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Clinics, Volume: 77, Published: 2022
  • COVID-19 pandemic repercussions on undergraduate teaching in obstetrics and gynecology Editorial

    Ribeiro, Lívia Sousa; Francisco, Rossana Pulcineli Vieira; Cabar, Fábio Roberto
  • A new era for the international representativeness of CLINICS Journal Editorials

    Moreira, Luiz Felipe P.; Soares Jr., José Maria
  • Long non-coding RNA DLGAP1 antisense RNA 1 accelerates glioma progression via the microRNA-628-5p/DEAD-box helicase 59 pathway Original Articles

    Hu, Ke-qi; Ao, Xiang-sheng

    Abstract in English:

    Abstract Objectives Abnormal expression of long non-coding RNAs (lncRNAs) plays a prominent role in glioma progression. However, the biological function and mechanism of lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) in gliomas are still unknown. Methods The authors assessed DLGAP1-AS1 and miR-628-5p expression in glioma tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and evaluated their effects on glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) using the cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay, Transwell assay, and western blot, respectively. The expression of DEAD-box helicase 59 (DDX59) was quantified using western blotting, and a dual-luciferase reporter gene assay was performed to detect the interaction between DLGAP1-AS1 and miR-628-5p. Results The authors observed increased DLGAP1-AS1 expression in glioma tissues and cell lines with higher WHO grades and shorter survival time. DLGAP1-AS1 promoted the proliferation, migration, invasion, and EMT of glioma cells, while miR-628-5p counteracted these effects. The authors identified DLGAP1-AS1 as a molecular sponge of miR-628-5p in glioma cells as the biological functions of DLGAP1-AS1 are partially mediated via miR-628-5p. In addition, DLGAP1-AS1 upregulated DDX59 expression by inhibiting miR-628-5p expression. Conclusion The DLGAP1-AS1/miR-628-5p/DDX59 axis regulates glioma progression.
  • Cardiopulmonary exercise test in patients with refractory angina: functional and ischemic evaluation Original Article

    Assumpção, Camila R.A. de; Prado, Danilo M.L. do; Jordão, Camila P.; Dourado, Luciana O.C.; Vieira, Marcelo L.C.; Montenegro, Carla G. de S.P.; Negrão, Carlos E.; Gowdak, Luís H.W.; Matos, Luciana D.N.J. De

    Abstract in English:

    Abstract Objectives Refractory angina (RA) is a chronic condition clinically characterized by low effort tolerance; therefore, physical stress testing is not usually requested for these patients. Cardiopulmonary exercise testing (CPET) is considered a gold standard examination for functional capacity evaluation, even in submaximal tests, and it has gained great prominence in detecting ischemia. The authors aimed to determine cardiorespiratory capacity by using the oxygen consumption efficiency slope (OUES) in patients with refractory angina. The authors also studied the O2 pulse response by CPET and the association of ischemic changes with contractile modifications by exercise stress echocardiography (ESE). Methods Thirty-one patients of both sexes, aged 45 to 75 years, with symptomatic (Canadian Cardiovascular Society class II to IV) angina who underwent CPET on a treadmill and exercise stress echocardiography on a lower limb cycle ergometer were studied. ClinicalTrials.gov: NCT03218891. Results The patients had low cardiorespiratory capacity (OUES of 1.74 ± 0.4 L/min; 63.9±14.7% of predicted), and 77% of patients had a flattening or drop in O2 pulse response. There was a direct association between Heart Rate (HR) at the onset of myocardial ischemia detected by ESE and HR at the onset of flattening or drop in oxygen pulse response detected by CPET (R = 0.48; p = 0.019). Conclusion Patients with refractory angina demonstrate low cardiorespiratory capacity. CPET shows good sensitivity for detecting abnormal cardiovascular response in these patients with a significant relationship between flattening O2 pulse response during CEPT and contractile alterations detected by exercise stress echocardiography. Highlights OUES analysis is useful for assessing functional capacity in refractory angina. O2 pulse curve is correlated with contractile alterations in exercise echocardiogram. Cardiopulmonary exercise test is useful toll in patients with refractory angina.
  • Readmission of late preterm and term neonates in the neonatal period Original Articles

    Kardum, Darjan; Serdarušić, Ivana; Biljan, Borna; Šantić, Krešimir; Živković, Vinko

    Abstract in English:

    Abstract Objective To determine the incidence of hospital readmissions in late preterm and term neonates, the most common reasons for readmission, and analyze the risk factors for readmission in the neonatal period. Methods Newborn infants admitted to a well-baby nursery ≥ 36 weeks gestation were included in this retrospective cohort study. Data for all infants born in a 3-year period and readmitted in the first 28 days of life were analyzed. Indication for readmission was one diagnosed during initial workup in the pediatric emergency room visit before readmission. Results The final cohort consisted of 5408 infants. The readmission rate was 4.0% (219/5408). Leading readmission causes were respiratory tract infection (29.58%), jaundice (13.70%), and urinary tract infection (9.59%). The mean ± SD age of readmitted infants was 13.3 ± 7.1 days. The mean ± SD treatment duration of treatment was 5.5 ± 3.0 days. In the multivariate regression analysis, infants that were during the initial hospitalization transferred to special care/NICU had a lower chance of readmission during the neonatal period (p = 0.04, OR = 0.23, 95% CI 0.06-0.93). Infants with mothers aged from 19-24 years had a higher risk of readmission (p = 0.005, OR = 1.62, 95% CI 1.16-2.26). Conclusions Finding that infants that were during the initial hospitalization transferred to special care or a NICU setting were less likely to require hospitalization in the neonatal period is an interesting one. Further research into how different approach in these settings reduce the risk of readmission is necessary. Highlights In infants gestational age ≥ 36 weeks the readmission rate is 4.0%. Most common causes are respiratory infections, jaundice, and feeding problems. Initial care in special care or NICU setting showed reduced readmission rates.
  • Effects of ganglioside GM1 and erythropoietin on spinal cord injury in mice: Functional and immunohistochemical assessments Original Articles

    Torelli, Alessandro Gonzalez; Cristante, Alexandre Fogaça; Barros-Filho, Tarcísio Eloy Pessoa de; Santos, Gustavo Bispo dos; Morena, Beatriz Cintra; Correia, Felipe Fernandes; Paschon, Vera

    Abstract in English:

    ABSTRACT Objectives: To evaluate the functional and immunohistochemical effects of ganglioside GM1 and erythropoietin following experimental spinal cord injury. Methods: Thirty-two male BALB/c mice were subjected to experimental spinal cord injury using the NYU Impactor device and were randomly divided into the following groups: GM1 group, receiving standard ganglioside GM1 (30 mg/kg); erythropoietin group, receiving erythropoietin (1000 IU/kg); combination group, receiving both drugs; and control group, receiving saline (0.9%). Animals were evaluated according to the Basso Mouse Scale (BMS) and Hindlimb Mouse Function Score (MFS). After euthanasia, the immunohistochemistry of the medullary tissue of mice was analyzed. All animals received intraperitoneal treatment. Results: The GM1 group had higher BMS and MFS scores at the end of the experiment when compared to all other groups. The combination group had higher BMS and MFS scores than the erythropoietin and control groups. The erythropoietin group had higher BMS and MFS scores than the control group. Immunohistochemical tissue analysis showed a significant difference among groups. There was a significant increase in myelinated axons and in the myelinated axon length in the erythropoietin group when compared to the other intervention groups (p < 0.01). Conclusion: Erythropoietin and GM1 have therapeutic effects on axonal regeneration in mice subjected to experimental spinal cord injury, and administration of GM1 alone had the highest scores on the BMS and MFS scales.
  • Influence of invertor and evertor muscle fatigue on functional jump tests and postural control: A prospective cross-sectional study Original Articles

    Castillo, Gabriela Borin; Brech, Guilherme Carlos; Luna, Nátalia Mariana Silva; Tarallo, Fernanda Botta; Soares-Junior, Jose Maria; Baracat, Edmund Chada; Alonso, Angelica Castilho; Greve, Júlia Maria D’Andréa

    Abstract in English:

    ABSTRACT Objective: Fatigue of the ankle’s stabilizing muscles may influence the performance of functional activities and postural control. The purpose of this study was to evaluate the performance of healthy young adults using functional jump tests and static posturography control under pre- and post-fatigue conditions of the ankle invertor and evertor muscles. Methods: Thirty physically active healthy male and female (15 male and 15 female) volunteers (24.3 years) were enrolled in this prospective cross-sectional study. Participants performed tests on one day under a non-fatigued state of invertor and evertor muscles and on the second day in a fatigued state. Tests included static posturography on a force platform in a bipedal stance with eyes open and closed and in one-legged support with eyes open and functional jump tests (figure-of-8, side hop, 6-m crossover hop, and square hop). Fatigue of the ankle invertor and evertor muscles was induced using isokinetic dynamometry with 30 repetitions at 120°/s. Results: Participants had an average age of 24.3 years (SD ± 2.08), the height of 1.73 m (SD ± 0.08), and a weight of 68.63 kg (SD ± 10.29). The average Body Mass Index (BMI) was 22.88 (SD ± 2.46). A decrease in performance was observed in functional activities and postural control under all conditions after the induction of muscle fatigue, except for the speed at a bipedal stance with eyes open. Conclusions: Functional jump tests are low cost and useful for clinical practice and evaluation of the effects of muscle fatigue and could be used in clinical practice.
  • Risk of osteoporotic fracture in women using the FRAX tool with and without bone mineral density score in patients followed at a tertiary outpatient clinic ‒ An observational study Original Articles

    Favarato, Maria Helena Sampaio; Almeida, Maria Flora de; Lichtenstein, Arnaldo; Martins, Milton de Arruda; Ferreira Junior, Mario

    Abstract in English:

    ABSTRACT Objectives: Fragility fractures increase morbidity and mortality. Adding assessment of clinical risk factors independently or as a previous step to Bone Densitometry (BD) should provide better accuracy in fracture risk prediction. FRAX tool might be used to stratify patients in order to rationalize the need for BD and risk classification. The primary objective of this study is to describe and perform comparisons between the estimated risk of fractures in 10 years using the FRAX calculator based on clinical factors with and without BD results for women aged 40 or more with clinical diseases monitored in tertiary care service in internal medicine. Methods: Cross-sectional. Women over 40 years with BD in the previous year. After medical chart review, identification of risk factors and risk estimations using FRAX-BRAZIL with (FRAX BDI) and without (FRAX BDNI) the inclusion of T-score. Results: 239 women. Age 65 ± 10.35 years. BMI 29.68 ± 6.27kg/m2. Risk factors: 32(13.4%) previous fractures; 23 (9.6%) current smoking; 78 (32.6%) corticosteroids use; 44 (18.4%) rheumatoid arthritis; 38 (15.9%) secondary causes; FRAX scores were higher when BD was not included. Spearman correlation coefficients between FRAX BDNI and FRAX BDI for major fractures r = 0.793 (95% CI 0.7388‒0.836). For hip fractures r = 0.6922 (95% CI 0.6174‒0.75446) Conclusion: Using FRAX to estimate 10-year fracture risk without BD data might be a reliable tool for screening, even for patients with a high prevalence of risk factors, improving accessibility and equity in health systems. The present study’s data suggest an overestimation of fracture risk with FRAX BDNI, suggesting that it is safe to be widely used as a screening tool.
  • Increasing rate of anti-SARS-CoV-2 antibodies between the first and second waves of COVID-19 in Sao Paulo, Brazil: A cross-sectional blood donors-based study Original Articles

    Vale, Nayara Moya Rios do; Latini, Flavia Roche Moreira; Arnoni, Carine Prisco; Parreira, Rafael Martins; Girão, Manoel João Batista Castelo; Cortez, Afonso Jose Pereira; Bonetti, Tatiana Carvalho de Souza

    Abstract in English:

    ABSTRACT Background: SARS-CoV-2 infections rapidly spread along with Brazilian territory with heterogeneous transmission and mortality rates, mostly depending on region and period. Investigation of SARS-CoV-2 antibodies is an important tool to understand virus circulation. Given that blood donors are a representative casuistic of a healthy population, the authors evaluated the seroprevalence of IgG and IgM COVID-19 antibodies in 2,806 blood donors from a blood bank located in São Paulo, Brazil. Methods: Aiming to evaluate viral behavior over time, the authors selected samples from blood donors who donated in June and October 2020, and February 2021. To determine whether socio-demographic features affected the seroprevalence, the authors analyzed samples from three different regions from São Paulo (capital, metropolitan and countryside regions) and evaluated predictors as gender, age, educational level, race, and use of public transportation. Results: As expected, the authors observed that seroprevalence increased over time. Seroprevalence was greater in São Paulo city compared to metropolitan and countryside regions, being smallest in the countryside. Characteristics associated with a lower percentage of antibodies were age above 50 years, higher educational level, self-declared Caucasian, and use of individual transportation. Conclusion: In conclusion, blood donors' samples proved to accurately reflect virus circulation in the healthy population.
  • Clinical value of preferred endoscopic ultrasound-guided antegrade surgery in the treatment of extrahepatic bile duct malignant obstruction Original Articles

    Zhao, Xuan; Shi, Lihong; Wang, Jinchen; Guo, Siming; Zhu, Sumin

    Abstract in English:

    ABSTRACT Objectives: To explore the clinical value of preferred ultrasound endoscopic guided biliary drainage in patients with extrahepatic biliary obstruction with intrahepatic biliary ectasis. Methods: A total of 58 patients with malignant obstruction and intrahepatic bile duct expansion, including 32 males, 26 females and median age 65 (58-81) were selected. A prospective randomized controlled study was randomized into EUS-AG and ERCP-BD, with 28 patients in EUS-AG and 30 in ERCP-BD. The efficacy of the two treatments, operation success rate, operation time, the incidence of complications, hospitalization days, cost, unimpeded stent duration, and survival time were compared. Results: 1) The surgical success rate in group EUS-AG was 100%, and in group, ERCP-BD was 96.67%. There was no statistical difference in surgical success rate in the two groups (p>0.05). 2) Average operating time in EUS-AG was (23.69±11.57) min, and in ERCP-BD was (36.75±17.69) min. The difference between the two groups has statistical significance (p<0.05). 3) The clinical symptoms of successful patients were significantly relieved. Compared with the preoperative procedure, the differences in group levels had statistical significance (p<0.05); TBIL, ALP, WBC and CRP levels, no statistical significance difference in groups (p>0.05). Conclusion: EUS-AG operation has short time, low incidence of complications, safe, effective, and can be used as the preferred treatment plan for patients with extrahepatic biliary duct malignant obstruction associated with intrahepatic biliary duct expansion; EUS-AG operation has more unique clinical advantages for patients with altered gastrointestinal anatomy or upper gastrointestinal obstruction.
  • MicroRNA-128b mediates lipopolysaccharide-induced apoptosis via reactive oxygen species in human pulmonary microvascular endothelial cells Original Articles

    Long, Guangwen; Yang, Xiulin; Ji, Chunling; Dong, Yukang

    Abstract in English:

    ABSTRACT Objectives: This study aimed to explore the effects of miR-128b in the regulation of Lipopolysaccharide (LPS) induced apoptosis. Methods: Human Pulmonary Microvascular Endothelial Cells (HPMECs) were transfected with an miR-128b inhibitor and stimulated with LPS for 24 h. FCM was performed to detect apoptosis and Reactive Oxygen Species (ROS) production. In addition, miRNA and caspase-3 expression levels were determined using real-time quantitative polymerase chain reaction and western blotting. Results: LPS significantly induced apoptosis and ROS production and upregulated miR-128b and caspase-3 expressions in HPMECs. However, LPS-induced effects were suppressed when an miR-128b inhibitor was used. Preincu-bation with NAC decreased the LPS-induced apoptosis of HPMECs. Conclusions: These effects were mediated by miR-128b via the caspase-3 pathway.
  • Lacticaseibacillus rhamnosus modulates the inflammatory response and the subsequent lung damage in a murine model of acute lung inflammation Original Articles

    Olimpio, Fabiana; Silva, Jose Roberto Mateus da; Vieira, Rodolfo P.; Oliveira, Carlos R.; Aimbire, Flavio

    Abstract in English:

    ABSTRACT Objective: The present study investigated the anti-inflammatory effect of the probiotic Lacticaseibacillus rhamnosus (Lr) on lung inflammation induced by Lipopolysaccharide (LPS) of Escherichia coli in C57BL/6 mice. Methods: C57BL/6 mice were divided into four groups: control, LPS, Lr (1 day) + LPS, and Lr (14 days) + LPS. Total and differential cells from Bronchoalveolar Lavage Fluid (BALF) were counted in a Neubauer 40X chamber, and pro-and anti-inflammatory cytokines (IL-1β, IL-6, CXCL-1, TNF-α, TGF-β, and IL-10) were measured by ELISA assay. The analysis of whole leukocytes in blood was performed using the automated system Sysmex 800i. Morphometry of pulmonary tissue evaluated alveolar hemorrhage, alveolar collapse, and inflammatory cells. Pulmonary vascular permeability was assessed by Evans blue dye extravasation, and bronchoconstriction was evaluated in a tissue bath station. The transcription factor NF-kB was evaluated by ELISA, and its gene expression and TLR-2, TLR-4, MMP-9, MMP-12, and TIMP by PCR. Results: The probiotic Lr had a protective effect against the inflammatory responses induced by LPS. Lr significantly reduced pro-inflammatory cells in the airways, lung parenchyma, and blood leukocytes. Furthermore, Lr reduced the production of pro-inflammatory cytokines and chemokines in BALF and the expression of TLRs, MMPs, and NF-kB in lung tissue and maintained the expression of TIMP in treated animals promoting a protective effect on lung tissue. Conclusions: The results of the study indicate that pre-treatment with the probiotic Lr may be a promising way to mitigate lung inflammation in endotoxemia.
  • Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil Original Articles

    Bensenor, Isabela M.; Goulart, Alessandra C.; Pereira, Alexandre C.; Brunoni, André R.; Alencar, Airlane; Santos, Raul D.; Bittencourt, Márcio S.; Telles, Rosa W.; Machado, Luciana Andrade Carneiro; Barreto, Sandhi Maria; de Almeida-Pititto, Bianca; Janovsky, Carolina Porto Silva; Sgarbi, José Augusto; Tebar, William R.; Meneghini, Vandrize; Barbosa Junior, Fernando; Ribeiro, Ana Cristina de Medeiros; Pasoto, Sandra Gofinet; Pereira, Rosa Maria R.; Bonfá, Eloísa; Sipahi, Aytan M.; Santos, Itamar de S.; Lotufo, Paulo A.

    Abstract in English:

    Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.
  • Circ_0075825 promotes gastric cancer progression via adsorbing miR-432-5p to modulate SOX9 Original Articles

    Li, He; Zhou, Xiaohua; Yu, Zhuangming; Tian, Youjing

    Abstract in English:

    Abstract Methods Circ_0075825 expression in adjacent tissues and GC tissues was evaluated by bioinformatics method and quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). How circ_0075825 regulated GC cell growth, migration, invasion, and apoptosis were investigated by cell counting kit-8 assay, transwell assay and flow cytometry. The targeted interplays among circ_0075825, and miR-432-5p and Sex-Determining Region Y-related high-mobility group box 9 (SOX9) were explored by bioinformatics analysis and luciferase reporter gene assay. The regulatory effects of circ_0075825 and miR-432-5p on SOX9 protein expression were probed by western blot. Results Circ_0075825 expression was raised in GC tissues and cell lines. Circ_0075825 overexpression promoted the proliferative, migrative and invasive abilities of GC cells, while inhibiting apoptosis, while depletion of circ_0075825 suppressed the malignant biological behaviors of GC cells. SOX9 was identified as one of the direct target genes of miR-432-5p, and circ_0075825 repressed the expression of miR-432-5p, to induce the expression of SOX9. Furthermore, miR-432-5p overexpression counteracted the promoting effect of circ_0075825 on the malignancy of GC cells. Conclusion Circ_0075825 promotes GC progression via sponging miR-432-5p to regulate SOX9 expression level, and it may be a novel therapeutic target for treating GC.
  • IRF4 suppresses osteogenic differentiation of BM-MSCs by transcriptionally activating miR-636/DOCK9 axis Original Articles

    Zhang, Xuepu; Zhang, Yue; Yang, Limin; Wu, Yuexin; Ma, Xiaohu; Tong, Gang; Ban, Zhaoliang; Zhao, Haosen

    Abstract in English:

    Abstract Objectives Osteoblasts are derived from Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs), which play an indispensable role in bone formation. In this study, the authors aim to investigate the role of IRF4 in the osteogenic differentiation of BM-MSCs and its potential molecular mechanism. Methods The authors used lentivirus infection to overexpress IRF4 in BM-MSCs. The expression of IRF4 and osteogenesis-related genes were detected by qRT-PCR and western blot analysis. The osteogenic differentiation of BM-MSCs was evaluated by Alkaline Phosphatase (ALP) activity, Alizarin red staining, and Alkaline Phosphatase (ALP) staining. Chromatin Immunoprecipitation (ChIP), Dual-Luciferase reporter assay and RNA Immunoprecipitation Assay were applied to confirm the regulatory mechanism between IRF4, miR-636 and DOCK9. Results The authors found IRF4 was down-regulated during the osteogenic differentiation of BM-MSCs, and IRF4 overexpression could decrease the osteogenic differentiation of BM-MSCs by specifically promoting the reduction of Alkaline Phosphatase (ALP) activity and down-regulating osteogenic indicators, including OCN, OPN, Runx2 and CollA1. Mechanistically, IRF4 activated microRNA-636 (miR-636) expression via binding to its promoter region, and Dedicator of Cytokinesis 9 (DOCK9) was identified as the target of miR-636 in BM-MSCs. Moreover, the damage in the capacity of osteogenic differentiation of BM-MSCs induced by IRF4 overexpression could be rescued by miR-636 inhibition. Conclusions In summary, this paper proposed that IRF4/miR-636/DOCK9 may be considered as targets for the treatment of osteoporosis (OP).
  • Incidental thyroid carcinoma: Correlation between FNAB cytology and pathological examination in 1093 cases Original Articles

    Rodrigues, Mariana Gonçalves; da Silva, Luiz Fernando Ferraz; Araujo-Filho, Vergilius José Furtado de; Mosca, Letícia de Moraes; Araujo-Neto, Vergilius José Furtado de; Kowalski, Luiz Paulo; Carneiro, Paulo Campos

    Abstract in English:

    Abstract Objective To investigate Incidental Thyroid Carcinoma (ITC) by comparing the results of Fine Needle Aspiration Biopsy (FNAB) cytology and the postoperative pathological findings. Methods Data of 1479 patients who underwent total thyroidectomy were retrieved. Three hundred eighty-six patients were excluded due to insufficient data. Each surgical specimen studied received two histopathological diagnoses: the local diagnosis ‒ for the same area in which the FNAB was performed; and the final diagnosis, which includes a study of the entire surgical specimen. Results A thousand and ninety-three patients were investigated. FNAB result was malignant in 187 patients, benign in 204, suspicious or indeterminate in 668 cases, and inconclusive in 34 cases. The prevalence of ITC was 15.1%. Most of the ITC in this series was less than 0.5 cm. The incidence of ITC was higher in Bethesda III (17.5% ITC) and IV (19% ITC) than in Bethesda II cases (1.5% false negatives and 9% ITC). Conclusion Although the incidence of false-negative results in Bethesda II nodules is only 1.5%, 9% of these patients had ITC in the thyroid parenchyma outside the nodule that underwent preoperative FNAB. The incidence of ITC in the same scenario was even higher in Bethesda III (17.5%) and Bethesda IV cases (19%). Ultrasonography-guided FNAB is an excellent method for the assessment of thyroid nodules. However, biopsy sites should be carefully selected. Despite the high incidence of incidentalomas, total thyroidectomy should not always be the treatment of choice due to its rare but potentially serious complications. The findings of the present study can assist future clinical decisions towards active surveillance strategies for the management of papillary thyroid carcinoma.
  • Clinical features of hereditary angioedema and warning signs (H4AE) for its identification Original Articles

    Giavina-Bianchi, Pedro; Aun, Marcelo Vivolo; Garcia, Juliana Fóes Bianchini; Gomes, Laís Souza; Ribeiro, Ana Júlia; Takejima, Priscila; Agondi, Rosana Câmara; Kalil, Jorge; Motta, Antonio Abilio

    Abstract in English:

    Abstract Objectives The study describes a case series of hereditary angioedema with C1 Inhibitor Deficiency (C1INH-HAE) in order to corroborate six clinical warning signs “HAAAAE (H4AE)” to enable early identification of this disease. Methods The authors analyzed the C1INH-HAE cohort to analyze the clinical aspects of the present study's patients and corroborate the six clinical warning signs of the Hereditary Angioedema Brazilian Guidelines. Data regarding demographics, the onset of disease, time to diagnosis, frequency of attacks per year, organs involved, triggers, crisis duration and their outcomes, and disease treatment were collected. Then the authors developed an acronym, H4AE, to help healthcare professionals remember the warning signs. Results The authors included 98 patients in the study, with a mean age of 38.1 years, 67.3% being female, and 75.3% with a family history of HAE. HAE diagnosis was delayed, on average, 13.7 years after its initial manifestation. Exploratory laparotomy was reported by 26.9%, and orotracheal intubation by 21.3% of the present study's patients; 61.3% and 30.3% of them were admitted at least once in the hospital and in the intensive care unit, respectively. The authors constructed an acronym “H4AE” with the six warning signs of HAE: Hereditary, recurrent Angioedema, Abdominal pain, Absence of urticaria, Absence of response to antihistamines, Estrogen association. Conclusion C1INH-HAE is still underdiagnosed and associated with high morbidity. The study showed clinical features of this disease, corroborating the warning signs, which may be useful in raising awareness and improving the diagnosis of C1INH-HAE. The authors suggest the acronym “H4AE” to remind the warning signs.
  • microRNA-181a-5p impedes the proliferation, migration, and invasion of retinoblastoma cells by targeting the NRAS proto-oncogene Original Articles

    Ouyang, Ming; Liu, Guiqin; Xiong, Cheng; Rao, Jing

    Abstract in English:

    Abstract Objectives Accumulating research have reported that microRNAs (miRNAs) play important roles in Retinoblastoma (RB). Nonetheless, the function and underlying mechanism of miR-181a-5p in RB remain ambiguous. Methods The relative expression levels of miR-181a-5p and NRAS mRNA were detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). RB cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) and 5′-Bromo-2′-deoxyuridine (BrdU) assays. Transwell assays and flow cytometry were performed to detect the migration, invasion, and apoptosis of RB cells. The interaction between miR-181a-5p and NRAS was explored using luciferase experiments, western blotting, and qRT-PCR. Results miR-181a-5p expression was found to be decreased in RB tissues and cell lines, and its expression was correlated with unfavorable pathological features of the patients. In vitro experiments revealed that miR-181a-5p reduced RB cell proliferation, migration, and invasion while enhancing apoptosis. Further research confirmed that NRAS is a direct target of miR-181a-5p. miR-181a-5p inhibited NRAS expression at both the mRNA and protein levels. Co-transfection of pcDNA-NRAS or NRAS small interfering RNA (siRNA) reversed the effects of miR-181a-5p mimics or miR-181a-5p inhibitors on RB cells. Conclusion miR-181a-5p was significantly downregulated during the development of RB, and it suppressed the malignant behaviors of RB cells by targeting NRAS.
  • Magnetic resonance imaging and previous cesarean section in placenta accrete spectrum disorder: Predictor model Original Articles

    Polizio, Rodrigo Pamplona; Yamauchi, Fernando Ide; Mendes, Renata Franco Pimentel; Peres, Stela Verzinhasse; Kondo, Mario Macoto; Francisco, Rossana Pulcineli Vieira

    Abstract in English:

    Abstract Objective To evaluate objective criteria of Magnetic Resonance Imaging (MRI) of Placenta Accreta Spectrum disorder (PAS) analyzing interobserver agreement and to derive a model including imaging and clinical variables to predict PAS. Methods A retrospective review including patients submitted to MRI with suspicious findings of PAS on ultrasound. Exclusion criteria were lack of pathology or surgical information and missing or poor-quality MRI. Two radiologists analyzed six MRI features, and significant clinical data were also recorded. PAS confirmed on pathology or during intraoperative findings were considered positive for the primary outcome. Variables were tested through logistic regression models. Results Final study included 96 patients with a mean age of 33 years and 73.0% of previous C-sections. All MRI features were significantly associated with PAS for both readers. After logistic regression fit, including MRI signs with a moderate or higher interobserver agreement, intraplacental T2 dark band was the most significant radiologic criteria, and ROC analysis resulted in an AUC = 0.782. After including the most relevant clinical data (previous C-section) to the model, the ROC analysis improved to an AUC = 0.893. Conclusion Simplified objective criteria on MRI, including intraplacental T2 dark band associated with clinical information of previous C-sections, had the highest accuracy and was used for a predictive model of PAS.
  • Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration Original Articles

    Nunes, Valéria Sutti; Ilha, Angela de Oliveira Godoy; Ferreira, Guilherme da Silva; Bombo, Renata de Paula Assis; Afonso, Milessa Silva; Lavrador, Maria Silvia Ferrari; Machado, Roberta Marcondes; Nakandakare, Edna Regina; Quintão, Eder Carlos Rocha; Lottenberg, Ana Maria

    Abstract in English:

    Abstract Objectives Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol). Method The authors studied 38 non-obese volunteers (58±12 years; Low-Density Lipoprotein Cholesterol ‒ LDL-C ≥ 130 mg/dL) randomly assigned to consume 400 mL/day of soy milk (Control phase) or soy milk + PS (1.6 g/day) for four weeks in a double-blind, cross-over study. PS and lathosterol were measured in plasma by gas chromatography coupled to mass spectrophotometry. Results PS treatment reduced plasma total cholesterol concentration (-5.5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration), but plasma lathosterol, campesterol and sitosterol expressed per plasma cholesterol increased. Conclusions The lathosterol-to-cholesterol plasma ratio predicted the plasma cholesterol response to PS feeding. The highest plasma lathosterol concentration during the control phase was associated with a lack of response of plasma cholesterol during the PS treatment period. Consequently, cholesterol synthesis in non-responders to dietary PS being elevated in the control phase indicates these cases resist to further synthesis rise, whereas responders to dietary PS, having in the control phase synthesis values lower than non-responders, expand synthesis on alimentary PS. Responders absorb more PS than non-responders, likely resulting from responders delivering into the intestinal lumen less endogenous cholesterol than non-responders do, thus facilitating greater intestinal absorption of PS shown as increased plasma PS concentration.
  • Gathering patients and rheumatologists' perceptions to improve outcomes in idiopathic inflammatory myopathies Original Articles

    Bertoglio, Isabela M.; Abrahao, Glaucia F.; de Souza, Fernando H.C.; Miossi, Renata; de Moraes, Paloma C.; Shinjo, Samuel K.; Bonfá, Eloisa; Lopes, Michelle R. Ugolini

    Abstract in English:

    Abstract Objective Therapeutic targets in Idiopathic Inflammatory Myopathies (IIM) are based on the opinions of physicians/specialists, which may not reflect the main concerns of patients. The authors, therefore, assessed the outcome concerns of patients with IIM and compared them with the concerns of rheumatologists in order to develop an IIM outcome standard set. Methods Ninety-three IIM patients, 51 rheumatologists, and one physiotherapist were invited to participate. An open questionnaire was initially applied. The top 10 answers were selected and applied in a multiple-choice questionnaire, inquiring about the top 3 major concerns. Answers were compared, and the agreement rate was calculated. Concerns were gathered in an IIM outcome standard set with validated measures. Results The top three outcome concerns raised by patients were medication side effects/muscle weakness/prevention functionality loss. The top three concerns among rheumatologists were to prevent loss of functionality/to ensure the quality of life/to achieve disease remission. Other's outcomes concerns only pointed out by patients were muscle pain/diffuse pain/skin lesions/fatigue. The agreement rate between both groups was 41%. Assessment of these parameters guided the development of an IIM standard set which included Myositis Disease Activity Assessment Visual Analogue Scale/Manual Muscle Testing/fatigue and pain Global Visual Analogue Scale/Health Assessment Questionnaire/level of physical activity. Conclusion The authors propose a novel standard set to be pursued in IIM routine follow-up, which includes not only the main patients/rheumatologist outcome concerns but also additional important outcomes only indicated by patients. Future studies are necessary to confirm if this comprehensive approach will result in improved adherence and ultimately in better assistance.
  • CLEC14A was up-regulated in hepatocellular carcinoma and may function as a potential diagnostic biomarker Original Articles

    Yan, Lang; Li, Xiang; Yuan, Yunfeng

    Abstract in English:

    Abstract Objective The current work aimed to investigate the expression and potential clinical significance of C-type Lectin domain family 14 (CLEC14A) in hepatocellular carcinoma. Methods The relative expressions of CLEC14A in the Hepatocellular Carcinoma (HCC) tissue and adjacent normal tissue of 105 HCC patients were examined using RT-qPCR methods. Furthermore, Receiver Operating Characteristic (ROC) curve was drawn for exploring the diagnostic value of CLEC14A. Next, the expressions of CLEC14A in HCC cell lines and normal liver epithelial cells were compared, and the effects of knockdown of CLEC14A on the growth and apoptosis of HCC cells were examined. Results The authors found that the expression of CLEC14A was markedly increased in hepatocellular carcinoma tumors in comparison with the adjacent tissue, and the expression level of CLEC14A was positively correlated with the size and differentiation of the tumor. Moreover, results of ROC analysis showed CLEC14A might function as a sensitive diagnostic biomarker for HCC. Furthermore, CLEC14A was up-regulated in HCC cell lines, and transient over-expression of CLEC14A decreased the proliferation and increased the apoptosis of HCC cells in vitro. Conclusions Our results suggested that CLEC14A was up-regulated in HCC and might function as a potential diagnostic marker.
  • Invariant Natural Killer T-cells and their subtypes may play a role in the pathogenesis of endometriosis Original Articles

    Correa, Frederico J.S.; Andres, Marina Paula; Rocha, Tainá Pezzin; Carvalho, Ana Eduarda Z.; Aloia, Thiago P.A.; Corpa, Marcus V.N.; Kallas, Esper G.; Mangueira, Cristóvão L.P.; Baracat, Edmund C.; Carvalho, Karina I.; Abrão, Mauricio S.

    Abstract in English:

    Highlights The frequency of iNKT cells in general and their subtype double-negative are related to endometriosis. The expression of IL-17 and CCR7 by iNKT cells are related to endometriosis-associated pain symptoms. iNKT cells are numerically and functionally altered in women with endometriosis.
  • Neuropathologic damage induced by radiofrequency ablation at different temperatures Original Articles

    Dong, Yu; Chen, Ying; Yao, Baoguo; Song, Peng; Xu, Ruiting; Li, Rui; Liu, Ping; Zhang, Yu; Mu, Li; Tong, Xin; Ma, Linwei; Yu, Jianjun; Su, Li

    Abstract in English:

    Highlights There is a positive correlation between temperature and neuropathological damage caused by RFA at different temperatures. There is a positive correlation between nerve conduction velocity and temperature. Nerve injury occurs when the temperature reaches 67°C, and the main pathogenesis is closely related to the expression of SCN9A, SCN3B and NFASC protein in sciatic nerve tissue caused by heat transfer injury.
  • Methyl-CpG binding protein 2 is associated with the prognosis and mortality of elderly patients with hip fractures Original Articles

    Gao, Xuejian; Xue, Shan; Yang, Fuqiang; Wu, Baoling; Yu, Xiaojing; An, Baoquan

    Abstract in English:

    Highlights MECP2 was downregulated in elderly patients with hip fracture. MECP2 was correlated with inflammatory factors in hip fractures. Lower MECP2 predicted poor clinical outcomes of hip fractures. Lower MECP2 predicted higher mortality and postoperative complications.
  • L1 cell adhesion molecule high expression is associated with poor prognosis in surgically resected brain metastases from lung adenocarcinoma Original Articles

    Wang, Jia-Wei; Wang, Song-Quan; Wu, Zhuo-Yi; Liu, Qi; Yuan, Qing; Cai, Hong-Qing; Wan, Jing-Hai

    Abstract in English:

    Highlights Brain metastasis aberrantly expresses L1CAM. L1CAM high expression is associated with poor prognosis in brain metastases.
  • Changes in postural balance associated with a woman's aging process Original Articles

    Brech, Guilherme Carlos; Bobbio, Tatiana Godoy; Cabral, Kelem de Negreiros; Coutinho, Patrícia Mota; Castro, Leila Regina de; Mochizuki, Luis; Soares-Junior, Jose Maria; Baracat, Edmund Chada; Leme, Luiz Eugênio Garcez; Greve, Julia Maria D'Andréa; Alonso, Angélica Castilho

    Abstract in English:

    Highlights Aging process increases postural oscillations, worsening the postural balance. Poor postural balance is more evident in the elderly over 80-years old. Deterioration of the postural control systems and the increased risk of falls. Important identify factors related to falls and postural balance.
  • Team emergency assessment measure (TEAM) of non-technical skills: The Brazilian Portuguese version of the TEAM tool Original Articles

    Giugni, Fernando Rabioglio; Dias, Roger Daglius; Rodrigues, Caio Godoy; Pinesi, Henrique Trombini; Scalabrini-Neto, Augusto

    Abstract in English:

    Highlights The authors translated and cross-culturally adapted the TEAM tool into Brazilian Portuguese. The Brazilian Portuguese TEAM version proved to be a consistent and reliable tool.
  • IPO7 promotes pancreatic cancer progression via regulating ERBB pathway Original Articles

    Li, Ming; Xu, Dongqiang; Zhan, Yijun; Tan, Shiyun

    Abstract in English:

    Highlights IPO7 remarkably enhanced pancreatic cancer cell proliferation, migration and invasion and suppressed apoptosis. IPO7 facilitated the malignant phenotype of pancreatic cancer cells by up-regulating ERBB2. Knockdown of IPO7 inhibited tumor growth and lung metastasis in vivo.
  • Sudden unexpected death in Parkinson's disease: Insights from clinical practice Review Articles

    Scorza, Fulvio A; Guimarães-Marques, Marcia; Nejm, Mariana; Almeida, Antônio Carlos G de; Scorza, Carla A; Fiorini, Ana C; Finsterer, Josef

    Abstract in English:

    Abstract Classified as the second most common neurodegenerative disorder associated with aging after Alzheimer's disease, Parkinson's disease (PD) is the most common movement disorder. In the last decade, despite advances in treatment, mortality rates linked with PD continued to reach significant figures. Available studies have shown that compared with healthy controls, patients with PD are accompanied by high rates of premature death. This is usually caused by factors such as pneumonia and cerebrovascular and cardiovascular diseases. Recently, it has been demonstrated that a significant proportion of patients with PD die suddenly. This is referred to as a sudden and unexpected death in PD (SUDPAR). Here, we focus on the magnitude of SUDPAR. Finally, it is important to learn more about SUDPAR for the implementation of effective prevention strategies.
  • From H1N1 to COVID-19: What we have seen in children with hemoglobinopathies Review Articles

    Oliveira, Claudia de Melo; Soares, Victor Jablonski; Rechenmacher, Ciliana; Daudt, Liane Esteves; Michalowski, Mariana Bohns

    Abstract in English:

    Abstract This work aimed to better understand the impact of pandemics of respiratory viruses on children with hemoglobinopathies through a comprehensive review of the literature. MEDLINE, SCIELO, LILACS, and PUBMED were used as data sources to find articles without time period restrictions. Previous observations suggest that patients with hemoglobinopathies are a group especially susceptible to the complications of viral respiratory infections, with greater morbidity and mortality related to them. Within this context, this review found that, during the 2009 H1N1 pandemic, the risk of hospitalization in children and adults increased, especially in patients with a history of complications such as acute chest syndrome. In addition, the Coronavirus Disease 2019 (COVID-19) pandemic appears to have less repercussion among children with hemoglobinopathies compared to adults, similar to what is seen in the general population. In the H1N1 pandemic, patients with hemoglobinopathies behaved as a group more susceptible to complications, with increased morbidity and mortality. However, for COVID-19, the existing data to date on these patients do not show the same clinical impact. Thus, although these children deserve attention in case of infection due to their potential risks, they seem to have a favorable evolution. Highlights Children with hemoglobinopathies have less severe conditions with Coronavirus 2019 Disease (COVID-19) compared to adults, which is similar to that observed in the general population In the H1N1 pandemic, patients with hemoglobinopathies behaved as the group most susceptible to complications, with increased morbidity and mortality
  • Ischemic stroke in 455 COVID-19 patients Review Articles

    Finsterer, Josef; Scorza, Fulvio Alexandre; Scorza, Carla Alessandra; Fiorini, Ana Claudia

    Abstract in English:

    ABSTRACT There is increasing evidence that COVID-19 can be associated with ischemic stroke (COVID-stroke). The frequency and pathogenesis of COVID-stroke, however, remains largely unknown. This narrative review aimed at summarizing and discussing current knowledge about frequency and pathogenesis of COVID-stroke in 455 patients collected from the literature. COVID-stroke occurs in all age groups and predominantly in males. The anterior circulation is more frequently affected than the posterior circulation. COVID-stroke is most frequently embolic. The severity of COVID-stroke ranges from NIHSS 3 to 32. Cardiovascular risk factors are highly prevalent in patients with COVID-stroke. COVID-stroke occurs simultaneously with the onset of pulmonary manifestations or up to 40 days later. Clinical manifestations of COVID-19 are most frequently mild or even absent. The majority of patients with COVID-stroke achieve complete or partial recovery, but in one-quarter of patients, the outcome is fatal. In conclusion, the frequency of ischemic stroke has not increased since the outbreak of the SARS-CoV-2 pandemic. COVID-stroke predominantly affects males and the anterior circulation. COVID-stroke is multifactorial but predominantly embolic and more frequently attributable to cardiovascular risk factors than to coagulopathy.
  • Arterial stiffness and atrial fibrillation: A review Review Articles

    Lage, Joao Gabriel Batista; Bortolotto, Alexandre Lemos; Scanavacca, Mauricio Ibrahim; Bortolotto, Luiz Aparecido; Darrieux, Francisco Carlos da Costa

    Abstract in English:

    ABSTRACT Arterial stiffness has been investigated as part of the physiopathology of arterial hypertension since the 1970s. Its role in increasing the “pulsatile load” imposed over the Left Ventricle (LV) has been intensely studied recently and has helped in understanding the mechanisms of Atrial Fibrillation (AF) in hypertensive patients. This paper aims to review the main evidence on this issue and establish possible mechanisms involved in the development of AF in patients with arterial stiffness. A PubMed search was performed, and selected articles were searched for references focusing on this topic. In the long term, lower blood pressure levels allow for arterial wall remodeling, leading to a lower stiffness index. To this day, however, there are no available treatments that directly promote the lowering of arterial wall stiffness. Most classes of anti-hypertensive drugs ‒ with stronger evidence for beta-blockers and diuretics ‒ could be effective in reducing arterial stiffness. There is strong evidence demonstrating an association between arterial stiffness and AF. New studies focusing on arterial stiffness and pre-fibrillatory stages would strengthen this causality relation.
  • Efficacy and safety in the use of intraperitoneal hyperthermia chemotherapy and peritoneal cytoreductive surgery for pseudomyxoma peritonei from appendiceal neoplasm: A systematic review Review Articles

    Floriano, Idevaldo; Silvinato, Antônio; Reis, João C.; Cafalli, Claudia; Bernardo, Wanderley Marques

    Abstract in English:

    Highlights Hyperthermia chemotherapy and cytoreductive surgery in patients with peritoneal pseudomyxoma.
  • Patient with agammaglobulinemia produces anti-SARS-CoV-2 reactive T-cells after CoronaVac vaccine Comments

    Oshiro, Telma Miyuki; Silva, Lais Teodoro da; Ortega, Marina Mazzilli; Perazzio, Sandro Felix; Duarte, Alberto Jose da Silva; Carneiro-Sampaio, Magda
  • Stigma in Parkinson's disease: Placing it outside the body Comments

    Rosa, Tomás de la; Scorza, Fúlvio Alexandre
  • Artificial intelligence in the medical profession: ready or not, here AI comes Comments

    Pucchio, Aidan; Papa, Joshua Del; Moraes, Fabio Ynoe de
  • Time-to-event assessment for the discovery of the proper prognostic value of clinical biomarkers optimized for COVID-19 Comments

    Ferreira Junior, José Raniery
  • Erratum to Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital” [Clinics. 2021;76:e3511] Errata

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