Updates in diagnosis and treatment of pediatric antiphospholipid syndrome.

PURPOSE OF REVIEW: This review offers an overview of the most important recent articles on pediatric APS. RECENT FINDINGS: Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes. The 2023 APS criteria were developed for adult APS patients, and there is still a lack of pediatric-specific APS criteria. Catastrophic APS was more commonly reported as the initial manifestation of pediatric APS than in adults. Regarding treatment, direct oral anticoagulants have been recently approval for pediatric patients with venous thrombosis. New approaches have been proposed for severe cases, for arterial thrombosis, and rituximab for refractory cases. Recurrences typically occurred early and were associated with older age at diagnosis. Current studies highlighted the multifaceted nature of pediatric APS. Further large prospective multicenter studies evaluating new medications capable of reducing recurrence risk and improving prognosis in this population will be required.

Development of clinical and laboratory biomarkers in an international cohort of 428 children with lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. METHODS: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. RESULTS: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. CONCLUSIONS: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission.

Long-Term Follow-Up of Anti-Infliximab Antibodies in Patients With Radiographic Axial Spondyloarthritis: A Marker of Drug Survival and Tapering.

OBJECTIVE: The aim of this study was to evaluate the influence of anti-infliximab (IFX) antibodies on three different points of care: response/tolerance to IFX, tapering strategy, and in a subsequent treatment with a second tumor necrosis factor inhibitor (TNFi). METHODS: A prospective cohort of 60 patients with radiographic axial spondyloarthritis who received IFX were evaluated retrospectively regarding clinical/laboratorial data, IFX levels, and anti-IFX antibodies at baseline, after 6, 12 to 14, 22 to 24, 48 to 54, 96 to 102 weeks, and before tapering or switching. RESULTS: Anti-IFX antibodies were detected in 27 patients (45%), of whom 23 (85.1%) became positive in the first year of IFX treatment. In comparison to the group that was negative for anti-IFX antibodies, patients who were positive for anti-IFX antibodies demonstrated the following: less use of methotrexate as a concomitant treatment to IFX (5 [18.5%] vs 14 [42.4%]; P = 0.048), more infusion reactions at 22 to 24 weeks (P = 0.020) and 48 to 54 weeks (P = 0.034), more treatment failures (P = 0.028) at 48 to 54 weeks, reduced overall IFX survival (P < 0.001), and lower sustained responses (P = 0.044). Of note, patients who were positive for anti-IFX antibodies exhibited a shorter tapering survival (9.9 months [95% confidence interval (CI) 4.0-15.8] vs 63.4 months [95% CI 27.9-98.8]; P = 0.004) in comparison with patients who were negative for anti-IFX antibodies. Conversely, for patients who failed IFX, patients who were positive for anti-IFX antibodies had better clinical response to the second TNFi at three months (15 [83.3%] vs 3 [27.3%]; P = 0.005) and six months (15 [83.3%] vs 4 [36.4%]; P = 0.017) than the patients who were negative for anti-IFX antibodies after switching. CONCLUSION: This study provided novel data that anti-IFX antibodies is a parameter for reduced tapering survival, reinforcing its detection to guide clinical decision. Additionally, we confirmed in a long-term cohort the anti-IFX antibody association with worse IFX performance and as predictor of the second TNFi good clinical response.

Updates in the care and management of children and adolescents with systemic lupus erythematosus.

PURPOSE OF REVIEW: This narrative review offers an update of the most important recent articles published in the previous year of childhood-onset systemic lupus erythematosus (cSLE), focusing on care and management. RECENT FINDINGS: Age-related disparities may play a significant role in the clinical and laboratory characteristics of cSLE, as well as its performance in distinct classification criteria. Monogenic lupus is associated with higher disease damage scores and mortality rate compared to sporadic cSLE. Adolescent face unique challenges, with comorbid psychiatric diagnosis, low resilience and nonadherence posing relevant challenges. A recent international task force has outlined pivotal principles and points-to-consider for treat-to-target (T2T) in cSLE patients. While the past year did yield new randomized controlled trial for cSLE treatment, publications focused on broader management strategies, including the impact of ultraviolet radiation exposure, immunization, and strict blood pressure control. Additionally, case reports and series have evaluated the efficacy/safety profiles of both available and emerging treatments. SUMMARY: Current studies highlighted the various facets of cSLE, epidemiology, clinical, laboratory, classification criteria, adolescent issues, prognosis, surveillance, T2T approach and drug management. Despite notable progress, the scarcity of randomized trials emphasizes the need to delineate safer and more efficacious treatment modalities in cSLE.

Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.

Background: Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement. Methods: Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels. Results: Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls. Conclusion: This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years

Abstract Objectives: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. Methods: A cross-sectional study including a sample of adolescents' autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59). Results: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018). Conclusion: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

Emotional, hyperactivity and inattention problems in adolescents with immunocompromising chronic diseases during the COVID-19 pandemic

Abstract Objective: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. Methods: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). Results: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00-7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08-3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12-4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93-0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95-0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16-0.77; p = 0.026) remained inversely associated with abnormal HI scores. Conclusion: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Abstract Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05-0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05-0.88, p = 0.034). After six months (D69-D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Seroconversion in asymptomatic COVID-19 pediatric patients with rheumatic diseases of one tertiary referral hospital

Objectives To evaluate seroconverted asymptomatic COVID-19 in pediatric Autoimmune Rheumatic Diseases (ARDs) patients and to identify the risk factors related to contagion. Methods A cross-sectional study was conducted in March 2021, before vaccination of children and adolescents in Brazil, including 77 pediatric ARDs patients, followed at a tertiary hospital and 45 healthy controls, all of them without a previous diagnosis of COVID-19. Data was obtained by a questionnaire with demographic data, symptoms compatible with COVID-19 over the previous year, and contact with people with confirmed COVID-19. Patient's medical records were reviewed to access data regarding disease and current medications. A qualitative immunochromatographic SARS-CoV-2 test was performed on all participants. Results Patients and controls were similar in terms of female gender (70.1% vs. 57.8%, p = 0.173), age (14 vs. 13 years, p = 0.269) and SARS-CoV-2 positive serology (22% vs. 15.5%, p = 0.481). 80.5% of rheumatic patients were in use of immunosuppressive drugs: 27.3% of them used corticosteroids (33.3% in high doses), and 7.8% on immunobiologicals. No statistical differences were found between positive (n = 17) and negative serology (n = 60) patients regarding demographic/socioeconomic data, contact with people with confirmed COVID-19, use and number of immunosuppressive drugs, use and dose of corticosteroids, use of hydroxychloroquine and immunobiological drugs (p > 0.05). Conclusions Pediatric rheumatic disease patients were infected at the same rate as healthy ones. Neither the underlying pathology nor its immunosuppressive treatment seemed to interfere with contagion risk.

Does [18F]F-FDG-PET/MRI add metabolic information to magnetic resonance image in childhood-onset Takayasu's arteritis patients? A multicenter case series

Abstract Background: The observation that 2-deoxy-2[18F]fluoro-D-glucose-positron emission tomography/magnetic resonance imaging ([18F]F-FDG-PET/MRI) revealed high-grade arterial wall FDG uptake, without arterial wall thickening with contrast-enhancement, in a considerable number of c-TA patients in our previous study, encouraged us to compare patients with both PET and MR angiography (MRA) positives, with those with PET positive but MRA negative. Our aim was to evaluate the relevance of these two imaging modalities together. Methods: A three-center cross-sectional study with 17 patients who fulfilled the EULAR/PRINTO/PReS criteria for c-TA and who underwent [18F]F-FDG-PET/MRI was previously performed. Herein we compared patients/vessels with positive PET (arterial wall 18F-FDG uptake higher than liver) and positive MRA (arterial wall thickening with contrast-enhancement)—group 1, with those with positive PET but negative MRA—group 2. Results: Median disease duration of 17 c-TA patients was 10.4 years. Nine patients were classified as group 1 and six as group 2. Median of metabolic inflammatory volume (MIV) of all arterial segments was significantly higher in group 1 (2346 vs. 1177 cm3; p = 0.036). Fifty-four (19%) from 284 available arterial segments presented positive findings in vessel wall in one or both images. Positive findings were concordant between PET and MRA in only 13% arterial segments (group 1); most changes (28-59.6%) that were discordant between both images, were positive in PET and negative in MRA (group 2). Conclusions: Our study demonstrated that [18F]F-FDG-PET/MRI added information about inflammation in vessel wall of c-TA patients. Prospective multicenter studies are needed in order to get solid data to guide immunosuppressive tapering and withdrawal.

Seroconversion in asymptomatic COVID-19 pediatric patients with rheumatic diseases of one tertiary referral hospital

Abstract Objectives: To evaluate seroconverted asymptomatic COVID-19 in pediatric Autoimmune Rheumatic Diseases (ARDs) patients and to identify the risk factors related to contagion. Methods: A cross-sectional study was conducted in March 2021, before vaccination of children and adolescents in Brazil, including 77 pediatric ARDs patients, followed at a tertiary hospital and 45 healthy controls, all of them without a previous diagnosis of COVID-19. Data was obtained by a questionnaire with demographic data, symptoms compatible with COVID-19 over the previous year, and contact with people with confirmed COVID-19. Patient's medical records were reviewed to access data regarding disease and current medications. A qualitative immunochromatographic SARS-CoV-2 test was performed on all participants. Results: Patients and controls were similar in terms of female gender (70.1% vs. 57.8%, p = 0.173), age (14 vs. 13 years, p = 0.269) and SARS-CoV-2 positive serology (22% vs. 15.5%, p = 0.481). 80.5% of rheumatic patients were in use of immunosuppressive drugs: 27.3% of them used corticosteroids (33.3% in high doses), and 7.8% on immunobiologicals. No statistical differences were found between positive (n = 17) and negative serology (n = 60) patients regarding demographic/socioeconomic data, contact with people with confirmed COVID-19, use and number of immunosuppressive drugs, use and dose of corticosteroids, use of hydroxychloroquine and immunobiological drugs (p > 0.05). Conclusions: Pediatric rheumatic disease patients were infected at the same rate as healthy ones. Neither the underlying pathology nor its immunosuppressive treatment seemed to interfere with contagion risk.

A qualidade de vida relacionada à saúde em adolescentes e adultos jovens com doença inflamatória intestinal está mais associada à redução na produtividade escolar e no trabalho do que ao comprometimento físico: um estudo multidisciplinar / Health-related quality of life in adolescents and young adults with inflammatory bowel disease is associated with reduction in school and work productivity rather than physical impairment: a multidisciplinary study

ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract that often have their onset among adolescents and young adults (AYA). IBD are characterized by episodes of active disease interspersed with periods of remission, and its activity is inversely correlated with health-related quality of life (HRQL). OBJECTIVE: This study aimed to determine whether AYA in remission or with low IBD activity would exhibit HRQL similar to that of age-matched healthy individuals, and whether demographic and disease factors could affect HRQL using a 'patient-reported outcome' instrument. METHODS: This study enrolled only AYA with IBD, with low activity. This research included five multidisciplinary clinics of two academic hospitals: Paediatric Gastroenterology, Gastroenterology, Coloproctology, Paediatric Rheumatology and Adolescent divisions, São Paulo, Brazil. A total of 59 AYA with IBD (age, 13-25 years) and 60 healthy AYA (age, 13-25 years) completed the Pediatric Quality of Life Inventory 4.0 and 36-Item Short-Form Health Survey questionnaires and the visual analogue scale (VAS) for pain. Demographic data, extra-intestinal manifestations, treatment, and outcomes regarding CD and UC were evaluated. RESULTS: AYA with IBD and healthy controls were similar with respect to median ages (18.63 [13.14-25.80] years vs 20.5 [13.68-25.84] years, P=0.598), proportion of female sex (42% vs 38%, P=0.654), and percentage of upper middle/middle Brazilian socioeconomic classes (94% vs 97%, P=0.596). The school/work score was significantly lower in AYA with IBD than in healthy controls (70 [10-100] vs 75 [5-100], P=0.037). The 'general health-perception' score was significantly lower in AYA with IBD than in healthy controls (50 [10-80] vs 0 [25-90], P=0.0002). The median VAS, FACES pain rating scale, and total VAS scores were similar between the two groups (2 [0-10] vs 3 [0-9], P=0.214). No association between HRQL and clinical and demographic parameters was identified among IBD patients. CONCLUSION: AYA with low IBD activity reported poor HRQL in school/work and general health perception domains, which highlights a disability criterion in this vulnerable population.

RESUMO CONTEXTO: As doenças inflamatórias intestinais (DII), que englobam a doença de Crohn e a colite ulcerativa, são doenças inflamatórias crônicas do trato gastrointestinal que frequentemente se manifestam em adolescentes e adultos jovens (AAJ). As DII são caracterizadas por episódios de doença ativa intercalados com períodos de remissão, e sua atividade se correlaciona inversamente com a qualidade de vida relacionada à saúde (QVRS). OBJETIVO: Este estudo teve como objetivo determinar se AAJ em remissão ou com baixa atividade de DII exibiria QVRS semelhante à de indivíduos saudáveis pareados por idade, e se fatores demográficos da doença poderiam afetar a QVRS usando um instrumento de medidas de desfecho relatadas pelo paciente. MÉTODOS: Este estudo envolveu apenas AAJ com DII, com baixa atividade. Esta pesquisa incluiu cinco clínicas multidisciplinares de dois Hospitais Universitários: Divisões de Gastroenterologia Pediátrica, Gastroenterologia, Coloproctologia, Reumatologia Pediátrica e Adolescentes, São Paulo, Brasil. Um total de 59 AAJ com DII (13-25 anos de idade) e 60 AAJ controle saudáveis (13-25 anos de idade) responderam os questionários Pediatric Quality of Life Inventory 4.0 e 36-Item Short-Form Health Survey e as escalas visuais de dor. Dados demográficos, manifestações extra intestinais, tratamentos e desfechos da doença de Crohn e a colite ulcerativa foram avaliados. RESULTADOS: AAJ com DII e os controles saudáveis foram grupos semelhantes com relação à média de idade (18,63 [13,14-25,80] vs 20,5 [13,68-25,84] anos, P=0,598), quanto à proporção de pacientes do sexo feminino (42% vs 38%, P=0,654), e quanto à porcentagem da classe socioeconômica brasileira média elevada/ média (94% vs 97%, P=0,596). Os escores escola/trabalho foram significativamente mais baixos nos AAJ com DII do que nos controles saudáveis (70 [10-100] vs 75 [5-100], P=0,037). O escore 'percepção geral de saúde' foi significativamente mais baixo nos AAJ com DII do que no agrupamento controle saudável (50 [10-80] vs 0 [25-90], P=0,0002). As escalas de avaliação visual de dor foram semelhantes entre os dois grupos (2 [0-10] vs 3 [0-9], P=0,214). Nenhuma associação entre QVRS e parâmetros clínicos e demográficos foi identificada entre os pacientes com DII. CONCLUSÃO: AAJ com baixa atividade das DII relataram baixa QVRS nos domínios da escola/trabalho e percepção geral da saúde, o que destaca um critério de incapacidade nesta vulnerável população.

Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.

Differences among severe cases of SARS-COV-2, influenza, and other respiratory viral infections inpediatric patients: symptoms, outcomes and preexisting comorbidities

OBJECTIVES: Previous studies focusing on pediatric patients hospitalized with severe coronavirus disease 2019 (COVID-19) have been limited to small case series. We aimed to evaluate the characteristics of a large population of pediatric patients with severe COVID-19 and compare them with patients with severe cases of influenza and other respiratory viruses (ORV). METHODS: We performed a cross-sectional study of Brazilian data from the National Epidemiological Surveillance Information System, gathered from January 1st to July 14th, 2020. The sample included 4,784 patients (2,570 with confirmed COVID-19, 659 with influenza, 1,555 with ORV). Outcome measures included clinical features, preexisting comorbidities, pediatric intensive care unit admissions, need for ventilatory support, and death. RESULTS: Compared with the influenza and ORV groups, the COVID-19 group had a higher proportion of newborns and adolescents, as well as lower frequencies of fever, cough, dyspnea, respiratory distress, and desaturation. Although use of invasive ventilatory support was similar among groups, death rate was highest for COVID-19 (15.2% vs. 4.5% vs. 3.2%, p<0.001), with death risk more than three times the other groups (adjusted OR=3.7 [95% CI 2.5-5.6]). The presence of two or more comorbidities further increased this risk (OR=4.8 [95% CI 3.5-6.6]). Preexisting comorbidities were reported in 986 patients with severe COVID-19 (38%). Mortality rate among COVID-19 patients was significantly higher for almost all comorbidities reported. CONCLUSION: Severe COVID-19 had a higher mortality rate than other viral respiratory illnesses, despite the lower frequency of fever, cough, dyspnea, respiratory distress, and desaturation. Death risk was strongly associated with preexisting comorbidities.

Mortality in adolescents and young adults with chronic diseases during 16 years: a study in a Latin American tertiary hospital / Mortalidade entre adolescentes e adultos jovens com doenças crônicas durante 16 anos: estudo em um hospital terciário da América Latina

ABSTRACT Objectives: To evaluate mortality in adolescents and young adult patients with chronic diseases followed in a Latin American tertiary hospital. Methods: A cross-sectional retrospective study was performed in a tertiary/academic hospital in the state of São Paulo, Brazil. Death occurred in 529/2850 (18.5%) adolescents and young adult patients with chronic diseases, and 25/529 (4.7%) were excluded due to incomplete medical charts. Therefore, 504 deaths were evaluated. Results: Deaths occurred in 316/504 (63%) of early adolescent patients and in 188/504 (37%) of late adolescent/young adult patients. Further comparisons between early adolescents (n = 316) and late adolescent/young adult patients (n = 188) with pediatric chronic diseases at the last hospitalization showed that the median disease duration (22.0 [0-173] vs. 43.0 [0-227] months, p < 0.001) was significantly lower in early adolescents vs. late adolescent/young adult patients. The median number of previous hospitalizations was significantly lower in the former group (4.0 [1-45] vs. 6.0 [1-52], p < 0.001), whereas the last hospitalization in intensive care unit was significantly higher (60% vs. 47%, p = 0.003). Regarding supportive measures, palliative care was significantly lower in the younger group compared to the older group (33% vs. 43%, p = 0.02). The frequencies of renal replacement therapy (22% vs. 13%, p = 0.02), vasoactive agents (65% vs. 54%, p = 0.01), and transfusion of blood products (75% vs. 66%, p = 0.03) were significantly higher in the younger group. The five most important etiologies of pediatric chronic diseases were: neoplasias (54.2%), hepatic diseases/transplantation (10%), human immunodeficiency virus (5.9%), and childhood-onset systemic lupus erythematosus and juvenile idiopathic arthritis (4.9%). Autopsy was performed in 58/504 (11%), and discordance between clinical and postmortem diagnoses was evidenced in 24/58 (41.3%). Conclusions: Almost 20% of deaths occurred in adolescents and young adults with distinct supportive care and severe disease patterns. Discordance between clinical diagnosis and autopsy was frequently observed.

RESUMO Objetivos: Avaliar a mortalidade entre adolescentes e pacientes adultos jovens com doenças crônicas acompanhados em um hospital terciário na América Latina. Métodos: Foi feito um estudo retrospectivo transversal em um hospital terciário/universitário no Estado de São Paulo, Brasil. Houve mortalidade de 529/2.850(18,5%) pacientes adolescentes e adultos jovens com doenças crônicas, porém 25/529(4,7%) foram excluídos devido a prontuários médicos incompletos. Portanto, foram avaliados 504 óbitos. Resultados: Ocorrem 316/504(63%) óbitos entre pacientes no início da adolescência e 188/504(37%) pacientes no fim da adolescência/adultos jovens. As comparações adicionais entre os pacientes no início da adolescência (n = 316) e no fim da adolescência/pacientes jovens (n = 188) com doenças crônicas pediátricas na última internação mostraram que a duração média da doença [22,0 (0-173) em comparação com 43,0 (0-227) meses, p < 0,001], foi significativamente menor nos pacientes no início da adolescência em comparação com os pacientes no fim da adolescência/adultos jovens. O número médio de internação anterior foi significativamente menor no primeiro grupo [4,0 (1-45) em comparação com 6,0 (1-52), p < 0,001], ao passo que a última internação na unidade de terapia intensiva foi significativamente maior (60% em comparação com 47%, p = 0,003). Com relação a medidas de suporte, o cuidado paliativo foi significativamente menor no grupo de pacientes no início da adolescência em comparação com o grupo de pacientes no fim da adolescência (33% em comparação com 43%, p = 0,02). As frequências de terapia de substituição renal (22% em comparação com 13%, p = 0,02), agentes vasoativos (65% em comparação com 54%, p = 0,01) e transfusão de hemoderivados (75% em comparação com 66%, p = 0,03) foram significativamente maiores no primeiro grupo. As cinco etiologias mais importantes de doenças crônicas pediátricas foram: neoplasias (54,2%), doenças hepáticas/transplante (10%), vírus da imunodeficiência humana (5,9%), lúpus eritematoso sistêmico de início na infância e artrite idiopática juvenil (4,9%). Foi feita autópsia em 58/504 (11%) e a discordância entre os diagnósticos clínico e pós-morte foi comprovada em 24/58 (41,3%). Conclusões: Quase 20% dos óbitos ocorreram em adolescentes e adultos jovens com diferentes padrões de cuidados de suporte e doenças graves. A discordância entre o diagnóstico clínico e a necropsia foi frequentemente observada.

Decreased health-related quality of life in children and adolescents with autoimmune hepatitis / Redução na qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune

Abstract Objective: The objective of this study was to evaluate the health-related quality of life in children and adolescents with autoimmune hepatitis. Methods: A cross-sectional assessment with the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) was completed for 80 patients with autoimmune hepatitis and 45 healthy controls. Demographic data, prednisone dose, disease remission state, disease severity, and abdominal pain were also evaluated. Results: Based on the child self-reports, physical, emotional, school, and total scores were significantly lower in autoimmune hepatitis patients when compared with controls (p < 0.05). Based on the parental reports, only the physical and total scores were significantly lower in autoimmune hepatitis patients versus controls (p < 0.05). Further analysis in autoimmune hepatitis patients with abdominal pain in the last month revealed significantly lower physical, social, and total median scores (p < 0.05). No differences were observed based on disease remission state or disease severity (p > 0.05). Autoimmune hepatitis patients who received a prednisone dose below 0.16 mg/kg/day at the time of the interview showed significantly higher physical scores than those who received a dose similar to or above 0.16 mg/kg/day (87.5 [50-100] vs. 75 [15.63-100], p = 0.006). Conclusions: Reduced scores in the physical, emotional, and school domains were observed in pediatric autoimmune hepatitis patients compared to control patients. Abdominal pain and corticosteroid dose negatively influenced the health-related quality of life in children and adolescents with autoimmune hepatitis.

Resumo Objetivo: Avaliar a qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune (HAI). Métodos: Foi concluída uma avaliação transversal com o Inventário Pediátrico de Qualidade de Vida 4.0 (PedsQL 4.0) para 80 pacientes com hepatite autoimune e 45 controles saudáveis. Os dados demográficos, a dose de prednisona, o estado de remissão da doença, a gravidade da doença e dor abdominal também foram avaliados. Resultados: Com base nos autorrelatos das crianças, os escores físico, emocional, escolar e total foram significativamente menores em pacientes com hepatite autoimune em comparação com os controles (p < 0,05). Com base nos relatos dos pais, apenas os escores físico e total foram significativamente menores em pacientes com hepatite autoimune em comparação com os controles (p < 0,05). Uma análise adicional em pacientes com hepatite autoimune com dor abdominal no mês passado revelou escores médios físico, social e total significativamente menores (p < 0,05). Nenhuma diferença foi observada com base no estado de remissão da doença ou na gravidade da doença (p > 0,05). Os pacientes com hepatite autoimune que receberam uma dose de prednisona abaixo de 0,16 mg/kg/dia no momento da entrevista mostraram escores físicos significativamente maiores que os que receberam uma dose semelhante ou acima de 0,16 mg/kg/dia [87,5 (50-100) em comparação com 75 (15,63-100), p = 0,006]. Conclusões: Escores reduzidos nos domínios físico, emocional e escolar foram observados em pacientes pediátricos com hepatite autoimune em comparação com pacientes do grupo de controle. Dor abdominal e dose de corticosteroide influenciaram negativamente a qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune.

Lower genital tract infections in young female juvenile idiopathic arthritis patients

Abstract Background: To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. Methods: After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. Results: The mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p =0.206) and biological agent use (p =0.238) were similar in both JIA groups. Conclusions: To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.

Pediatric chronic patients at outpatient clinics: a study in a Latin American University Hospital / Pacientes pediátricos crônicos em clínicas ambulatoriais: estudo em um hospital universitário da América Latina

Abstract Objective: To describe the characteristics of children and adolescentes with chronic diseases of outpatient clinics at a tertiary university hospital. Methods: A cross-sectional study was performed with 16,237 patients with chronic diseases followed-up in one year. The data were collected through the electronic system, according to the number of physician appointments in 23 pediatric specialties. Patients were divided in two groups: children (0-9 years) and adolescents (10-19 years). Early (10-14 years) and late (15-19 years) adolescent groups were also analyzed. Results: Of the total sample, 56% were children and 46% were adolescents. The frequencies of following pediatric specialties were significantly higher in adolescents when compared with children: cardiology, endocrinology, hematology, nephrology/renal transplantation, neurology, nutrology, oncology, palliative and pain care, psychiatry, and rheumatology (p < 0.05). The frequencies of emergency service visits (30% vs. 17%, p < 0.001), hospitalizations (23% vs. 11%, p < 0.001), intensive care unit admissions (6% vs. 2%, p < 0.001), and deaths (1% vs. 0.6%, p = 0.002) were significantly lower in adolescents than in children. However, the number of physician appointments (≥13) per patient was also higher in the adolescent group (5% vs. 6%, p = 0.018). Further analysis comparison between early and late adolescents revealed that the first group had significantly more physician appointments (35% vs. 32%, p = 0.025), and required more than two pediatric specialties (22% vs. 21%, p = 0.047). Likewise, the frequencies of emergency service visits (19% vs. 14%, p < 0.001) and hospitalizations (12% vs. 10%, p = 0.035) were higher in early adolescents. Conclusions: This study evaluated a large population in a Latin American hospital and suggested that early adolescents with chronic diseases required many appointments, multiple specialties and hospital admissions.

Resumo Objetivo: Descrever características de crianças e adolescentes com doenças crônicas de clínicas ambulatoriais em um hospital universitário terciário. Métodos: Um estudo transversal foi realizado com 16.237 pacientes com doenças crônicas acompanhados em um ano. Os dados foram coletados por meio de dados do sistema eletrônico de acordo com o número de consultas médicas em 23 especialidades pediátricas. Os pacientes foram divididos em dois grupos: crianças (0-9 anos) e adolescentes (10-19 anos). Também foram analisados grupos de jovens adolescentes (10-14 anos) e adolescentes mais velhos (15-19 anos). Resultados: 54% eram crianças e 46% eram adolescentes. As frequências das seguintes especialidades pediátricas foram significativamente maiores em adolescentes em comparação a crianças: cardiologia, endocrinologia, hematologia, nefrologia/transplante renal, neurologia, nutrologia, oncologia, cuidados paliativos e cuidado da dor, psiquiatria e reumatologia (p < 0,05). As frequências de visitas a serviços de emergência (30%, em comparação a 17%, p < 0,001), internações (23%, em comparação a 11%, p < 0,001), internações em unidade de terapia intensiva (6%, em comparação a 2%, p < 0,001) e óbitos (1%, em comparação a 0,6%, p = 0,002) foram significativamente menores em adolescentes do que em crianças. Contudo, o número de consultas médicas (≥ 13) por paciente (também) foi maior em grupos de adolescentes (5%, em comparação a 6%, p = 0,018). A comparação de análises adicionais entre jovens adolescentes e adolescentes mais velhos revelou que o primeiro grupo apresentou um número significativamente maior de consultas médicas (35%, em comparação a 32%, p = 0,025) e precisou de mais de duas especialidades pediátricas (22%, em comparação a 21%, p = 0,047). Da mesma forma, as frequências de visitas a serviços de emergência (19%, em comparação a 14%, p < 0,001) e internações (12%, em comparação a 10%, p = 0,035) foram maiores em jovens adolescentes. Conclusões: Este estudo avaliou uma grande população em um hospital da América Latina e sugeriu que jovens adolescentes com doenças crônicas precisaram de muitas consultas, diversas especialidades e internações hospitalares.