HAL UVSQ
Not a member yet
57319 research outputs found
Sort by
Combined minimally invasive vagal cranial nerve and trigeminocervical complex peripheral nerve stimulation produces prolonged improvement of severe painful peripheral neuropathy and hyperglycemia in type 2 diabetes
No full textInternational audienceDiabetic Peripheral Neuropathy (DPN), a debilitating complication of type 2 diabetes mellitus (T2DM), stems from bioenergetic failure and reduced vascular endothelial growth factor-A expression (VEGF-A), persisting despite optimal glycemic control. The meteoric rise of "diabesity"-the coexistence of obesity and T2DM-underscores the ongoing failure of symptom control strategies and the critical need to immediately address the root cause of metabolic dysfunction and neuropathic pain. An analysis was performed on patients who received combined minimally invasive auricular vagus cranial nerve stimulation (aVNS) and trigeminocervical complex (TCC) peripheral nerve stimulation in 83 Native American patients (91 initial, 8 lost to follow-up) with severe T2DM and DPN pain who were offered stimulation in the routine course of clinical care. Participants were implanted on branches of their vagal and trigeminal cranial nerves, along with their upper cervical peripheral nerves and stimulated for 19 days prior to explantation. Numerical Rating Pain Scores (NRS) and mean blood glucose levels were measured at 30-, 60-, and 90-days post-explant. Notable results include: NRS pain scores dropping 87% (7.92 to 1.04), mean blood glucose decreasing 37% (209 to 121 mg/dL), and HbA1c levels falling from 8.9% to 5.8% at 90 days. These improvements were all sustained for an average of 7.85 months of follow up. Additionally, a random subset decreased 80% of all pain and diabetes medications. This efficacy surpasses prior outcomes from cervical VNS alone, highlighting the synergy of targeting both the vagal and trigeminal cranial nerves along with the trigeminocervical complex. These findings position combined minimally invasive aVNS and TCC peripheral nerve stimulation as a promising immediate therapy for the current DPN and diabesity crisis, as well as a potential non-pharmacologic alternative for the management of type 2 diabetes
Intravenous thrombolysis before endovascular treatment in acute vertebrobasilar occlusions: Pooled analysis of the French and German Stroke Registries
No full textInternational audienceIntroduction: Whether intravenous thrombolysis (IVT) provides additional benefit in eligible patients with acute vertebrobasilar occlusion who undergo endovascular treatment (EVT) remains an open question. Patients and methods: We conducted a pooled analysis using data from two national stroke registries, the ETIS registry in France and GSR-ET registry in Germany. Patients who underwent EVT for vertebral and/or basilar artery occlusions from January 2015 to December 2023 were included. The primary efficacy outcome was a favorable shift toward better functional outcomes on modified Rankin Scale (mRS) scores at 90 days. Safety outcomes included 90-days mortality and symptomatic haemorrhagic transformation (sICH). Comparisons between IVT + EVT and direct EVT groups were made combining inverse propensity score matching, probability of treatment weighting (IPTW) and regression models. Results: Among 2028 patients treated during the study period, 797 (39.2%) received IVT before EVT, while 1231 (60.7%) had EVT alone. After IPTW matching, we compared 211 patients treated with IVT + EVT to 260 direct EVT patients. Patients in the IVT + EVT group had a favorable shift across the 90-day mRS distribution (common aOR 1.43 per 1-point mRS improvement, 95% CI 1.01–2.04; p = 0.046), higher odds of 90-day favorable functional outcome (aOR 1.56, 95% CI 1.00–2.44; p = 0.049) and lower odds of 90-day mortality (aOR 0.62, 95% CI 0.39–0.99; p = 0.045). IVT was not associated with increased risk of sICH (aOR 1.65, 95% CI 0.62–4.35; p = 0.313). Discussion: This registry-based study suggests a potential benefit of IVT before EVT in eligible patients with vertebrobasilar occlusions. Conclusion: Randomized clinical trials are necessary to confirm these findings and to validate the benefits of IVT in this clinical context
Immune response and clinical severity are shaped by skin-adapted Staphylococcus aureus in chronically infected patients
No full textInternational audienceDespite the well-described association of skin lesions with Staphylococcus aureus, the distinct ability of clinical isolates to influence the local and systemic inflammatory response in a patient-specific manner is insufficiently characterized. In this study, we analyzed clinical recessive dystrophic epidermolysis bullosa (RDEB), which is characterized by wounds chronically colonized with S. aureus, to explore the relationship between inflammatory immune response and strain diversity. Children with RDEB (moderate phenotype, n = 5; severe phenotype, n = 10) and controls (n = 18) were enrolled in the study. Profiling of plasma proteins (n = 800), immune cells (n = 30 subsets and cytokine-producing cells), and cytokines (n = 38) identified a specific inflammatory signature in severe disease. Furthermore, patients with severe RDEB presented a high frequency of interleukin-17A+ (IL-17A+) cells among CD4+ and mucosal-associated invariant T (MAIT) lymphocytes. Positive S. aureus cultures from the skin of patients with RDEB allowed whole-genome sequencing of patient strains and assessment of primary keratinocyte immune response upon bacterial challenge. S. aureus secretome and conditioned medium from keratinocytes challenged with S. aureus strains from patients with severe but not from those with moderate RDEB promoted strong activation and a pro-IL-17 response in both CD4+ and MAIT cells. Our findings show that S. aureus strains isolated from patients with severe RDEB induce an IL-17-skewed immune response and pave the way for precision microbiology to explain and predict the highly variable virulence potential of bacterial clinical isolates
Efficacy and safety of nivolumab plus ipilimumab for patients with pre-treated type B3 thymoma and thymic carcinoma: Results from the EORTC-ETOP NIVOTHYM phase II trial.
No full textInternational audience8016 Background: Thymic malignancies represent a therapeutic challenge in the advanced, metastatic setting, with limited options after the failure of platinum-based chemotherapy. Methods: NIVOTHYM is a multicenter phase II, 2-cohort, single-arm trial evaluating the use of nivolumab (N)+/-ipilimumab (I) in patients ≥18yo, with advanced/relapsed type B3 thymoma or thymic carcinoma (TC), after previous exposure to platinum-based chemotherapy.Primary endpoint wasProgression-Free Survival (PFS) rate at 6 months based on RECIST1.1 per independent radiological review. We report the results of cohort 2 with patients who received N 240 mg Q2W and I 1mg/kg Q6W. Results: From Feb 2021 to Jan 2023, 56 patients – 8 (14%) with type B3 thymoma, 48 (86%) with TC - were enrolled in 15 centers/5 countries, of which 37 (66%) men/19 (34%) women. Median age was 64 years. 23 (41%) patients had had surgery. After a median follow-up of 16.0 months, 50 patients had discontinued N+I for: progression in 36 (72%) pts, treatment-related adverse events (TRAEs) in 11 (22%) pts, completion in 2 (4%) pts, and pt decision for 1 pt (2%). Maximal grade of adverse events was 1/2 in 29 (52%) patients, and 3/4 in 27 (48%) patients. Grade ≥3 TRAEs occurred in 16 (29%) pts: myocarditis (2 pts), colitis (4 pts), infusion-related reaction/allergy (2 pts), skin rash (2 pts), heart failure, immune-related hepatitis, arthritis, myositis, hypophysitis, Gougerot Sjogren syndrome, pharyngitis, fatigue, fever, infusion-related reaction (1 pt each); there was no grade 5 TRAE. PFS rate at 6 months was 21.6%. Objective Response and Disease Control Rates were 17.7% and 60.8%, respectively. Median PFS and Overall Survival were 3.2 (95%CI 2.1-3.6) and 22.0 (95%CI 16.6-NR) months, respectively; median duration of response was 7.1 (95%CI 1.4-17.0) months, and 8 (14%) pts received treatment for ≥12 months. Conclusions: N+I demonstrated limited efficacy in advanced thymic tumors, as prespecified PFS rate at 6 months of 40% was not reached, compared to the previously reported cohort 1 of this trial with N as single-agent. Numerically more patients experienced grade ≥3 TRAEs, while efficacy endpoints were not numerically higher. Clinical trial information: NCT03134118
Hyperintense acute reperfusion marker and gadolinium leakage in ocular structures in stroke: a systematic review
No full textInternational audienceIntroduction :The Hyperintense Acute Reperfusion Marker (HARM) and Gadolinium Leakage in Ocular Structures (GLOS) are pivotal radiological findings in post-contrast fluid-attenuated inversion recovery imaging (pcFLAIR), attesting to gadolinium leakage into the cerebrospinal fluid (CSF) in various neurological disorders. Often observed following acute strokes, HARM and GLOS, however, exhibit considerable variability in their prevalence ranging from 5.5 to 85% and 30–76%, respectively. Given their similarity and association of HARM with poor outcomes in stroke, accurately evaluating these markers may be crucial for advancing our understanding of stroke pathophysiology and improving clinical management. Our work aims to identify the major methodological challenges and confounding factors limiting the understanding of HARM and GLOS in stroke.Methods :To address these issues, we thoroughly conducted a literature search in Embase, Scopus, and PubMed until July 2022. Our search yielded 38 stroke studies, with only 6 evaluating GLOS. Guided by major findings, we adapted the Newcastle-Ottawa scale for bias risk assessment. Effect estimates were synthetized considering cohort size, statistical significance, and bias risk.Results :Methodological issues emerged from the lack of time-specific data, omission of differential CSF hyperintensities, imprecise definitions, and overlooking of adjusting variables like assessment timing, contrast dosages or renal function. Discrepancy results mainly arise from an inadequate time window of investigation, and further research should stratify patients based on the timing of gadolinium injection.Conclusion :Our findings emphasize the importance of a more detailed exploration of their timing and localization, rather than simply their binary presence, extent, or severity
Endometriosis Diagnostic Delay and Its Correlates: Results from the ComPaRe-Endometriosis Cohort
No full textInternational audienceBackground : An average time to diagnosis of 7 years is commonly described for endometriosis; diagnostic delay for adenomyosis is unknown. This cross-sectional study aimed to describe diagnostic delay for endometriosis and adenomyosis and to investigate the factors associated with this delay.Methods : Community of Patients for Research (ComPaRe)-Endometriosis is a prospective e-cohort of women with endometriosis and/or adenomyosis in France. About 6,949 participants were included. We used linear regression modeling to assess factors associated with diagnostic delay, after adjustment for age, education level, body mass index, number of comorbidities, and family history of the disease or of chronic pelvic pain (CPP).Results : The average diagnostic delay was 10 years for endometriosis and 11 years for adenomyosis. Factors associated with a significantly longer diagnostic delay were year of diagnosis (+0.34 years, p < 0.0001), unemployment (+0.7 years, p = 0.01), number of comorbidities (+0.3 years, p < 0.0001), family history of the disease or of CPP (+1.1 years, p < 0.0001), severe dysmenorrhea before diagnosis (numeric-rating scale: +0.8 years, p < 0.0001), number of health professionals consulted before diagnosis (+0.3 years, p < 0.0001), and presence of multiple symptoms leading to first consultation (+1.6 years, p < 0.0001). In contrast, factors associated with a shorter delay were a financial position perceived as comfortable (−1.4 years, p < 0.0001), age at menarche (−0.6 years, p < 0.0001), and age at first symptoms (−0.8 years, p < 0.0001).Conclusions : This study highlights several factors associated with diagnostic delay among women with self-reported endometriosis and/or adenomyosis and provides new insights to improve care by informing both clinicians and patients. Attention to these profiles may improve disease management
Assessment of GFR Estimation Methods in Patients with Obesity
No full textInternational audienceAbstract Purpose Obesity is an independent risk factor for chronic kidney disease, and accurate estimation of the glomerular filtration rate (GFR) is crucial. However, limited data are available on the performance of the European Kidney Function Consortium (EKFC) equation in individuals with overweight or obesity. We evaluated the performance of the EKFC equation by comparing its estimated GFR (eGFR) to values obtained from the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and machine learning (ML) models, using measured GFR (mGFR, obtained via plasma iohexol clearance) as a reference standard in a cohort of patients with overweight or obesity. Methods To evaluate the performance of the non-indexed EKFC equation compared with the 2021 CKD-EPI equation and machine learning models, we calculated the median bias (eGFR minus mGFR) and the concordance correlation coefficient for each method. Results The non-indexed EKFC equation exhibited the highest median bias (−4.80mL/min, 95%CI:−7.49 to −2.92), particularly in patients with overweight (−7.81mL/min, 95%CI:−12.87 to −4.80) and obesity (−4.57mL/min, 95%CI:−8.57 to −1.72), with lower bias in healthy BMI individuals (−2.50mL/min, 95%CI:−6.85 to 2.23). The EKFC equation showed lower concordance with mGFR than both the CKD-EPI 2021 equation and ML models, and was the least accurate for CKD stage classification in patients with obesity, particularly those with hyperfiltration. Conclusion In patients with overweight or obesity, the EKFC equation performed worse than the ML-based models and the CKD EPI 2021 equation despite limitations of the latter in European populations. Our findings highlight the need for more accurate GFR estimation in this population, optimization of these models, and their validation in larger, more diverse cohorts
QT-Prolonging Medications: Prevalence of Use and Associated Risks in CKD
No full textInternational audienceChronic kidney disease (CKD) affects over 10% of the global adult population and is associated with substantial cardiovascular morbidity and mortality. Sudden cardiac death (often precipitated by ventricular arrhythmias like torsades de pointes) is a leading cause of death in patients with CKD. Prolongation of the QT interval (a marker of delayed ventricular repolarization) is a significant risk factor for arrhythmia in patients with CKD, whether they are on dialysis or not. QT prolongation in CKD is multifactorial and may result from electrolyte imbalances, myocardial remodelling, autonomic dysfunction, and exposure to QT-prolonging drugs. Patients on haemodialysis are particularly vulnerable to QT prolongation, due to rapid intradialytic electrolyte and fluid shifts. Many drugs known to prolong the QT interval (including various selective serotonin reuptake inhibitors, antibiotics, antiemetics, and antipsychotics) are frequently prescribed to patients with CKD, even though there are few data on their safety in this population. The results of several well-designed pharmaco-epidemiological analyses (all based on data from the United States Renal Data System) have shown associations between QT-prolonging drugs and an elevated risk of sudden cardiac death among patients on dialysis. These findings are concerning, given the widespread use of such drug. The objective of this narrative review is to critically evaluate the pathophysiological relevance, prevalence, and cardiovascular consequences of QT-prolonging drug use in the CKD setting
The Greenhouse Gas Budget of Southeast Asia for 2000–2019 and Pathways Toward Climate Neutrality
No full textInternational audienceMember countries of the Association of Southeast Asian Nations ratified the Paris Agreement and have initiated their own efforts to reduce greenhouse gas (GHG) emissions. However, the progress of these countries toward climate neutrality remains uncertain. Here, we estimated the combined budget for carbon dioxide (CO 2 ), methane (CH 4 ), and nitrous oxide (N 2 O) in Southeast Asia for 2000-2019 using bottom-up and top-down approaches. The CO 2 emissions from deforestation were the largest source, followed by anthropogenic fire emissions, which together exceeded the CO 2 uptake by natural vegetation and land-use change legacy (e.g., regrowth), yielding a net source of CO 2 in the biosphere. The region's biosphere was also a net source of CH 4 and N 2 O, which, combined with the CO 2 budget, makes the Southeast Asian biosphere a net source of GHGs to the atmosphere, ranging from 2,003.2 ± 406.1 Tg CO 2 eq yr 1 (bottom-up) to 2,227.5 ± 572.8 Tg CO 2 eq yr 1 (top-down) for 2000-2019. Among non-biospheric GHG emissions (e.g., fossil fuels and waste-related emissions), coal usage has resulted in an unprecedented increase in CO 2 emissions. The total GHG budget (the biospheric GHG budget plus the non-biospheric GHG fluxes) was calculated as a net source of 3,226.3 ± 406.2 Tg CO 2 eq yr 1 (bottom-up) and 3,406.4 ± 572.9 Tg CO 2 eq yr 1 (top-down) for 2000-2019. Our study revealed that Southeast Asia is experiencing the dual challenge of large emissions from land-usechanges and coal usage
