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Abstract Introduction This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators. Methods This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years). Results Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan–Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs. Conclusion Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA. Trial Registration ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

Abstract Objectives To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). Methods ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. Results 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62–8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02–5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33–24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02–0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41–53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03–0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02–0.76; p = 0.02) remained at final model as protective factor. Conclusions Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Abstract Background Preserved skeletal muscle is essential for the maintenance of healthy bone. Loss of bone mineral density (BMD) and muscle strength, considered a predictor of BMD, have been demonstrated in patients with cirrhosis, but they are poorly studied in chronic hepatitis C (CHC) without cirrhosis. Thus, we aimed to evaluate the prevalence of low BMD and its association with body composition, muscle strength, and nutritional status in CHC. Methods One hundred and four subjects [mean age, 50.5 ± 11.3 years; 75.0% males; 67.3% non‐cirrhotic; and 32.7% with compensated cirrhosis] with CHC, prospectively, underwent scanning of the lean tissue, appendicular skeletal muscle mass (ASM), fat mass, lumbar spine, hip, femoral neck, and whole‐body BMD by dual‐energy X‐ray absorptiometry. Muscle strength was assessed by dynamometry. Sarcopenia was defined by the presence of both low, ASM/height2 (ASMI) and low muscle strength according to the European Working Group on Sarcopenia in Older People criteria. The cut‐off points for low ASMI and low muscle strength, for women and men, were 50 years, the T‐score of osteopenia is between −1.0 and −2.49 standard deviation (SD) below the young average value and of osteoporosis is ≥−2.5 SD below the young normal mean for men, and the Z‐score of low bone mass is ≤−2.0 SD below the expected range in men aged

A síndrome do anticorpo antifosfolipídeo (SAF) é uma doença sistêmica autoimune caracterizada por trombose arterial e venosa, morbidade gestacional e presença de níveis séricos de anticorpos antifosfolipídeos elevados e persistentemente positivos. O tratamento da SAF ainda é sujeito a controvérsias, já que qualquer decisão terapêutica potencialmente irá confrontar-se com o risco de uma cobertura antitrombótica insuficiente ou com o risco excessivo associado à anticoagulação e seus principais efeitos adversos. Esta diretriz foi elaborada a partir de nove questões clínicas relevantes e relacionadas ao tratamento da SAF pela Comissão de Vasculopatias da Sociedade Brasileira de Reumatologia. O objetivo deste trabalho foi criar uma diretriz que incluísse as questões mais relevantes e controversas no tratamento da SAF, com base na melhor evidência científica disponível. As questões foram estruturadas por meio do P.I.C.O. (paciente, intervenção ou indicador, comparação e outcome/desfecho), o que possibilitou a geração de estratégias de busca da evidência nas principais bases primárias de informação científica (MEDLINE/Pubmed, Embase, Lilacs/Scielo, Cochrane Library, Premedline via OVID). Também realizou-se busca manual da evidência e de teses (BDTD e IBICT). A evidência recuperada foi selecionada a partir da avaliação crítica, utilizando instrumentos (escores) discriminatórios de acordo com a categoria da questão terapêutica (JADAD para ensaios clínicos randomizados e New Castle Ottawa Scale para estudos não randomizados). Após definir os estudos potenciais para sustento das recomendações, eles foram selecionados pela força da evidência e pelo grau de recomendação, segundo a classificação de Oxford.

OBJETIVO: Analisar a utilidade da contagem total de linfócitos, contagem global de leucócitos, hemoglobina, estado nutricional, contagem de linfócitos T CD4+ e carga viral como marcadores de progressão da doença e/ou óbito em crianças infectadas pelo HIV. MÉTODOS: Estudo de coorte retrospectiva em população de crianças infectadas pelo HIV, assintomáticas ou com sintomas leves e/ou moderados e virgens de tratamento antirretroviral. Os eventos de interesse foram: progressão para categoria clínica C (de acordo com a classificação dos Centers for Disease Control and Prevention - CDC, de 1994) ou óbito. Valores da contagem global de leucócitos, contagem total de linfócitos, hemoglobina, escore z peso/idade, contagem de linfócitos T CD4+ e carga viral plasmática obtidos à admissão foram considerados na análise do risco de ocorrência dos eventos de interesse. A população foi estratificada em faixas etárias: 12 e < 36, > 36 e < 60 meses. RESULTADOS: Cento e vinte pacientes, admitidos entre 1997 e 2003, preencheram os critérios para inclusão deste estudo. A mediana global do tempo de acompanhamento foi de 7,4 meses (intervalo interquartil 25-75% = 3,8-21,1). Em análise multivariada, apenas a contagem de linfócitos T CD4+, segundo as categorias da Organização Mundial da Saúde, e o escore z peso/idade ≤ -2 foram preditores do risco de progressão da doença em crianças maiores de 12 meses de idade. Em menores de 12 meses, nenhuma das variáveis analisadas esteve associada ao risco de progressão. CONCLUSÃO: Evidencia-se a importância do estado nutricional na avaliação do risco de progressão da doença em crianças maiores de 12 meses de idade infectadas pelo HIV.OBJECTIVE: To analyze total lymphocyte count, total leukocyte count, hemoglobin levels, nutritional status, CD4+ T-lymphocyte count and viral load as markers of disease progression and/or death in HIV-infected children. METHODS: This retrospective cohort study assessed antiretroviral naïve HIV-infected children who were asymptomatic or had mild and/or moderate symptoms. The events of interest were: progression to clinical category C (according to the classification of the Centers for Disease Control and Prevention - CDC, 1994) or death. Values of total leukocyte count, total lymphocyte count, hemoglobin, weight-for-age z score, CD4+ T-lymphocyte count and plasma viral load obtained at admission were considered in the risk analysis of events of interest. The population was stratified into age groups: < 12, > 12 to < 36, > 36 to < 60 months. RESULTS: One hundred and twenty patients, admitted between 1997 and 2003, met the inclusion criteria for the present study. The total median of follow-up duration was 7.4 months (25-75% interquartile range = 3.8-21.1). In the multivariate analysis, only CD4+ T-lymphocytes count, according to the categories of the World Health Organization, and weight-for-age z score ≤ -2 were predictors of risk for disease progression in children older than 12 months. In children younger than 12 months, none of the variables was associated with risk of progression. CONCLUSION: Nutritional status is an important aspect in the assessment of risk of disease progression in HIV-infected children older than 12 months.

BACKGROUND: Osteoporosis affects approximately 30% of postmenopausal women. Gastrectomy, pernicious anemia, and more recently Helicobacter pylori infection, have all been implicated in the pathogenesis of osteoporosis. A reduced parietal cell mass is a common feature in these conditions. AIM: To study a possible relationship between chronic gastritis, parietal cell density of the oxyntic mucosa and bone mineral density in postmenopausal women, as chronic gastritis, Helicobacter pylori infection and osteoporosis are frequently observed in the elderly. METHODS: Fifty postmenopausal women (61.7 ± 7 years) were submitted to gastroduodenal endoscopy and bone densitometry by dual energy X-ray absorptiometry. Glandular atrophy was evaluated objectively by the determination of parietal cell density. Helicobacter pylori infection was evaluated by histology, urease test and breath test with 13C. RESULTS: Thirty-two patients (64%) presented chronic multifocal gastritis, and 20 of them (40%) showed signs of gastric mucosa atrophy. Lumbar spine osteoporosis was found in 18 patients (36%). The parietal cell density in patients with and without osteoporosis was 948 ± 188 and 804 ± 203 cells/mm², respectively. Ten osteoporotic patients (55%) and 24 non-osteoporotic patients (75%) were infected by Helicobacter pylori. CONCLUSION: Postmenopausal women with osteoporosis presented a well-preserved parietal cell density in comparison with their counterparts without osteoporosis. Helicobacter pylori infection was not different between the two groups. We concluded that neither atrophic chronic gastritis nor Helicobacter pylori seem to be a reliable risk factor to osteoporosis in postmenopausal women.RACIONAL: A osteoporose afeta aproximadamente 30% das mulheres na pós-menopausa. Gastrectomia, anemia perniciosa e mais recentemente, a infecção pelo H. pylori, têm sido implicados na patogênese da osteoporose. A diminuição da massa de células parietais constitui aspecto comum a estas condições. OBJETIVOS: Estudar possível relação entre gastrite crônica, densidade de células parietais da mucosa oxíntica e a densidade mineral óssea em mulheres na pós-menopausa. MÉTODOS: Cinqüenta mulheres na pós-menopausa (média de idade 61.7 ± 7 anos) foram submetidas a endoscopia digestiva alta e a densitometria óssea pela absorciometria com raio-X de dupla energia. A atrofia glandular foi avaliada, histologicamente e pela determinação da densidade das células parietais na mucosa do corpo gástrico. A infecção pelo H. pylori foi avaliada através da histologia, teste da urease e teste respiratório com C13. RESULTADOS: Trinta e dois pacientes (64%) apresentaram gastrite crônica e 20 (40%) deles apresentaram sinais de atrofia de mucosa gástrica através da análise histopatológica rotineira. Osteoporose da coluna lombar foi encontrada em 18 (36%) pacientes. A densidade de células parietais em pacientes com e sem osteoporose foi 948 ± 188 e 804 ± 2003 células/mm², respectivamente. Dez pacientes (55%) com osteoporose e 24% (75%) pacientes sem osteoporose estavam infectados pelo H. pylori. CONCLUSÃO:Mulheres na pós-menopausa com osteoporose apresentaram mucosa gástrica e população de células parietais mais conservadas em relação àquelas sem osteoporose. A infecção pelo H.pylori não foi estatisticamente diferente entre mulheres com e sem osteoporose, indicando que a infecção por esta bactéria, com ou sem atrofia da mucosa gástrica, não se constitui em fator de risco para osteoporose em mulheres na pós-menopausa.

We assessed the development of drug resistance in women exposed to antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) after 24 weeks postpartum in a prospective cohort of HIV-1-infected women. HIV-1-infected women, who received prophylactic ART during pregnancy, had genotypic resistance testing performed at the start (T1) of and 24 weeks after ART interruption (T2). The women had CD4 counts >250 cellsml and no AIDS defining conditions. Of the 30 eligible women, the median age was 27 years [25–75 interquartile range (IQR) 21–32] and the median gestational age of ART initiation was 22 weeks (IQR 19–27) 19 (63.3) received zidovudine (ZDV) plus lamivudine (3TC) plus nelfinavir (NFV). At entry, most women (96.7) were asymptomatic (CDC93 A1A2), with a median CD4 count of 446 (IQR 353–686) and median viral load (VL) of 8560 copiesml (IQR 3,252–19,515). No HIV-1 vertical transmission was observed. HIV subtype B was the most prevalent (70). The development of new mutations associated with ART resistance was analyzed at T2. NFV resistance was observed in 4 out of 17 (23.5) patients exposed to this drug two major mutations D30N (117) and L90M (117) and minor mutations (N88S, 217). Mutations on positions 44, 69, and 118 (128) were present on reverse transcriptase (RT) analysis. No new nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated mutation was observed. In this cohort, ART regimens were very efficient at blocking HIV vertical transmission. However, the high rate of NFV-resistant mutations observed in the postpartum period indicates the need for discussion of ART choices during pregnancy and the potential impact on future therapeutic options for these women. Women previously exposed to ART for PMTCT who will start HIV treatment should have genotypic resistance testing performed. [ABSTRACT FROM AUTHOR]