HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil

Abstract Background The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. Aim To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. Methods This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. Results From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. Conclusions Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.

Extra-musculoskeletal manifestations driving the therapeutic decision-making in patients with Spondyloarthritis: a 12-month follow-up prospective cohort study

Abstract Background The extra-musculoskeletal manifestations (EMMs) such as recurrent acute anterior uveitis (rAAU), psoriasis (Ps), and inflammatory bowel disease (IBD), are related to the Spondyloarthritis (SpA), as well as they are associated with disease activity and poor prognosis. However, there are no data addressing its relevance regarding therapeutic decision-making in clinical practice. Objective To evaluate the impact of EMMs to drive the treatment decision-making in patients with SpA in a 12-month follow-up. Patients and methods SpA patients, according to the axial and peripheral ASAS classification criteria, as well as CASPAR criteria, with any active EMM, defined as main entry criteria, were included in this longitudinal cohort study. Individuals with a history of any disease or condition that could be associated with some of the studied endpoints, including neoplasms and infectious diseases, were excluded. Specific tools related to each EMM, including Psoriasis Area Severity Index (PASI), ophthalmologic evaluation, according to the Standardization of Uveitis Nomenclature (SUN) criteria, and gut complaints were used at baseline and during the 3-, 6- and 12-month of follow-up as outcomes measures over time. Descriptive and inferential analyses were used appropriately, including Pearson's correlation test, chi-squared test, and ANOVA. P value less than 0.05 was considered as significant. Results A total of 560 patients were enrolled, of whom 472 meet the eligibility criteria. The majority (N = 274; 59.6%) had one or more EMM related to SpA umbrella concept. Among the EMM, the one that most influenced therapeutic decision-making was psoriasis (28.5%), followed by uveitis (17.5%) and IBD (5.5%), regardless of musculoskeletal manifestations. Clinical improvement of EMMs outcomes was observed in most patients over 12-month follow-up, especially in those with rAAU and IBD (P < 0.001). Conclusion Our results showed that EMMs guided the therapeutic decision-making in half of SpA patients, regardless of musculoskeletal condition, suggesting the inter-disciplinarity among the rheumatologist, ophthalmologist, dermatologist, and gastroenterologist plays a crucial role to manage them.

HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis - data from the ReumaCov-Brasil Registry

Abstract Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immunemediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study

ABSTRACT Objective: The occurrence of partial remission (honeymoon phase) in type 1 diabetes (T1D) has been associated with a reduced risk of chronic microvascular complications of diabetes. We have published case reports showing that a combination therapy with the DPP-4 inhibitor sitagliptin plus vitamin D3 (VIDPP-4i) can prolong the honeymoon phase in patients with new-onset T1D. In the present case-control study, we investigated the frequency of occurrence of clinical remission (CR) in patients with new-onset T1D after VIDPP-4i treatment. Subjects and methods: In this case-control study, we collected data spanning 10 years from medical records of 46 patients (23 females) recently diagnosed with T1D. Overall, 27 participants with CR (insulin dose-adjusted glycated hemoglobin [IDAA1c] ≤ 9) at 12 or 24 months composed the case group, and 19 participants without CR served as the control group. Chi-square with Yates correction was used to analyze the association between VIDPP-4i use and CR, and odds ratio (OR) was used to determine the chance of CR due to VIDPP-4i treatment exposure. Results: In all, 37 patients (80.4%) experienced CR at some time over 24 months. The mean CR duration was 13.15 ± 9.91 months. Treatment with VIDPP-4i was significantly associated with CR. At 24 months, the OR of CR after VIDPP-4i exposure was 9.0 (95% confidence interval [CI] 2.21-30.18, p = 0.0036). Additionally, 9 (33.6%) and 4 (14.8%) patients in the VIDPP-4i group experienced insulin-free CR at 12 and 24 months, respectively. Conclusion: Therapy with VIDPP-4i was associated with a higher frequency and duration of the honeymoon phase. Randomized controlled trials are needed to confirm these findings.

Guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force

Abstract Objective: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process. Methods: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle-Ottawa Scale to assess the quality of nonrandomized studies. Results: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4—agree—and 5—strongly agree—, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response. Conclusion: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment.

Factors associated with hospitalizations for Covid-19 in patients with rheumatoid arthritis: data from the Reumacov Brazil registry

Abstract Background: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID 19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID 19 hospitalizations in patients with RA. Methods: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID 19 were compared to 220 patients who tested negative for COVID 19 (control group). All patient data were collected from the Research Electronic Data Capture database. Results: The participants were predominantly female (90.6%) with a mean age of 53 ±12 years. Of the patients with COVID 19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR =4.61, 95% CI 1.06-20.02. P < 0.001) and current use of glucocorticoids (OR =20.66, 95% CI 3.09-138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR =0.26; 95% CI 0.10-0.67, P < 0.005). Conclusion: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID 19 in patients with RA. Trial registration: Brazilian Registry of Clinical Trials RBR 33YTQC.

Official Position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry—part II (clinical aspects): interpretation, reporting, and special situations

Abstract Objective: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice. Materials and methods: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism ( Associação Brasileira de Avaliação Óssea e Osteometabolismo , ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals. Conclusion: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil.

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil

Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

Brazilian recommendations for the use of nonsteroidal anti-inflammatory drugs in patients with axial spondyloarthritis

Abstract Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. Over some decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been the basis for the pharmacological treatment of patients with axial spondyloarthritis (axSpA). However, the emergence of the immunobiologic agents brought up the discussion about the role of NSAIDs in the management of these patients. The objective of this guideline is to provide recommendations for the use of NSAIDs for the treatment of axSpA. A panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of randomized clinical trials for 15 predefined questions. The Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations were used, and at least 70% agreement of the voting panel was needed. Fourteen recommendations for the use of NSAIDs in the treatment of patients with axSpA were elaborated. The purpose of these recommendations is to support clinicians' decision making, without taking out his/her autonomy when prescribing for an individual patient.(AU)

Severe COVID-19: what have we learned with the immunopathogenesis?

Abstract The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself. Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena. Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS- CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.(AU)

Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases

Abstract Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.(AU)

The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis - 2019

Abstract Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013. A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed. These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.

Fatores Associados à Manutenção do Vício de Fumar e do Consumo de Álcool entre Acadêmicos de Medicina em uma Capital do Nordeste do Brasil / Factors Associated with Continued Smoking Addiction and Alcohol Consumption among Medical Students in Capital City in the Northeast of Brazil

RESUMO Introdução Há um aumento no consumo de drogas entre os jovens no Brasil. Esse consumo se destaca entre os estudantes universitários, acarretando uma preocupação adicional quando associado aos estudantes da área da saúde. Objetivo Identificar os fatores associados à manutenção do vício de fumar e do consumo de álcool entre acadêmicos de Medicina. Métodos Trata-se de um estudo analítico, de prevalência, envolvendo estudantes de Medicina das quatro escolas médicas da cidade de Fortaleza, Nordeste do Brasil. Foi aplicado um questionário semiestruturado, contendo 46 perguntas objetivas, aos estudantes que cursavam o primeiro ano (S1/S2) durante o ano de 2012 e novamente em 2016, quando esses mesmos estudantes se encontravam no internato (I3/I4). A amostra foi calculada considerando como população do estudo o número máximo de alunos nos dois períodos avaliados.O projeto foi aprovado pelo CEP, por meio do Parecer nº020/2012. Resultados Foram entrevistados 360 estudantes no primeiro momento da pesquisa e 354 estudantes no segundo momento. O consumo de tabaco passou de 17,4% durante o primeiro ano do curso para 28,2% durante o internato (p<0,001). O mesmo ocorreu com o consumo de álcool, que já era elevado no início do curso (84,6%) e aumentou para 92,6% (p<0,001). No primeiro ano do curso, 40,5% dos estudantes referiram já ter se embriagado pelo menos uma vez. Durante a faculdade, esse percentual subiu para 59,5% (RP=1,66; p<0,001). Conclusão O consumo de álcool e tabaco aumentou de forma importante durante o curso de Medicina. Há necessidade de intervenções nos hábitos dos acadêmicos de Medicina com o objetivo de reduzir o consumo exagerado de álcool e a manutenção do tabagismo nesta população.

ABSTRACT Introduction Drug use among young people in Brazil is increasing, particularly among the university students, leading to additional health-related concerns for students. Objective To identify factors associated with continued smoking addiction and alcohol consumption among medical students. Methods An analytical, prevalence study was carried out involving medical students at the four medical schools of Fortaleza, northeastern Brazil. A semi-structured questionnaire with 46 objective questions was applied to students in their first year of the course (S1/S2) in 2012 and again in 2016, when these same students were taking their internship (I3/I4). The sample was calculated based on a study population consisting of all the students in the two periods evaluated. The project was approved by the REC, through opinion no. 020/2012. Results 360 students were interviewed in the first phase of the research, and 354 students in the second phase. Tobacco consumption increased from 17.4% during the first year of the course to 28.2% during the internship (p <0.001). The same occurred with alcohol consumption, which was already high at the beginning of the course (84.6%) and increased to 92.6% (p <0.001). In the first year of the course, 40.5% of the students reported having got drunk at least once. During their time at medical school, this percentage rose to 59.5% (PR = 1.66, p <0.001). Conclusion Alcohol and tobacco consumption increased significantly during medical school. There is a need for interventions in the habits of medical student, in order to reduce excessive alcohol consumption and smoking in this population.

Lack of association between dietary inflammatory index and low impact fractures in the Brazilian population: the Brazilian Osteoporosis Study (BRAZOS)

Abstract Introduction: Adequate nutrition, including intake of dietary calcium and vitamin D, is important to maintain bone health. Evidence suggests that a deficiency in micronutrients may contribute to bone loss during aging and exert generalized effects on chronic inflammation. Recently, the Dietary Inflammatory Index (DII) was developed to assess the inflammatory potential of individual diets. Our aim was to evaluate the DII in a representative sample and verify its association with low-impact fractures. Methods: Individuals from The Brazilian Osteoporosis Study (BRAZOS) database had their DII calculated. BRAZOS is an important cross-sectional epidemiological study carried out with a representative sample of men and women ≥40 years old. The research was conducted through in-home interviews administered by a trained team. Nutrition Database System for Research (NDSR) software was used to analyze data on the intake of nutrients, which were employed to calculate the DII using Statistical Analysis Software (SAS®) and Statistical Package for the Social Sciences (SPSS®) to assess its association with low-impact fractures. Results: A total of 2269 subjects had their DII score calculated using information from 24-h recall data. Males had lower DII than females (DII = 1.12 ± 1.04 vs DII = 1.24 ± 0.99, p = 0.012). Women taking statins had lower DII (DII = 0.65 ±1.14 vs DII + 1.26 ± 0.98, p = 0.002), indicating a greater potential for diet-related anti-inflammatory effects. Conclusion: Our findings suggest that women might have a pro-inflammatory diet pattern compared to men. However, we did not find any association between DII scores and low-impact fractures.

Incidence of Cytomegalovirus Antigenemia in patients with autoimmune rheumatic diseases: a 3-year retrospective study

Abstract Objective: To determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients. Methods: From January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least. Results: CMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1-7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40. 9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ±55.4 mg vs. 71.7 ±46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm3 vs. 821 ± 692.9/ mm3; p = 0.06). Conclusions: Our data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis.

Topographic MRI evaluation of the sacroiliac joints in patients with axial spondyloarthritis / Avaliação topográfica das articulações sacroilíacas por ressonância magnética em pacientes com espondiloartrite axial

Abstract Objective: To evaluate the imaging features of spondyloarthritis in magnetic resonance imaging (MRI) of the sacroiliac (SI) joint and topography (in thirds) and affected margin, considering that this issue is rarely addressed in the literature. Methods: A cross-sectional study evaluating MRI (1.5 T) of SI in 16 patients with axial spondyloarthritis, for the presence of acute (subchondral bone edema, enthesitis, synovitis and capsulitis) and chronic (erosions, subchondral bone sclerosis, bony bridges, and fatty infiltration) changes, performed by two blinded radiologists. MRI findings were correlated with clinical data, including age, duration of disease, medications, HLA-B27, BASDAI, ASDAS-ESR and ASDAS-CRP, BASMI, BASFI, and mSASSS. Results: Bone edema pattern and erosions were predominant in the upper third of SI (p = 0.050 and p = 0.0014, respectively). There was a correlation between disease duration and structural changes by affected third (p = 0.028-0.037), as well as between the presence of bone bridges with BASMI (p = 0.028) and mSASSS (p = 0.014). Patients with osteitis in the lower third showed higher values for ASDAS (ESR: p = 0.011 and PCR: p = 0.017). Conclusion: Chronic inflammatory changes and the pattern of bone edema predominated in the upper third of SI, but a simultaneous involvement of middle or lower thirds of the joint was also noted. The location of involvement in the upper third of SI is insufficient to differentiate between degeneration and inflammation.

Resumo Objetivo: Avaliar as características de imagem das espondiloartrites na ressonância magnética (RM) das articulações sacroilíacas (SI) quanto à topografia (em terços) e margem acometida, uma vez que esse aspecto é pouco abordado na literatura. Métodos: Estudo transversal com avaliação por RM (1,5 T) das SI em 16 pacientes com diagnóstico de espondiloartrite axial quanto à presença de alterações agudas (edema ósseo subcondral, entesite, sinovite e capsulite) e crônicas (erosões, esclerose óssea subcondral, ponte óssea e substituição gordurosa), feita por dois radiologistas, cegos para os dados clínicos. Os achados da RM foram correlacionados com dados clínicos, incluindo idade, tempo de doença, medicações, HLA-B27, BASDAI, ASDAS-VHS e ASDAS-PCR, BASMI, BASFI e mSASSS. Resultados: Padrão de edema ósseo e erosões apresentaram predomínio no terço superior das SI (p = 0,050 e p = 0,0014, respectivamente). Houve correlação entre o tempo de doença e alterações estruturais por terço acometido (p = 0,028-0,037), bem como a presença de pontes ósseas com o BASMI (p = 0,028) e o mSASSS (p = 0,014). Pacientes com osteíte no terço inferior apresentaram maiores valores de ASDAS (VHS: p = 0,011 e PCR: p = 0,017). Conclusão: As alterações inflamatórias crônicas e o padrão de edema ósseo predominaram no terço superior das SI, mas também havia acometimento concomitante dos terços médio ou inferior da articulação. A localização do acometimento no terço superior das SI se mostra insuficiente para a diferenciação entre degeneração e inflamação.

Prevalência e Fatores Associados ao Consumo de Álcool e Tabaco entre Estudantes de Medicina no Nordeste do Brasil / Prevalence and Associated Factors of Alcohol Consumption and Smoking among Medical Students in Northeastern Brazil

RESUMO Introdução O consumo de derivados de tabaco e álcool é apontado como importante causa de doenças e agravos no mundo. No Brasil, há um aumento no consumo dessas drogas entre os jovens, principalmente estudantes universitários. Objetivo Conhecer a prevalência e os fatores associados ao tabagismo e consumo de bebidas alcoólicas entre estudantes de Medicina, além do nível de conhecimento acerca das técnicas de cessação do hábito tabagista em diferentes momentos da vida acadêmica. Métodos Estudo analítico, de prevalência, envolvendo estudantes de Medicina de Fortaleza, Ceará, Brasil. Foram selecionadas todas as escolas médicas e os estudantes do primeiro ano (S1/S2), quarto ano (S7/S8) e aqueles do último ano do internato (I3/I4). A amostra foi calculada considerando uma frequência esperada de 10% de pessoas fumantes, com um erro de 3%, estimando 726 estudantes das quatro instituições. Foi aplicado um questionário estruturado, com 46 perguntas. Os dados foram analisados pelo software Stata 11.2. Resultados Foram entrevistados 1.035 estudantes, distribuídos proporcionalmente nos três períodos, 392 (37,9%) do primeiro ano (S1-S2), 319 (30,8%) do quarto ano (S7-S8) e 324 (31,3%) do internato (I3-I4). Quinhentos e cinquenta e três (53,4%) eram do sexo feminino, a maioria era solteira (993; 96,3%), nascidos em Fortaleza (748; 72,4%), residiam com os pais (896; 86,8%) e com renda familiar acima de dez salários mínimos (652; 61,8%). Ao todo, 533 (51,5%) eram alunos de instituições particulares. Do total, 254 (24,6%) já haviam fumado. Esse consumo foi significativamente maior entre o sexo masculino (p = 0,025), sem diferença em relação ao estado civil (p = 0,247) ou renda familiar (p = 0,191). Todos os acadêmicos que experimentaram alguma substância derivada do tabaco já haviam ingerido bebida alcoólica alguma vez na vida (p < 0,000). O consumo de álcool foi referido por mais de 80% dos estudantes, sendo maior entre aqueles cuja família apresentou renda superior a nove salários mínimos (p = 0,001). Houve relato de embriaguez em mais de 70% dos estudantes, tendo esse fato ocorrido antes dos 18 anos. Cerveja e vodca são as bebidas mais consumidas. Apenas 39,5% afirmaram estar aptos a aconselhar um paciente a não ingerir bebidas alcoólicas e apenas 28,4% receberam algum treinamento sobre o assunto em sua universidade. Conclusão A prevalência do consumo de álcool é muito elevada entre os estudantes de Medicina, principalmente entre aqueles que relataram fumar. Esses temas são abordados de forma incipiente em sua formação. É preciso reforçar esses aspectos na formação desses futuros profissionais de saúde.

ABSTRACT Introduction Tobacco and alcohol consumption is considered a major cause of diseases and disorders in the world. In Brazil, there has been increased consumption of these drugs among young people, especially university students. Objective To discover the prevalence of and factors associated to smoking and alcohol consumption among medical students, as well as their level of knowledge about techniques to stop smoking at different times of their academic life. Methods Analytical study of prevalence among medical students in Fortaleza, Ceará, Brazil. The study sample included all the city's medical schools and their first year (S1/S2) and fourth year (S7/S8) students and students in the final year of their internship (I3/I4). The sample was calculated considering an expected smoker frequency of 10%, with a 3% margin of error, estimating 726 students in the four institutions. A structured questionnaire containing 46 questions was applied. Data were analyzed using Stata 11.2 software. Results 1,035 students were interviewed, distributed proportionally in the three periods: 392 (37.87%) from the first year (S1 / S2), 319 (30.82%) from the fourth year (S7/S8) and 324 (31.30%) interns (I3/I4). 553 students (53.4%) were female; most of the students were single (993; 96.3%), born in Fortaleza (748; 72.4%), living with their parents (896; 86.8%) and with a household income of more than 10 minimum wages (652; 61.8%). In total, 533 (51.5%) were students at private institutions. Of the total, 254 (24.6%) had smoked. This consumption was significantly higher among males (p = 0.025), with no difference in relation to marital status (p = 0.247) or household income (p = 0.191). All the students who reported having experienced any tobacco derivative also reported using alcohol in their lifetime (p < 0.000). Alcohol consumption was reported by more than 80% of the students, and was higher among those whose family income was more than nine times the minimum wage (p = 0.001). Alcoholic intoxication was reported by over 70% of the students - where this had occurred before the age of 18 years. Beer and vodka are the most consumed beverages. Only 39.5% said they were inclined to advise a patient to avoid alcoholic beverages and only 28.4% had received training on the subject at their university. Conclusion The prevalence of alcohol consumption is very high among medical students, especially among those who reported smoking. These issues are addressed in a primitive manner in their training. We must strengthen these aspects in the training of future health professionals.

Effect of Bauhinia holophylla treatment in Streptozotocin-induced diabetic rats

ABSTRACT Bauhinia holophylla, commonly known as "cow's hoof", is widely used in Brazilian folk medicine for the diabetes treatment. Therefore, the aim of this study was at evaluating the aqueous extract effect of Bauhinia holophylla leaves treatment on the streptozotocin-induced diabetic rats. Diabetes was induced by Streptozotocin (40 mg/Kg) in female Wistar rats. Oral administration of aqueous extract of Bauhinia holophylla leaves was given to non-diabetic and diabetic rats at a dose of 400 mg/kg during 21 days. On day 17 of treatment, the Oral Glucose Tolerance Test was performed to determine the area under the curve. At the end of the treatment, the animals were anesthetized and blood was collected for serum biochemical parameters analysis. After treatment with Bauhinia holophylla extract, non-diabetic and diabetic rats presented no glycemic changes. On the other hand, the plant treatment decreased body weight and increased ALT and AST activities. In conclusion, the treatment with aqueous extract of B. holophylla leaves given to diabetic rats presented no hypoglycemic effect in nondiabetic animals and no antidiabetic effect in diabetic animals with the doses studied. In addition, the diabetic animals treated with the B. holophylla extract showed inconvenient effects and its indiscriminate consumption requires particular carefulness.

Incidence of tuberculosis among patients with rheumatoid arthritis using TNF blockers in Brazil: data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil) / Incidência de tuberculose em pacientes com artrite reumatoide em uso de bloqueadores do TNF no Brasil: dados do Registro Brasileiro de Monitoração de Terapias Biológicas BiobadaBrasil

Abstract Objectives To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. Patients and methods This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Statistical analysis: Unpaired t-test and Fisher's two-tailed test; p < 0.05. Results The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab = 676, infliximab = 547 and etanercept = 521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab = 4.43/1000 patient-years; etanercept = 1.92/1000 patient-years and infliximab = 1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group. Conclusions The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure.

Resumo Objetivos Avaliar incidência de tuberculose e triagem para tuberculose latente em brasileiros com artrite reumatoide em uso de agentes biológicos na prática clinica. Pacientes e métodos Estudo de coorte com dados do Registro Brasileiro de Monitoração de Terapias Biológicas (BiobadaBrasil), de 01/2009 a 05/2013, abrangeu 1.552 tratamentos, 415 somente com drogas modificadoras do curso da doença (MMCDs) sintéticas, 942 MMCDs sintéticas em associação com anti-TNF (etanercepte, infliximabe, adalimumabe) e 195 MMCDs sintéticas em associação com outros biológicos (abatacepte, rituximabe e tocilizumabe). Avaliaram-se ocorrência de tuberculose, tempo de exposição às drogas e triagem para TB. Análise estatística: teste t não pareado e teste de Fisher bicaudal; p < 0,05. Resultados O tempo de exposição dos controles foi de 981 pacientes-ano, do grupo de anti-TNF foi de 1.744 pacientes-ano (adalimumabe = 676, infliximabe = 547 e etanercepte = 521 pacientes-ano) e o de outros biológicos de 336 pacientes-ano. A incidência de TB foi de 1,01/1.000 pacientes-ano nos controles e de 2,87 pacientes-ano nos usuários de anti-TNF (adalimumabe = 4,43/1.000 pacientes-ano; etanercepte = 1,92/1.000 pacientes-ano e infliximabe = 1,82/1.000 pacientes-ano). Não houve casos de tuberculose no grupo de outros biológicos. O tempo médio de exposição até a ocorrência de tuberculose foi de 27(11) meses para o grupo anti-TNF. Conclusões A incidência de tuberculose foi maior nos usuários de MMCDs sintéticas e anti-TNF do que nos usuários de MMCDs sintéticas e de MMCDs sintéticas e biológicos não anti-TNF, e também mais tardia, sugerindo infecção durante o tratamento, e não falha na triagem.

A new musculoskeletal ultrasound scoring system (US10) of the hands and wrist joints for evaluation of early rheumatoid arthritis patients / Novo sistema de escore ultrassonográfico (US10) musculoesquelético das articulações das mãos e punho para avaliação de pacientes com artrite reumatoide em fase inicial

ABSTRACT Objective: To propose a novel ultrasound scoring system for hand and wrist joints (US10) for evaluation of patients with early rheumatoid arthritis (RA) and to correlate the US10 with clinical, laboratory and functional variables. Methods: Forty-eight early RA patients underwent clinical and laboratory evaluations as well as blinded ultrasound (US) examinations at baseline, three, six and 12 months. The proposed US10 system involved the assessment of the wrist, second and third metacarpophalangeal and proximal interphalangeal joints. The score consisted of inflammation parameters (synovial proliferation [SP], power Doppler [PD] and tenosynovitis [TN]) and joint damage parameters (bone erosion [BE] and cartilage damage [CD]). SP, PD, BE and CD were scored qualitatively (0–1) and semi-quantitatively (grades 0–3). Tenosynovitis was scored as presence/absence. The evaluation also involved the 28-Joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and C-reactive protein level (CRP). Results: Mean duration of symptoms was 7.58 ± 3.59 months. Significant correlations (p < 0.05) were found between inflammation parameters and CRP at baseline and between the changes in these variables throughout the study. Significant correlations (p < 0.05) were found between DAS28 score and both PD and TN at baseline and between the changes in DAS28 score and both SP and TN throughout the follow up. Moreover, significant correlations were found between the changes in inflammation parameter scores and HAQ score throughout the follow up. Conclusion: The proposed US10 scoring system proved to be a useful tool for monitoring inflammation and joint damage in early RA patients, demonstrating significant correlations with longitudinal changes in disease activity and functional status.

RESUMO Objetivo: Propor um novo sistema de escore ultrassonográfico das articulações da mão e punho (US10) para a avaliação de pacientes com artrite reumatoide (AR) e correlacionar o US10 com variáveis clínicas, laboratoriais e funcionais. Métodos: Foram submetidos 48 pacientes com AR em fase inicial a avaliações clínicas e laboratoriais, bem como a exames cegos de ultrassom (US) no início do estudo e com 3, 6 e 12 meses. O sistema US10 proposto envolveu a avaliação do punho e das articulações metacarpofalângicas e interfalângicas proximais do segundo e terceiro dígitos. O escore consistiu em parâmetros inflamatórios (proliferação sinovial [PS], Power Doppler [PD] e tenossinovite [TN]) e parâmetros de danos articulares (erosão óssea [EO] e danos na cartilagem [DC]). PS, PD, EO e DC foram pontuados qualitativamente (0 a 1) e semiquantitativamente (graus 0 a 3). A tenossinovite foi pontuada como presença/ausência. A avaliação envolveu também o escore 28-Joint Disease Activity (DAS28), o Health Assessment Questionnaire (HAQ) e o nível de proteína C-reativa (PCR). Resultados: A duração média dos sintomas foi de 7,58 ± 3,59 meses. Foram encontradas correlações estatisticamente significativas (p < 0,05) entre os parâmetros de inflamação e a PCR no início do estudo e entre as mudanças nessas variáveis ao longo do estudo. Foram encontradas também correlações significativas (p < 0,05) entre o escore DAS28 e a PD e TN no início do estudo e entre as mudanças no escore DAS28 e PS e TN em todo o seguimento. Além disso, foram encontradas correlações significativas entre as mudanças no escore dos parâmetros de inflamação e no escore HAQ ao longo do seguimento. Conclusão: O sistema de escore US10 proposto provou ser uma ferramenta útil para monitorar a inflamação e o dano articular em pacientes com AR em fase inicial, demonstra correlações significativas com as alterações longitudinais na atividade da doença e no estado funcional.