Desenvolvimento de neoplasias/adenomas avançados colorretais no seguimento a longo prazo de pacientes submetidos a colonoscopia com polipectomia Development of colorectal advanced neoplasia/adenomas in the long-term follow-up of patients submitted to colonoscopy with polipectomy

CONTEXTO: A colonoscopia e a polipectomia diminuem a incidência do câncer colorretal, assim como a mortalidade dele decorrente. O intervalo efetivo entre os exames de seguimento é determinado por características clínicas e achados endoscópicos considerados como preditivos para o desenvolvimento de lesões neoplásicas colônicas avançadas. OBJETIVOS: Avaliar a taxa de surgimento de lesões neoplásicas avançadas em pacientes submetidos a colonoscopias de seguimento em serviço de referência. MÉTODOS: Foram incluídos 392 pacientes submetidos a dois ou mais exames colonoscópicos completos entre 1995 e 2005, constantes no banco de dados e que apresentavam, em pelo menos um dos exames, um adenoma colorretal. Foram analisados os dados da primeira e da última colonoscopias realizadas por cada paciente, ou daquela que mostrava lesão neoplásica avançada - considerado o desfecho principal do estudo. Os pacientes foram divididos de acordo com os achados endoscópicos do primeiro exame em grupos 1 ou de alto risco, 2 ou de baixo risco e 3 ou sem adenoma na colonoscopia inicial. Foram analisados e comparados entre os grupos o aparecimento de neoplasia colônica avançada e o tempo de seguimento até o desfecho. RESULTADOS: Do total de pacientes, 27% apresentavam à colonoscopia inicial, adenomas avançados, 58,4% lesões neoplásicas com displasia de baixo grau e 14,5% não apresentavam adenomas no exame inicial. A média etária foi de 59,54 ± 11,74 anos. Vinte e seis vírgula quatro por cento das pessoas do grupo 1 apresentaram lesão neoplásica avançada ao longo do seguimento, enquanto tal desfecho ocorreu em 10,9% e 5,3% dos pacientes nos grupos 2 e 3, respectivamente (P<0,05). O período médio de acompanhamento foi de 123,35 meses, sendo que o tempo médio entre o primeiro exame e aquele com o desfecho diferiu estatisticamente entre o grupo 1 e os demais, sendo de 104,02, 115,31 e 120,61 meses, respectivamente. CONCLUSÕES: Pacientes com neoplasia avançada à colonoscopia índice apresentam maior chance de possuir tais lesões, em relação aos demais grupos, durante o seguimento, e o surgimento de neoplasia avançada ocorre mais precocemente neste grupo.<br>CONTEXT: Colonoscopy with polypectomy reduces the incidence of colorectal cancer and its associated mortality. The ideal interval between surveillance examinations is determined by clinical features and endoscopic findings considered as risk factors to the development of advanced colonic neoplasias. OBJECTIVE: To determine the development rate of advanced neoplasia in patients submitted to surveillance colonoscopy in a tertiary referral center. METHODS: Three hundred and ninety two patients who underwent two or more complete colonoscopies between 1995 and 2005, and who have at least one diagnosed colorectal adenoma entered into the study. The endoscopic findings of the first and subsequent colonoscopies of each patient were analysed, considering advanced neoplasia as the main outcome. The patients enrolled were divided in accordance to the first colonoscopy findings in groups 1 or high risk; 2 or low risk; and 3 or without adenoma at the first colonoscopy. The development of advanced colorectal neoplasia and the period of surveillance until the outcome were analysed and compared among groups. RESULTS: Twenty eight per cent of patients had advanced adenomas at index colonoscopy; 57.8% presented with low grade dysplasia neoplastic lesions and 14.1% had no adenoma at the first examination. The mean age was 59.54 ± 11.74 years. Twenty six point four per cent of subjects from group 1 presented with advanced neoplasia during the surveillance period, while this outcome occurred in 10.9% and 5.3% of patients from groups 2 and 3, respectively (P<0,05). The mean period of surveillance was 123.35 months, and the mean time between the first examination and the one which presented with the outcome statistically differed among group 1 and the others, being 104.02, 115.31 and 120.61 months, respectively. CONCLUSIONS: Patients with advanced neoplasia at index colonoscopy presented with a higher probability of harbouring this condition during the follow-up when compared with other two groups. These lesions also occur earlier in this patients than in the ones without these lesions at the first examination

Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry

International audienceTropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease -modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. Methods: We initiated a registry including patients with disease -modifying antirheumatic drugs -treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. Results: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. Conclusions: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation. (c) 2023 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association

Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis

This work was supported by research grants from the Societe Francaise de Rhumatologie, Club Rhumatismes Inflammation, la Chancellerie des Universites de Paris (legs Poix), Sorbonne Paris Cite (FPI-SPC Program), Agence Nationale de la Recherche (grants ANR-10-LABX-46, ANR-10-EQPX-07-01, ANR-14-CE10-0006 and ANR-10-INBS-09), France Genomique National Infrastructure, unrestricted grants from Pfizer, Roche and Chugai, and the Centre de Resources Biologiques Hopital Bichat, Paris, FranceDespite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45x10-4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87x10-2)

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease

International audienceBACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7x10(-17)). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7x10(-35)) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3x10(-49)). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4x10(-5)), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5x10(-6)). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Societe Francaise de Rhumatologie and others.)

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease

BackgroundGiven the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA.MethodsUsing a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls.ResultsAnalysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone.ConclusionsWe found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.)

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study

International audienceBackgroundProspective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome.MethodsThis multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396.FindingsBetween May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5–15) had a thrombotic (six [4%] women; 95% CI 1–8) or severe haemorrhagic event (12 [7%] women; 95% CI 4–12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030).InterpretationDespite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies