Participating as a research team during the COVID-19 pandemic benefits mental health of undergraduate medical students in Brazil.

During the COVID-19 pandemic, undergraduate medical students (UMS) exposed to isolation, social distancing and complete or partial face-to-face educational activities interruption may present increased stress, depression and anxiety. This study was undertaken to evaluate if, during isolation, UMS involved in online group activities as investigators of a research project (volunteer group) would present better mental health than their colleagues, not involved in that research (control group). A Web-based survey, via the Google Forms platform, including details on demographic data, life habits, previous health conditions, worries with the COVID-19 pandemic, sleep pattern modifications and depression, anxiety and mental stress, using the DASS-21 (Depression, Anxiety and Stress Scale) was implemented from 20 July to 31 August 2020. Statistical analysis was performed using the SPSS version 20.0. A p-value <0.05 was significant. A total of 684 UMS were included, 228 as a volunteer group and 456 as a control group. Mean age was 23.15 (3.16) years. The groups were paired for age, gender, ethnicity, life habits and previous health conditions. Older age, male gender, participation in the research project, unchanged sleep pattern during the pandemic, lack of fear from getting the COVID-19 and lack of previous health conditions were associated with lower DASS21 scores (better mental health). Participating as investigators of a research project foreseeing frequent interaction with patients, colleagues and professors (other investigators) lead to better mental health during the COVID-19 quarantine in Brazil.

Análise vacinal de estudantes em uma faculdade de medicina / Analysis of the vaccination status of students at a medical school / Análisis de vacunación de estudiantes de una facultad de medicina

Objetivo: O estudo analisa a situação vacinal dos estudantes de medicina de uma faculdade do interior de São Paulo, além de verificar seu conhecimento em relação à imunização. Método: Foi realizada a análise na carteira vacinal de 277 estudantes de medicina e disponibilizado um questionário autoaplicável. A análise dos dados foi conduzida de maneira estatística descritiva para interpretação dos resultados. Resultados: Verificou-se que mais da metade dos estudantes apresentam carteiras vacinais desatualizadas e poucos conhecem quais vacinas são indicadas aos profissionais de saúde, embora mais da metade dos estudantes reconheça o risco de contágio e transmissão de doenças relacionadas ao esquema vacinal incompleto. Conclusão: Esses resultados demonstram a necessidade de conscientização dos acadêmicos de medicina quanto à atualização de seus cartões vacinais e do aprofundamento do conhecimento e domínio sobre o tema vacinação (AU).

Objective: The study analyzes the vaccination status of medical students at a college in the interior of São Paulo, in addition to verifying their knowledge regarding immunization. Method: An analysis was carried out on the vaccination records of 277 medical students and a self-administered questionnaire was made available. Data analysis was conducted in a descriptive statistical manner to interpret the results. Results: It was found that more than half of the students have outdated vaccination records and few know which vaccines are indicated to health professionals, although more than half of the students recognize the risk of contagion and transmission of diseases related to an incomplete vaccination schedule. Conclusion: These results demonstrate the need for medical students to be aware of updating their vaccination cards and deepening their knowledge and mastery of the topic of vaccination (AU).

Objetivo: El estudio analiza el estado de vacunación de estudiantes de medicina de una facultad del interior de São Paulo, además de verificar sus conocimientos sobre vacunación. Método: Se realizó un análisis de los registros de vacunación de 277 estudiantes de medicina y se dispuso de un cuestionario autoadministrado. El análisis de datos se realizó de manera estadística descriptiva para interpretar los resultados. Resultados: Se encontró que más de la mitad de los estudiantes tienen cartilla de vacunación desactualizada y pocos saben qué vacunas están indicadas a los profesionales de la salud, aunque más de la mitad de los estudiantes reconocen el riesgo de contagio y transmisión de enfermedades relacionadas con un esquema de vacunación incompleto. Conclusión: Estos resultados demuestran la necesidad de que los estudiantes de medicina estén atentos a la actualización de sus carnés de vacunación y profundicen en el conocimiento y dominio del tema de la vacunación (AU).

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

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).

Serum biomarker profile orchestrating the seroconversion status of patients with autoimmune diseases upon planned primary 17DD Yellow fever vaccination.

The present study aimed to investigate whether the serum biomarkers of immune response orchestrate the seroconversion status in patients with autoimmune diseases (AID) upon planned primary 17DD-YF vaccination. For this purpose a total of 161 individuals were enrolled in a prospective study, including patients with Rheumatoid Arthritis (RA = 38), Spondyloarthritis (SpA = 51), Systemic Lupus Erythematosus (SLE = 21) and Sjögren's Syndrome (SS = 30) along with a group of healthy controls (HC = 21). Analysis of plaque reduction neutralization test (PRNT) titers and seropositivity rates along with the 17DD-YF viremia and serum biomarkers were carried out at distinct time points (D0/D3-4/D5-6/D7/D14-28). The results demonstrated an overall lower PRNT titer and seropositivity rate (170 vs. 448; 77 vs. 95%) in AID as compared to HC, especially in SpA and SLE subgroups. No significant differences were observed in the viremia levels amongst groups. In general, a more prominent serum biomarker response was observed in AID as compared to HC, throughout the timeline kinetics. Remarkably, AID/PRNT(-) exhibited higher levels of several biomarkers at baseline as compared to AID/PRNT+. Moreover, while AID/PRNT(+) exhibited earlier increase in serum biomarkers at D3-4/D5-6, the AID/PRNT(-) displayed higher response at later time points (D7/D14-D28). Of note, a synchronic increase of IFN-γ at the peak of viremia (D5-6) was observed in HC and AID/PRNT(+) groups, whereas a later asynchronous IFN-γ response was reported for AID/PRNT(-) at D7. The biomarker profile tends to deflate at post-vaccination timeline, highlighting a putative immunomodulatory effect of live attenuated 17DD-YF vaccine in AID/PRNT(+), but not in AID/PRNT(-). Altogether these data suggested that inflammatory status prior vaccination, low IFN-γ at viremia peak and the occurrence of asynchronous biomarker storm after 17DD-YF vaccination may orchestrate the lack of neutralizing antibody response γ.

Effects of Participating in a Research Project During the COVID-19 Pandemic on Medical Students' Educational Routines and Mental Health: Protocol for a Web-Based Survey Study.

BACKGROUND: The COVID-19 pandemic has resulted in social isolation, which has a potential negative impact on the educational routines (eg, the suspension of face-to-face appointments) and mental health of medical students. The Mario Pinotti II (MPII) study is a 24-week observational study that conducted scheduled telephone calls every 2 weeks to verify the occurrence of COVID-19 in patients with rheumatic diseases on chronic hydroxychloroquine therapy (from March 29, 2020, to September 30, 2020). The effects of voluntarily participating in a research project (ie, one that involves interactions via telephone contact with patients, professors, rheumatologists, and colleagues) on the daily lives and mental health of medical students requires evaluation. OBJECTIVE: As medical students are professionals in training and have a high level of responsibility in terms of handling the emotional and physical aspects of several diseases, this study aims to evaluate the impacts of the COVID-19 pandemic and participation in the MPII study on the educational routines and mental health of medical students. METHODS: A web-based survey was carried out to perform a cross-sectional comparative assessment of medical students who participated in the MPII study and their colleagues who were not involved in the MPII study. Participants from both groups were matched based on sex, age, and medical school. The web questionnaire was developed by a panel composed of graduate medical students, rheumatologists, medical school professors, and a psychology professor. The questionnaire included details on demographic and life habits data and evaluated participants' impressions of the MPII study and the impact of the COVID-19 pandemic on their educational routines and medical training. In addition, depression, anxiety, and stress were evaluated using the Brazilian version of the Depression, Anxiety, and Stress Scale (DASS)-21, and currently, the DASS-21 scores are grouped as those that indicate a low, moderate, or high risk of mental distress. This project was approved by the Federal University of São Paulo Ethics Committee (CAAE: 34034620.0.0000.5505). RESULTS: Data were collected from both medical student groups from July 20 to August 31, 2020. Data extraction was completed in September 2020. The data analysis is ongoing. We expect the results to be published in the first semester of 2021. CONCLUSIONS: This study will provide insight into the effects of participating in a research project on depression, anxiety, and stress, which will be determined by applying the DASS-21 to a large sample of Brazilian undergraduate medical students. We will also evaluate the impact of the COVID-19 pandemic on medical students' educational routines and medical training. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24617.

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).

Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in patients with juvenile dermatomyositis: a real-world multicentre study.

BACKGROUND: Concerns about the safety and efficacy of vaccines in patients with autoimmune diseases (AID) have led to contradictions and low vaccination coverage in this population, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccines have been recommended for immunocompromised patients, there is still a lack of data to support its use for AID patients, such as juvenile dermatomyositis (JDM) patients. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in a cohort of JDM patients. METHODS: JDM patients aged from 9 to 20 years and healthy controls (HC) were enrolled to receive a 3-dose schedule of qHPV vaccine from March/2014 to March/2016. Study visits were performed before the first dose, 1 month after the second and third doses, and 6 months after the third dose. Participants completed a diary of possible adverse events for 14 days following each dose of vaccination (AEFV). Disease activity and current therapy were analyzed at each visit for JDM patients. In addition, serum samples from all participants were collected to test antibody concentrations against HPV16 and 18 at each visit. Participant recruitment was conducted in ten Brazilian centres. From 47 eligible JDM patients and 41 HC, 42 and 35, respectively, completed the 3-dose schedule of the vaccine, given that five JDM patients and two HC had received doses prior to their inclusion in the study. RESULTS: The AEFVs presented by the participants were mild and in general did not differ between JDM and HC groups. No severe AEFVs were related to the vaccination. Disease activity was stable, or even improved during the follow-up. One month after the third dose of the vaccine the JDM group presented seropositivity of 100% for HPV16 and 97% for HPV18, similarly to the HC group, who presented 100% for both serotypes (p = 1.000). Six months after the third dose the seropositivity for the patient group was 94% for both HPV types. CONCLUSIONS: The HPV vaccination in this cohort of JDM patients was safe and immunogenic. Since the seropositivity against HPV16 and 18 was very high after the 3-dose schedule, this regimen should be recommended for JDM patients. TRIAL REGISTRATION: Brazilian Clinical Trials Registry, number: RBR-9ypbtf . Registered 20 March 2018 - Retrospectively registered.

Planned Yellow Fever Primary Vaccination Is Safe and Immunogenic in Patients With Autoimmune Diseases: A Prospective Non-interventional Study.

Yellow Fever (YF) vaccination is suggested to induce a large number of adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in patients with AID. This prospective non-interventional study conducted between March and July, 2017 assessed the safety and immunogenicity of planned 17DD-YF primary vaccination in patients with AID. Adult patients with AID (both sexes) were enrolled, along with healthy controls, at a single hospital (Vitória, Brazil). Included patients were referred for planned vaccination by a rheumatologist; in remission, or with low disease activity; and had low level immunosuppression or the attending physician advised interruption of immunosuppression for safety reasons. The occurrence of AE, neutralizing antibody kinetics, seropositivity rates, and 17DD-YF viremia were evaluated at various time points (day 0 (D0), D3, D4, D5, D6, D14, and D28). Individuals evaluated (n = 278), including patients with rheumatoid arthritis (RA; 79), spondyloarthritis (SpA; 59), systemic sclerosis (8), systemic lupus erythematosus (SLE; 27), primary Sjögren's syndrome (SS; 54), and healthy controls (HC; 51). Only mild AE were reported. The frequency of local and systemic AE in patients with AID and HC did not differ significantly (8 vs. 10% and 21 vs. 32%; p = 1.00 and 0.18, respectively). Patients with AID presented late seroconversion profiles according to kinetic timelines of the plaque reduction neutralization test (PRNT). PRNT-determined virus titers (copies/mL) [181 (95% confidence interval (CI), 144-228) vs. 440 (95% CI, 291-665), p = 0.004] and seropositivity rate (78 vs. 96%, p = 0.01) were lower in patients with AID after 28 days, particularly those with SpA (73%) and SLE (73%), relative to HC. The YF viremia peak (RNAnemia) was 5-6 days after vaccination in all groups. In conclusion, consistent seroconversion rates were observed in patients with AID and our findings support that planned 17DD-YF primary vaccination is safe and immunogenic in patients with AID.

Correction to: Mortality burden associated with all-cause pneumonia among adults with autoimmune inflammatory rheumatic diseases, human immunodeficiency virus infection, and malignancies: a population-based comparative study for informed decision-making in public health policies.

The Table 2 in the original version of the above article was incorrectly presented. The data where misaligned during publication process.].

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases.

BACKGROUND: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. CONCLUSION: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV.

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases

BACKGROUND: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving >/=80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. CONCLUSION: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting Vaccination practices. We recommended a shared decision-making approach on taking or not the YFV

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases

Abstract Background: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Main body of the abstract: Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. Conclusion: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV.

Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications / Sinais e sintomas sugestivos de doenças reumáticas como primeira manifestação de doenças neoplásicas na infância: implicações no diagnóstico e prognóstico

ABSTRACT Objective: To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Methods: Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Results: Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. Conclusion: The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition.

RESUMO Objetivo: Avaliar a prevalência e descrever as principais manifestações clínicas, os exames complementares, o tratamento e a evolução de crianças com doenças neoplásicas atendidas inicialmente em um serviço terciário de reumatologia pediátrica. Métodos: Analisamos retrospectivamente o prontuário médico de pacientes com diagnóstico definitivo de neoplasia, identificados entre 250 casos novos atendidos no ambulatório de reumatologia pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP, de julho de 2013 a julho de 2015. Resultados: Dos 250 pacientes, cinco (2%) tiveram diagnóstico de neoplasia. Desses, 80% apresentavam sintomas constitucionais, principalmente perda de peso e astenia e 60% artrite. Inicialmente, todos apresentavam pelo menos uma série alterada no hemograma, 80% aumento da desidrogenase lática (LDH) e 60% mielograma confirmatório. Dois pacientes necessitaram de biópsia, óssea e de intestino, para o diagnóstico final. Artrite idiopática juvenil foi o diagnóstico inicial mais frequente. Os diagnósticos definitivos foram leucemia linfoide aguda (dois casos), leucemia mieloide aguda-M3, neuroblastoma e linfoma (um caso cada). Dos pacientes estudados, três (60%) estão em remissão. Dois pacientes foram a óbito (40%), um deles com uso prévio de corticoide. Conclusão: Os sintomas constitucionais e musculoesqueléticos comuns às doenças reumáticas e neoplásicas podem retardar o diagnóstico e consequentemente agravar o prognóstico das neoplasias. O hemograma inicial, assim como o mielograma, podem estar normais no quadro inicial das neoplasias. Dessa forma, o seguimento clínico evolutivo desses casos torna-se imperativo e o tratamento, principalmente com corticoides, deve ser retardado até definição diagnóstica.

Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications.

OBJECTIVE: To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. METHODS: Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. RESULTS: Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. CONCLUSION: The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition.

Uveitis in childhood-onset systemic lupus erythematosus patients: a multicenter survey.

The aim of this study is to assess uveitis prevalence in a large cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. A retrospective multicenter cohort study including 852 cSLE patients was performed in ten pediatric rheumatology centers (Brazilian cSLE group). An investigator meeting was held and all participants received database training. Uveitis was diagnosed through clinical assessment by the uveitis expert ophthalmologist of each center. Patients with and without uveitis were assessed for lupus clinical/laboratory features and treatments. Uveitis was observed in 7/852 cSLE patients (0.8%). Two of them had ocular complications: cataract and irreversible blindness in one patient and retinal ischemia with subsequent neovascularization and unilateral blindness in another. Uveitis was identified within the first 6 months of cSLE diagnosis in 6/7 patients (86%). Comparison of a subgroup of cSLE patients with (n = 7) and without uveitis (n = 73) and similar length of disease duration showed that patients with uveitis had increased SLEDAI-2K score (19 vs. 6; p < 0.01). In addition, fever (71 vs. 12%; p < 0.01), lymphadenopathy (29 vs. 1.4%; p = 0.02), arthritis (43 vs. 7%; p = 0.02), and use of intravenous methylprednisolone (71 vs. 22%; p = 0.01) were higher in cSLE patients with uveitis, as compared to those without this manifestation, respectively. Presence of fever was significantly associated with uveitis, independently of SLEDAI scores or use of intravenous methylprednisolone pulses, as shown by adjusted regression analysis (adjusted prevalence ratio 35.7, 95% CI 2.4-519.6; p < 0.01). Uveitis was a rare and initial manifestation of active cSLE patients. Early recognition is essential due to the possibility of irreversible blindness.

New strategy for testing efficacy of immunotherapeutic compounds for diabetes in vitro.

BACKGROUND: The valuable role of immunotherapy in treating autoimmune diseases is increasingly recognized by those involved in the research and clinical application of new biopharmaceuticals products. However, many aspects related to the mechanisms of immune-modulated therapies remain to be elucidated in order to explore fully the emerging opportunities. The non-obese diabetic NOD mouse develops insulin-dependent diabetes mellitus spontaneously as a consequence of an autoimmune process in the presence of pathogenic CD4(+) T cells that typically exhibit Th17 cell phenotypes. The change of a Th17 phenotype into a pattern of regulatory T cells (Treg) is extremely important in controlling autoimmune diseases. Heat shock proteins (HSPs) are stress-induced proteins with immunoregulatory properties. In the current study, the capacity of Hsp65 and Hsp70 mycobacterial HSPs and a constructed DNA encoded Hsp65 (DNAhsp65) to transform the pattern of the immune response from Th17 into Treg cells has been studied in vitro using co-cultures of antigen presenting cells (APCs) and T cells in NOD mice. RESULTS: Cells harvested from NOD mice and cultured for 48 h (without immunoregulatory compounds) presented with Th1/Th17 patterns and secretions of IL-6, IFN-γ, IL-10 and IL-17 cytokines. The cultured cells from the non-diabetic BALB/C mice exhibited a Th1 pattern and the production of IL 6 and IFN-γ secretions. An up-regulation was observed in the supernatants from the co-cultures of NOD cells that were stimulated with DNAhsp65, Hsp65 or Hsp70 through increased levels of IL-10 secretion and the suppression of IL-6, IFN-γ and IL-17 production. In addition, immunoregulation was demonstrated through IL-17 suppression in the co-culture stimulated by the specific insulin antigen. Moreover, an increase of immunoregulatory compounds were observed in the co-culture through the expression of CD11b(+)CD86(+) activation markers on APCs, as well as the frequency of Treg cells expressing CD4(+)CD3(+) and CD4(+)CD25(hi). CONCLUSIONS: The in vitro observation of Th17 cells differentiating into Tregs in NOD mice could raise the hypothesis that the immune regulatory activity of HSPs could be an efficient strategy for diabetes prevention and treatment.

2012 Brazilian Society of Rheumatology Consensus on vaccination of patients with rheumatoid arthritis.

OBJECTIVE: To elaborate recommendations to the vaccination of patients with rheumatoid arthritis (RA) in Brazil. METHOD: Literature review and opinion of expert members of the Brazilian Society of Rheumatology Committee of Rheumatoid Arthritis and of an invited pediatric rheumatologist. RESULTS AND CONCLUSIONS: The following 12 recommendations were established: 1) Before starting disease-modifying anti-rheumatic drugs, the vaccine card should be reviewed and updated; 2) Vaccines against seasonal influenza and against H1N1 are indicated annually for patients with RA; 3) The pneumococcal vaccine should be indicated for all patients with RA; 4) The vaccine against varicella should be indicated for patients with RA and a negative or dubious history for that disease; 5) The HPV vaccine should be considered for adolescent and young females with RA; 6) The meningococcal vaccine is indicated for patients with RA only in the presence of asplenia or complement deficiency; 7) Asplenic adults with RA should be immunized against Haemophilus influenzae type B; 8) An additional BCG vaccine is not indicated for patients diagnosed with RA; 9) Hepatitis B vaccine is indicated for patients with RA who are negative for antibodies against HBsAg; the combined hepatitis A and B vaccine should be considered; 10) Patients with RA and at high risk for tetanus, who received rituximab in the preceding 24 weeks, should undergo passive immunization with tetanus immunoglobulin in case of exposure; 11) The YF vaccine is contraindicated to patients with RA on immunosuppressive drugs; 12) The above described recommendations should be reviewed over the course of RA.