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Background: This study aimed at describing the demographic and clinical characteristics, treatment patterns and overall survival of patients with MM in Brazil to identify gaps in the disease diagnosis and treatment., Methods: MMyBRAve (NCT03506386) was a multicenter, observational study of patients diagnosed with MM in Brazil between January 2008 and December 2016, with data collection between August 2018 and September 2019 at 17 participating centers., Results: Of 943 patients included, 914 had complete data for overall survival (OS) analysis. The most used frontline regimens were cyclophosphamide, thalidomide and dexamethasone; bortezomib, cyclophosphamide and dexamethasone; and thalidomide and dexamethasone. After a median follow-up of 63 months, the median OS from diagnosis was 70 months. These results indicate continuous improvements in comparison with previous observational studies from Brazil. The median OS in transplantation-ineligible (N = 491) and eligible (N = 452) patients were 49 and 93 months, respectively (hazard ratio [HR] = 0.52; 95% confidence interval [CI], 0.43 to 0.63; P < .001). The median OS also differed between patients with and without known prognostic factors., Conclusion: Despite the improvements, our results suggest that access to novel agents and transplantation continue to hinder further progress in patient outcomes in Brazil and countries with similar health-care constraints., Competing Interests: Disclosure V. HUNGRIA and D.L.C. FARIAS received honoraria as speaker from Takeda. V. HUNGRIA and R. BITTENCOURT received honoraria for advisory committee from Takeda. G. MARTINEZ, J.A. SANTOS, D.R. ALMEIDA, V.L.P. FIGUEIREDO, K.R. ZANELLA, L.B. MUNIZ and E.R. MATTOS don´t have any disclosure. J.T. SENRA and R.M. ABREU are Takeda Pharmaceuticals, Brazil-São Paulo-SP employees., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of information from Brazil regarding therapies used and outcomes in patients with acute coronary syndrome with ST elevation (STEMI)., Objectives: To evaluate evidence-based therapies, occurrence of outcomes, reperfusion use, and predictors of not receiving reperfusion in patients with STEMI in a national multicenter registry., Methods: Patients with STEMI from the ACCEPT registry, with up to 12 hours of symptoms, were followed for 1 year for the occurrence of major adverse cardiovascular events. A significance level of p < 0.05 was applied for all analyses., Results: In the analysis of 1553 patients, the reperfusion rate was 76.8%, ranging from 47.5% in the North Region to 80.5% in the Southeast Region. The rate of major adverse cardiovascular events was 12.5% at 1 year. The prescription of evidence-based therapies at hospital admission was 65.6%. The presence of hypertension (odds ratio [OR] 1.47; 95% confidence interval [CI] 1.11 to 1.96; p < 0.01); prior acute myocardial infarction (OR 1.81; 95% CI 1.32 to 2.48; p < 0.001); and the North (OR 4.65; 95% CI 2.87 to 7.52; p < 0.001), Central-West (OR 4.02; 95% CI 1.26 to 12.7; p < 0.05), and Northeast Regions (OR 1.70; 95% CI 1.17 to 2.46; p < 0.01) were independent predictors of not receiving reperfusion therapy., Conclusion: In the 1-year follow-up of the ACCEPT Registry, we were able to verify a wide variation within Brazilian geographical regions regarding adherence to best care practices. The following were independent predictors of not receiving reperfusion therapy: being treated in the North, Central-West, and Northeast Regions; having systemic arterial hypertension; and prior infarction.

Objective: To verify the prevalence and factors associated with Non-Alcoholic Fatty Liver Disease (NAFLD) among women with Polycystic Ovary Syndrome (PCOS)., Methods: A cross-sectional study was conducted with 53 patients with PCOS. The diagnosis of PCOS followed the Rotterdam criteria. The diagnosis of NAFLD was made through US showing hepatic steatosis, excluding significant alcohol consumption and chronic liver disease. The following variables were compared between the groups of women with and without NAFLD: age, race, anthropometric data, blood pressure levels, liver enzymes, glycemic and lipid profiles, total testosterone, presence of hirsutism, and metabolic syndrome (MS). Variables were compared between the groups using T-test, Mann-Whitney, and Chi-square tests., Results: Among 53 patients with PCOS, 50.9% had NAFLD. The NAFLD group had higher weight (p=0.003), BMI (p=0.001), waist circumference (p≤0.001), fasting glucose (p=0.021), HbA1C% (p=0.028), triglycerides (p=0.023), AST (p=0.004), ALT (p=0.001), higher prevalence of MS (p=0.004), and lower levels of HDL cholesterol (p=0.043). The other variables did not differ between the groups. Both groups were predominantly of caucasian race, and there was no significant difference in age., Conclusion: The prevalence of NAFLD among patients with PCOS was 50.9%. Metabolic and hepatic enzyme abnormalities were more prevalent in this group compared to the group without the disease. Obesity tripled the prevalence of NAFLD., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Objective: To assess the genotypic and allelic distribution of the rs10046 polymorphism in the CYP19A1 gene and evaluate whether this aromatase gene variant is associated with cardiovascular risk in postmenopausal women., Materials and Methods: This cross-sectional study analyzed repository-stored samples from 370 postmenopausal women aged 44-72 years. Clinical, metabolic, and hormonal data were collected. The patients' estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk was calculated using the ASCVD Risk Estimator Plus, as recommended by the American College of Cardiology/American Heart Association. Genotyping of the rs10046 polymorphism of the CYP19A1 gene was carried out using real-time polymerase chain reaction with allelic discrimination assays., Results: The participants had a mean age of 56.07 ± 5.58 years and a mean body mass index (BMI) of 27.73 ± 5.41 kg/m². The 10-year ASCVD risk was estimated to be low, borderline, intermediate, and high in 64.7%, 12.8%, 19.8%, and 2.7% of the participants, respectively. The CC genotype of the rs10046 polymorphism was associated with low estradiol levels (p = 0.003) and high ASCVD scores (p = 0.014). In a multivariate model, age (p < 0.001) and CC genotype (p = 0.021) were independently associated with higher ASCVD risk., Conclusion: The present study found that the CC genotype of the rs10046 polymorphism in the CYP19A1 gene is associated with low estradiol levels and an increased ASCVD risk. Additionally, the results indicated that, among postmenopausal women, age and the CC genotype of rs10046 were associated with a high prevalence of ASCVD risk, independent of BMI., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Objective: To evaluate deaths, hospitalizations, and persistence of symptoms in patients with COVID-19 after infection in an outpatient setting during the first COVID-19 wave in Brazil., Methods: This prospective cohort was between April 2020 and February 2021. Hospitalized or non-hospitalized COVID-19 patients until five days after symptom onset were included. The outcomes measured were incidence of death, hospitalization, and persistence of more than two symptoms 60 days after discharge., Results: Out of 1,198 patients enrolled in the study, 66.7% were hospitalized. A total of 289 patients died (1 [0.3%] non-hospitalized and 288 [36%] hospitalized). At 60 days, patients non-hospitalized during admission had more persistent symptoms (16.2%) compared to hospitalized (37.1%). The COVID-19 severity variables associated with the persistence of two or more symptoms were increased age (OR= 1.03; p=0.015), respiratory rate at hospital admission (OR= 1.11; p=0.005), length of hospital stay of more than 60 days (OR= 12.24; p=0.026), and need for intensive care unit admission (OR= 2.04; p=0.038)., Conclusion: COVID-19 survivors who were older, tachypneic at admission, had a hospital length of stay >60 days, and were admitted to the intensive care unit had more persistent symptoms than patients who did not require hospitalization in the early COVID-19 waves.ClinicalTrials.gov Identifier: NCT04479488.

Objectives: The proportion of older transplant recipients has increased. Cognitive impairment is not rare after kidney transplant, but data on this issue in liver transplant recipients are scarse., Materials and Methods: In this cross-sectional study, we evaluated all liver transplant recipients from a single center in Brazil from July 2018 to June 2020 in terms of cognitive performance to determine the prevalence of neurocognitive disorder. We compared liver transplant recipients with neurocognitive disorder with liver transplant recipients without neurocognitive disorder. We also compared those with an alcoholic cause of liver transplant with other patients. The presence of depressive symptoms was assessed. We performed correlations of clinical data with cognitive scores., Results: In a sample of 100 recipients with median age of 62 years (interquartile range, 56.2-69 y), neurocognitive disorder was present in 21% of the group. Patients with cognitive impairment were older (68 y [61-72] vs 61 y [52-68]; P = .019) and had a trend to higher proportion of persistent kidney injury (33.3% vs 13.9%; P = .055) versus patients without cognitive impairment. Recipients with alcoholic cause of liver transplant exhibited worse cognitive performance in the Mini-Mental State Examination (score of 26 [23.7-28.2] vs 28 [26-29]; P = .024) and the Alzheimer Disease Assessment Scale-cognitive (score of 10.4 [8.6-14.2] vs 8 [6.3-10]; P = .008) than other patients. Weak negative correlations were shown in cognitive performance scores versus recipient age (Semantic Verbal Fluency test, r = -0.334 [P = .001]; Clock Drawing test, r = -0.209 [P = .037]; Alzheimer Disease Assessment Scale-cognitive, r = -0.323 [P = .001])., Conclusions: Neurocognitive disorder was common in liver transplant recipients, in part due to increased age. This study also suggested a role for alcoholic cause of liver transplant and persistent kidney injury in the development of cognitive impairment.

Competing Interests: Conflicts of interest The author declares no conflicts of interest.

Rupture of the pectoralis major muscle is extremely rare in adolescents. The current literature contains only 5 reports of this condition in patients under 20 years old, with 2 reports in subjects under 16. In the present article, we report the case of a 15-year-old volleyball player who suffered a traumatic rupture of the pectoralis major in a match during the serve movement. After excluding endocrinological abnormalities as a cause of tendon weakening, the patient underwent surgical treatment due to muscle retraction, strength deficit, high demand, and esthetic concerns. Early diagnosis is crucial to successful outcomes, and the surgical intervention enabled early rehabilitation and a provided a higher likelihood of return to high-level competitive sports., Competing Interests: Conflito de Interesses Os autores não têm conflito de interesses a declarar., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Competing Interests: Conflito de Interesses Os autores não têm conflitos de interesse a declarar.

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Background: An individual's dietary pattern contributes in different ways to the prevention and control of recurrent cardiovascular events. However, the quality of the diet is influenced by several factors. The present study aimed to evaluate the quality of the diet of individuals with cardiovascular diseases and determine whether there is an association between sociodemographic and lifestyle factors., Methods: This is a cross-sectional study carried out with individuals with atherosclerosis (coronary artery disease, cerebrovascular disease or peripheral arterial disease) recruited from 35 reference centres for the treatment of cardiovascular disease in Brazil. Diet quality was assessed according to the Modified Alternative Healthy Eating Index (mAHEI) and stratified into tertiles. For comparing two groups, the Mann-Whitney or Pearson's chi-squared tests were used. However, for comparing three or more groups, analysis of variance or Kruskal-Wallis was used. For the confounding analysis, a multinomial regression model was used. p < 0.05 was considered statistically significant., Results: In total, 2360 individuals were evaluated: 58.5% male and 64.2% elderly. The median (interquartile range [IQR]) of the mAHEI was 24.0 (20.0-30.0), ranging from 0.4 to 56.0 points. When comparing the odds ratios (ORs) for the low (first tertile) and medium (second tertile) diet quality groups with the high-quality group (third tertile), it was observed that there was an association between diet quality with a family income of 1.885 (95% confidence intervals [CI] = 1.302-2.729) and 1.566 (95% CI = 1.097-2.235), as well as physical activity of 1.391 (95% CI = 1.107-1.749) and 1.346 (95% CI = 1.086-1.667), respectively. In addition, associations were observed between diet quality and region of residence., Conclusions: A low-quality diet was associated with family income, sedentarism and geographical area. These data are extremely relevant to assist in coping with cardiovascular disease because they enable an assessment of the distribution of these factors in different regions of the country., (© 2023 The British Dietetic Association Ltd.)

Background: It is estimated that atrial fibrillation (AF) affects approximately 1.5 million people in Brazil; however, epidemiological data are limited. We sought to evaluate the characteristics, treatment patterns, and clinical outcomes in patients with AF in Brazil by creating the first nationwide prospective registry., Methods: RECALL was a multicenter, prospective registry that included and followed for 1 year 4,585 patients with AF at 89 sites across Brazil from April 2012 to August 2019. Patient characteristics, concomitant medication use, and clinical outcomes were analyzed using descriptive statistics and multivariable models., Results: Of 4,585 patients enrolled, the median age was 70 (61, 78) years, 46% were women, and 53.8% had permanent AF. Only 4.4% of patients had a history of previous AF ablation and 25.2% had a previous cardioversion. The mean (SD) CHA 2 DS 2 -VASc score was 3.2 (1.6); median HAS-BLED score was 2 (2, 3). At baseline, 22% were not on anticoagulants. Of those taking anticoagulants, 62.6% were taking vitamin K antagonists and 37.4% were taking direct oral anticoagulants. The primary reasons for not using an oral anticoagulant were physician judgment (24.6%) and difficulty in controlling (14.7%) or performing (9.9%) INR. Mean (SD) TTR for the study period was 49.5% (27.5). During follow-up, the use of anticoagulants and INR in the therapeutic range increased to 87.1% and 59.1%, respectively. The rates/100 patient-years of death, hospitalization due to AF, AF ablation, cardioversion, stroke, systemic embolism, and major bleeding were 5.76 (5.12-6.47), 15.8 (14.6-17.0), 5.0 (4.4-5.7), 1.8 (1.4-2.2), 2.77 (2.32-3.32), 1.01 (0.75-1.36), and 2.21 (1.81-2.70). Older age, permanent AF, New York Heart Association class III/IV, chronic kidney disease, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, and dementia were independently associated with increased mortality while the use of anticoagulant was associated with lower risk of death., Conclusions: RECALL represents the largest prospective registry of patients with AF in Latin America. Our findings highlight important gaps in treatment, which can inform clinical practice and guide future interventions to improve the care of these patients., (Copyright © 2023. Published by Elsevier Inc.)

Background: The prevalence of pain in patients with multiple sclerosis is remarkable. Fibromyalgia has been considered as one of the forms of chronic pain encompassed in multiple sclerosis, but data are restricted to studies from Europe and North America., Objective: To assess the prevalence of fibromyalgia in a series of Brazilian patients with multiple sclerosis and the characteristics of this comorbidity., Methods: The present cross-sectional study included 60 consecutive adult patients with multiple sclerosis. Upon consent, participants underwent a thorough evaluation for disability, fatigue, quality of life, presence of fibromyalgia, depression, and anxiety., Results: The prevalence of fibromyalgia was 11.7%, a figure similar to that observed in previous studies. Patients with the comorbidity exhibited worse scores on fatigue (median and interquartile range [IQR]: 68 [48-70] versus 39 [16.5-49]; p  < 0.001), quality of life (mean ± standard deviation [SD]: 96.5 ± 35.9 versus 124.8 ± 28.8; p  = 0.021), anxiety (mean ± SD: 22.7 ± 15.1 versus 13.8 ± 8.4; p  = 0.021), and depression (median and IQR: 23 [6-28] versus 6 [3-12.5]; p  = 0.034) indices than patients without fibromyalgia. There was a strong positive correlation between depression and anxiety scores with fatigue (r = 0.773 and r = 0.773, respectively; p < 0.001). Conversely, a moderate negative correlation appeared between the Expanded Disability Status Scale (EDSS), fatigue, and depression scores with quality of life (r= -0.587, r= -0.551, r= -0.502, respectively; p  < 0.001)., Conclusion: Fibromyalgia is a comorbidity of multiple sclerosis that can enhance fatigue and decrease quality of life, although depression, anxiety, and disability are factors that can potentiate the impact of the comorbidity., Competing Interests: The authors have no conflict of interest to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: Surgeon visual estimation of shoulder range of motion (ROM) is commonplace in the outpatient office setting and routinely reported in clinical research, but the reliability and accuracy of this practice remain unclear. The purpose of this study is to establish the reliability and accuracy of remote visual estimation of shoulder ROM in healthy volunteers and symptomatic patients among a large group of shoulder surgeons. Our hypothesis is that remote visual estimation would be reliable and accurate compared with the digital goniometer method., Methods: Fifty shoulder surgeon members of the PacWest Shoulder and Elbow Society independently determined the active shoulder forward flexion (FF), internal rotation at 90° abduction (IR90), external rotation at 90° abduction, external rotation at the side , and maximal spinal level reached with internal rotation (IR spine ) through visual estimation of video recordings taken from 10 healthy volunteers and 10 symptomatic patients. Variations in measurements were quantified using the interobserver reliability through calculation of the intraclass correlation coefficient. Accuracy was determined through comparison with digital goniometer measurements obtained with an on-screen protractor application using Bland-Altman mean differences and 95% limits of agreement., Results: The interobserver reliability among examiners showed moderate to excellent correlation, with intraclass correlation coefficient ranging from 0.768 to 0.928 for the healthy volunteers and 0.739 to 0.878 for the symptomatic patients. Accuracy was limited, with upper limits of agreement exceeding the established minimal clinically important differences (MCIDs) for FF (20° vs. MCID of 14°) and IR90 (25° vs. 18°) in the healthy volunteers and for FF (33° vs. 16°), external rotation at 90° abduction (21° vs. 18°), and IR90 (31° vs. 20°) in the symptomatic patients., Conclusion: Despite generally high intersurgeon reliability in the visual estimation of shoulder ROM, there was questionable accuracy when compared to digital goniometer measurements,with measurement errors often exceeding established MCID values. Given the potential implications for the clinical response to treatment and the significance of research findings, the adoption of validated instruments to measure ROM and the standardization of examination procedures should be considered., (© 2023 The Authors.)

Background: COVID-19 progression is associated with an increased risk of arterial and venous thrombosis. Randomised trials have demonstrated that anticoagulants reduce the risk of thromboembolism in hospitalised patients with COVID-19, but a benefit of routine anticoagulation has not been demonstrated in the outpatient setting., Methods: We conducted a randomised, open-label, controlled, multicentre study, evaluating the use of rivaroxaban in mild or moderate COVID-19 patients. Adults ≥18 years old, with probable or confirmed SARS-CoV-2 infection, presenting within ≤7 days from symptom onset with no clear indication for hospitalization, plus at least 2 risk factors for complication, were randomised 1:1 either to rivaroxaban 10 mg OD for 14 days or to routine care. The primary efficacy endpoint was the composite of venous thromboembolic events, need of mechanical ventilation, acute myocardial infarction, stroke, acute limb ischemia, or death due to COVID-19 during the first 30 days. ClinicalTrials.gov: NCT04757857., Findings: Enrollment was prematurely stopped due to sustained reduction in new COVID-19 cases. From September 29th, 2020, through May 23rd, 2022, 660 patients were randomised (median age 61 [Q1-Q3 47-69], 55.7% women). There was no significant difference between rivaroxaban and control in the primary efficacy endpoint (4.3% [14/327] vs 5.8% [19/330], RR 0.74; 95% CI: 0.38-1.46). There was no major bleeding in the control group and 1 in the rivaroxaban group., Interpretation: On light of these findings no decision can be made about the utility of rivaroxaban to improve outcomes in outpatients with COVID-19. Metanalyses data provide no evidence of a benefit of anticoagulant prophylaxis in outpatients with COVID-19. These findings were the result of an underpowered study, therefore should be interpreted with caution., Funding: COALITION COVID-19 Brazil and Bayer S.A., Competing Interests: OB reports grants from AstraZeneca, Pfizer, Bayer, Servier, and Amgen, and Novartis, unrelated to this submitted work. RDL reports grants and personal fees from Bristol Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and personal fees from Amgen, Bayer, Daiichi Sankyo, Merck, Portola and Boehringer Ingelheim, outside of this submitted work. The other authors have no conflict to declare., (© 2023 The Author(s).)

Objectives: To create a practice guideline for the appropriate indications of an extra-articular procedure in primary anterior cruciate ligament reconstruction (ACLR)., Methods: The formal consensus method described by the Haute Autorité de Santé was used. The Latin American Society of Arthroscopy, Articular Replacement, and Sports Injuries (SLARD) recruited three groups of experts on ACLR. Initially, the steering group, consisting of eight surgeons, performed a systematic review of the literature and elaborated on 192 scenarios for primary ACLR. The rating group, composed of 23 surgeons, rated each scenario in two rounds, with an in-between in-person meeting for discussion. Median scores and agreement levels were estimated to classify each scenario as inappropriate, uncertain or appropriate for adding anterolateral reconstruction. Finally, the lecture group, consisting of 10 surgeons, revised each stage of the method, results and interpretation., Results: Of the scenarios, 11.97% were rated as appropriate for adding an extra-articular lateral procedure, 7.81% as inappropriate and 80.21% as uncertain. The key recommendations for the addition of extra-articular lateral techniques were as follows: it is appropriate when the patient is under 25 years of age, has high-grade physical examination findings, practises a pivoting sport and has hyperlaxity; meanwhile, it is inappropriate when the patient has low-grade physical examination findings, has normal laxity and does not practise a pivoting sport., Conclusions: The appropriate indications of extra-articular lateral procedures in primary ACLR were determined on the basis of the best available evidence and expert opinion following a formal consensus method., Level of Evidence: V., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Germ-cell tumors (GCTs) are the most common malignancy in young men. There is a paucity of data on GCTs in developing countries. LACOG 0515 study aimed to evaluate clinical characteristics and treatment outcomes in patients with GCTs from Brazilian cancer centers., Materials and Methods: This is a retrospective cohort study evaluating male patients diagnosed with GCTs from 2000 to 2018 in 13 Brazilian hospitals. We described baseline characteristics, progression-free survival (PFS), and overall survival (OS)., Results: A total of 1232 patients were included, with a median age of 30 years. Histology was seminoma in 47.1% and non-seminoma GCT (NSGCT) in 52.9%. The primary tumor site was testis in 96.5%. At diagnosis, clinical stage I was present in 68.1% and 34.7% and clinical stages IS/II/III in 31.9% and 65.2% of patients with seminoma and NSCGT, respectively. Following orchiectomy, 55.2% of patients with clinical stage I were managed with surveillance. The 5-year disease-free survival rates among patients with stage I were 98.0% in seminoma and 92.3% in NSGCT, with 5-year OS of 99.6% and 97.6%, respectively. Among patients with advanced disease (IS, II, and III), the 5-year PFS were 88.7% in seminoma and 68.7% in NSGCT, with 5y-OS of 97.6% and 82.8%, respectively., Conclusion: This is the largest Brazilian cohort of GCTs. Our results show a high rate of adjuvant chemotherapy in patients with clinical stage I. Although our data demonstrate slightly inferior PFS compared with the International Germ Cell Cancer Collaborative Group and other contemporary series, the OS rates were similar., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Posterior interosseous nerve syndrome is the most frequent syndrome of radial nerve compression, with the arcade of Frohse being the main site of compression. Its symptoms include difficulties in finger and wrist extension with possible radial deviation. Herein, we present a case of posterior interosseous syndrome caused by a schwannoma, a type of neurological tumor., Competing Interests: Conflito de Interesses Os autores declaram que não há conflito de interesses., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers., Methods: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540., Findings: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04])., Interpretation: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting., Funding: COALITION COVID-19 Brazil and EMS., Competing Interests: AA reports consultant and lectures fees from Bayer, NovoNordisk and Lilly outside of this submitted work, and research grants from Bayer, EMS Pharma and Population Health Research Institute. GBFO received honoraria for lectures from Novartis and Janssen outside of this submitted work; AD reports lecture fees from Bayer, Libbs, Apsen, and Biolab outside of this submitted work. ASS reports lectures fees from BioLab, Torrents and Servier. AVS reported research grants from AstraZeneca, MSD, Esperion, Clover Biopharm e Enanta Pharmaceutical outside of this submitted work. ABC received honoraria for lectures from EMS Pharma. LCPA reports personal fees from Baxter, Pfizer, and Halex-Istar; and grants from Ache Laboratorios Farmaceuticos, outside of this submitted work. OB reports grants from AstraZeneca, Pfizer, Bayer, Boehringer Ingelheim, Servier, and Amgen, and advisory board and personal fees from Novartis, outside of this submitted work. RBA reports to be an EMS employee. RDL reports grants and personal fees from Bristol Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and personal fees from Amgen, Bayer, and Boehringer Ingelheim, outside of this submitted work. RCR received honoraria for lectures from Novartis outside of this submitted work; VCV reports grants from Aspen Pharma, Pfizer, and Cristalia, outside of this submitted work. The other authors have no conflict to declare., (© 2022 The Authors.)

Gentamicin sulfate (GEN) is an aminoglycoside antibiotic with a narrow therapeutic range of plasma concentrations. The collection of venous blood represents a significant burden for patients, especially in neonatology. Dried blood spots (DBS) obtained from capillary blood can be an alternative for drug measurements in this particular population. This study aimed to develop and validate an assay for the quantification of GEN in DBS using UHPLC-MS/MS. Total GEN concentrations were obtained by adding the individual concentrations of the GEN forms C1, C1a, and C2. The assay used a DBS disk containing approximately 17 μL of blood for GEN quantitation in the range of 0.1-40 mg L -1 . Measurement accuracy for total GEN was in the range of 102.6-108.6%, inter-assay precision was 11.3-13.1% and intra-assay precision was 9.1-12.8.% GEN was stable for 21 days at - 20 and 8 °C, but only for 24 h at room temperature. Blood Hct affected the accuracy within acceptable limits (93.8-95% at Hct% of 30, 104.3-113% at Hct% of 50). Blood spotted volume did not affect GEN measurement accuracy. Concentrations of GEN in DBS obtained after heel pricks were correlated to plasma levels in a small cohort of neonatal patients. However, percentual differences between estimated plasma concentrations and actual plasma levels presented values between - 64-35.3% (average difference of - 1.9%). The use of DBS for the measurement of GEN concentrations can increase access to TDM of this antibiotic due to the ease of sample collection and the facilitated specimen transportation logistics when testing is not available onsite., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background No study has evaluated the impact of the additional manipulation demanded by multiple resheathing (MR) in patients undergoing transcatheter aortic valve replacement with repositionable self-expanding valves. Methods and Results This study included a real-world, multicenter registry involving 16 centers from Canada, Germany, Latin America, and Spain. All consecutive patients who underwent transcatheter aortic valve replacement with the Evolut R, Evolut PRO, and Portico valves were included. Patients were divided according to the number of resheathing: no resheathing, single resheathing (SR), and MR. The primary end point was device success. Secondary outcomes included procedural complications, early safety events, and 1-year mortality. In 1026 patients, the proportion who required SR and MR was 23.9% and 9.3%, respectively. MR was predicted by the use of Portico and moderate/severe aortic regurgitation at baseline (both with P <0.01). Patients undergoing MR had less device success (no resheathing=89.9%, SR=89.8%, and MR=80%; P =0.01), driven by more need for a second prosthesis and device embolization. At 30 days, there were no differences in safety events. At 1 year, more deaths occurred with MR (no resheathing=10.5%, SR=8.0%, and MR=18.8%; P =0.014). After adjusting for baseline differences and center experience by annual volume, MR associated with less device success (odds ratio, 0.42; P =0.003) and increased 1-year mortality (hazard ratio, 2.06; P =0.01). When including only the Evolut R/PRO cases (N=837), MR continued to have less device success ( P <0.001) and a trend toward increased mortality ( P =0.05). Conclusions Repositioning a self-expanding valve is used in a third of patients, being multiple in ≈10%. MR, but not SR, was associated with more device failure and higher 1-year mortality, regardless of the type of valve implanted.

Background: To improve the comparability of multiple sclerosis (MS) prevalence across Brazilian regions, the Brazilian Committee for Treatment and Research in MS has implemented a standardized approach to assess the prevalence of the disease in five key cities, which were deemed representative of their regions in terms of socio-geographical features and where in-person revision of each case was feasible., Objective: To report the point-prevalence of MS in Passo Fundo, one of the key cities in Southern Brazil., Methods: We sought to identify all MS patients who were living in Passo Fundo on July 1st, 2015. The primary source for case ascertainment was records from the offices of neurologists and neurosurgeons practicing in the city. Multiple secondary sources were used to maximize identification of cases. All patients underwent in-person review of the diagnosis by a panel of neurologists with experience in MS., Results: We identified 52 MS patients living in Passo Fundo on July 1st, 2015. The point-prevalence rate for MS was 26.4/100,000 population (95% confidence interval, 19.7 to 34.6/100,000). Among the MS cases, 42 (80.8%) were female, for a sex ratio of 4.2:1. Forty-six cases (88.5%) were categorized as relapsing-remitting MS, and the remaining 6 cases, as secondary progressive MS (11.5%). Other epidemiological and clinical features were comparable to national and international MS populations., Conclusions: The prevalence of MS in Passo Fundo is one of the highest reported in Brazil so far. Studies in other key Brazilian cities, using the same methodology, are currently being carried out.

Background: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear., Methods: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed., Results: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group., Conclusions: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Therapeutic drug monitoring (TDM) of gentamicin sulfate (GEN) is usually recommended, particularly in critical patients. Only a few reports had described the determination of GEN in plasma or plasma using LC-MS/MS., Objective: This study aimed to develop and validate a sensitive ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) assay for the quantification of GEN in small volumes of human plasma., Results: The use of a very low concentration of the ion-pairing agent HFBA allowed significant retention of the very polar GEN forms in a reversed phase UHPLC column. The solid-phase extraction (SPE) procedure allowed clean extracts, with no interferences detected in blank samples, and high sensitivity. The assay was linear on the range of 0.2-40 mg L -1 of GEN complex. The combined GEN complex had inter-assay CV of 8.8-10.0%, intra-assay CV of 10.2-11.0%, and accuracy of 96.8-104.0%. The assay was applied to 17 clinical samples obtained from neonate patients. Measured concentrations were in the range of 0.15-3.57 mg L -1 for GEN C1, 0.12-3.55 mg L -1 for GEN C1a, 0.20-5.77 mg L -1 for GEN C2, and 0.47-12.88 mg L -1 for the GEN complex, all within the linear range of the assay., Conclusion: A sensitive assay for the quantification of gentamicin in plasma using anion-exchange SPE and UHPLC-MS/MS was validated. The assay can be used for TDM of gentamicin, particularly in centers with access to proper instrumentation and with a low demand for gentamicin measurements, where immunoassays are not cost-effective., (© 2021 Published by Elsevier B.V.)

In this crossover trial, we evaluated a new technique for enteral nutrition using orogastric intubation. Twelve volunteers were randomly assigned to both orogastric (OGI) and conventional nasogastric intubation (NGI) with a 15-day interval. The tip of the orogastric tube was fixed intraorally into an upper molar. Participants were asked to remain intubated for 24 hours and rated efficacy and safety using a Likert scale (1: worst / 10: best). Tolerance in hours was longer during OGI (median 21 versus 12.5; p=0.022). OGI was superior in comfort (median 7 versus 3; p=0.002), aesthetic (median 10 versus 1; p=0.002), speech (median 5.5 versus 3; p=0.014) and swallowing (median 8 versus 2; p=0.004). Both procedures were tolerated with mild local complaints. Diet volume through the tube was greater during NGI (p = 0.014). In healthy participants, orogastric intubation with dental fixation showed greater efficacy and similar safety to nasogastric intubation. CLINICAL TRIALS NUMBER: NCT03670238., (Copyright © 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Cognitive decline is a common condition, but is still underrepresented in studies conducted in developing countries., Objective: To calculate the prevalence of cognitive decline and depression in an elderly community-dwelling population in a city in southern Brazil., Methods: We calculated the prevalences of dementia, cognitive impairment with no dementia (CIND) and symptoms of depression in an elderly population relying on the public healthcare system. This epidemiological study in Pelotas, Brazil, was conducted within the primary care setting. It included 299 older adults (mean age = 69.75 ± 7.6 years) who presented low levels of education (mean = 4.16 ± 3.17 years of education). They underwent cognitive screening and their medical records were analyzed., Results: Among these older adults, 142 (47.5%) presented cognitive decline: 104 (34.8%) matching the cognitive criteria for CIND and 38 (12.7%) matching the cognitive criteria for dementia. Among all the individuals who completed the cognitive screening, 141 (48.4%) were positive for symptoms of depression, of whom 99 (34%) did not have any previous diagnosis in their medical records., Conclusion: There was high prevalence of cognitive impairment among these older adults in a primary care setting. A large number of older adults were found to have symptoms of depression without any diagnosis.

Objectives: To assess the vitamin D levels, prevalence of vitamin D deficiency and genotypes of Fok-I, Bsm-I, Apa-I and Taq-I polymorphisms in the VDR gene and to determine whether vitamin D deficiency and VDR gene variants are associated with blood pressure levels and systemic arterial hypertension as defined by the 2017 ACC/AHA criteria., Study Design: A cross-sectional study of biobanked blood samples from 339 postmenopausal women., Main Outcome Measures: Blood pressure strata were defined according to the 2017 ACC/AHA cutoffs. Circulating 25(OH)D levels were considered deficient if <20 ng/mL., Results: Mean serum total 25(OH)D levels were 22.99 ± 8.54 ng/mL, and 40.1% of participants were deficient in vitamin D. Overall, 7.7% had elevated blood pressure, 36.6% had stage 1 and 37.8% had stage 2 hypertension. Mean total (p = 0.014) and free 25(OH)D levels (p = 0.029) were lower in women with stage 2 hypertension than in those with normal blood pressure. A higher prevalence rate of stage 2 hypertension was associated with age (PR 1.058; 95%CI 1.033-1.083; p < 0.001), BMI (PR 1.046; 95%CI 1.025-1.068; p < 0.001), vitamin D deficiency (PR 1.333; 95%CI 1.016-1.749; p = 0.038) and Taq-I polymorphism (PR 1.764; 95%CI 1.030-3.019; p = 0.039). Women with vitamin D deficiency and the AA+AG genotype of Taq-I polymorphism were 33% and 76% more likely to have stage 2 hypertension, respectively, but these associations lost significance when adjusted for age and BMI., Conclusion: The results suggest that vitamin D deficiency and Taq-I polymorphism are associated with stage 2 hypertension, depending on age and BMI, in postmenopausal women., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective  To outline the profile of self-citations from Revista Brasileira de Ortopedia (Rev Bras Ortop) and citations of this journal in other medical orthopaedic journals with general or specific content in a knowledge area of the specialty. Methods  This is an observational cross-sectional study of the frequency of self-citations and citations from Rev Bras Ortop in five other medical orthopaedic journals from different countries, all published in English. The last 15 articles published in 2020 in each of the six journals were analyzed. The references used in each of them were evaluated to identify the journal in which they were originally published. The frequency of distribution of the four main journals cited, their position, and the relative percentage to the total number of citations were observed and recorded in each of the six journals. The number of times that the Rev Bras Ortop was cited in each of the selected foreign journals was assessed using its absolute and relative frequencies. Results  The total number of citations evaluated in this study was 2,527 (ranging from 386 to 486 per magazine). Rev Bras Ortop showed a low rate of self-citation (2.6%), being the sixth journal cited in the journal itself (10 out of a total of 386 references). Moreover, Rev Bras Ortop was not mentioned in any of the other five medical journals included in the study (absolute frequency 0, relative frequency 0). Conclusion  Rev Bras Ortop has a low reference of itself, with a self-citation rate of 2.6% in the studied period, showing that the Brazilian orthopaedic surgeons do not mention the Brazilian orthopaedic surgeon who publishes in the journal. We suggest the elaboration and implementation of strong strategies to improve the journal's visibility in the world academic-scientific scenario. In addition, it is essential that Brazilian orthopaedic surgeons understand this reality and assist directly and effectively to change this scenario., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses, (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective  To evaluate and compare clinically and functionally patients undergoing primary total knee arthroplasty (TKA) with preservation or replacement of the patella. Methods  In a cross-sectional study, the functional results were evaluated and compared, using the Western Ontario and McMaster Universities (WOMAC) and Lequesne scores, of 158 patients undergoing primary TKA (162 knees); in 81 knees the patella was submitted to arthroplasty and in 81 the joint surface of the patella was preserved. Results  No significant differences were identified in terms of the Lequesne score (p = 0.585), global WOMAC score (p = 0.169), nor in terms of its subdivisions regarding stiffness (p = 0.796) and functional capacity (p = 0.190). There was a significant difference only in terms of the subdivision that evaluates pain in the WOMAC score, being lower in the group undergoing patellar arthroplasty (p = 0.036). Conclusion  In the present study, there was no difference in functional assessment in patients who underwent or not patellar replacement during primary knee arthroplasty surgery. However, individuals in whom the patella was preserved reported more pain., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective: This study aims to describe the epidemiological characteristics and survival rates of children with acute myeloid leukemia treated in hospitals in southern Brazil and compare them with international data., Methods: A multicenter cohort study was conducted with retrospective data collection of all new patients with acute myeloid leukemia under 18 treated at five referral centers in pediatric hematology-oncology in southern Brazil between January 2005 and December 2015., Results: Of the 149 patients with acute myeloid leukemia, 63.0% (n=94) were male. The median age at diagnosis was 10.5 years (range 0-18 years) and 40.3% (n=60) had a white blood cell count below 50,000/mm 2 . The most common Franco-American-British (FAB) subtype was M3 (n=43, 28.9%). Nine (6.0%) patients had central nervous system disease. In M3 patients, overall survival (OS) was 69.2% and 3-year event-free survival was 67.7%; in non-M3 patients, these rates were 45.3% and 36.7%, respectively. In non-M3 patients, OS was significantly different between transplanted (61.8%) and non-transplanted (38.2%) patients (p=0.031)., Conclusions: These results show a higher prevalence of the Franco-American-British M3 subtype than that reported in the international literature, as well as a decreased OS compared with that of developed countries. Further multicenter Brazilian studies with a larger sample size are encouraged to better understand the characteristics of acute myeloid leukemia, and to improve the treatment and prognosis in this population., (Copyright © 2020 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: Drug-induced immune hemolytic anemia is a rare condition that occurs primarily because of drug-induced antibodies, either dependent or independent and positive direct antiglobulin test. Our aim was to evaluate the association of positive DAT with nonreactive eluate and DIHA., Materials and Methods: From 2014-2018, we evaluated 159 patients who presented positive DAT with a nonreactive eluate. Laboratory and clinical analyses were performed including HIV, HBV and HCV testing. All patients were exposed to the following drugs: Dipyrone in 63.5 %, Furosemide in 28.9 %, Metoclopramide in 34.6 % and Ondansetron in 41.5 %., Results: Results of DAT showed IgG in 125 (78.4 %) patients and C3d in 24 (15.1 %) with reactions varying from 1+ to 4+. HIV test was positive in 10 (16.1 %) patients, HBV was positive in 3 (4.7 %) and HCV was positive in, 1 (1.5 %). There was no clinical significance when the parameters of hemoglobin, hematocrit, reticulocytes and LDH were evaluated, only a slight increase in bilirubin, especially, in patients with positive DAT reacting 3+/4+ due to IgG and C3d sensitization. Clinical evaluations showed that all patients were asymptomatic., Conclusions: The association of drugs with positive DAT can be a challenge to transfusion services and immunohematology reference laboratories. There was no evidence of any case of severe hemolysis with clinical repercussion through the clinical and laboratory findings analyzed with the drugs associated with positive DAT. Dipyrone and Furosemide have already been associated with DIHA but there are no studies reporting the association of Metoclopramide and Ondansetron with DIHA., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Conclusions: The prevalence of blood group antigens and phenotypes varies significantly in Brazil. To ensure a proper rare blood supply, it is essential to establish a local and regional database of rare donors connected to the national registry. The objective of this study was to create a database of rare blood donors in the northern region of southern Brazil. From November 2011 to December 2018, red blood cell (RBC) phenotyping and genotyping were performed on common and high-prevalence antigens in donors and patients in southern Brazil. During this study period, 17 patients and 33 blood donors with rare phenotypes were identified. Six patients had already been alloimmunized to clinically significant antigens. Patients with the following phenotypes (i.e., negative for highprevalence antigens) were found: Yt(a-), Jk(a-b-), Lu(a-b-), Oh (Bombay), Tc(a-), k-, and Fy(a-b-). Among the donors, Kp(a+b-), Fy(a-b-), Lu(a-b-), and k- phenotypes were identified. We also found four donors with the weak D type 18 phenotype. In conclusion, we observed that the prevalence of rare blood phenotypes in our region corresponds more to the prevalence found in the Caucasian population when compared with other regions in Brazil. Our results show the importance of continuous screening for rare donors in different regions of the country and the creation of a local database to support RBC transfusions in patients who need rare blood.

Evaluate the results of a series of 28 cases of high obstetric paralysis treated with the Sever-L'Episcopo technique modified by Hoffer, between 2003 and 2016. Children (mean age, four years and seven months) with adduction contracture and internal rotation of the shoulder without secondary bone deformities (Mallet class II) underwent lengthening of the pectoralis major muscle and tenotomy of the subscapularis muscle associated with transfer of the latissimus dorsi and teres major muscle to the infraspinatus muscle, moving to the function of external rotators and elevators. The mean follow-up was three years and 10 months. At the end of the study, 24 patients achieved excellent functional assessment scores, mainly of the abduction and external rotation, passing from Mallet class II to class IV. Four patients still demonstrated some degree of global movement limitation, passing from class II to class III. Regardless of the final functional gain, all patients were able to perform tasks that were previously difficult. The data from this study suggest that Hoffer's surgery is an effective method in the treatment of the sequelae of high obstetric paralysis without secondary bone deformities., Competing Interests: Conflito de Interesses Os autores não têm conflito de interesses a declarar., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Tuberous Sclerosis Complex (TSC) is a complex and heterogeneous genetic disease that has well-established clinical diagnostic criteria. These criteria do not include gastrointestinal tumors., Case Presentation: We report a 45-year-old patient with a clinical and molecular diagnosis of TSC and a family history of cancer, presenting two rare associated findings: gastrointestinal polyposis and pancreatic neuroendocrine tumor. This patient was subjected to a genetic test with 80 cancer predisposing genes. The genetic panel revealed the presence of a large pathogenic deletion in the TSC2 gene, covering exons 2 to 16 and including the initiation codon. No changes were identified in the colorectal cancer and colorectal polyposis genes., Discussion and Conclusions: We describe a case of TSC that presented tumors of the gastro intestinal tract that are commonly unrelated to the disease. The patient described here emphasizes the importance of considering polyposis of the gastrointestinal tract and low grade neuroendocrine tumor as part of the TSC syndromic phenotype.

Background: Highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality at all stages of infection and reduced transmission of HIV. Currently, the immediate start of HAART is recommended for all HIV patients, regardless of the CD4 count. There are several concerns, however, about starting treatment in critically ill patients. Unpredictable absorption of medication by the gastrointestinal tract, drug toxicity, drug interactions, limited reserve to tolerate the dysfunction of other organs resulting from hypersensitivity to drugs or immune reconstitution syndrome, and the possibility that subtherapeutic levels of drug may lead to viral resistance are the main concerns. The objective of our study was to compare the early onset (up to 5 days) with late onset (after discharge from the ICU) of HAART in HIV-infected patients admitted to the ICU., Methods: This was a randomized, open-label clinical trial enrolling HIV-infected patients admitted to the ICU of a public hospital in southern Brazil. Patients randomized to the intervention group had to start treatment with HAART within 5 days of ICU admission. For patients in the control group, treatment should begin after discharge from the ICU. The patients were followed up to determine mortality in the ICU, in the hospital and at 6 months. The primary outcome was hospital mortality. The secondary outcome was mortality at 6 months., Results: The calculated sample size was 344 patients. Unfortunately, we decided to discontinue the study due to a progressively slower recruitment rate. A total of 115 patients were randomized. The majority of admissions were for AIDS-defining illnesses and low CD4. The main cause of admission was respiratory failure. Regarding the early and late study groups, there was no difference in hospital (66.7% and 63.8%, p = 0.75) or 6-month (68.4% and 79.2%, p = 0.20) mortality. After multivariate analysis, the only independent predictors of in-hospital mortality were shock and dialysis during the ICU stay. For the mortality outcome at 6 months, the independent variables were shock and dialysis during the ICU stay and tuberculosis at ICU admission., Conclusions: Although the early termination of the study precludes definitive conclusions being made, early HAART administration for HIV-infected patients admitted to the ICU compared to late administration did not show benefit in hospital mortality or 6-month mortality. ClinicalTrials.gov, NCT01455688. Registered 20 October 2011, https://clinicaltrials.gov/show/NCT01455688., Competing Interests: The authors have declared that no competing interests exist.

Background There is lack of prospective data on evolution within one year of acute coronary syndromes (ACS) in a representative population of Brazilian patients. Objectives To assess the prescription of evidence-based therapies, the incidence of severe outcomes and the predictors for these outcomes in a multicenter Brazilian registry of ACS patients. Methods The ACCEPT is a prospective observational study, which included patients hospitalized with a diagnostic of ACS in 47 Brazilian hospitals. The patients were followed for a 1 year and data were collected on the medical prescription and the occurrence of major cardiovascular events (cardiovascular mortality, reinfarction and cerebrovascular accident - CVA). Values of p < 0.05 were considered statistically significant. Results A total of 5,047 patients were included in this registry from August 2010 to April 2014. The diagnosis of ACS was confirmed in 4,782 patients (94.7%) and, among those, the most frequent diagnosis was ACS with ST segment elevation (35.8%). The rate of major cardiovascular events was 13.6 % within 1 year. Adherence to prescription of evidence-based therapy at admission was of 62.1%. Age, public service, acute myocardial infarction, CVA, renal failure, diabetes and quality of therapy were associated independently with the occurrence of major cardiovascular events. Conclusions During the one-year follow-up of the ACCEPT registry, more than 10% of the patients had major cardiovascular events and this rate ranged according with the quality of therapy. Strategies must be elaborated to improve the use of evidence-based therapies to minimize the cardiovascular events among the Brazilian population. (Arq Bras Cardiol. 2020; 114(6):995-1003).

Objective: To evaluate the impact of laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) on gastroesophageal reflux disease (GERD) in patients with obesity., Methods: Patients with class II or III obesity were treated with LSG or LRYGB. Procedure choice was based on patients and surgeon preferences. GERD symptoms, endoscopy, barium swallow X-ray, esophageal manometry, and 24-h pH monitoring were obtained before and 1 year after surgery., Results: Seventy-five patients underwent surgery (83% female, 39.3 ± 12.1 years, BMI of 41.5 ± 5.1 kg/m 2 ): 35 (46.7%) had LSG and 40 (53.3%) LRYGB. LSG patients had lower BMI (40.3 ± 4.0 kg/m 2 vs. 42.7 ± 5.7 kg/m 2 ; p = 0.041) and trend toward lower prevalence of GERD (20% vs. 40%; p = 0.061). One year after surgeries, GERD was more frequent in LSG patients (74% vs. 25%; p < 0.001) and all LSG patients with preoperative GERD continue to have GERD postoperatively. De novo GERD occurred in 19 of 28 (67.9%) of LSG patients and 4 of 24 (16.7%) patients treated with LRYGB (OR 10.6, 95%CI 2.78-40.1). Independent predictors for post-operative GERD were as follows: LSG (OR 12.3, 95%CI 2.9-52.5), preoperative esophagitis (OR 8.5, 95% CI 1.6-44.8), and age (OR 2.0, 95%CI 1.1-3.4)., Conclusions: One year after surgery, persistent or de novo GERD were substantially more frequent in patients treated with LSG compared with LRYGB. LSG was the strongest predictor for GERD in our trial. Preoperative counseling and choice of bariatric surgical options must include a detailed assessment and discussion of GERD-related surgical outcomes.

Vitamin D deficiency is highly prevalent worldwide, and vitamin D-binding protein (DBP) a major regulator of serum vitamin D levels. The rs4588 and rs7041 polymorphisms of the GC gene constitute the genetic basis of the three major isoforms of circulating DBP (GC1s, GC1f, and GC2), while the rs2282679 variant is located in an important regulatory region of the GC gene. The aim of this study was to assess the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency and to ascertain whether it is associated with DBP levels and with GC gene variants. Biorepository samples of 443 women aged 20 to 72 years, with no evidence of clinical disease, were analyzed. Circulating levels of 25(OH)D were considered sufficient if ≥20 ng/mL and deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR. Mean age was 53.4±9.4 years; mean BMI was 27.8±5.8 kg/m2. The overall sample had mean 25(OH)D levels of 22.8±8.3 ng/mL; 39.7% of participants had deficient circulating 25(OH)D levels. Higher prevalence ratios (PR) of 25(OH)D deficiency were found for the CC genotype of rs2282679 (PR 1.74; 95%CI 1.30 to 2.24; p<0.001), GC2 isoform (PR 1.66; 95%CI 1.17 to 2.38; p = 0.005), time since menopause (PR 1.02; 95%CI 1.003 to 1.03, p = 0.016), and HOMA-IR (PR 1.02; 95%CI 1.01 to 1.03, p = 0.004). DBP levels (per 30 μg/mL increase in DBP) were associated with lower PR for 25(OH)D deficiency (PR 0.89; 95%CI 0.80;0.99; p = 0.027). Except for HOMA-IR, these prevalence ratios remained significant after adjustment for age and BMI. In conclusion, the rs2282679 polymorphism and the GC2 isoform of DBP were associated with lower serum DBP levels and with susceptibility to 25(OH)D deficiency in Brazilian women with no evidence of clinical disease., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Breast cancer (BC) in young women is uncommon and tends to present with more aggressive characteristics. To better understand and characterize this scenario in Brazil through real-world data, we performed a subanalysis of AMAZONA III study (ClinicalTrials.gov identifier: NCT02663973)., Methods: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2,950 women newly diagnosed with invasive BC in Brazil from January 2016 until March 2018 at 22 sites. Valid data were obtained from 2,888 patients regarding age at diagnosis and complete baseline information. To compare epidemiologic and clinicopathological features at the time of diagnosis, patients with BC were divided into two groups according to age: ≤ 40 years and > 40 years. Quantitative variables were described as means, and categorical variables were described as frequencies and percentages and compared using the Pearson's χ 2 test., Results: Of 2,888 women diagnosed with BC, 486 (17%) were ≤ 40 years old. Young women had higher educational level, most were employed and a significant number were married ( P < . 001 for all associations). Younger patients were more symptomatic at BC diagnosis ( P < . 001), and they also presented more frequently with stage III, T3/T4, grade 3 tumors, HER-2-positive, luminal B, and triple-negative subtypes., Conclusion: Brazilian women younger than age 40 years have unfavorable clinicopathological features of BC at diagnosis, with more aggressive subtypes and advanced stage when compared with older women. These differences are not explained by socioeconomic or ethnic imbalances. The causes of a higher prevalence of BC among young women in Brazil deserve additional investigation.

Background: Appropriate dietary recommendations represent a key part of secondary prevention in cardiovascular disease (CVD). We evaluated the effectiveness of the implementation of a nutritional program on quality of diet, cardiovascular events, and death in patients with established CVD., Methods: In this open-label, multicenter trial conducted in 35 sites in Brazil, we randomly assigned (1:1) patients aged 45 years or older to receive either the BALANCE Program (experimental group) or conventional nutrition advice (control group). The BALANCE Program included a unique nutritional education strategy to implement recommendations from guidelines, adapted to the use of affordable and regional foods. Adherence to diet was evaluated by the modified Alternative Healthy Eating Index. The primary end point was a composite of all-cause mortality, cardiovascular death, cardiac arrest, myocardial infarction, stroke, myocardial revascularization, amputation, or hospitalization for unstable angina. Secondary end points included biochemical and anthropometric data, and blood pressure levels., Results: From March 5, 2013, to Abril 7, 2015, a total of 2534 eligible patients were randomly assigned to either the BALANCE Program group (n = 1,266) or the control group (n = 1,268) and were followed up for a median of 3.5 years. In total, 235 (9.3%) participants had been lost to follow-up. After 3 years of follow-up, mean modified Alternative Healthy Eating Index (scale 0-70) was only slightly higher in the BALANCE group versus the control group (26.2 ± 8.4 vs 24.7 ± 8.6, P < .01), mainly due to a 0.5-serving/d greater intake of fruits and of vegetables in the BALANCE group. Primary end point events occurred in 236 participants (18.8%) in the BALANCE group and in 207 participants (16.4%) in the control group (hazard ratio, 1.15; 95% CI 0.95-1.38; P = .15). Secondary end points did not differ between groups after follow-up., Conclusions: The BALANCE Program only slightly improved adherence to a healthy diet in patients with established CVD and had no significant effect on the incidence of cardiovascular events or death., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective  The purpose of the present study was to evaluate factors associated with the presence of deep chondral lesions (Konan/Haddad grades III and IV) in patients submitted to hip arthroscopy to treat femoroacetabular impingement (FAI). Method  This was a prospective, cross-sectional study of a series of 125 consecutive hip arthroscopies performed between May 2016 and May 2017. After applying the exclusion criteria, 107 hips of 92 patients submitted to surgical treatment for mixed and CAM FAI were analyzed. For purposes of analysis, the present study considered groups with lesions considered mild and deep, which were associated with symptom score, lateral coverage angle, α angle, age, gender, and radiological classification of arthrosis. Results with a p -value < 0.05 were considered statistically significant. Results  Patients whose hips had lesions considered deep had significantly higher nonarthritic hip scores (NAHSs) than those whose hips presented lesions considered mild or who did not present chondral lesions (67.9 ± 19.4 versus 57.0 ± 21.9, p  = 0.027). The prevalence of deep lesions was higher in hips with Tonnis 1 compared with hips with Tonnis 0: 15 (55.6%) versus 10 (12.7%), respectively, p  < 0.001. Men presented a higher prevalence of grades III and IV lesions than women, 23 (34.3%) versus 2 (5.0%), p  = 0.001, and had significantly higher functional scores (65.6 ± 19.6 versus 49.3 ± 21.6, p  < 0.001). Conclusion  Men presented a higher prevalence of deep lesions. Hips classified as Tonnis 1 presented a 4.4-fold higher probability of presenting these lesions. Patients with deep chondrolabral lesions had a better preoperative functional score.

Background: Fabry disease is a rare, X-linked, lifelong progressive lysosomal storage disorder. Severely deficient α-galactosidase A activity in males is associated with the classic phenotype with early-onset, multisystem manifestations evolving to vital organ complications during adulthood. We assessed the ability of 2 low-dose agalsidase beta regimens to lower skin, plasma, and urine globotriaosylceramide (GL-3) levels, and influence clinical manifestations in male pediatric Fabry patients., Methods: In this multicenter, open-label, parallel-group, phase 3b study, male patients aged 5-18 years were randomized to receive agalsidase beta at 0.5 mg/kg 2-weekly (n = 16) or 1.0 mg/kg 4-weekly (n = 15) for 5 years. All had plasma/urine GL-3 accumulation but no clinically evident organ involvement. The primary outcome was GL-3 accumulation in superficial skin capillary endothelium (SSCE)., Results: The mean age was 11.6 (range: 5-18) years and all but one of the 31 patients had classic GLA mutations. In the overall cohort, shifts from non-0 to 0-scores for SSCE GL-3 were significant at years 1, 3, and 5, but results were variable. Plasma GL-3 normalized and urine GL-3 reduced substantially. Higher anti-agalsidase beta antibody titers were associated with less robust SSCE GL-3 clearance and higher urine GL-3 levels. Renal function remained stable and normal. Most Fabry signs and symptoms tended to stabilize; abdominal pain was significantly reduced (-26.3%; P = .0215). No new clinical major organ complications were observed. GL-3 accumulation and cellular and vascular injury were present in baseline kidney biopsies (n = 7). Treatment effects on podocyte GL-3 content and foot process width were highly variable. Fabry arteriopathy overall increased in severity. Two patients withdrew and 2 had their agalsidase beta dose increased., Conclusions: Our findings increase the limited amount of available data on long-term effects of enzyme replacement therapy in pediatric, classic Fabry patients. The low-dose regimens studied here over a period of 5 years did not demonstrate a consistent benefit among the patients in terms of controlling symptomatology, urine GL-3 levels, and pathological histology. The current available evidence supports treatment of pediatric, classic male Fabry patients at the approved agalsidase beta dose of 1.0 mg/kg 2-weekly if these patients are considered for enzyme replacement therapy with agalsidase beta., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective  To analyze the stability of humerus supracondylar fracture fixation with Kirschner wires comparing intramedullary and lateral (Fi), and two parallel lateral wires (FL) fixation in experimental models, to define which configuration presents greater stability. Methods  A total of 72 synthetic humeri were cross-sectioned to simulate the fracture. These bones were divided into two equal groups and the fractures were fixed with parallel Kirschner wires (FL) and with a lateral and intramedullary (Fi) wire. Then, the test specimens were subjected to stress load tests on a universal test machine, measured in Newtons (N). Each group was subdivided into varus load, valgus, extension, flexion, external rotation and internal rotation. An analysis of the data was performed comparing the subgroups of the FL group with their respective subgroups of the Fi group through the two-tailed t test. Results  The two-tailed t test showed that in 4 of the 6 evaluated conditions there was no significant statistical difference between the groups ( p  > 0.05). We have found a significant difference between the group with extension load with a mean of 19 N (FL group) and of 28.7 N (Fi group) ( p  = 0.004), and also between the groups with flexural load with the mean of the forces recorded in the FL group of 17.1 N and of 22.9 N in the Fi group ( p  = 0.01). Conclusion  Fixation with one intramedullary wire and one lateral wire, considering loads in extension and flexion, presents greater stability when compared to a fixation with two lateral wires, suggesting similar clinical results.