databases were used. Only randomized controlled trials without restrictions on the year or language of publication were included. Two reviewers assessed the risk of bias using the Joanna Briggs Institute Critical Appraisal Tool. A meta-analysis using a random-effects model estimated the combined relative risk (RR). The Grading of Recommendations, Assessment, Development and Evaluations approach was used to assess the certainty of the evidence. Initially, 2,337 studies were identified, of which 4 were considered in the systematic review and 3 in the meta-analysis (total sample: 796 patients). The studies were published between 2009 and 2017. All eligible studies had a low risk of bias. The meta-analysis revealed that the risk of VAP was 24% lower in patients receiving chlorhexidine combined with toothbrushing than in those receiving chlorhexidine alone (RR: 0.76; 95% confidence interval: 0.55-1.06), with moderate certainty of evidence and without statistical significance. In conclusion, considering the limitations of this study, a standard protocol for the prevention of VAP is not yet recommended. More studies with larger sample sizes are needed to draw strong conclusions. However, considering that toothbrushing is a simple intervention, it should be a common practice in mechanically ventilated patients, especially among patients with coronavirus disease.
  • Efficacy and Safety of Emricasan in Liver Cirrhosis and/or Fibrosis Review Article

    Mu, Li-ya; Li, Shu-qin; Tang, Li-xin; Li, Rui

    Abstract in English:

    This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted.
  • Influence of CYP19A1 gene expression levels in women with breast cancer: a systematic review of the literature Review Article

    Barros-Oliveira, Maria da Conceição; Costa-Silva, Danylo Rafhael; dos Santos, Alesse Ribeiro; Pereira, Renato Oliveira; Soares-Júnior, José Maria; Silva, Benedito Borges da

    Abstract in English:

    Breast cancer is the most frequently diagnosed malignant neoplasm in women and is considered a multifactorial disease of unknown etiology. One of the major risk factors is genetic alteration. Changes in CYP19A1 gene expression levels have been associated with increased risk and increased aggressiveness of breast cancer. Increased CYP19A1 gene expression and/or aromatase activity are among the major regulatory events for intratumoral production of estrogens in breast malignant tissues. This systematic review aimed to investigate the influence of CYP19A1 gene expression levels in women with breast cancer. The research was carried out using the PubMed, Scopus, and Web of Science databases. Searches were conducted between February 2 and May 15, 2019. Inclusion criteria were studies published between 2009 and 2019, English language publications, and human studies addressing the gene expression of CYP19A1 in breast cancer. A total of 6.068 studies were identified through PubMed (n=773), Scopus (n=2,927), and the Web of Science (n=2,368). After selecting and applying the inclusion and exclusion criteria, six articles were included in this systematic review. This systematic review provides evidence that increased or decreased levels of CYP19A1 gene expression may be related to pathological clinical factors of disease, MFS, OS, DFS, WATi, markers of metabolic function, concentrations of E1, FSH, and in the use of multiple exons 1 of the CYP19A1 gene in breast cancer.
  • Prognostic power of conventional echocardiography in individuals without history of cardiovascular diseases: A systematic review and meta-analysis Review Article

    Fernandes, Luciana Pereira; Barreto, Ana Terra Fonseca; Neto, Mansueto Gomes; Câmara, Edmundo José Nassri; Durães, André Rodrigues; Roever, Leonardo; Aras-Júnior, Roque

    Abstract in English:

    Echocardiographic abnormalities are associated with a higher incidence of adverse cardiovascular outcomes. This systematic review and meta-analysis aimed to evaluate whether echocardiographic abnormalities are predictors of cardiovascular events in individuals without previous cardiovascular diseases. The PubMed, Scopus, and SciELO databases were searched for longitudinal studies investigating the association between echocardiographic abnormalities and cardiovascular events among individuals without known cardiovascular diseases. Two independent reviewers analyzed data on the number of participants, age and sex, echocardiographic alterations, follow-up time, and cardiovascular outcomes. The meta-analysis estimated the risk ratio (RR) and 95% confidence interval (CI). Heterogeneity was assessed using I2 test. Twenty-two longitudinal studies met the eligibility criteria, comprising a total of 55,603 patients. Left ventricular hypertrophy (LVH) was associated with non-fatal cardiovascular events (RR 2.16; 95% CI 1.22-3.84), death from cardiovascular disease (RR 2.58; 95% CI 1.83- 3.64), and all-cause mortality (RR 2.02; 95% CI 1.34-3.04). Left ventricular diastolic dysfunction (LVDD) and left atrial dilation (LA) were associated with fatal and non-fatal cardiovascular events (RR 2.01; 95% CI 1.32-3.07) and (RR 1.78; 95% CI 1.16-2.73), respectively. Aortic root dilation was associated with non-fatal cardiovascular events (RR 1.25; 95% CI 1.09-1.43). In conclusion, LVH, LVDD, dilations of the LA, and of the aortic root were associated with an increased risk of adverse events in individuals without previous cardiovascular diseases. This study suggests that simple data obtained on conventional echocardiography can be an important predictor of cardiovascular outcomes in a low-risk population.
  • Preemptive use of intravenous ibuprofen to reduce postoperative pain after lower third molar surgery: a systematic review of randomized controlled trials Review Article

    Silva, Pedro Urquiza Jayme; Meneses-Santos, Daniela; Vieira, Walbert de Andrade; Ramacciato, Juliana Cama; Silva, Ricardo Pedro da; Silva, Marcelo Caetano Parreira da; Rode, Sigmar de Mello; Paranhos, Luiz Renato

    Abstract in English:

    This study aimed to systematically review the literature to assess the effect of preemptive intravenous ibuprofen on pain reduction after lower third molar surgery. Nine databases (PubMed, Scopus, LILACS, SciELO, Embase, Web of Science, Cochrane, Open Gray, and Open Thesis) were used as sources of research, including “grey literature.” The protocol was registered in PROSPERO. Only randomized clinical trials evaluating the effects of preemptive intravenous ibuprofen on pain during and immediately after the extraction of lower third molars were included, without restrictions of year and language. Two reviewers independently performed the study selection, data extraction, and assessment of the risk of bias. The “Joanna Briggs Institute for Randomized Controlled Trials” tool was used to assess the risk of bias. Each study was categorized according to the percentage of positive responses to the questions corresponding to the assessment instrument. The results were measured narratively/descriptively. The initial search resulted in 3,257 records, of which only three studies (n=150 participants) met the eligibility criteria and were included in the qualitative analysis. All studies were published in 2019. The risk of bias ranged from low to moderate. Two studies found significant pain reduction within 48 h after the procedure. In conclusion, the use of preemptive intravenous ibuprofen for extracting third molars reduces pain and analgesic consumption after the surgical procedure.
  • Current status of research regarding Blastocystis sp., an enigmatic protist, in Brazil Review Article

    Melo, Gessica Baptista de; Bosqui, Larissa Rodrigues; Costa, Idessania Nazareth da; Paula, Fabiana Martins de; Gryschek, Ronaldo Cesar Borges

    Abstract in English:

    The present study aimed to evaluate the occurrence of Blastocystis sp. in Brazilian studies over a period of years (2000-2020), as well as point out relevant aspects of this enigmatic organism. We performed a literature search using six sources of international databases. The data were divided into diagnostic by parasitological and molecular techniques, and relevant aspects. After applying the inclusion and exclusion criteria, 52 studies were included in the final analysis. The occurrence of Blastocystis sp. in Brazil ranged from 0.5% to 86.6%, as determined using parasitological techniques. The highest occurrence was in the North (27.3%) and the lowest, in the Midwest region (13.4%). In Brazil, most studies have employed molecular techniques and are concentrated in the Southeast region. The Blastocystis sp. subtype ST3 had the highest average positivity, followed by ST1 and ST2. These findings represent a panorama that reflects the reality of Brazil; thus, we believe that the effectiveness of parasitological diagnosis should be considered with regard to making an appropriate choice of technique for detecting Blastocystis sp. Additionally, we emphasize the importance of further studies in the context of molecular epidemiology with regard to this genus. Blastocystis sp. is not well understood yet, and very little information regarding this genus is available; hence, further research regarding this genus is urgently needed.
  • Meta-analysis of the relationship between interleukin-6 levels and the prognosis and severity of acute coronary syndrome Review Article

    Yang, Chongzhe; Deng, Zhiyong; Li, Jie; Ren, Zhilei; Liu, Feng

    Abstract in English:

    This study aimed to explore the relationship between plasma interleukin 6 (IL-6) levels, adverse cardiovascular events, and the severity of acute coronary syndrome (ACS). A literature review was performed of studies regarding IL-6 and ACS extracted from databases including EMBASE, Cqvip, MEDLINE, Web of Knowledge, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang data. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of the literature. The literature was screened, its quality was evaluated, and relevant data were extracted for performing meta-analysis using RevMan software (version 5.3). A total of 524 studies were included in the initial survey. After several rounds of screening and analysis, six studies met the inclusion criteria and underwent meta-analysis using a fixed-effect model. Patients were divided into non-severe and severe groups based on the concentration of high-sensitivity C-reactive protein. Meta-analysis of the relationship between IL-6 and the severity of ACS showed that the plasma IL-6 level of patients in the severe group was significantly higher than that of patients in the non-severe group (p<0.00001). Additionally, patients with experience of major adverse cardiovascular events had significantly higher plasma IL-6 levels than did patients without experience of such events (p<0.00001). In summary, patients with ACS and high IL-6 levels tended to be in a critical condition, with a higher risk of adverse cardiovascular events and worse prognosis. Thus, IL-6 levels could indicate whether patients with ACS may have adverse cardiovascular events and determine the severity of ACS.
  • Extrapulmonary onset manifestations of COVID-19 Review Article

    Finsterer, Josef; Scorza, Fulvio A.; Scorza, Carla A.; Fiorini, Ana C.

    Abstract in English:

    Coronavirus disease (COVID-19) usually starts with pulmonary signs and symptoms. However, in some cases, the initial clinical presentations are extrapulmonary. This literature review aimed at summarizing and discussing the extrapulmonary onset manifestations of COVID-19. The most frequent initial extrapulmonary manifestations include hypogeusia, hyposmia, non-specific abdominal symptoms, corneal congestion, and deep venous thrombosis. Several rarer extrapulmonary manifestations in locations such as the brain, peripheral nerves, muscles, eyes, ears, myocardium, intestines, skin, or vessels have been additionally reported as onset presentations of COVID-19. In conclusion, it is crucial for clinicians and health care providers to consider extrapulmonary presentations at the onset of COVID-19 to avoid overlooking the infection and contributing to the spread of the disease.
  • Sentinel lymph node biopsy in oral cavity cancer using indocyanine green: A systematic review and meta-analysis Review Article

    Chen, Yongfeng; Xiao, Qi; Zou, Weina; Xia, Chengwan; Yin, Hongling; Pu, Yumei; Wang, Yuxin; Zhang, Kai

    Abstract in English:

    This meta-analysis was conducted to evaluate the value of indocyanine green (ICG) in guiding sentinel lymph node biopsy (SLNB) for patients with oral cavity cancer. An electronic database search (PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science) was performed from their inception to June 2020 to retrieve clinical studies of ICG applied to SLNB for oral cavity cancer. Data were extracted from 14 relevant articles (226 patients), and 9 studies (134 patients) were finally included in the meta-analysis according to the inclusion and exclusion criteria. The pooled sentinel lymph node (SLN) sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 88.0% (95% confidence interval [CI], 74.0-96.0), 64.0% (95% CI, 61.0-66.0), 2.45 (95% CI, 1.31-4.60), 0.40 (95% CI, 0.17-0.90), and 7.30 (95% CI, 1.74-30.68), respectively. The area under the summary receiver operating characteristic curve was 0.8805. In conclusion, ICG applied to SLNB can effectively predict the status of regional lymph nodes in oral cavity cancer.
  • Perspectives of bilateral thoracic sympathectomy for treatment of heart failure Review Article

    Coutinho e Silva, Raphael dos Santos; Zanoni, Fernando Luiz; Simas, Rafael; Moreira, Luiz Felipe Pinho

    Abstract in English:

    Surgical neuromodulation therapies are still considered a last resort when standard therapies have failed for patients with progressive heart failure (HF). Although a number of experimental studies have provided robust evidence of its effectiveness, the lack of strong clinical evidence discourages practitioners. Thoracic unilateral sympathectomy has been extensively studied and has failed to show significant clinical improvement in HF patients. Most recently, bilateral sympathectomy effect was associated with a high degree of success in HF models, opening the perspective to be investigated in randomized controlled clinical trials. In addition, a series of clinical trials showed that bilateral sympathectomy was associated with a decreased risk of sudden death, which is an important outcome in patients with HF. These aspects indicates that bilateral sympathectomy could be an important alternative in the treatment of HF wherein pharmacological treatment barely reaches the target dose.
  • Incidence of central nervous system metastases in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer treated with trastuzumab: A meta-analysis Review Article

    Bai, Xue; Lin, Xue; Song, Jin; Chang, Jia-han; Han, Li-li; Fan, Cibo

    Abstract in English:

    This study aimed to estimate the incidence of central nervous system (CNS) metastases in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) treated with trastuzumab. Studies were identified through a literature search of electronic databases. Random-effects meta-analyses were performed to estimate the incidence rate of CNS metastases, trastuzumab therapy duration, and time from trastuzumab therapy to CNS metastasis diagnosis. A meta-analysis of odds ratios was performed to evaluate the significance of a difference in CNS metastasis incidence between patients with and without trastuzumab treatment. Thirty studies (8121 trastuzumab-treated and 3972 control patients) were included. The follow-up duration was 18.9 months (95% confidence interval [CI]: 13.8, 24.1). The trastuzumab treatment duration was 9.0 months (95% CI: 7.0, 11.0). The median interval between the start of trastuzumab therapy and CNS metastasis diagnosis was 12.2 months (95% CI: 9.5, 14.7). The incidence of CNS metastasis after the start of trastuzumab therapy was 22% (95% CI: 16, 27). The incidence of CNS metastases was significantly higher in trastuzumab-treated than in non-trastuzumab-treated patients (odds ratio: 1.39 [95% CI: 1.06, 1.82], p=0.02). The survival time from the start of the study was 23.4 months (95% CI: 19.7, 27.1) in trastuzumab-treated patients and 18.4 months (95% CI: 12.7, 24.1) in patients treated with control regimens. The survival time after the development of CNS metastases in trastuzumab-treated patients was 19.2 months (95% CI: 15.6, 25.9). Approximately 22% of patients with HER2-positive MBC who were treated with trastuzumab developed CNS metastases. However, trastuzumab-treated patients had a longer survival than patients who were not treated with trastuzumab.
  • Coronavirus Disease 2019 and Human Reproduction: A Changing Perspective Review Article

    Delamuta, Luciana C.; Monteleone, Pedro A.A.; Ferreira-Filho, Edson S.; Heinrich-Oliveira, Vanessa; Soares-Júnior, José Maria; Baracat, Edmund C.; Maciel, Gustavo A.R.

    Abstract in English:

    Since the outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 has had a wide range of effects on human health. This paper summarizes the data related to the effects of the SARS-CoV-2 infection on human reproduction. Both the male and female reproductive tract express high levels of receptors and proteins needed for viral cell entry. There is presently no evidence that gametes are affected by the infection. Male fertility may be temporarily reduced due to inflammatory responses following infection. The endometrium is highly susceptible to SARS-CoV-2 cell entry; however, it remains unclear whether this could alter receptivity and embryo implantation. Menstrual cycle changes were reported in women who experienced severe infection; however, they tended to be reversible. For couples undergoing assisted reproduction treatment, the pandemic led to a significant psychological burden, with changes in lifestyle that could directly affect the success of the treatment. Human reproduction societies recommend screening all patients prior to cycle initiation and avoiding treatment of women with severe comorbidities until the pandemic is under control. Finally, for pregnant women, it is expected that the infection is more severe in women in the third trimester and in those with comorbidities. Those who are symptomatic for SARS-CoV-2 are more likely to have increased rates of prematurity and intrapartum fetal distress than those who are asymptomatic. Vertical transmission cannot be completely ruled out, but neonatal infection rates are low. Vaccination appears to be safe and is indicated for use in pregnant and lactating women because the benefits outweigh the risks.
  • The role of serum levels of vitamin D in children's muscle strength: A systematic review Review Article

    Silva, Ana B.J. da; Carmo, Taciane S. do; Souza, Ana P.S.; Silva, Mariluce R.M.; Fernandes, Matheus S.S.; Souza, Viviane O.N.; Barros, Waleska M.A.

    Abstract in English:

    This review aims to investigate the different levels of vitamin D and its role in muscle strength in healthy children and non-athletes. A search conducted in three databases (PubMed, Scopus, and Psycinfo) resulted in 655 articles, which were systematically analyzed and selected based on the following criteria: (a) original cross-sectional studies and clinical trials; (b) healthy children aged 5-11 years; (c) no language restriction or year of publication; and (d) studies that assessed the possible relationship between vitamin D levels and muscle strength. Six studies were included because they met all the inclusion criteria. According to the findings of this review, factors such as sex, skin color, and vitamin D supplementation early in life modulate the levels of vitamin D in the body, and there is a relationship between muscle strength and vitamin D levels. Interestingly, vitamin D supplementation is not always significantly associated with increased muscle grip strength. However, there is a scarcity of studies that aim to analyze the possible effects of different levels of vitamin D on muscle function and neuromuscular variables in physically inactive children and non-athletes without previously diagnosed disease. Further studies are warranted in the future to address the gap in the literature.
  • Efficacy and safety of secukinumab in patients with psoriatic arthritis: A meta-analysis of different dosing regimens Review Article

    Zhang, Kai-Lin; Hou, Si-Yuan; Wu, Dan

    Abstract in English:

    The appropriate dosing regimens of secukinumab for psoriatic arthritis (PsA) are not well defined. We performed a meta-analysis to evaluate the efficacy and safety of different dosing regimens of secukinumab in the treatment of PsA. A systematic search was conducted using major electronic databases to identify relevant randomized controlled trials (RCTs) comparing secukinumab 300 mg versus secukinumab 150 mg in patients with PsA. Meta-analysis was performed using Review Manager software (version 5.3). Six studies with a total of 1141 patients were included. At week 24, secukinumab 300 mg was associated with a higher American College of Rheumatology 20% response (ACR 20), ACR 50, PASI 75 response rate, and dactylitis resolution rate than secukinumab 150 mg, especially in the anti-TNF-IR subgroup. At week 52, secukinumab 300 mg was associated with a higher psoriasis area and severity index (PASI) 75 and PASI 90 response rate than secukinumab 150 mg. There was no significant difference between secukinumab 300 mg and secukinumab 150 mg in the risk of any adverse events (AEs) and serious AEs at either week 24 or week 52. Secukinumab 300 mg was significantly more effective than 150 mg, especially for patients with PsA who have failed TNF therapy, and it was well tolerated.
  • Immunogenicity to biological drugs in psoriasis and psoriatic arthritis Review Article

    Valenzuela, Fernando; Flores, Rodrigo

    Abstract in English:

    Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the disease, providing greater efficacy and safety than conventional treatment strategies. Virtually all therapeutic proteins elicit an immune response, producing anti-drug antibodies (ADAs) against hypervariable regions of immunoglobulins. Immunogenicity against biological drugs can alter their pharmacokinetic and pharmacodynamic properties, thereby reducing the efficacy of these drugs. In more severe cases, ADAs can neutralize the therapeutic effects of the drug or cause serious adverse effects, mainly hypersensitivity reactions. The prevalence of ADAs varies widely depending on the type of test used, occurrence of false-negative results, and non-specific binding to the drug, making it difficult to accurately assess their clinical impact. Concomitant use of immunosuppressors efficiently reduces the immunogenicity in a dose-dependent manner, either by decreasing the frequency of detectable ADAs or by delaying their appearance, thereby enhancing the effectiveness of biological therapies. Among the new therapeutic strategies for the management of psoriasis, biological agents have gained increasing importance in recent years as they interrupt key inflammation pathways involved in the physiopathology of the disease. Reports regarding ADA in new biologics are still scarce, but the most recent evidence tends to show little impact on the clinical response to the drug, even with prolonged treatment. It is therefore essential to standardize laboratory tests to determine the presence and titles of ADAs to establish their administration and management guidelines that allow the determination of the real clinical impact of these drugs.
  • Melatonin and the cardiovascular system in animals: systematic review and meta-analysis Review Article

    Veiga, Eduardo Carvalho de Arruda; Simões, Ricardo dos Santos; Caviola, Leonardo L.; Abreu, Luiz Carlos; Cavalli, Ricardo Carvalho; Cipolla-Neto, José; Baracat, Edmund Chada; Soares Júnior, José Maria

    Abstract in English:

    Melatonin, a hormone released by the pineal gland, demonstrates several effects on the cardiovascular system. Herein, we performed a systematic review and meta-analysis to verify the effects of melatonin in an experimental model of myocardial infarction. We performed a systematic review according to PRISMA recommendations and reviewed MEDLINE, Embase, and Cochrane databases. Only articles in English were considered. A systematic review of the literature published between November 2008 and June 2019 was performed. The meta-analysis was conducted using the RevMan 5.3 program provided by the Cochrane Collaboration. In total, 858 articles were identified, of which 13 were included in this review. The main results of this study revealed that melatonin benefits the cardiovascular system by reducing infarct size, improving cardiac function according to echocardiographic and hemodynamic analyses, affords antioxidant effects, improves the rate of apoptosis, decreases lactate dehydrogenase activity, enhances biometric analyses, and improves protein levels, as analyzed by western blotting and quantitative PCR. In the meta-analysis, we observed a statistically significant decrease in infarct size (mean difference [MD], -20.37 [-23.56, -17.18]), no statistical difference in systolic pressure (MD, -1.75 [-5.47, 1.97]), a statistically significant decrease in lactate dehydrogenase in animals in the melatonin group (MD, -4.61 [-6.83, -2.40]), and a statistically significant improvement in the cardiac ejection fraction (MD, -8.12 [-9.56, -6.69]). On analyzing potential bias, we observed that most studies presented a low risk of bias; two parameters were not included in the analysis, and one parameter had a high risk of bias. Melatonin exerts several effects on the cardiovascular system and could be a useful therapeutic target to combat various cardiovascular diseases.
  • Mepolizumab in Hypereosinophilic Syndrome: A Systematic Review and Meta-analysis Review Article

    Alves Júnior, José Mario; Prota, Francisco Eduardo; Villagelin, Danilo; Bley, Fernanda; Bernardo, Wanderley Marques

    Abstract in English:

    We aimed to evaluate the efficacy and safety of mepolizumab (MEP) in the management of hypereosinophilic syndrome (HES). A systematic search was performed, and articles published until March 2021 were analyzed. The primary efficacy results evaluated were hospitalization rate related to HES, morbidity (new or worsening), relapses/failure, treatment-related adverse effects, prednisone dosage ≤10 mg/day for ≥8 weeks, and eosinophil count <600/μL for ≥8 weeks. A meta-analysis was conducted, when appropriate. Three randomized controlled trials (RCTs), with a total of 255 patients, were included. The studies contemplated the use of MEP 300 mg/SC or 750 mg/IV. According to the evaluation of the proposed outcomes, when relapse rates/therapeutic failures were assessed, there was a 26% reduction with MEP 300 mg/SC (RD=-0.26; 95% CI: -0.44 to -0.08; p=0.04) and 48% reduction with MEP 750 mg/IV (RD=-0.48; 95% CI: -0.67, -0.30; p<0.00001). For the outcomes, prednisone dosage ≤10 mg/day for ≥8 weeks was 48% (RD=0.48; 95% CI: 0.35 to 0.62; p<0.00001), and the eosinophil count <600/μL for ≥8 weeks was 51% (RD=0.51; 95% CI: 0.38 to 0.63; p<0.00001), both showed a reduction with MEP 300 mg/IV and 750 mg/IV. No statistically significant differences in treatment-related adverse effects outcomes were observed for either dosage (RD=0.09; 95% CI: -0.05 to 0.24; p=0.20; RD=0.09; 95% CI: -0.11 to 0.29; p=0.39). Despite the positive effects observed for the studied outcomes, the exact significance remains unclear.
  • Post SARS-CoV-2 vaccination Guillain-Barre syndrome in 19 patients Review Article

    Finsterer, Josef; Scorza, Fulvio A.; Scorza, Carla A.

    Abstract in English:

    SARS-CoV-2 vaccinations are not free from side effects. Usually, they are mild or moderate but occasionally severe. One of these severe side effects is Guillain-Barré syndrome (GBS). This review summarizes and discusses GBS as a side effect of SARS-CoV-2 vaccinations (SCoVaG) based on recent research reports. Altogether, nine articles reporting 18 patients with SCoVaG were identified and one more report on another patient is under review. The age for the studies ranged between 20-86y. Nine patients were male, and ten were female. In all 19 patients, SCoVaG developed after the first dose of the vaccine. The Astra Zeneca vaccine was used in fourteen patients, the Pfizer vaccine in four patients, and the Johnson & Johnson vaccine was applied in one patient. The latency between vaccination and onset of GBS ranged from 3h to 39d. The treatment of SCoVaG included IVIGs (n=13), steroids (n=3), or no therapy (n=3). Six patients required mechanical ventilation. Only a single patient recovered completely and partial recovery was achieved in nine patients. In conclusion, GBS may develop time-linked to the first dose of a SARS-CoV-2 vaccination. Though a causal relationship between SARS-CoV-2 vaccinations and SCoVaG remains speculative, more evidence is in favour than against it.
  • Relationship between vitamin D deficiency and psychophysiological variables: a systematic review of the literature Review Article