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Outcomes After Kidney Transplantation in Antiglomerular Basement Membrane Disease
No full textInternational audienceIntroduction: Goodpasture disease, or antiglomerular basement membrane (anti-GBM) disease, is a rare autoimmune disorder that often leads to end-stage kidney disease (ESKD). Although kidney transplantation (KT) is the preferred treatment, concerns exist about disease recurrence and graft outcomes in patients with GBM-associated glomerulonephritis (GBM-GN). This study aimed to evaluate posttransplant outcomes in patients with GBM-GN compared with matched controls.Methods: This retrospective, multicenter study included 100 patients with anti-GBM who received KT between 2005 and 2023 in 13 French transplant centers, matched with 200 control recipients. We compared the incidence of delayed graft function (DGF), graft failure, relapse, acute rejection, and death between groups and analyzed risk factors using multivariable models.Results: No significant differences in DGF incidence (22% vs. 19%, P ¼ 0.5), graft survival (87% vs. 88% at 5 years, P ¼ 0.4), or patient survival (93% vs. 89% at 5 years, P ¼ 0.4) were found between patients with GBM-GN and controls. Patients with GBM-GN tended to have lower risk of acute rejection (hazard ratio [HR] ¼ 0.51, 95% confidence interval: 0.25-1.02, P ¼ 0.055). Only 1 patient with GBM-GN (1%) experienced disease relapse. Although patients with GBM-GN were waitlisted and transplanted later than controls, specific transplant timing was not associated with improved outcomes.Conclusion: KT in patients with GBM-GN offers comparable outcomes to other nephropathies in the current era. Disease relapse is rare, even in the few patients with detectable antibodies pretransplantation. The lower incidence of acute rejection in the GBM-GN group warrants further investigation. These findings support KT as a viable option in patients with GBM-GN, though specific pre-and posttransplant monitoring is advised
High Psychological Impact of Covid‐19 on French Healthcare Workers: An Observational Cohort Study of PTSD, Depression and Burn‐Out
No full textInternational audienceIntroduction:The Covid-19 outbreak hit the world forcing public institutions to rethink their core functioning. Healthcare workers (HCWs) were particularly at risk for negative mental health outcomes, given their direct exposure to many pandemicrelated stressors. Our study aimed to assess the psychological outcomes of French HCWs during the Covid-19 pandemic, including PTSD, depression and burn-out. Methods: This study presents the baseline data of a large cohort study conducted during the pandemic. Participants were 849 French HCWs (mostly single women, working as nurses) assessed for PTSD with the PCL-5 (PTSD Checklist for DSM-5), for depression with the PHQ-9 (Patient Health Questionnaire), and for burn-out and compassion satisfaction with the ProQOL (Professional Quality of Life). Other pandemic-related variables were also collected, including characteristics related to participants' Covid-19 experience, as well as psychological and clinical measures.</div
Metabolic responses to energetic stimuli in female athletes using or not hormonal contraceptives during a high training load period
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Manipulation under anesthesia for the treatment of stiffness after total knee arthroplasty: A French multicenter study at 5 years’ follow-up including 344 cases
No full textInternational audienceIntroduction: knee stiffness is a common complication following total knee replacement (TKA), causing important morbidity. Although manipulation under anesthesia (MUA) is a safe method for the treatment of stiffness, its benefits over long-term and for large cohorts are not precisely known. The aim of this retrospective study was to assess clinical and functional outcomes and patients satisfaction after MUA over 5 years of follow-up. Hypothesis: Our hypothesis was that range of motion (ROM) improvement would be superior to 30◦ and would be sustained at 5 years follow-up leading to a patient satisfaction rate exceeding 70%. Material and methods: This was an observational retrospective study organized with 14 French centers implied in the SOFCOT. Three hundred and forty four patients who underwent MUA following TKA were reviewed between January 2023 and June 2024. Among the cohort, patients who underwent a second MUA were analyzed separately. The collected data included patient demographics, Devane activity, ASA score, functional scores, knee amplitudes and satisfaction rates. Statistical analysis was performed with EasyMedStat. Results: The mean time between TKA and MUA was 2.9 ± 6.9 months and the mean follow-up was 5.5 ± 2.5 years. In comparison with the ROM at stiffness diagnosis (66.6◦± 21.0◦), at 5 years post-MUA, the ROM was improved by 36.0◦ ± 26.1 (p < 0.001), at a mean of 102.2◦ ± 22.6◦. The subgroup of patients having a second MUA had a ROM gain of 16.8◦ ± 12.3◦ at 5-years post-MUA. The global complication rate after MUA was 2.3% (n = 8) including hematoma, wound dehiscence, infection, tibial tubercle fracture and patellar tendon rupture. At last follow-up, OKS was 35.4 ± 9.6. The KOOS for all subscales ranged from 38.5 ± 30.9 to 57.5 ± 33.8 and the mean FJS was 35.0 ± 14.3. A high satisfaction rate was recorded (77.5%). Conclusion: The improvement in ROM was substantial throughout the 5-year follow-up period. MUA was associated with low complication rates and high patient satisfaction, suggesting that it is an effective treatment for knee stiffness
Subcutaneous vedolizumab dose intensification in inflammatory bowel disease patients: the OPTI-VEDO multicenter study from the GETAID
No full textInternational audienceBackground and Aims While this strategy is frequently used for other biologics, real-world evidence on subcutaneous (SC) vedolizumab (VDZ) dose intensification in inflammatory bowel disease (IBD) is lacking. This study aimed to assess the effectiveness and safety of SC VDZ intensification. Methods We conducted a retrospective study in 25 centers including all patients with active ulcerative colitis (UC) or Crohn’s disease (CD) (defined by PRO2), and incomplete or loss of response to SC VDZ 108mg EOW when the drug was intensified. The primary outcome was steroid-free clinical response (SFCr) defined by at least 50% of PRO2 improvement, no treatment change, no surgery, and SC VDZ persistence at 3 months. Results Out the 154 included patients (66% UC, 34% CD), prior anti-TNF exposure was reported in 85% of CD and 50% of UC patients. SC VDZ was intensified for an incomplete response in 73% of CD and 53% of UC patients, mostly at 108mg weekly (95%). At 3 months, SFCr was achieved in 35% of CD and 43% of UC patients. In multivariate analysis, factors associated with response were secondary loss of response in CD, and prior anti-TNF exposure in UC. At 12 months, 51% of CD and 37% of UC patients maintained SC VDZ. Adverse events occurred in 10 patients including one severe pneumonia and one angioedema. Conclusions In this real-world study evaluating SC VDZ intensification, a SFCr was observed in at least one third of IBD patients at 3 months, suggesting the benefit of this strategy in clinical practice
Blood proteomic signatures associated with disease activity in Inflammatory Bowel Diseases
No full textInternational audienceBackground and aims Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), remain heterogeneous disorders with variable response to biologics. Post-operative recurrence in CD is common despite surgery and prophylactic biotherapies. Understanding the inflammatory mediators associated with recurrence and treatment response could pave the way for personalized strategies. Methods We analyzed serum inflammatory protein signatures using proteomics in two prospective cohorts. The REMIND cohort included post-operative CD patients undergoing ileocecal resection with endoscopic assessment at 6 months (M6). Serum samples were collected at surgery and six months later. The ELYP cohort consisted of active IBD patients starting new biotherapies (anti-TNF, ustekinumab, or vedolizumab). Serum samples were collected pre- and post-treatment (Weeks 14 and 52). Results In the REMIND cohort, proteomic analysis revealed elevated levels of IFN-γ, CXCL9, and MMP-10 in patients with recurrence, with concentrations associated with recurrence severity. Preoperative MMP-10 levels predicted severe recurrence (AUC = 0.70). Under biotherapies, treatment-specific proteins were associated with recurrence: CXCL9 for anti-TNF and OSM/TGFα modules for ustekinumab. In the ELYP cohort, IFN-γ and CXCL9 were significantly elevated in CD compared to UC and associated with disease activity. Early response to anti-TNF treatment (Week 14) was associated with reductions in CXCL9, MMP-10, and OSM, while deep remission (Week 52) correlated with decreases in CXCL9 and OSM. Conclusion Our findings reveal inflammatory blood proteomic signatures associated with post-operative recurrence and biologic treatment failure in IBD. Several key biomarkers were identified. These results support the rationale for personalized approaches, including combination therapies targeting multiple pathways. ClincialTrials.gov number, NCT02693340 and NCT0269334
Optimization of freezing and thawing protocols for human ovarian tissue cryopreservation through thermophysical characterisation of freezing medium by Differential Scanning Calorimetry
No full textInternational audienceAim: To perform an extensive thermodynamic characterisation of the most commonly and successfully used freezing medium for ovarian tissue cryopreservation (OTC) using Differential Scanning Calorimetry (DSC) to optimize freezing and thawing protocols.Methods: Leibovitz-L15 medium with 4 mg/mL HSA, 1.5M DMSO and 0.1M sucrose was used as freezing medium. Its thermodynamic properties were obtained using a differential scanning calorimeter (DiamondDSC, PerkinElmer): crystallization temperature (Tc), end-of-melting temperature (Tm), and transition temperature (Tg’1). A freezing and a thawing protocol were developed according to these parameters. To evaluate the post-thawing human ovarian tissue quality and functionality, we used our pericystic ovarian tissue model (three patients, <37 years, no ovulatory disorder). Tissues were evaluated fresh, immediately after thawing, and after 7 days of organotypic culture, by analysing the stage and morphology of ovarian follicles (HES staining).Results: The following thermodynamic properties were obtained for the freezing medium and used to set up a freezing and a thawing protocol: -20.31°C (±3.37°C) for Tc, -4.11°C (± 0.49°C) for Tm and -120.49°C (±0.41°C) for Tg'1. The freezing protocol was performed in a programmable freezer (NanoDigitCool, Cryo Bio System). The following ramps were chosen: sample introduction: 5 min at +4°C, 1°C/min up to -7°C, seeding: 60°C/min up to -32°C in order to reach up Tc (-20.31°C), and 10°C/min up to -15°C, 0.3°C/min up to -40°C, 10°C/min up to -140°C (Fig. 1A). For the thawing protocol, we selected a 2.5-min step in a cold chamber to reach slowly Tg'1, limiting thermal and mechanical shocks, and then a 2-min incubation at 37°C to quickly reach Tm (Fig. 1B). To validate these protocols, a total of 782 follicles from fresh tissues and 392 from frozen/thawed tissues were analysed. At Day 0, follicle stage distribution was similar between fresh and frozen/thawed tissues, with a majority of primordial and intermediate follicles. After 7 days of culture a clear decrease in the percentage of reserve follicles was observed between D0 and D7 in both fresh (14.20% vs 2.93%, p=0.000 for primordial follicles and 69.67% vs 31.49%, p=0.002 for intermediate follicles) and frozen-thawed tissue (16.85% vs 2.91%, p=0.021 for primordial follicles). Concomitantly, an increase in the percentage of growing follicles (mainly primary follicles) was observed between D0 and D7 in fresh tissue (8.92% vs 57.61%, p=0.000) and a tendency in frozen-thawed tissue (22.45% vs 47.65% p=0.052).Conclusions: Thawed ovarian tissues maintained a quality comparable to fresh tissue with evidence of follicle activation post-thawing. These findings support the development of an optimized OTC protocol for clinical use, improving fertility preservation for women
2024 re-emergence of coxsackievirus A24 variant causing an outbreak of acute hemorrhagic conjunctivitis in the South West Indian Ocean
No full textInternational audienceIn early 2024, an outbreak of acute hemorrhagic conjunctivitis occurred in Mayotte and in Madagascar, two islands in the Indian Ocean. Real-time diagnosis and genotyping identified a different lineage of coxsackievirus A24 variant (CVA24v) from the current Asian outbreak. Although no recombination event had been detected in all previously reported CVA24v-associated outbreaks associated with the subgenotype IV, we characterized a putative recombinant strain by full-length genome sequencing
Multicentre Retrospective Analysis of Lung Function Impairment and Risks for Restrictive Syndrome During Childhood After Type III Esophageal Atresia Repair
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Deciphering Auditory Hyperexcitability in Otogl Mutant Mice Unravels an Auditory Neuropathy Mechanism
No full textInternational audienceAuditory neuropathies affect the spiral ganglion neurons of the auditory nerve or their synapses with the sensory hair cells, distorting the sound information transmitted from the ear to the brain. Deciphering the underlying pathophysiological mechanisms remains challenging owing to the diversity of spiral ganglion neuron subtypes and associated central auditory circuits. An auditory neuropathy mechanism is unraveled by investigating the origin of auditory hyperexcitability in a mouse model for hereditary congenital deafness. Otogl encodes the large Otogelin‐like protein, which is related to secreted epithelial mucins and is implicated in the mechanical stimulation of cochlear outer hair cells. Heterozygous Otogl +/− mutant mice display auditory hyperexcitability, highlighted by their susceptibility to audiogenic seizures induced by loud sounds. It is shown that Otogl is transiently expressed in a subpopulation of spiral ganglion neurons during cochlear development. Despite their apparently normal hearing, Otogl +/− mice display poor activation of the spiral ganglion neurons processing loud sounds and an elevation of the activation threshold of the middle the ear muscle reflex that attenuates loud sounds. The findings reveal how a neuropathy affecting spiral ganglion neurons specialized in loud sound processing and associated with the middle the ear muscle reflex can manifest itself as auditory hyperexcitability