HAL-HCL
Not a member yet
19000 research outputs found
Sort by
Classification of GBA1 variants and their impact on Parkinson’s disease: an in silico score analysis
No full textInternational audienceBi-allelic pathogenic GBA1 variants cause Gaucher disease (GD), whereas certain heterozygous missense variants increase the risk of Parkinson’s disease (PD), although the underlying mechanisms are unclear. Here, we classified GBA1 missense variants using predictive and structural scores, and analysed their associations with enzyme activity, Saposin C (SapC) interaction and PD progression in 639 patients with heterozygous GBA1 variants from five cohorts. Principal component analysis (PCA) identified two components: PC1, associated with reduced β-glucocerebosidase activity, the GD clinical severity classification, younger age at PD diagnosis, and faster cognitive and motor decline; and PC2, associated with surface-exposed, flexible regions involved in SapC interactions, younger age at PD diagnosis, and slightly with motor decline. These findings highlight that impaired SapC interactions, in addition to reduced activity, may contribute to PD severity in GBA1 variant carriers. This is relevant for therapeutic approaches aimed at stabilizing β-glucocerebosidase or enhancing its enzymatic activity in PD
Prostatic diseases in transgender women: a systematic review of diagnosis, risk, and management
No full textInternational audienceIntroduction: Most transgender women have their prostate left in situ throughout and after their transition. Managing prostate-related conditions in transgender women remains challenging due to the lack of clear recommendations. This review aims to summarize the available data on prostate health, including cancer screening and treatment, lower urinary tract symptoms, and prostate evaluation.Material and methodsA comprehensive literature review was conducted in accordance with the PRISMA statement using PubMed, Embase, and The Cochrane Library, with the keywords (prostate), (lower urinary tract symptoms (LUTS)), (prostate evaluation), and (transgender women). All relevant data were analyzed.ResultsTwenty studies were included in the final analysis: 15 focused on prostate cancer, four on LUTS, and one on prostate evaluation. A total of 961 prostate cancer cases were identified. Of the 17 detailed oncologic treatments, the most common were surgery and hormone therapy. Data regarding LUTS and prostate evaluation were very limited; the most frequently reported symptom was a split urinary stream. Surgical interventions for LUTS included two cases of transurethral resection of the prostate (TURP) and one Rezum procedure. Prostate evaluation was performed via transvaginal exam in 50 patients. Transvaginal ultrasonographic assessment of the prostate was feasible in 67 out of 70 patients (96%).ConclusionThe present systematic review demonstrates that prostatic diseases can occur in transgender women. Neovaginal prostatic exam appears as the appropriate way to assess the prostate on physical exam. The paucity of data highlights the need to raise awareness of healthcare professionals and to promote further research on this critical issue
Ten to 15-Year Outcomes of Monoblock Uncemented Dual Mobility Cups
No full textInternational audienceBackground: Dual mobility cups (DMCs) have effectively prevented dislocations after total hip arthroplasty (THA). However, use of these cups in primary THAs remains controversial, especially in young patients. This study aimed to determine the long-term survival rate and functional outcomes of a contemporary DMC used in primary THA. Methods: This retrospective multicenter study identified a cohort of 614 primary THAs performed with the same uncemented monoblock DMC between 2007 and 2010. Survival analysis included 572 THAs, while clinical analysis involved 394 THAs at a minimal follow-up of 10 years. The mean follow-up was 11.1 ± 1.2 years. The mean age was 71.4 ± 11.7 years, with 4.2% of patients under 50 years old. The mean body mass index was 27.0 ± 5.3 kg/m 2 . The 10-year Kaplan-Meier survival rate was calculated based on cup removal for any reason or cup revision for an aseptic reason as the end point. Harris hip scores were collected at the last follow-up. Results: The cup-revision-free survival rate was 98.6% at 10 years and 96.2% at 13 years. No cup revisions were reported due to aseptic loosening or dislocation. The cup revisions were due to infection (7 of 572; 1.2%), acetabular fracture (1 of 572; 0.17%), and psoas impingement due to cup malpositioning (n = 1 of 572; 0.17%). Only 3 dislocations (0.52%) were observed, and they did not require revision. The mean Harris hip score significantly improved from 54.1 ± 14.4 preoperatively to 88.0 ± 14.3 at the last follow-up (p < 0.0001). For patients under 50 years old at the time of surgery, the mean Harris hip score showed significant improvement from 53.0 ± 10.2 preoperatively to 89.7 ± 12.8 at the last follow-up (p < 0.0001), with no significant difference compared with the older patients (p = 0.50). No revision or complication was reported in the younger patient population at 13 years of follow-up. Conclusions: The monoblock uncemented DMC demonstrated excellent survival rates with no DMC-specific complications during a minimum 10-year follow-up. The dislocation rate was very low, and a younger age was not identified as a risk factor for failure. Therefore, monoblock cementless DMCs can be safely used, even in primary THA. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence
Quantitative imaging outperforms No-reflow in predicting functional outcomes in a translational stroke model
No full textInternational audienceMicrovascular dysfunction and no-reflow are considered a major cause of secondary damage despite revascularization in acute ischemic stroke (AIS), ultimately affecting patient outcomes. We used quantitative PET-MRI imaging to characterize early microvascular damages in a preclinical non-human primate model mimicking endovascular mechanical thrombectomy (EVT). During occlusion, PET perfusion and MRI diffusion were used to measure ischemic and lesion core volumes respectively. Following revascularization, multiparametric PET-MRI included perfusion, diffusion, blood-brain barrier (BBB) permeability MRI, and 15 O-oxygen metabolism PET. Lesion growth on MRI was evaluated at one week, and the neurological score was assessed daily; a poor outcome was defined as a score>6 (0-normal, 60-death) after one week. Early after recanalization, the gold-standard PET ischemic threshold (<0.2 mL/min/g) identified post-EVT hypoperfusion in 67 % of the cases (14/21) located in the occlusion acute lesion. Acquired 110 min post-EVT, the area of MRI Tmax hypoperfusion was larger and even more frequent (18/20) and was also located within the acute lesion. Eight of the total cases (38 %) had a poor outcome, and all of them had no-reflow (7/8 MRI no-reflow and 6/8 PET no-reflow). Diffusion ADC alterations and post-EVT oxygen extraction fraction (OEF) values were significantly different in PET no-reflow cases compared to those without no-reflow, exhibiting an inverse correlation. Independently of no-reflow, long perfusion Tmax and post-EVT high BBB Ktrans in the lesion core were the hallmarks of poor outcome and infarct growth. This early quantitative imaging signature may predict infarct growth and poor outcome and help to identify neuroprotection targets
DARJELY, le dispositif lyonnais d’accompagnement multidisciplinaire des jeunes migrants en errance
No full textInternational audienc
Prevention of refeeding syndrome: Evaluation of an enteral refeeding protocol for severely undernourished children
No full textInternational audienceAbstract Objectives Refeeding syndrome (RS) defines the deleterious clinical and metabolic changes occurring during nutritional support of severely malnourished patients. Pediatric guidelines to prevent and treat RS are scarce and highly variable. This study aimed to evaluate the effectiveness and safety of an enteral refeeding protocol in severely undernourished hospitalized children with anorexia nervosa (AN) or organic diseases (OD). Methods This ancillary study to the Preventing Malnutrition and Restoring Nutritional Status in Hospitalized Children (PREDIRE) trial (NCT01081587), included severely undernourished children hospitalized between January 2010 and June 2018 and treated with an enteral refeeding protocol drafted for the study. The effectiveness was assessed by weight gain and safety by clinical and laboratory abnormality occurrence over the initial 3‐week refeeding period, which represents the most critical period for the development of RS. Results After 3 weeks of refeeding, the mean weight for height ratio increased from 72% to 82%, and half of the patients with severe undernutrition improved their nutritional status. The prevalence of RS was 10.4%. No clinical cardiac or neurological complication occurred. The most frequent laboratory complication was hypophosphatemia in 13.7% of patients; but symptomatic in only two patients (2.5%). Compared with patients with OD, patients with AN improved their weight‐for‐height ratio faster without significantly more frequent complications, except for hepatic cytolysis which was less prevalent in AN (8.3% vs. 36.8%). Conclusions The proposed enteral refeeding protocol appears safe for treating severely undernourished children of different etiologies, with a low prevalence of RS and half of the patients recovered from severe malnutrition within a 3‐week period
γδ T Cells’ Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental Models
No full textInternational audienceThe generation of donor-specific antibodies (DSA) requires that alloreactive B cells receive help from follicular helper T (T FH ) cells. Recent works have suggested that γδ T cells could contribute to T cell-dependent humoral responses, leading us to investigate their role in DSA generation. Analysis of a cohort of 331 kidney transplant recipients found no relation between the number of circulating γδ T cells and the risk to develop DSA. Coculture models demonstrated that activated γδ T cells were unable to promote the differentiation of B cells into plasma cells, ruling out that they can be “surrogate” T FH . In line with this, γδ T cells preferentially localized outside the B cell follicles, in the T cell area of lymph nodes, suggesting that they could instead act as “antigen-presenting cell” (APC) to prime αβ T FH . This hypothesis was proven wrong since γδ T cells failed to acquire APC functions in vitro . These findings were validated in vivo by the demonstration that following transplantation with an allogeneic Balb/c (H2 d ) heart, wild-type and TCRδKO C57BL/6 (H2 b ) mice developed similar DSA responses, whereas TCRαKO recipients did not develop DSA. We concluded that the generation of DSA is unfazed by the absence of γδ T cells
Multimodal use of endoscopy in pain surgery: Overview, applications, and future directions
No full textInternational audienc
Twelve Years of LabEx PRIMES (2012-2024)
No full textInternational audienceAn overview of the research performed in the Auvergne Rhône Alpes Region within theLaboratoire d’Excellence Physics, Radiobiology, Medical Imaging, and Simulatio
P1056 Effectiveness and Safety of Upadacitinib Induction Therapy in Real-World Setting for 234 Patients with Crohn’s Disease: A GETAID Multicentre Cohort Study
No full textInternational audienceBackgroundWhile upadacitinib has demonstrated its efficacy as an induction treatment for Crohn’s disease (CD) in two phase 3 randomized, placebo-controlled trials1, real-world data remain limited.MethodsFrom September 2022 to September 2024, all consecutive patients with refractory CD treated with once-daily upadacitinib 45 mg in 30 French and Belgian GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission (SFCR) at week 12, defined as a Harvey-Bradshaw Index (HBI) score of < 4. Secondary endpoints included clinical response (decrease of ≥ 3 points in the HBI score and/or an HBI score < 4), clinical remission, biological remission (calprotectin ≤ 250 µg/g, or CRP ≤ 5 if calprotectin was unavailable), endoscopic or radiological (IUS and/or MRI) response, and adverse events (AEs).Results234 patients were included, all of whom had been previously exposed to at least one biologic (median 4, IQR[3-4]), and 125 (53.9%) had undergone prior intestinal resection (Table 1). At week 12, SFCR was observed in 107 patients (n=107/197, 54%), clinical response in 120 (n=120/190, 63%) and clinical remission in 111 (n=111/197, 56%). Ninety-two (n=92/179, 51%) achieved biological remission and endoscopic or radiological response was observed in 19 (n=19/40, 48%) patients (Figure 1). Respectively 28 (n=28/37, 76%) and 20 (n=20/37, 54%) of patients with articular EIMs achieved clinical response and remission. For cutaneous EIM, clinical response was achieved in 10 patients (n=10/11, 91%), and clinical remission was achieved in nine patients (n=9/11, 82%). In multivariate analysis, body mass index < 18.5 kg/m2 (OR=0.09, 95%CI: 0.01-0.33, p=0.002) and HBI > 7 (OR=0.24, 95%CI: 0.12-0.47, p<0.0001) were associated with lower rates of SFCR at W12 while the number of prior biologics did not influence SFCR (OR = 0.72, 95% CI: 0.35-1.48; p = 0.36).At week 12, 35 (15%) patients discontinued upadacitinib (lack of effectiveness, n=31; AEs, n=2 and other, n=2). CD-related hospitalization was needed in 18 (7.7%) patients, and 4 (1.7%) underwent intestinal resection. Sixty-eight AEs occurred in 61 patients (26%), including 19 serious AEs, corresponding to 18 cases of CD exacerbation and one case of colonic EBV-associated lymphoproliferative disorder. Acne was observed in 25 (10.7%), justifying treatment discontinuation in one (0.4%).ConclusionIn this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response in about two-thirds of patients and SFCR in half of patients