Puberty in girls with Prader-Willi syndrome: cohort evaluation and clinical recommendations in a Latin American tertiary center.

Introduction: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypothalamic-pituitary deficiencies including hypogonadism. In girls with PWS, hypogonadism can present early in childhood, leading to genital hypoplasia, delayed puberty, incomplete pubertal development, and infertility. In contrast, girls can present with premature activation of the adrenal axis leading to early pubarche and advanced bone age. We aim to evaluate the progression of puberty and adrenarche signals in girls with PWS. Methodology: A longitudinal retrospective cohort study included girls with PWS followed at a Pediatric Endocrinology Outpatient Clinic in a Tertiary University Hospital in Sao Paulo, Brazil from 2002 to 2022. Data collected via chart review included clinical information on birth history, breast and pubic hair Tanner stages, presence of genital hypoplasia, age at menarche, regularity of menstrual cycles, body mass index (BMI) z-score, final height, age of initiation of estrogen replacement and growth hormone replacement, as well as results for PWS genetic subtype; biochemical investigation (LH, FSH, estradiol, DHEA-S); radiographic bone age and pelvic ultrasound. Results: A total of 69 girls were included in the study and the mean age of puberty onset was 10.2 years in those who started puberty after the age of 8 years. Breast Tanner stage IV was reached by 29.1% girls at a mean age of 14.9 years. Spontaneous menarche was present in 13.8% and only one patient had regular menstrual cycles. Early adrenarche was seen in 40.4% of cases. Conclusion: Our study demonstrated in a large sample that girls with PWS often present with delayed onset of puberty despite frequent premature adrenarche. Based on our results, we suggest an estrogen replacement protocol for girls with PWS to be started at the chronological age or bone age of 12-13 years, taking into consideration the uterus size. Further prospective studies are needed.

Sicca syndrome/Sjögren's disease associated with cancer immunotherapy: a narrative review on clinical presentation, biomarkers, and management.

INTRODUCTION: Almost one-quarter of immune checkpoint inhibitor (ICI) recipients experience sicca syndrome, while Sjögren's disease (SjD) is estimated at 0.3-2.5%, possibly underreported. AREAS COVERED: This narrative review (Medline/Embase until January/31/2024) addresses the pathophysiology, incidence, demographic/clinical features, biomarkers, labial salivary gland biopsy (LSGB), fulfillment of the idiopathic SjD (iSjD) classificatory criteria, differential diagnosis, and management of sicca syndrome/SjD associated with ICIs. EXPERT OPINION: SjD associated with ICIs is underdiagnosed, since studies that performed the mandatory SjD investigation identified that 40-60% of patients with sicca syndrome associated with ICIs meet the iSjD classificatory criteria. LSGB played a fundamental role in recognizing these cases, as most of them had negative anti-Ro/SS-A antibody. Despite the finding of focal lymphocytic sialoadenitis in LSGB samples mimicking iSjD, immunohistochemical analysis provided novel evidence of a distinct pattern for sicca syndrome/SjD associated with ICIs compared to iSjD. The former has scarcity of B lymphocytes, which are a hallmark of iSjD. Additionally, patients with sicca syndrome/SjD associated with ICIs have demographical/clinical/serological and treatment response dissimilarities compared to iSjD. Dryness symptoms are more acute in the former than in iSjD, with predominance of xerostomia over xerophthalmia, and partial/complete response to glucocorticoids. Dryness symptoms in ICI-treated patients warrant prompt SjD investigation.

Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis.

OBJECTIVE: To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA, sJIA). METHODS: Patients with pJIA or sJIA from two open-label, 52-week phase 1 b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight-based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years and safety for up to 5 years in the LTE. RESULTS: Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 µg/ml; sJIA, ∼75 µg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 kg and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection). CONCLUSION: Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile.

Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review.

BACKGROUND: Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. METHOD: A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. RESULTS: Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. CONCLUSION: Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Assessment of hydroxychloroquine blood levels in Sjögren's disease patients: drug adherence and clinical associations.

Hydroxychloroquine (HCQ) has been used to treat Sjögren's disease (SjD) patients. However, there are no studies evaluating drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. The relationship of HCQ blood levels with glandular/extraglandular disease parameters was also poorly assessed. This cross-sectional observational study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5 mg/kg/day, actual weight) for at least 3 months before study inclusion. HCQ blood levels were quantified by high-performance liquid chromatography coupled to mass spectrometry. Adherence was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory, Ocular Surface Disease Index, EULAR (European League Against Rheumatism) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, Schirmer's I test and non-stimulated/stimulated salivary flow rates. HCQ blood levels were 775.3(25.0-2,568.6)ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200ng/mL (non-adherent group); 11(14.9%), 200-499ng/mL (sub-therapeutic levels group); and 52(70.2%), ≥ 500ng/mL (adherent group). PR classified incorrectly all non-adherent/sub-therapeutic patients and 2/52(3.9%) adherent patients. Using MAT, the overall misclassification was 24/52(46.2%) in the adherent group, and were correctly identified 9/11(81.8%) patients in non-adherent and 7/11(63.6%) in sub-therapeutic groups. MAT sensitivity and specificity to identify non-adherent/sub-therapeutic patients were 72.7% and 53.9%, respectively. The three groups were comparable regarding glandular/extraglandular disease parameters (p > 0.05). The assessment of HCQ blood levels is a promising tool for evaluating drug adherence in SjD. This is particularly crucial as one-third of patients exhibited non-adherence/sub-therapeutic levels, and neither PR nor MAT reliably identified these patients.

Autoinflammatory diseases: a Latin American multicenter study according to age and sex / Doenças autoinflamatórias: um estudo multicêntrico latino-americano de acordo com o sexo e a idade

ABSTRACT Objective: To evaluate autoinflammatory diseases (AID) according to age at diagnosis and sex, and response to therapy in a large population. Methods: This is a cross-sectional observational study of a Latin American registry using a designed web system for data storage, collected between 2015 and 2018. Any altered findings during follow-up were recorded. The forms were translated into Portuguese and Spanish, including demographic, clinical, laboratory, genetic and treatment characteristics. Results: We included 152 patients, 51.3% male and 75% Caucasian. The median age at disease onset was 2.1 years (0-15.6 years) and median age at diagnosis 6.9 years (0-21.9 years); 111 (73%) were children (0-9 years old), and 41 (27%) were adolescents and young adults (AYA) (10-21 years old). Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) occurred in 46/152 (30%), chronic non-bacterial osteomyelitis (CNO) in 32/152 (21%), and familial Mediterranean fever (FMF) in 24/152 (15.7%). PFAPA was significantly higher in young children than in AYA (38.7% vs. 7.3%, p<0.001), while CNO were lower (13.5% vs. 41.5%, p<0.001). The frequency of females was significantly higher in CNO (28.4% vs. 14.1%, p=0.031) and lower in FMF (8.1% vs. 23.1%, p=0.011). The most used drugs were glucocorticoids, non-steroidal anti-inflammatory drugs (NSAID), and colchicine. Glucocorticoids and colchicine treatment were used in all AID with good to moderate response. However, cryopyrin-associated periodic syndromes (CAPS) seemed unresponsive to glucocorticoids. NSAIDs and methotrexate were the main medications used to treat CNO. Conclusions: Differences among AID patients were observed in the LA population regarding sex and age at disease diagnosis.

RESUMO Objetivo: Avaliar as doenças autoinflamatórias (DAI) de acordo com sexo e idade no momento do diagnóstico e a resposta terapêutica em uma grande população. Métodos: Este é um estudo observacional transversal de um registro latino-americano que usou um sistema de dados coletados entre 2015 e 2018. Quaisquer achados alterados ao longo do acompanhamento foram registrados. Os formulários foram traduzidos para os idiomas português e espanhol, incluindo características demográficas, clínicas, laboratoriais, genéticas e de tratamento. Resultados: Incluímos 152 pacientes, sendo 51,3% do sexo masculino e 75% da raça branca. A média de idade de início da doença foi de 2,1 anos (0-15,6 anos) e a média de idade de diagnóstico 6,9 anos (0-21,9 anos); 111 (73%) eram crianças (0-9 anos) e 41 (27%) adolescentes/adultos jovens (10-21 anos). A síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA) ocorreu em 46/152 (30%), osteomielite não bacteriana crônica (CNO) em 32/152 (21%) e febre familiar do Mediterrâneo (FMF) em 24/152 (15,7%). A PFAPA foi significativamente maior em crianças pequenas (38,7 vs. 7,3%, p<0,001), e a CNO, em adolescentes/adultos jovens (13,5 vs. 41,5%, p<0,001). A frequência do sexo feminino foi significativamente maior na CNO (28,4 vs. 14,1%, p=0,031) e menor na FMF (8,1 vs. 23,1%, p=0,011). Os medicamentos mais utilizados foram glicocorticoides, anti-inflamatórios não esteroidais (AINE) e colchicina. O tratamento com glicocorticoides e colchicina foi usado em todas as DAI com resposta boa a moderada. No entanto, as síndromes periódicas associadas à criopirina (CAPS) pareciam não responder aos glicocorticoides. AINE e metotrexato foram os principais medicamentos utilizados no tratamento da CNO. Conclusões: Diferenças de pacientes com DAI foram observadas na população latino-americana em pacientes agrupados por sexo e idade ao diagnóstico da doença.

Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review

Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR Classification Criteria for Granulomatosis with Polyangiitis in Children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in pediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of pediatric patients with GPA in 20 centers from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls (immunoglobulin A vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1), and Cogan's syndrome (n = 1)) with a median age of 17.8 and 15.2 years, respectively. Of patients with GPA, constitutional symptoms (85.7%) and ear-nose-throat involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (p= 0.229 and p= 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Impact of COVID-19 on physical and mental functioning in adolescents with disabilities in a sports nongovernmental organization / Impacto da COVID-19 no funcionamento físico e mental de adolescentes com deficiência em organização não governamental esportiva

Abstract Objective: This study aimed to assess physical and mental health, and health-related quality of life (HRQL) parameters in adolescents with physical disabilities enrolled in a sports nongovernmental organization (NGO) versus adolescents without disabilities during coronavirus disease 2019 (COVID-19) pandemic. Methods: This cross-sectional study included 30 adolescents with disabilities and 86 adolescents without disabilities who responded to an online questionnaire with sociodemographic data and self-rated healthcare routine information during the COVID-19 quarantine. Validated self-report versions of the Strengths and Difficulties Questionnaire (SDQ), Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0), Pittsburgh Sleep Quality Index (PSQI), and Pediatric Outcome Data Collection Instrument (PODCI) were also applied. Results: The median of emotional [4 (0-10) vs. 5 (0-10), p=0.018] and prosocial [7 (0-10) vs. 9 (3-10), p=0.006] problems was lower in adolescents with disabilities versus adolescents without disabilities. Adolescents with disabilities had significantly lower global function [68 (21-99) vs. 94 (67-100), p<0.001] and higher happiness scores in the PODCI scale [90 (65-100) vs. 80 (0-100), p=0.016] compared to controls. Logistic regression analysis demonstrated that physical activity/week (OR=1.03; 95%CI 1.01-1.05, p=0.002) was higher in adolescents with disabilities compared to adolescents without disabilities. However, housework activities (OR=0.14; 95%CI 0.04-0.43, p=0.001) and screen time ≥3 h/day (OR=0.09; 95%CI 0.02-0.38, p=0.001) were lower in adolescents with disabilities compared to adolescents without disabilities. Conclusion: Adolescents with disabilities attending a sports NGO were not at higher risk of adverse health-related indicators; despite showing reduced physical function, they reported more physical activity, higher happiness, and less screen time compared to adolescents without disabilities during the COVID-19 pandemic.

Resumo Objetivo: Avaliar os parâmetros de saúde física e mental, de qualidade de vida relacionada à saúde (QVRS), em adolescentes com deficiência física matriculados em organização não governamental (ONG) esportiva vs. em adolescentes sem deficiência, durante a pandemia da doença do coronavírus 2019 (COVID-19). Métodos: Este estudo transversal incluiu 30 adolescentes com deficiência e 86 adolescentes sem deficiência que responderam a questionário online com dados sociodemográficos e informações de rotina de saúde autoavaliadas durante a quarentena da COVID-19. Versões validadas de autorrelato do Strengths and Difficulties Questionnaire (SDQ), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), Pittsburgh Sleep Quality Index (PSQI) e Pediatric Outcome Data Collection Instrument (PODCI) também foram aplicadas. Resultados: A mediana de problemas emocionais [4(0-10) vs. 5(0-10),p=0,018] e pró-social [7(0-10) vs. 9(3-10),p=0,006] foi menor em adolescentes com deficiência vs. adolescentes sem deficiência. Adolescentes com deficiência tiveram função global significantemente inferior [68(21-99) vs. 94(67-100),p <0,001] e pontuações de felicidade mais altas do PODCI [90(65-100) vs. 80(0-100),p=0,016] em comparação com o grupo sem deficiências. A análise de regressão logística demonstrou que a atividade física/semana (odds ratio — OR=1,03; intervalo de confiança — IC95%=1,01-1,05,p=0,002) foi maior nos adolescentes com deficiência. No entanto, atividades domésticas (OR=0,14; IC95%=0,04-0,43,p=0,001) e tempo de tela ≥3 horas/dia (OR=0,09; IC95%=0,02-0,38,p=0,001) foram menores nos adolescentes com deficiência. Conclusões: Os adolescentes com deficiência que frequentam uma organização não governamental (ONG) esportiva não tiveram maior risco de apresentar indicadores adversos à saúde; apesar de apresentarem função física reduzida, relataram mais atividade física, maior felicidade e menos tempo de tela em comparação com adolescentes sem deficiência durante a pandemia da COVID-19.

Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition

Abstract Background Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. Methods Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. Results ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations. Conclusion We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).

Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus

Abstract Introduction Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. Objective To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. Methods 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/ INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. Results JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 ( p = 0.713), as well as between patients with and without current use of prednisone ( p = 0.420), azathioprine ( p = 1.0), mycophenolate mofetil ( p = 0.185), and methotrexate ( p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups ( p > 0.05). Conclusion This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www.clinicaltrials.gov , NCT03540823).

Physical and mental health impacts during COVID-19 quarantine in adolescents with preexisting chronic immunocompromised conditions

Abstract Objective: To evaluate physical and mental health indicators in adolescents with preexisting chronic immunocompromised conditions during coronavirus disease 2019 (COVID-19) quarantine. Methods: A cross-sectional study included 355 adolescents with chronic conditions and 111 healthy adolescents. An online self-rated survey was used to investigate socio-demographic features, healthcare routine, and the quarantine impact on physical and mental health. The validated self-reported version of the Strengths and Difficulties Questionnaire (SDQ) was also applied. Results: The median of age [14 (10-18) vs. 15 (10-18) years, p = 0.733] and frequencies of female (61% vs. 60%, p = 0.970) were similar between adolescents with preexisting chronic conditions and healthy adolescents during quarantine of COVID-19 pandemic. The frequencies of abnormal total difficulties score of SDQ were similar in patients and controls (30% vs. 31%, p = 0.775). Logistic regression analysis showed that being female (OR = 1.965; 95% CI = 1.091-3.541, p = 0.024), fear of underlying disease activity/complication (OR = 1.009; 95%CI = 1.001-1.018, p = 0.030) were associated with severe psychosocial dysfunction in adolescents with chronic conditions, whereas school homework (OR = 0.449; 95% CI = 0.206-0.981, p = 0.045) and physical activity (OR = 0.990; 95% CI = 0.981-0.999, p = 0.030) were protective factors. Further analysis of patients with chronic immunocompromised conditions and previous diagnosis of mental disorders (9%) compared with patients without diagnosis showed higher median of total difficulties score (p = 0.001), emotional (p = 0.005), conduct (p = 0.007), peer problems (p = 0.001) and hyperactivity (p = 0.034) in the former group. Conclusion: Adolescents with preexisting chronic immunocompromised conditions during COVID-19 quarantine were not at higher risk of adverse health indicators. Being female, fear of underlying disease activity/complication, and household members working outside of the home were relevant issues for adolescents with preexisting chronic conditions. This study reinforces the need to establish mental health strategies for teens with chronic conditions, particularly during the pandemic.

Idiopathic musculoskeletal pain, musculoskeletal pain syndromes, and use of electronic devices in adolescents with asthma

Abstract Objective: To evaluate idiopathic musculoskeletal pain, musculoskeletal pain syndromes, and use of electronic devices in adolescents with asthma and healthy controls. Methods: Cross-sectional study was conducted on 150 asthmatic adolescents and 300 controls. Adolescents completed a self-administered questionnaire regarding painful symptoms, use of electronic devices, and physical activity. Seven musculoskeletal pain syndromes were evaluated, and Asthma Control Test (ACT) was assessed. Results: Musculoskeletal pain (42% vs. 61%, p = 0.0002) and musculoskeletal pain syndromes (2.7% vs. 15.7%, p = 0.0006) were significantly lower in asthmatic adolescents than in controls. The frequency of pain in the hands and wrists was reduced in asthmatic than in controls (12.6% vs. 31.1%, p = 0.004), in addition to cell phone use (80% vs. 93%, p < 0.0001), simultaneous use of at least two electronic media (47% vs. 91%, p < 0.0001), myofascial syndrome (0% vs. 7.1%, p = 0.043), and tendinitis (0% vs. 9.2%, p = 0.008). Logistic regression analysis, including asthma with musculoskeletal pain as the dependent variable, and female sex, ACT > 20, simultaneous use of at least two electronic devices, cell phone use, and weekends and weekdays of cell phone use, as independent variables, showed that female sex (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.929-6.316; p = 0.0009) and ACT ≥ 20 (OR, 0.194; 95% CI, 0.039-0.967; p = 0.045) were associated with asthma and musculoskeletal pain (Nagelkerke R2 = 0.206). Conclusion: Musculoskeletal pain and musculoskeletal pain syndromes were lower in adolescents with asthma. Female sex was associated with musculoskeletal pain in asthmatic, whereas patients with asthma symptoms and well-controlled disease reported a lower prevalence of musculoskeletal pain.

SARS-CoV-2 and rhinovirus infections: are there differences in clinical presentation, laboratory abnormalities, and outcomes in the pediatric population?

ABSTRACT This study aims to assess COVID-19 and other respiratory viruses in pediatric patients. Between April 17 and September 30, 2020, we collected 1,566 respiratory samples from 1,044 symptomatic patients who were younger than 18 years old to assess SARS-CoV-2 infection. Of these, 919 were analyzed for other respiratory pathogens (ORP). Patients with laboratory-confirmed COVID-19 or ORP were included. We evaluated 76 pediatric COVID-19 infections and 157 other respiratory virus infections. Rhinovirus occurred in 132/157 (84%). COVID-19 patients who were significantly older, had more fevers, headaches and pneumonia than those with ORP. The median white blood cell count was lower in patients with SARS-CoV-2 than in those with ORP (6,470 versus 8,170; p=0.02). COVID-19 patients had significantly worse symptoms than those with ORP.

Nonsexual violence against children and adolescents: a study in a Latin American tertiary and university hospital / Violência não sexual contra crianças e adolescentes: um estudo em um hospital universitário e terciário da América Latina

Abstract Objective: The objective of this study was to assess interpersonal nonsexual violence against children and adolescents in a tertiary university hospital. Methods: A cross-sectional study was performed in 240 patients under nonsexual violence situation for 15 consecutive years. Data analyses included demographic data, hospital referral site, type and author of nonsexual violence, legal referral, laboratorial and imaging examinations, and outcomes. Results: Nonsexual violence situation was diagnosed in 240 (0.1%) of 295,993 patients for 15 years: 148 (61.7%) in children and 92 (38.3%) in adolescents. Out of 240, the most frequent types of violence were negligence in 156 (65.0%), physical 62 (25.8%), psychological/emotional aggression 52 (21.7%), Munchausen by proxy syndrome 4 (1.7%), and bullying/cyberbullying in 3 (1.3%). Out of 123, the most common pediatric chronic conditions were chronic kidney disease 24 (19.5%), human immunodeficiency virus 14 (11.4%), prematurity 9 (7.3%), cerebral palsy 8 (6.5%), and asthma 8 (6.5%). Further comparison between children versus adolescent under nonsexual violence situation revealed significant difference between the hospital referral sites. The frequency of patients under violence referred from outpatient clinics was significantly reduced in children versus adolescents (27.7 vs. 62%), whereas emergency department was higher in the former group (57.4 vs. 25.0%; p<0.001). All types of violence situations and pediatric chronic conditions were similar in both groups (p>0.05). Conclusions: Nonsexual violence against our pediatric population was rarely diagnosed in a tertiary hospital, mainly negligence, physical, and psychological/emotional aggression. Approximately two-thirds of violence diagnosis occurred in children, referred mainly by the emergency department. In contrast, approximately one-third of violence diagnosis occurred in adolescents, referred mostly by outpatient clinics.

Objetivo: Avaliar violência interpessoal não sexual contra crianças e adolescentes em um hospital universitário terciário. Métodos: Foi realizado um estudo transversal com 240 pacientes em situação de violência não sexual por 15 anos. A análise incluiu: dados demográficos, local de referência do hospital, tipo e autor da violência, encaminhamento legal, exames laboratoriais e de imagem, e desfechos graves. Resultados: Situações de violência não sexual foram diagnosticadas em 240 de 295.993 (0,1%) pacientes durante os 15 anos do período: 148/240 (61,7%) em crianças e 92/240 (38,3%) em adolescentes. Os tipos de violências mais frequentes foram negligência em 156/240 (65,0%), violência física 62/240 (25,8%), agressão psicológica/emocional 52/240 (21,7%), síndrome de Münchausen por procuração 4/240 (1,7%) e bullying/cyberbullying em 3/240 (1,3%). As condições crônicas pediátricas mais frequentes foram: doença renal crônica 24/123 (19,5%), vírus da imunodeficiência humana 14/123 (11,4%), prematuridade 9/123 (7,3%), paralisia cerebral 8/123 (6,5%) e asma 8/123 (6,5%). Comparações entre crianças e adolescentes em situação de violência não sexual revelaram que houve diferença significativa entre os locais de referência do hospital. A frequência de pacientes sob violência encaminhados de ambulatórios foi significantemente reduzida em crianças versus adolescentes (27,7 vs. 62%), enquanto encaminhamentos de pronto-socorro foram mais numerosos no primeiro grupo (57,4 vs. 25%, p<0,001). Os tipos de violências e condições pediátricas crônicas foram semelhantes nos dois grupos(p>0,05). Conclusões: Violência não sexual na nossa população pediátrica foi raramente diagnosticada em um hospital terciário, principalmente negligência, agressão física e psicológica/emocional. Aproximadamente dois terços dos diagnósticos de violência ocorreram em crianças, preferencialmente encaminhadas pelo departamento de emergência. Em contrapartida, cerca de um terço dos diagnósticos de violência ocorreu em adolescentes, encaminhados principalmente pelos ambulatórios.

Telehealth for children and adolescents with physical disabilities during the covid-19 pandemic / Teleatendimento a crianças e adolescentes com deficiências físicas durante a pandemia covid-19

ABSTRACT Children and adolescents with physical disabilities have motor and social-emotional challenges that interfere with their health-related quality of life and put them at greater risk of developing secondary conditions. Moreover, services that provide them therapies are more likely to be restricted, especially for the low-income population. There must be broader actions towards health promotion, offering not only means for physical habilitation and rehabilitation but for social and emotional improvements as well. This goal is attainable by adaptive sports and recreational activities where physical conditioning is accompanied by an improvement in self-esteem and social benefits. With the COVID-19 pandemic and social isolation, children and adolescents with physical disabilities were even further deprived of assistance. Our aim was to report the efforts of a non-governmental sports organization in maintaining physical and psychological care through virtual consultations and to analyze the perceptions of those affected by the process. Level of evidence IV; case series .

RESUMO Crianças e adolescentes com deficiência física apresentam desafios motores e socioemocionais que interferem na qualidade de vida relacionada à saúde e os colocam em maior risco de desenvolver doenças secundárias. Além disso, estão mais sujeitos a restrições de serviços adequados que ofereçam terapias, principalmente para a população de baixa renda social. Torna-se necessário oferecer ações voltadas para a promoção da saúde em um sentido mais amplo, oferecendo não só meios de habilitação e reabilitação física, mas também de ganhos sociais e emocionais. Este objetivo pode ser atingido com esportes adaptados e atividades recreativas nos quais o condicionamento físico é acompanhado por ganhos em autoestima e benefícios sociais. Com a pandemia de COVID-19 e o isolamento social, crianças e adolescentes com deficiência física ficaram ainda mais privados de assistência. Relatamos aqui o esforço de uma organização não-governamental esportiva em manter o atendimento físico e psicológico por meio de consultas virtuais, e avaliamos as percepções das partes interessadas no processo. Nível de evidência IV; série de casos .

Spotlight on latent tuberculosis infection screening for juvenile idiopathic arthritis in two countries, comparing high and low risk patients

Abstract Background: Rheumatic diseases are associated with an increase in overall risks of tuberculosis (TB). The aim of this study was to evaluate the frequency of TB and the frequency of latent TB infection (LTBI), in clinical practice, for juvenile idiopathic arthritis (JIA) patients from high and low risk of TB incidence endemic countries. Methods: This is an international, multicenter, cross-sectional, observational study of data collection from Brazil and Registry of Portugal at REUMA.PT. The inclusion criteria were patients with Juvenile Idiopathic Arthritis (JIA) with age ≤ 18 years who underwent screening for Mycobacterium tuberculosis infection [tuberculin skin test (TST) and/or interferon gamma release assay (IGRA)]. Chest X-rays and history of exposure to TB were also assessed. Results: 292 JIA patients were included; mean age 14.3 years, mean disease duration 7.5 years, 194 patients (66.4%) performed only TST, 14 (4.8%) only IGRA and 84 (28.8%) both. The frequency of LTBI (10.6%) and TB was similar between the two countries. The reasons for TB screening were different; in Brazil it was performed more often at JIA onset while in Portugal it was performed when starting Disease Modified Anti-Rheumatic Drugs (DMARD) treatment (p < 0.001). Isoniazid therapy was prescribed in 40 (13.7%) patients (31 with LTBI and 9 with epidemiologic risks and/or due to contact with sick people). Only three patients (1%) developed active TB. Conclusion: We found nearly 10% of patients with LTBI, a small percentage of patients with treatment due to epide-miologic risks and only 1% with active TB. Distinct reasons and screening methods for LTBI were observed between the two countries.