Scielo RSS <![CDATA[Clinics]]> vol. 70 num. 8 lang. es <![CDATA[SciELO Logo]]> <![CDATA[The negative prognostic impact of bone metastasis with a tumor mass]]> OBJECTIVE: Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer. METHODS: Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p&lt;0.001). RESULTS: According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11–1.76). Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers), and spinal cord compression. CONCLUSION: Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients. <![CDATA[Ocular risk management in patients undergoing general anesthesia: an analysis of 39,431 surgeries]]> OBJECTIVE: This study sought to describe and analyze ocular findings associated with nonocular surgery in patients who underwent general anesthesia. METHODS: The authors retrospectively collected a series of 39,431 surgeries using standardized data forms. RESULTS: Ocular findings were reported in 9 cases (2.3:10,000), which involved patients with a mean age of 58.9±19.5 years. These cases involved patients classified as ASA I (33%), ASA II (55%) or ASA III (11%). General anesthesia with propofol and remifentanil was used in 4 cases, balanced general anesthesia was used in 4 cases, and regional block was used in combination with balanced general anesthesia in one case. Five patients (55%) underwent surgery in the supine position, one patient (11%) underwent surgery in the lithotomy position, two patients (22%) underwent surgery in the prone position, and one patient (11%) underwent surgery in the lateral position. Ocular hyperemia was detected in most (77%) of the 9 cases with ocular findings; pain/burning of the eyes, visual impairment, eye discharge and photophobia were observed in 55%, 11%, 11% and 11%, respectively, of these 9 cases. No cases involved permanent ocular injury or vision loss. CONCLUSION: Ophthalmological findings after surgeries were uncommon, and most of the included patients were relatively healthy. Minor complications, such as dehydration or superficial ocular trauma, should be prevented by following systematic protocols that provide appropriate ocular occlusion with a lubricating ointment and protect the eye with an acrylic occluder. These procedures will refine the quality of anesthesia services and avoid discomfort among patients, surgeons and anesthesia staff. <![CDATA[Flow-through anastomosis using a T-shaped vascular pedicle for gracilis functioning free muscle transplantation in brachial plexus injury]]> OBJECTIVE: In gracilis functioning free muscle transplantation, the limited caliber of the dominant vascular pedicle increases the complexity of the anastomosis and the risk of vascular compromise. The purpose of this study was to characterize the results of using a T-shaped vascular pedicle for flow-through anastomosis in gracilis functioning free muscle transplantation for brachial plexus injury. METHODS: The outcomes of patients with brachial plexus injury who received gracilis functioning free muscle transplantation with either conventional end-to-end anastomosis or flow-through anastomosis from 2005 to 2013 were retrospectively compared. In the flow-through group, the pedicle comprised a segment of the profunda femoris and the nutrient artery of the gracilis. The recipient artery was interposed by the T-shaped pedicle. RESULTS: A total of 46 patients received flow-through anastomosis, and 25 patients received conventional end-to-end anastomosis. The surgical time was similar between the groups. The diameter of the arterial anastomosis in the flow-through group was significantly larger than that in the end-to-end group (3.87 mm vs. 2.06 mm, respectively, p&lt;0.001), and there were significantly fewer cases of vascular compromise in the flow-through group (2 [4.35%] vs. 6 [24%], respectively, p=0.019). All flaps in the flow-through group survived, whereas 2 in the end-to-end group failed. Minimal donor-site morbidity was noted in both groups. CONCLUSIONS: Flow-through anastomosis in gracilis functioning free muscle transplantation for brachial plexus injury can decrease the complexity of anastomosis, reduce the risk of flap loss, and allow for more variation in muscle placement. <![CDATA[Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors - a single center experience]]> OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p&lt;0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p&lt;0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary. <![CDATA[The effect of elemene on lung adenocarcinoma A549 cell radiosensitivity and elucidation of its mechanism]]> OBJECTIVE: To investigate the effect of elemene on the radiosensitivity of A549 cells and its possible molecular mechanism. METHODS: Apoptosis of A549 cells was detected by flow cytometry and fluorescence microscopy. The effect of double-strand break (DSB) damage repair in A549 cells was evaluated using the neutral comet assay. Protein expression levels were detected using western blotting, and the correlation between protein levels was analyzed. RESULTS: Elemene exhibited a radiosensitizing effect on A549 cells. The level of apoptosis induced by elemene combined with radiation was significantly greater (p&lt;0.01) than that elicited by either radiation or elemene alone. Following radiation and subsequent repair for 24 h, the tail intensity of A549 cells treated with a combination of elemene and radiation was greater than that of cells treated with either elemene or radiation alone (p&lt;0.01). This result indicates that elemene inhibits cellular DSB repair. Both elemene combined with radiation and radiation alone decreased the protein expression of DNA-PKcs and Bcl-2 compared to elemene alone (p&lt;0.01), while p53 protein expression was increased (p&lt;0.01). A negative correlation was observed between DNA-PKcs and p53 expression (r=−0.569, p=0.040), while a positive correlation was found between DNA-PKcs and Bcl-2 expression (r=0.755, p=0.012). CONCLUSIONS: Elemene exhibits a radiosensitizing effect on A549 cells, and its underlying molecular mechanism of action may be related to the downregulation of DNA-PKcs gene expression. <![CDATA[Non-alcoholic steatohepatitis-related liver cirrhosis is increasing in China: A ten-year retrospective study]]> OBJECTIVE: Little is known about metabolic factors in cirrhotic patients in China. Therefore, we aimed to quantify the prevalence of both metabolic factors and non-alcoholic steatohepatitis-related liver cirrhosis in China. METHODS: The medical records of 1,582 patients diagnosed with liver cirrhosis from June 2003 to July 2013 at Daping Hospital (Chongqing, China) were retrospectively reviewed through a computer-generated search. RESULTS: Serum hepatitis B virus surface antigen was present in 1,083 (68.5%) patients, and hepatitis B was found to be the only etiological factor in 938 (59.3%) of all patients. Obesity, diabetes mellitus, and arterial hypertension were observed in 229 (14.5%), 159 (10.1%), and 129 (8.2%) patients, respectively. From 2012-2013, the proportion of non-alcoholic steatohepatitis-related liver cirrhosis increased to 3.2%, whereas the average proportion of non-alcoholic steatohepatitis-related liver cirrhosis in the previous ten years was 1.9%. The incidence of hepatocellular carcinoma was much higher in males than in females (6.3% vs. 3.7%, respectively, p=0.036). Obesity and diabetes mellitus did not significantly increase the incidence of hepatocellular carcinoma in the whole cirrhotic group. The presence of hepatitis B virus was the only risk factor for hepatocellular carcinoma in cirrhotic patients (p&lt;0.001). CONCLUSIONS: Although hepatitis B virus remains the main etiology of liver cirrhosis in China, steatohepatitis-related liver cirrhosis is increasing in frequency. Hepatitis B virus was the sole significant risk factor for hepatocellular carcinoma in the whole cirrhotic group in the present study, in contrast to obesity and diabetes mellitus, for which only a trend of increased hepatocellular carcinoma was found. <![CDATA[Glutamine treatment attenuates hyperglycemia-induced mitochondrial stress and apoptosis in umbilical vein endothelial cells]]> OBJECTIVE: The aim of this study was to determine the in vitro effect of glutamine and insulin on apoptosis, mitochondrial membrane potential, cell permeability, and inflammatory cytokines in hyperglycemic umbilical vein endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells were grown and subjected to glutamine and insulin to examine the effects of these agents on the hyperglycemic state. Mitochondrial function and the production of inflammatory cytokines were assessed using fluorescence analysis and multiple cytotoxicity assays. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. RESULTS: Glutamine maintains the integrity of the mitochondria by reducing the cell permeability and cytochrome c levels and increasing the mitochondrial membrane potential. The cytochrome c level was significantly (p&lt;0.005) reduced when the cells were treated with glutamine. An apoptosis assay revealed significantly reduced apoptosis (p&lt;0.005) in the glutamine-treated cells. Moreover, glutamine alone or in combination with insulin modulated inflammatory cytokine levels. Interleukin-10, interleukin-6, and vascular endothelial growth factor were up-regulated while tumor necrosis factor-α was down-regulated after treatment with glutamine. CONCLUSION: Glutamine, either alone or in combination with insulin, can positively modulate the mitochondrial stress and cell permeability in umbilical vein endothelial cells. Glutamine regulates the expression of inflammatory cytokines and maintains the balance of the mitochondria in a cytoprotective manner. <![CDATA[Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs]]> OBJECTIVES: Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid. METHODS: Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis. RESULTS: Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups. CONCLUSIONS: Hypertonic saline infusion after intratracheal hydrochloric acid instillation does not have an effect on inflammatory biomarkers or respiratory gas exchange. <![CDATA[Operative versus nonoperative treatment for displaced midshaft clavicle fractures: a meta-analysis based on current evidence]]> Literature searches of the Cochrane Library, PubMed, EMBASE, Web of Science, LILACS, China National Knowledge Infrastructure, and Wanfang Data databases were performed from 1966 to September 2014. Only randomized and quasi-randomized controlled clinical trials comparing operative and nonoperative treatments for displaced midshaft clavicle fractures were included. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Thirteen studies were considered in the meta-analysis. Constant scores and the Disabilities of the Arm, Shoulder and Hand scores were improved in the operative fixation group at a follow up of one year or more. The nonunion and symptomatic malunion rates were significantly lower in the operative group. Additionally, the nonoperative group had a higher likelihood of neurological symptoms compared with the operative group. A significantly higher risk of complications was found in patients treated conservatively than in those who underwent operative fixation. However, when patients with nonunion and symptomatic malunion were excluded from the analysis, no significant differences in the complication rate were found. We concluded that based on the current clinical reports, operative treatment is superior to nonoperative treatment in the management of displaced midshaft clavicle fractures. However, we do not support the routine use of primary operative fixation for all displaced midshaft clavicle fractures in adults. <![CDATA[The association between the rs11196218A/G polymorphism of the TCF7L2 gene and type 2 diabetes in the Chinese Han population: a meta-analysis]]> Transcription factor 7-like 2 has been shown to be associated with type 2 diabetes mellitus in multiple ethnic groups in recent years. In the Chinese Han population in particular, numerous studies have evaluated the association between the rs11196218A/G polymorphism of the transcription factor 7-like 2 gene and type 2 diabetes mellitus. However, the results have been inconsistent, so we performed a meta-analysis to assess the association. Odds ratio and 95% confidence interval values were calculated using a random-effects model or a fixed-effects model based on heterogeneity analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Subgroup analyses were conducted based on conformity with Hardy-Weinberg equilibrium in the control group as well as on other variables, such as age, sex and body mass index. Sensitivity analysis was also performed to detect heterogeneity and to assess the stability of the results. In total, 10 case-control studies comprising 7,491 cases and 12,968 controls were included in this meta-analysis. The combined analysis indicated that the rs11196218A/G polymorphism was not associated with type 2 diabetes mellitus (G vs. A, OR=1.04, 95% CI=0.97–1.13, p=0.28). The subgroup analyses also did not show any association between the rs11196218A/G polymorphism and the risk of type 2 diabetes mellitus. Furthermore, the results of the subgroup analyses indicated that the absence of an association was not influenced by age, sex or body mass index. The results of the sensitivity analysis verified the reliability and stability of this meta-analysis. In conclusion, this study indicated that there is no significant association between the rs11196218A/G polymorphism and the risk of type 2 diabetes mellitus in the Chinese Han population.