Screening by high-throughput sequencing for pathogenic variants in cystic fibrosis: Benefit of introducing personalized therapies.

This short report documented cystic fibrosis transmembrane conductance regulator (CFTR) variants in 37 patients with cystic fibrosis (CF) in the Rio Grande do Norte region of Northeast Brazil. The high-throughput sequencing technology (HTS) genetic testing provided a definitive molecular diagnosis in 31 patients (83.8%). Among them, 25 patients' carriers of the c.1521_1523delCTT variant, categorized as a class 2 mutation, can be currently treated with CFTR modulator drugs. Five children aged 2-5 years could benefit from double lumacaftor/ivacaftor therapy, and 20 patients aged >6 years could be treated with the triple-combination elexacaftor/tezacaftor/ivacaftor therapy. Thus, the identification of pathogenic variants associated with the development of this disease allows for the introduction of therapy with CFTR modulators that favour better patient management.

Prevalência de alterações bucais nas doenças gastrointestinais inflamatórias crônicas: análise de 10 casos / Prevalence of oral abnormalities in chronic inflammatory gastrointestinal diseases: analysis of 10 cases

Introdução: Doenças gastrointestinais inflamatórias crônicas (DGIC) é um grupo de doenças em que se enquadram a doença de Crohn (DCr), a colite ulcerativa e a doença celíaca (DC) cuja origem ainda é incerta e são caracterizadas por terem um curso clínico crônico e intercalarem períodos de remissão com episódios agudos. Por sua vez, as manifestações bucais nas DGIC são achados clínicos comuns, podendo apresentar ulcerações e defeitos de desenvolvimento em esmalte, sendo aquelas, as lesões mais frequentes. Objetivo: Verificar a presença de alterações bucais em pacientes com DGIC. Métodos: A coleta de informações foi obtida através da aplicação de um questionário e de exame clínico em 10 pacientes diagnosticados com DGIC. Resultados: Os pacientes com DGIC apresentaram líquen plano oral, língua fissurada, dente supranumerário, torus palatino, microdentes, agenesia dentária, disfunção da ATM, granuloma piogênico, linha Alba e dente rosa de Mummery. O defeito de desenvolvimento de esmalte mais frequente nos pacientes com DC foi a opacidade difusa, na DCr foi a opacidade demarcada e na colite ulcerativa foram a hipoplasia e outros defeitos. Conclusão: De fato, as manifestações bucais e dentárias podem fazer parte do quadro das DGIC sendo importante a integração multidisciplinar no tratamento e acompanhamento desses pacientes. Além disso, foi evidente a relação entre alterações de desenvolvimento de esmalte e as DGIC (AU).

Introduction: Chronic gastrointestinal inflammatory diseases (CGID) is a group of diseases that are Crohn's disease (CrD), ulcerative colitis and celiac disease (CD) whose origin is still uncertain and are characterized by having a chronic clinical course and interleave periods of remission with acute episodes. Oral manifestations in CGID are common clinical findings and may have ulcerations, enamel developmental defects, ulcers are the most frequent injuries. Objective: Verify the presence of oral abnormalities in patients with CGID and oral manifestations. Methods: Data collection was obtained through a questionnaire and clinical examination in 10 patients diagnosed with CGID. Results: Patients with CGID presented oral lichen planus, fissured tongue, supernumerary tooth, palatal torus, micro tooth, tooth agenesis, TMJ disorder, pyogenic granuloma, Alba line and rose Mummery tooth. The most frequent defect enamel development in patients with CD was diffuse opacity for CrD was demarcated opacity were ulcerative colitis and hypoplasia and other defects. Conclusion: In fact, the oral and dental manifestations may be part of CGID framework is important multidisciplinary integration in the treatment and monitoring of these patients. Furthermore, it was evident relationship between enamel development and changes CGID (AU).

Hepatic stellate cell activation and hepatic fibrosis in children with type 1 autoimmune hepatitis: an immunohistochemical study of paired liver biopsies before treatment and after clinical remission.

OBJECTIVES: The activation of hepatic stellate cells (HSC) is considered the most important event in hepatic fibrogenesis. The precise mechanism of this process is unknown in autoimmune hepatitis (AIH), and more evidence is needed on the evolution of fibrosis. The aim of this study was to assess these aspects in children with type 1 AIH. METHODS: We analyzed 16 liver biopsy samples from eight patients, paired before treatment and after clinical remission, performed an immunohistochemical study with anti-alpha actin smooth muscle antibody and graded fibrosis and inflammation on a scale of 0-4 (Batts and Ludwig scoring system). RESULTS: There was no significant reduction in fibrosis scores after 24+/-18 months (2.5+/-0.93 vs. 2.0+/-0.53, P=0.2012). There was an important decrease in inflammation: portal (2.6+/-0.74 vs. 1.3+/-0.89, P=0.0277), periportal/periseptal (3.0+/-0.76 vs. 1.4+/-1.06, P=0.0277), and lobular (2.8+/-1.04 vs. 0.9+/-0.99, P=0.0179). Anti-alpha actin smooth muscle antibodies were expressed in the HSC of the initial biopsies (3491.93+/-2051.48 mum), showing a significant reduction after remission (377.91+/-439.47 microm) (P=0.0117). CONCLUSION: HSC activation was demonstrated in the AIH of children. The reduction of this activation after clinical remission, which may precede a decrease in fibrosis, opens important perspectives in the follow-up of AIH.