Expression of the miR-9-5p, miR-125b-5p and its target gene NFKB1 and TRAF6 in childhood-onset systemic lupus erythematosus (cSLE).

Childhood- onset systemic lupus erythematosus (cSLE) is a multisystem inflammatory disease that can lead to severe clinical conditions resulting in early comorbidities. Several genetic, environmental, and immunological factors are known to influence the onset of the disease. MiRNAs have been already considered as potential actors involved in the development and activity of the SLE. Thus, understanding the behavior of these regulators can contribute to clarify the inflammatory process affecting SLE patients. Among miRNAs, miR-125b-5p and miR-9-5p targeting NFKB1 and TRAF6 genes can be involved in the etio-pathogenesis of the disease by modulating inflammation. In this study we evaluated miR-9-5p and miR-125b-5p expression and its target genes NFKB1 and TRAF6 in peripheral blood samples (PBMC) from the 35 cSLE patients and 35 healthy controls. MiRNAs and gene target expression have been evaluated by using RT-PCR with specific TaqMan® probes. Both miR-9-5p [Fold Change (FC) = -2.21; p = 0.002] and miR-125b-5p (FC= -3.30; p < 0.0001) and NFKB1 (FC = -1.84; p < 0.001) were downregulated in cSLE patients, while TRAF6 was upregulated (FC = 1.80; p = 0.006) in cSLE patients when compared to controls. A significant correlation was found between miR-125b-5p and its target gene NFKB1 [Spearman (r) = 0.47; p = 0.023]. Our results showed miR-125b-5p and miR-9-5p differential expression in cSLE patients, possibly contributing to better understanding the role of these regulators in cSLE development and disease pathogenesis.

Chronic neutropenia in childhood: experience of a tertiary center

Abstract Objective: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. Methods: Retrospective observational study carried out by collecting data from the patient's medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher's exact tests were used to compare variables; the significance level was 5 %. Results: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. Conclusion: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist.

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.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

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

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

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

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

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

Avaliação da pressão positiva expiratória final utilizando o aparelho fisioterápico Quale / Evaluation of positive end expiratory pressure using a physiotherapy device called Quake

O objetivo deste estudo foi avaliar, em voluntários saudáveis, o valor médio da pressão positiva expiratória final (PEEP) na utilização do recurso fisioterápico Quake, relativamente novo no mercado. Participaram 62 indivíduos de ambos os sexos, entre 18 e 30 anos, que foram submetidos a: prova de função pulmonar; avaliação do pico de fluxo expiratório, da sensação subjetiva de esforço (escala de Borg) e da saturação de oxigênio; e à utilização do aparelho, acoplado a um anovacuômetro, para efetuar duas seqüências respiratórias, de 10 e 20 incursões por minuto, monitoradas por retroalimentação visual. Os dados foram tratados estatisticamente. Foi observada diferença significativa entre os valores das pressões geradas apenas na seqüência de 10 incursões por minuto (p=0,03). Na comparação das pressões entre as seqüências, os valores foram significativamente menores na de 10 incursões (29,42±8,04 cmH2O; p=0,03). Não foram encontradas correlações entre as pressões e as variáveis da espirometria, idade e pico de fluxo expiratório. Foi observada uma fraca correlação significativa antes (r=0,36; p=0,003) e depois (r=0,31; p=0,014) da seqüência de 20 incursões entre as pressões nessa seqüência e os escores de fadiga na escala de Borg, tendo o mesmo ocorrido com a saturação de oxigênio. A PEEP gerada pelo Quake em indivíduos saudáveis varia de acordo com a frequência em incursões por minuto, sendo maior durante a seqüência mais rápida, que também gera maior cansaço...

The aim of this study was to assess the mean positive end expiratory pressure(PEEP) during use of the Quake, a relatively new device, in healthy volunteers. Participants were 62 subjects of both sexes aged 18 to 30 years old, who were submitted to: pulmonary function tests; expiratory peak flow evaluation; the Borg scale; assessment of oxygen saturation; and use of the device, coupled to amanometer, in two sequences, of 10 and 20 breaths per minute, with monitoring by visual feedback. Data were statistically analysed. Significant differences between pressures were found only at the 10-breath per minute sequences (p=0.03). When comparing pressures between the sequences, values were significantly lower in the 10-breath per minute sequence (29.42±8.04 cmH2O; p=0.03). No correlations were found between pressures and pulmonary function test measures, age, or expiratory peak flow. A weak, significant correlation was found between Borg scale scores and pressures before (r=0.36; p=0.003) and after (r=0.31; p=0.014) the 20-breath per minute sequence, the same occurring with oxygen saturation. In healthy volunteers, then, Quake PEEP values are higher during the quickest (20-breath per minute) sequence, which also requires more exertion...

Histerctomia no ciclo gravídico-puerperal: estudo retrospectivo de 15 anos / Hysterectomy during the pregnant-puerperal period: a retrospective study

Um estudo retrospectivo de 43 histerectomias realizadas no "Hospital Escola da FMTM" de janeiro de 1978 a julho de 1993 foi realizado com o objetivo de analisar esta cirurgia e qual o tipo de histerectomia (total ou bubtotal) é melhor indicada durante o período gravídico-puerperal. Analisou-se o tempo cirúrgico, quantidade de derivados sanguíneos transfundidos durante o intra e pós-operatório, tempo de hospital;izaçåo pós-cirurgia, número de complicaçöes no intra e pós-operatório e óbitos. Os resultados destas análises nåo mostraram diferenças estatisiticamente entre os dois tipos de histerectomia. Em nossa opiniåo, a histerectomia é a melhor indicaçåo nesta situaçåo clínica

Artrite reumatóide juvenil: atraso no diagnóstico e no encaminhamento para o especialista / Juvenile rheumatoid arthritis

Objetivo: A artrite reumatóide juvenil (ARJ) pode ser causa de incapacidade física irreversível, especialmente nos casos de diagnóstico e tratamento tardios. O objetivo deste trabalho multicêntrico é de avaliar o intervalo de tempo entre os primeiros sintomas da doença e a primeira consulta com o reumatologista pediátrico. Métodos: Foram estudados 111 pacientes com ARJ seguidos em serviços de Reumatologia Pediátrica do Estado de São Paulo. Os pais responderam a um questionário elaborado pelos membros do Departamento de Reumatologia da Sociedade de Pediatria de São Paulo sobre o diagnóstico e o encaminhamento para o especialista. Resultados: O número de médicos consultados entre o primeiro atendimento e a primeira consulta com o reumatologista pediátrico variou de 1 a 20, com média de 3,6. O intervalo de tempo entre o 1º atendimento e a avaliação especializada variou de poucos dias a 10 anos (média = 1,4 ano). Em 32 pacientes (29 por cento), a consulta com o especialista só ocorreu depois de 12 meses do início dos sintomas. Conclusão: O atraso no diagnóstico da ARJ é uma realidade em nosso meio; pediatras e reumatologistas pediátricos devem estar atentos para este problema. O encaminhamento para o especialista deve ser feito precocemente, especialmente nos casos de dúvida diagnóstica.