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Behavioral changes in exposure patterns after genetic counseling among asymptomatic first-degree relatives of patients with pulmonary fibrosis and carrier of a telomere-related gene variant
No full textInternational audienc
Insights from a novel monogenic autoinflammatory disease: overview of a multicentric European cohort of 38 patients with COPA syndrome
No full textInternational audienceObjectivesCOPA (coatomer subunit alpha) syndrome is a rare monogenic autoinflammatory disease due to heterozygous mutations in COPA. It has phenotypic overlap with STING (Stimulator of interferon genes)-associated vasculopathy with onset in infancy (SAVI), although the spectrum of clinical manifestations is not yet fully defined. Our aim was to better delineate the clinical phenotype of this rare disorder in a European cohort.MethodsMethods include assessment of clinical, imaging, and immunological data from 46 individuals (29 families) carrying a COPA mutation.ResultsAmong the 46 individuals carrying a COPA mutation, 38 had at least 1 clinical manifestation likely related to their mutant state (clinical penetrance of 83%). Twenty-two (58%) symptomatic patients were female, with a median age at disease onset of 3 years (range 0-50 years). Pulmonary involvement was observed in 34 patients, with interstitial lung disease in most cases (n = 31) and diffuse alveolar haemorrhage in 11 individuals. Twenty-six patients demonstrated joint involvement, and 7 had documented kidney disease. Previously undescribed features included skin (n = 12), cardiac (n = 8), gastrointestinal (n = 7), and hepatic involvement (n = 5). All but 1 patient tested positive for autoantibodies, and increased interferon signalling was noted in all those tested. Twenty-two patients were treated with Janus kinase inhibitors with promising efficacy.ConclusionsWe report a large European cohort of patients with COPA syndrome. While confirming the core organ features (lung, joint, and kidney) of the disease, our data expand the phenotype to include cardiac, skin, and gastrointestinal features, further demonstrating the clinical overlap with SAVI and other type I interferonopathies
Subcutaneous Infliximab for Perianal Crohn's Disease: The BioLap-Rem Multicenter Study From the GETAID
No full textInternational audienceINTRODUCTION: Intravenous infliximab (IFX) is the cornerstone for treating patients with perianal Crohn's disease (pCD). Data on the recently launched subcutaneous (SC) IFX for pCD are limited. The aim of our study was to evaluate the effectiveness and safety of SC IFX in pCD. METHODS: We conducted a multicenter retrospective cohort study from the GETAID, including patients with either active (group 1) or inactive (group 2) pCD when they started SC IFX. Inclusion criteria were, for group 1: active pCD in the 6 months before initiation of SC IFX; for group 2: inactive pCD for >6 months at the time of IV to SC switch. The primary end points were clinical remission at 6 months in group 1 and pCD relapse in group 2. RESULTS: Of the 183 patients included in 24 centers, 66 were in group 1 and 117 in group 2. The median follow-up was 50.4 (27.0–64.6) and 53.4 (40.6–67) weeks, respectively. In group 1 at 6 months, clinical remission was observed in 44.6% of patients and clinical response in 87.7%. Clinical remission including seton removal occurred in 35.5% of patients. In multivariable analysis, high body mass index was the only independent predictor of remission (odds ratio 0.88, 95% confidence interval 0.77–0.99). In group 2, rates of relapse-free survival were 94.3% and 87.9% at 6 and 12 months, respectively. Sixteen cases (8.3%) of adverse events related to SC injection were observed. DISCUSSION: SC IFX was effective and safe for the treatment of active pCD and for maintaining remission after switching in this large multicenter cohort, thus supporting its use in routine practice in this indication
Concordance between presenting features and relapse in granulomatosis with polyangiitis: implications for risk assessment and counselling
No full textInternational audienceObjective To investigate the concordance between organ involvement at diagnosis and relapse in granulomatosis with polyangiitis and factors associated with new disease features at relapse. Methods Data from a national database of newly diagnosed patients was analysed. Clinical features were recorded at diagnosis and relapse, grouped by organ system. ORs and HRs were used to assess associations between baseline features and first relapse. Factors independently associated with new organ involvement at relapse were identified using multivariable logistic regression. Results Among 795 patients (median follow-up 3.5 years), 394 (50%) relapsed; organ involvement at relapse was available for 376 patients. Relapses most often affected ear, nose and throat (ENT), lungs and kidneys. Organ involvement at diagnosis was associated with a higher likelihood of relapse in the same organ: eyes (OR 6.69), lungs (OR 3.35), kidneys (OR 3.58), nervous system (OR 2.90), and mucocutaneous (OR 4.53). Major manifestations associated with a higher likelihood of recurrence were scleritis, pachymeningitis, subglottic stenosis and worsening renal function. For 56% of patients, the first relapse affected only the initially involved organs. Of the 165 patients with new organ manifestations, these were rarely isolated (n=34) and usually occurred alongside involvement of at least one previously affected organ (n=131). In multivariable analysis, systemic, ENT and lung manifestations at diagnosis were associated with a lower risk of new organ disease at relapse. Conclusion Although new features can still emerge, organ involvement at diagnosis is associated with a higher likelihood of relapse in the same organ
A-priori Free Spectral Unmixing based on Tensor Low-rank Decompositionfor Intraoperative Hyperspectral Functional Imaging
No full textInternational audienc
Labour induction and adverse perinatal outcomes: a retrospective cohort study
No full textInternational audienceBackgroundThe rising overall prevalence of induction of labour (IOL) in high-income countries raises questions about the appropriateness of its clinical indications and concerns about potential adverse perinatal outcomes. The underlying reasons for this increase remain unclear but may include broader clinical indications, changing maternal or foetal conditions, or more maternal requests. This study aimed to assess changes in prevalence of IOL and adverse perinatal outcomes.MethodsWe conducted a retrospective, population-based cohort study using data from a perinatal registry encompassing all births in a French region. The study included all women who delivered a live-born infant. IOL and perinatal outcomes were obtained from medical records. We first described the overall prevalence of these outcomes, followed by a stratified analysis based on the eight-group Grenoble Classification for IOL indications. Variations in IOL and perinatal outcomes were assessed from 2020 (reference) to 2023, both overall and by group, using Poisson regression models with generalized estimating equations.ResultsThe study population included 54,089 women. Overall IOL prevalence rose from 20.7% in 2020 to 28.1% in 2023 (adjusted risk-ratio (aRR) 1.31, 95%CI 1.15–1.49). This increase was mainly driven by higher aRRs in Group-5 [Single cephalic pregnancy ≥41 weeks of gestation (WG)] (34.6% to 42.9%; aRR 1.21, 95%CI 1.10-1.40), Group-6 [Single cephalic pregnancy with maternal pathology from 37 to 40+6 WG] (31.5% to 49.7%; aRR 1.56, 95%CI 1.38–1.75), and Group-7 [Single cephalic pregnancy with foetal pathology from 37 to 40+6 WG] (52.9% to 77.2%; aRR 1.46, 95%CI 1.14–1.88). Adverse outcome changes were observed only in these three groups, with increased emergency caesarean rates in Group-5 (12.4% to 16.4%; aRR 1.22, 95% CI 1.10–1.40) and Group-7 (13.1% to 19.6%; aRR 1.40, 95%CI 1.04–1.80), as well as higher postpartum haemorrhage rates in Group-5 (5.8% to 7.7%; aRR 1.31, 95% CI 1.01–1.69) and Group-6 (4.9% to 7.0%; aRR 1.41, 95%CI 1.05–1.90). Neonatal morbidity remained stable.ConclusionsThe rise in overall IOL prevalence was driven by higher rates in three groups (pregnancies ≥41 WG, maternal and foetal pathology), in which we also observed a clinically meaningful increase in adverse maternal outcomes
Monitoring Liver Viability: Fluorescence Spectroscopy of Cellular Metabolites in Ischemia-Reperfusion
No full textInternational audienceThe growing demand for organ transplantation and the shortage of available organs has led to the use of extended criteria donors and perfusion machines to expand the donor pool. However, current clinical practice lacks effective methods for real-time graft monitoring during perfusion. Graft monitoring on perfusion machines represents a promising approach for continuous assessment of their functional status . During the reperfusion phase, it becomes possible to monitor the graft's condition in real-time through the study of respiratory chain metabolites. This respiratory chain is particularly affected during ischemia and reperfusion phases, making its monitoring essential for optimizing preservation conditions and predicting graft viability prior to transplantation
Chikungunya virus replicates in the human testis ex vivo and impacts peritubular myoid cells functional markers
No full textInternational audienceChikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for debilitating, long-lasting arthralgia and myalgia. In light of recent findings of prolonged CHIKV RNA shedding in human semen and testicular tropism in animals infected with related alphaviruses, it is imperative to investigate CHIKV's capacity to infect the human testis, an established reservoir for arboviruses like Zika, and to delineate its implications for testicular function. Using an ex vivo human testicular tissue model, we demonstrate that CHIKV rapidly infects peritubular myoid cells (PMCs) and a range of interstitial cells, with robust viral production peaking at day 3 before declining. Importantly, seminiferous tubule cells and isolated testicular germ cells proved nonpermissive to CHIKV infection, indicating a potential limitation for seminal shedding of virions. Infected testicular explants exhibited a broad antiviral response but limited pro-inflammatory cytokines upregulation. CHIKV replication in the testis induced apoptosis and cell death, with a marked impact on PMC markers including decreased transcriptional expression of genes crucial for PMC contractile properties and extracellular matrix production. In summary, our study highlights the susceptibility of human testicular tissue to CHIKV infection, marked by robust viral replication that primarily compromises PMC function. The observed cellular impairment and damage suggest that CHIKV infection might negatively affect key testicular functions, such as tubular contractility and sperm release. These findings warrant further investigation into semen parameters and viral shedding in CHIKV-infected men
Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial
No full textInternational audienceAbstract Immune checkpoint inhibitors improve the treatment of many solid tumors and have shown encouraging results in advanced squamous cell carcinoma (SCC), yet only a minority of patients respond to immune checkpoint inhibitor monotherapy. We conducted the PEVOsq trial, an open-label, nonrandomized, multicenter, basket phase 2 trial to evaluate the combination of pembrolizumab and vorinostat in recurrent/metastatic SCC of various origins. The primary endpoint was the objective response rate (ORR) in each tumor cohort during treatment as per the investigators’ assessment. Secondary endpoints included safety and antitumor activity evaluation in terms of centrally confirmed ORR, progression-free survival, overall survival and duration of response. In the efficacy population ( n = 107), the ORR was met in cervical (39%), anal (31%) and vulvar/vaginal (19%) cancer cohorts, but not in head and neck SCC (19%) or penile (18%) cancer cohorts (overall ORR = 26%). Median progression-free survival was 4.0 months (95% confidence interval: 2.6–4.3), and median overall survival was 11.1 months (95% confidence interval: 9.2–17.4). In the safety population, 101 (91%) of 111 patients developed at least one treatment-related adverse event, with 39% and 5.4% of patients experiencing at least one grade 3 and grade 4 treatment-related adverse event, respectively. Vorinostat-related toxicity prompted a dose reduction/interruption in 66% of patients. Whole-exome sequencing analyses revealed several potential predictive biomarkers of response to treatment. Further studies in a larger number of patients are required to validate these findings. ClinicalTrials.gov identifier: NCT04357873
