Impact of cardiac resynchronization therapy optimization inside a heart failure programme : a real‐world experience

Aims: This study sought to describe and evaluate the impact of a routine in‐hospital cardiac resynchronization therapy (CRT) programme, including comprehensive heart failure (HF) evaluation and systematic echo‐guided CRT optimization. Methods and results: CRT implanted patients were referred for optimization programme at 3 to 12 months from implantation. The program included clinical and biological status, standardized screening for potential cause of CRT non‐response and systematic echo‐guided atrioventricular and interventricular delays (AVd and VVd) optimization. Initial CRT‐response and improvement at 6 months post‐optimization were assessed with a clinical composite score (CCS). Major HF events were tracked during 1 year after optimization. A total of 227 patients were referred for CRT optimization and enrolled (71 ± 11 years old, 77% male, LVEF 30.6 ± 7.9%), of whom 111 (48.9%) were classified as initial non‐responders. Left ventricular lead dislodgement was noted in 4 patients (1.8%), and loss or ≤90% biventricular capture in 22 (9.7%), mostly due to arrhythmias. Of the 196 patients (86%) who could undergo echo‐guided CRT optimization, 71 (36.2%) required VVd modification and 50/144 (34.7%) AVd modification. At 6 months post‐optimization, 34.3% of the initial non‐responders were improved according to the CCS, but neither AVd nor VVd echo‐guided modification was significantly associated with CCS‐improvement. After one‐year follow‐up, initial non‐responders maintained a higher rate of major HF events than initial responders, with no significant difference between AVd/VVd modified or not. Conclusions: Our study supports the necessity of a close, comprehensive and multidisciplinary follow‐up of CRT patients, without arguing for routine use of echo‐guided CRT optimization

Déterminisme des fuites aortiques après implantation d'une valve aortique per cutanée, étude comparative du diamètre de l'anneau aortique en échocardiographie et en tomodensitométrie pour le choix de la valve implantée, conséquences pronostiques

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

Vitamin K antagonists and emergencies

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: Rebamipide and colonic barrier

International audienceOur aim was to study the effect of a mucosal protective agent, rebamipide, on the colonic barrier and the immune response in colitis-prone interleukin-10 deficient (IL-10-/-) C57BL/6 mice infected with Helicobacter hepaticus. After sacrifice, in all mice, control, or previously infected with H. hepaticus, or previously infected and treated with rebamipide enema, a histological examination of colonic samples was performed, intestinal permeability was studied in Ussing chamber, and mesenteric lymph node proliferation and cytokine secretion were measured. Mice treated with rebamipide, presented a reinforcement of the distal colonic epithelial barrier, an increase of mesenteric lymph node cells proliferation and of IFNΓ and IL-12 secretion. These results indicate that in IL-10-/- mice with mild colitis, rectally administered rebamipide reinforces the distal colonic barrier and has a slight Th1 immuno-stimulatory effect on mesenteric lymph node cells. These properties could be helpful in the management of some inflammatory bowel diseases

PIK3CA gain-of-function mutation in adipose tissue induces metabolic reprogramming with Warburg-like effect and severe endocrine disruption

International audiencePIK3CA -related overgrowth syndrome (PROS) is a genetic disorder caused by somatic mosaic gain-of-function mutations of PIK3CA . Clinical presentation of patients is diverse and associated with endocrine disruption. Adipose tissue is frequently involved, but its role in disease development and progression has not been elucidated. Here, we created a mouse model of PIK3CA -related adipose tissue overgrowth that recapitulates patient phenotype. We demonstrate that PIK3CA mutation leads to GLUT4 membrane accumulation with a negative feedback loop on insulin secretion, a burst of liver IGFBP1 synthesis with IGF-1 sequestration, and low circulating levels. Mouse phenotype was mainly driven through AKT2. We also observed that PIK3CA mutation induces metabolic reprogramming with Warburg-like effect and protein and lipid synthesis, hallmarks of cancer cells, in vitro, in vivo, and in patients. We lastly show that alpelisib is efficient at preventing and improving PIK3CA -adipose tissue overgrowth and reversing metabolomic anomalies in both animal models and patients

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study

International audienceBackground: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France.Methods: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease.Results: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]).Conclusion: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19

Cardiac Adverse Events and Remdesivir in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial

International audienceBackground We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with Coronavirus Disease 2019 (COVID-19) receiving remdesivir plus standard of care (SoC) compared to SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. Methods This post-hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19 (NCT04315948). Any first AE occurring between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves and Kaplan-Meier estimates were calculated for event rates. Results Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (HR 1.0, 95% CI 0.7-1.5, p = 0.98), even when evaluating serious and non-serious cardiac AEs separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between remdesivir and control groups in the occurrence of different cardiac AE subclasses, including arrhythmic events (HR 1.1, 95% CI: 0.7-1.7, p = 0.68). Conclusions Remdesivir treatment was not associated with an increased risk of cardiac AEs, whether serious or not, and regardless of AE severity, compared to control, in patients hospitalized with moderate or severe COVID-19. This is consistent with the results of other randomized controlled trials and meta-analyses

Impact of the first wave of COVID-19 epidemy on the surgical management of sigmoid diverticular disease in France: National French retrospective study

International audienceObjective: To analyze the surgical management of sigmoid diverticular disease (SDD) before, during, and after the first containment rules (CR) for the first wave of COVID-19.Methods: From the French Surgical Association multicenter series, this study included all patients operated on between January 2018 and September 2021. Three groups were compared: A (before CR period: 01/01/18-03/16/20), B (CR period: 03/17/20-05/03/20), and C (post CR period: 05/04/20-09/30/21).Results: A total of 1965 patients (A n = 1517, B n = 52, C n = 396) were included. The A group had significantly more previous SDD compared to the two other groups (p = 0.007), especially complicated (p = 0.0004). The rate of peritonitis was significantly higher in the B (46.1%) and C (38.4%) groups compared to the A group (31.7%) (p = 0.034 and p = 0.014). As regards surgical treatment, Hartmann's procedure was more often performed in the B group (44.2%, vs A 25.5% and C 26.8%, p = 0.01). Mortality at 90 days was significantly higher in the B group (9.6%, vs A 4% and C 6.3%, p = 0.034). This difference was also significant between the A and B groups (p = 0.048), as well as between the A and C groups (p = 0.05). There was no significant difference between the three groups in terms of postoperative morbidity.Conclusion: This study shows that the management of SDD was impacted by COVID-19 at CR, but also after and until September 2021, both on the initial clinical presentation and on postoperative mortality

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

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