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Management of bleeding and invasive procedures in patients treated with anti-factor XI(a) anticoagulants: proposals from the French Working Group on Perioperative Haemostasis (GIHP) and the French Society of Thrombosis and Haemostasis (SFTH)
No full textInternational audienceBackground: Several anti-FXI(a) agents with distinct mechanisms of action and pharmacological properties are currently under clinical development. While these anticoagulants are not yet available, there is a need to address bleeding risk management for patients already enrolled in phase III trials. These patients may face elective or unplanned invasive procedures and bleeding events in anticipation of marketing authorization.Experience from managing patients with inherited FXI deficiency, along with data from early clinical trials, suggests that the bleeding risk associated with anti-FXI(a) is likely to be low but can vary depending on the clinical situation. Anti-FXI(a) reversal options include tranexamic acid, FXI concentrates, and recombinant activated factor VII. However, these options may not always be suitable, can be expensive, and may carry a thrombotic risk.Objectives: The French Working Group on Perioperative Haemostasis (Groupe d'Intérêt en Hémostase Péri-opératoire (GIHP)) and the French Society of Thrombosis and Haemostasis (SFTH) aimed to develop proposals to manage bleeding and invasive procedures in patients treated with anticoagulants targeting Factor XI or XIa (anti-FXI(a)).Methods: Literature review and development of practical guidelines by an expert panel.Results: We propose pragmatic recommendations for optimizing safety in patients treated with anti-FXI(a), considering bleeding and thrombosis risks, the drug's mechanism of action, and available reversal options.Conclusion: These proposals will be re-evaluated as more data becomes available. The implementation of a registry for managing anti-FXI(a) anticoagulants in patients undergoing invasive procedures or experiencing bleeding complications is needed
Beneficial Effects of Omega-3 Fatty Acids on Obesity and Related Metabolic and Chronic Inflammatory Diseases
No full textInternational audienceOmega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to help resolve inflammation through generation of anti-inflammatory eicosanoids and specialized pro-resolving mediators, including resolvins, protectins, and maresins. Through binding to the GPR120/FFAR4 receptor, their beneficial effects result from phospholipid membrane remodeling, impairment of inflammatory signaling molecules clustering, subsequent inhibition of NF-κB and inflammasome activation, and a reduction in oxidative stress. Obesity, a chronic inflammatory disease that contributes to metabolic disorders, is alleviated by n-3 PUFAs. In the adipose tissue (AT) of individuals with obesity, n-3 PUFAs counteract hypoxia, inhibit immune cell infiltration and AT inflammation, improve insulin sensitivity, and reduce fat mass. Beyond AT, n-3 PUFAs also alleviate other metabolic disorders such as metabolic-associated steatotic liver disease (MASLD), gut dysbiosis, and/or renal dysfunction. In cardiovascular disease (CVD), they are mainly recommended as a secondary prevention for patients with coronary heart disease risks. This review provides an in-depth analysis of the benefits of n-3 PUFAs in obesity and related metabolic diseases, examining both the mechanistic and clinical aspects. Additionally, it also explores the effects of n-3 PUFAs in obesity-related chronic inflammatory conditions, including inflammatory bowel disease, psoriasis, rheumatoid arthritis, osteoarthritis, and multiple sclerosis, by targeting specific pathophysiological mechanisms. Clinical applications and limitations of n-3 PUFAs are discussed based on findings from human clinical trials
Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia
No full textInternational audienceHost-directed therapy, using nasal administration of the Toll-like receptor 5 agonist flagellin in combination with antibiotics, has proven effective against pneumococcal pneumonia. In this study, we investigated the immune mechanisms underlying the therapy-induced protective effects. Transcriptomic analysis of lung tissue during infection revealed that flagellin not only enhanced pathways associated with myeloid cell infiltration into the airways and antimicrobial functions, but also promoted the early and transient mobilization of neutrophils and inflammatory monocytes. Neutrophils were identified as crucial for the protective effects of flagellin. The adjunct activity of flagellin correlated with the increased recruitment of neutrophils into airways, their localization at the periphery of bronchi, alveoli, and lung vessels, along with alterations in phagocytic activity. Clustering analysis identified seven neutrophil subsets; notably, flagellin adjunct treatment expanded clusters involved in recruitment and antibacterial activity, and primed augmented functionality. In conclusion, this study highlights specific neutrophil subsets as a promising target for host-directed therapy in infection
Inherited and Acquired Defects of Megakaryopoiesis and Thrombopoiesis
No full textInternational audienc
Varicella Zoster Virus Vaccination in Patients With Immune-Mediated Inflammatory Diseases: Drivers and Barriers.
No full textInternational audienc
Modeling the impact of ivermectin-based optimal strategies on malaria control: the role of formulation, coverage, and mosquitocidal efficacy timing
No full textBackground: Despite wide use of insecticidal nets and indoor spraying, residual malaria transmission persists due to insecticide resistance and mosquito behaviors like early and outdoor biting. Ivermectin (IVM) kills mosquitoes post-blood feeding regardless of resistance. However, oral IVM's short efficacy and frequent dosing limits impact. Using pharmacokinetic data from a novel long-acting injectable IVM (BEPO ® technology), we modeled its effect on malaria transmission.Methods: We developed a mathematical model incorporating IVM's pharmacodynamic memory and stratifying humans by age and sex. Three regimens were evaluated: (i) monthly oral IVM at 3×300 µg/kg for 4 months, (ii) monthly oral IVM at 1×400 µg/kg for 3 months, and (iii) long-acting BEPO ® injection at 0.6 or 1.0 mg/kg. The model includes post-exposure effects on mosquitoes and the target population excludes women of childbearing age or pregnant women, and children under 15 kg. Efficacy data came from published oral studies and injectable data.Findings: Campaigns delivering ivermectin are projected to lower clinical prevalence, with slightly greater benefits in Burkina Faso-like seasonal settings when aligned with the transmission peak. Under perennial transmission and 50-90% coverage, oral regimens reduced total cases (all ages) by 7-11% (RIMDAMAL II K ), 9-14% (BOHEMIA), and 24-38% (RIMDAMAL II S ) over one year. A single longacting injectable IVM campaign achieved 16-29%, rising to 33-57%, 48-74%, and 59-78% with two, three, and four campaigns, respectively.Interpretations: Long-acting injectable ivermectin offers prolonged efficacy and simpler delivery to tackle residual malaria transmission. Phase 1 trials are timely and warranted
Transferability of European-derived Alzheimer’s disease polygenic risk scores across multiancestry populations
No full textInternational audienceA polygenic score (PGS) for Alzheimer’s disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with the AD risk, age at onset and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E locus (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries. A cross-ancestry polygenic risk score improved the association with the AD risk in most of the multiancestry populations tested when the APOE region was included. Finally, we found that the PGS/polygenic risk score captured AD-specific information because the association weakened as the diagnosis was broadened. In conclusion, a simple PGS captures the AD-specific genetic information that is common to populations of different ancestries, although studies of more diverse populations are still needed to better characterize the genetics of AD
Breaking down malaria outbreak: A multidisciplinary approach in a border village of French Guiana
No full textInternational audienceBackground Isolated areas of malaria transmission can persist in countries nearing malaria elimination. To tailor interventions accordingly, smaller-scale surveillance and a deeper understanding of local conditions are needed, including human, environmental and vectorial parameters, and how these parameters interact. This study investigated the potential at-risk situations that could explain the dynamics of malaria persistence in an isolated recurrent high transmission area in French Guiana, using a transdisciplinary approach. Methodology/Principal Findings We implemented an ancillary study in Trois-Palétuviers (200 inhabitants), an isolated village in French Guiana bordering Brazil. This was based on two cross-sectional surveys conducted from September to December in 2017 and 2018 that collected both malaria prevalence and behavioural data. Entomological data were collected using 4 Mosquito Magnet traps for three consecutive nights each month. A total of 182 participants were included. The median age was 12.5 years in 2017 (IQR [5;27]). Malaria PCR prevalence was 51% (n = 92) in 2017 and 16% (n = 30) in 2018. Almost all participants used bed nets (99%, n = 180) – but 88% had at least one factor of bed nets ineffectiveness (mainly inadequate drying and washing) –, 63% (n = 114) used indoor insecticides and 32% (n = 57) used skin repellents. Anopheles darlingi , representing 99.7% of the Anopheles caught, were captured throughout the night, with higher abundance in the evening and early morning. No An. darlingi were found in slash-and-burn fields. The high relative abundance of An. darlingi before bedtime exposed inhabitants to the vector’s bites. Conclusions/Significance The absence of An. darlingi in expected locations, such as slash-and-burn fields, points to the complex ecology of malaria transmission and underscores the need for a nuanced understanding of environmental influences, with continuous surveillance. Cross-description of the data suggests a high risk of exposure to mosquito bites by residents before they are protected by bed nets. The inadequacy of anti-vectorial protective measures could be mitigated by education campaigns about protective tools, and by additional protective tools and a frequent distribution of bed nets
The One Health approach to manage Rift Valley fever transmission
No full textSource Agritrop Cirad (https://agritrop.cirad.fr/614886/)International audienc