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A novel in vitro system for simultaneous infections with hepatitis B, C, D and E viruses
No full textInternational audienc
Evaluation of transcutaneous electrical tibial nerve stimulation in lower urinary tract dysfunction secondary to a parkinsonian syndrome: Uroparktens—a multicenter randomized placebo-controlled study
No full textInternational audiencePurpose: Lower urinary tract dysfunction (LUTD) is common in parkinsonian syndromes (PS) and requires special treatment due to limitations in the use of certain drugs and the progression of the disease. Tibial nerve stimulation by transcutaneous electrical nerve stimulation (TENS) is a simple, well-tolerated treatment with proven effectiveness in LUTD. The aim of our study was to evaluate the efficacy on urinary symptoms in patients with a parkinsonian syndrome.Method: A prospective, double-blind, multicenter, randomized study to compare the effects of TENS 20 min a day for 3 months with sham stimulation using the 3-month Patient Global Impression of Improvement (PGI-I) score in adults with PS and LUTD for whom conventional treatments had failed. The secondary endpoints studied were 3-month changes in PGI-S (Severity), Urinary Symptom Profile (USP), Qualiveen questionnaire, voiding diary (VD), post-void residue and the rate of complications.Results: Between 2015 and 2020, 100 patients with a mean age of 68.6 ± 8.4 years were randomized and included in the intention to treat analysis population (ITT). Among them were 71 men and 85 patients with idiopathic Parkinson’s disease. Initially, the PGI-S was moderate to severe (score of 3–4) in 80 patients: 38 (83%) in the TENS group and 42 (82%) in the sham group. After 3 months of treatment, 68 patients felt an improvement (PGI-I 1–3): 30 (64%) in the TENS group and 38 (72%) in the sham-stimulation group (p = 0.399). There was no statistically significant difference between the 2 groups regardless of the endpoint considered.Conclusion: The effect of tibial neuromodulation by TENS on urinary disorders in patients with parkinsonian syndrome after 3 months of stimulation was not significantly different from the placebo effect obtained with sham stimulation
Dendritic cells: the central partner for cancer immunity
No full textInternational audienceDendritic cells (DCs) are central players in the immune system, serving as a bridge between innate and adaptive immunity. Their unique abilities to capture, process, migrate, and present tumor-associated antigens to T cells make them essential actors in initiating and regulating anti-tumor immune responses. This review provides an overview of the phenotypic heterogeneity and functional diversity of DC in cancer immunity, with an emphasis on their interactions with other immune cells within the tumor microenvironment, highlighting their collaborative efforts in driving effective antitumor immunity. Additionally, we examined the impact of tumor-derived signals and immunosuppressive mechanisms on DC functions and their implications for DCbased cancer immunotherap
Mixed precision implicit numerical schemes for systems of ordinary differential equations
No full textInternational audienceOrdinary differential equations (ODEs) are widely used to model complex systems in biology, which result from the interactions of a large number of cells or organisms. This can lead to a substantial system size. These complex interactions can quickly alter their behavior, and some biological systems are stiff when represented as ODEs [59]. Therefore, these stiff ODEs could benefit from implicit numerical schemes. However, each iteration of these schemes involves solving a large nonlinear system, typically using the Newton method. To guarantee the global convergence of this method, we use line search (LS) and trust region (TR) algorithms. In this paper, we introduce a new approach to accelerate the computation of the implicit schemes by using mixed precision arithmetic, combining float and double precision, within the LS and TR algorithms, as well as in the Newton method. This approach aims at balancing the performance of lower precision arithmetic with the accuracy of higher precision arithmetic. We give theoretical results that show the efficiency of our approach. Numerical experiments show that our approach, running in either sequential or in parallel with MPI, is up to twice as fast as the double precision approach with the same level of accuracy. These experiments also show that increasing the size of the ODEs does not impact the quality of our mixed precision solution
Predicting algorithm for GRFS after allogeneic hematopoietic stem cell transplantation: A study by the SFGM-TC
No full textInternational audienceAbstract Context : Allogeneic stem cell transplantation (alloHCT) is used in majority of acute myeloid leukemia and myelodysplastic syndromes to obtain complete remission. Graft-versus-Host disease (GVHD) and relapse are is the most important complications after alloHCT. Numerous prognostic scores are used pre-transplant to guide therapeutic strategies, but none has been sufficient to predict graft-versus-host disease/relapse-free survival (GRFS). In this study, we studied clinical, biological and therapeutic factors associated with GRFS and attempted to build a predictive score. Material & Methods : Patients over 18 years of age who received a first hematopoietic stem cell transplant between 01/01/2015 and 31/12/2022 at the University Hospitals of Saint-Etienne, Lyon, Grenoble-Alpes and Clermont-Ferrand for acute myeloid leukemia or myelodysplastic syndrome were included. Data was extracted from the allogeneic EBMT registry and patient medical records. Several parameters about clinical and biological characteristics of patient, disease, conditioning regimen and type of donor were studied. Statistics were performed with Kaplan-Meier method and Cox analysis. Regression models and supervised machine learning models were explored by the Henri Fayol Institute of the Ecole des Mines de Saint-Etienne in order to establish a predictive model. Results : Analysis included851 patients. The cohort consisted of 59% men, with a median age of 58 years. More than 70% of the patients received alloHCT for acute myeloid leukemia. The median follow-up was 938 days, and median overall survival was not reached. Median GRFS was 210 days. At the end of follow-up, GRFS was estimated at 30%. Log-rank tests found 15 significant variables. Concerning pre-transplantation characteristics, Performance Status ≥ 2, neutropenia, lymphopenia, low creatinine level, elevated lactate dehydrogenase or c-reactive protein, and pre-transplant hypoalbuminemia were associated with lower survival. Therapy-related disease or secondary to a predisposing hematologic disorder was also predictive of GRFS, as well as adverse 2022 European LeukemiaNet risk group. Patients with refractory disease or positive residual disease before transplantation had poorer survival. A mismatch unrelated donor or a graft CD3+ cell count greater than 10^7/kg were associated with reduced GRFS. Finally, alloHCT performed more than 12 months after diagnosis was linked to improved GRFS. We used these variables to develop predictive models for GRFS using linear regression and machine learning algorithms (Alternating Decision Trees, Random Forest, Support Vector Machine, Association Rules). The highest predictive performance power was achieved by association rules. Non-redundant rules, with a lift greater than 1, a minimal confidence of 0.8 and a minimal support of 0.011 (9 patients) were kept to predict GRFS at 6 months, 9 months, 1 year, 18 months and 2 years. More than 800,000 rules were generated. Accuracy was respectively 0.95, 0.96, 0.90, 0.80, and 0.73 for each timepoint. An online tool is under development to simplify the calculation of the score and will be presented at the meeting.Conclusion : Our findings are consistent with existing literature on GRFS and overall survival following alloHCT. We identified significant clinical, biological and therapeutic parameters for development of a predictive algorithm for GRFS using association rules algorithm
Clinical and environmental implications of a high-density clip closure after endoscopic submucosal dissection: is it worth it?
No full textInternational audienc
F8 gene variants influence the response to desmopressin in hemophilia A carriers
No full textInternational audienceDesmopressin (DDAVP) is often administered to correct factor VIII (FVIII) levels in female hemophilia A carriers (HACs). However, the post-DDAVP FVIII pharmacokinetic profiles have been reported only in small series in HACs. Therefore, this study analyzed the post-DDAVP FVIII and von Willebrand factor (VWF) response in 361 HACs. A population pharmacokinetic/pharmacodynamic model was developed to analyze the VWF and FVIII levels by taking into account the F8 gene variants (n = 143 [39.6%] with null; and n = 218 [60.4%] with non-null variants), demographic and laboratory covariates. The before/after DDAVP mean basal, peak and recovery FVIII activity (FVIII:C) levels were 0.34 IU/mL (0.08-0.65), 1.13 IU/mL (0.19-2.69), and 2.85 IU/mL (1.06-7.13), respectively. Peak FVIII:C was >= 0.5 IU/mL in 95.6% (345/361) and >= 0.8 IU/mL in 78.7% (284/361) of patients. The covariate analysis showed a poorer DDAVP FVIII:C response for null than non-null F8 variants: lower mean FVIII:C peak (1.04 vs 1.23 IU/mL; P < 5 x 10(-5)) and patients percentage with normalized FVIII:C (91.6% vs 98.1%; P = .0068), higher mean FVIII:C clearance (5898.83 vs 2704.06 IU/h; P = 1.58 x 10(-15)), lower mean FVIII:C area under the curve during the first 12 hours (AUC(0-12h) =7.73 vs 9.06 IU/mL per hour; P < 5 x 10(-6)), and shorter mean time with FVIII:C >= 0.8 IU/mL (1.9 vs 4.1 hours; P < 6 x 10(-6)). HAC with body weight <35 kg had lower peak FVIII:C, higher FVIII:C clearance, lower AUC(0-12h), and shorter time with FVIII:C >= 0.8 IU/mL than HAC with body weight 35 to 70 kg. In HACs, the post-DDAVP FVIII response is strongly influenced by the F8 genotype and body weight
Spironolactone in patients on chronic haemodialysis at high risk of adverse cardiovascular outcomes (ALCHEMIST): a multicentre, double-blind, randomised, placebo-controlled trial and updated meta-analysis
No full textInternational audienc
Association between late access to care and mortality for PWH: insights from the French Hospital Database on HIV (ANRS CO4-FHDH) from 2002 to 2016
No full textInternational audienceIntroduction: Using three categories of stages of HIV disease at access to care (advanced, intermediate, early HIV disease), we explored the impact of delayed access on the risk of death at up to 5 years and whether progress in antiretroviral regimens has mitigated this impact.Methods: Adults from the French Hospital Database on HIV (ANRS CO4-FHDH) cohort with HIV-1 infection and first access to care during 2002-2021 were included. To study the impact of the stage of HIV disease at first access to care on the risk of death, only participants included from 2002 to 2016 were analysed to allow for at least 5 years of follow-up until 31 December 2021. Fine and Gray competing risk models considering lost to follow-up as a competing event were used adjusting for age, gender, mode of acquisition, region of origin, time between diagnosis and access to care, period of access to care (2002-2013 vs 2014-2016).Results: Among the 64 400 people living with HIV included, 18 305 (28.4%) had advanced and 13 042 (20.3%) intermediate HIV disease. The 5-year cumulative incidence of death was estimated as 1.8% (95% CI 1.7% to 1.9%) overall, from 0.9% (0.8% to 1.0%) for those with early HIV disease to 6.0% (5.4% to 6.7%) for those with AIDS. People with AIDS had a much higher risk of death than those with early HIV disease, with a sub-distribution HR (sHR) of 18.4 (95% CI 12.0 to 28.4) in the first 6 months of follow-up, which remained significant at 48-60 months: sHR=2.1 (1.3 to 3.3). The risk of death was higher for the other categories of advanced HIV disease but to a smaller extent. The risk of death was not statistically different depending on the calendar period.Conclusions: Delayed access to care remains associated with an elevated risk of death, even after 48 months. There was no significant improvement in the risk of death after 2014 when immediate initiation of combined antiretroviral therapy was recommended and integrase strand transfer inhibitor-based regimens became the preferred first-line
Chronic pain and post-traumatic stress in older patients with psychiatric disorders during the Covid-19 pandemic: co-occurrence and influence of attachment and personality factors
No full textInternational audienceAbstract Objectives The Covid-19 pandemic context may have had numerous effects on the health of older patients with psychiatric disorders (PD), confronting them with a new source of stress and hindering their access to care. The aim of this study was to assess the long-term effects of the pandemic on both chronic pain (CP) and post-traumatic stress (PTS); the comorbidity of the two disorders; and to identify common psychological risk factors. Design Medical interviews were conducted during and after (12 and 18 months later) the first lockdown. Setting The STERACOVID longitudinal cohort study, conducted in two French hospitals. Participants 71 patients aged 65 or over; treated in an outpatient psychiatric service; and free of major neurocognitive disorders. Measurements Validated scales were used to assess CP (ICD-11 criteria); PTS (PCL-S); personality traits (BFI-Fr); attachment style (RSQ); and coping strategies (BRIEF-COPE). χ² and Student’s t-tests, analyses of variance and logistic regression were used to compare patients with or without CP and/or PTS, in terms of attachment styles, personality traits and coping strategies. Results CP and PTS were frequent and often co-occurring at T2. Fearful and preoccupied attachment styles and neurotic and extraverted personality traits were associated with the development of these two disorders; while coping strategies were not determinant. Conclusions Our study identified factors associated with a higher risk of developing CP and/or PTS in the pandemic context. Assessment of attachment style and personality traits in clinical routine could help identify patients who are most vulnerable to this type of stress, and prevent the development of disabling chronic conditions