Inherited metabolic diseases are genetic diseases that are individually rare but collectively common. Although they are classically considered as pediatric diseases, many patients are seen in adulthood, either due to a misdiagnosis over several years or a late initial presentation. A diagnosis in adulthood is crucial because it can lead to the implementation of specific treatments that improve patients' quality of life. Once a diagnosis is made, specialized genetic counseling helps identify and potentially treat other at-risk family members. Les maladies héréditaires du métabolisme sont des maladies génétiques rares individuellement, mais fréquentes collectivement dans la population générale. Bien qu’elles soient classiquement considérées comme des maladies pédiatriques, de nombreux patients sont diagnostiqués à l’âge adulte, soit après une errance diagnostique de plusieurs années, soit en raison d’une présentation initiale tardive. Le diagnostic à l’âge adulte est très important, car il peut permettre de mettre en place des traitements spécifiques qui améliorent la qualité de vie des patients. Une fois le diagnostic posé, le conseil génétique spécialisé aide à identifier et, le cas échéant, à traiter d’autres membres de la famille à risque.
Antiretroviral therapy (ART) reduces human immunodeficiency virus type 1 (HIV-1) replication to undetectable levels but does not eliminate HIV-1 reservoirs, which persist in memory CD4+ T-cells of various antigenic specificities. Hepatitis C virus (HCV) coinfection is associated with an increase in HIV-DNA burden, but whether HCV-specific CD4+ T-cells are susceptible to HIV-1 infection and harbour replication-competent HIV reservoirs upon HCV resolution is unknown. In this cross-sectional study, we examined the impact of HCV infection on CD4+ T-cell susceptibility to HIV-1 infection in vitro and reservoir persistence during ART in subjects with chronic HCV infection and uninfected controls (n = 20/group) and longitudinally in one ART-treated HCV+HIV+ individual who spontaneously resolved multiple episodes of HCV infection. Memory CD4+ T-cells from subjects with chronic HCV exhibited superior permissiveness to productive HIV-1 infection in vitro (p = 0.03) compared to uninfected. This was proportional to plasma HCV-RNA levels (p = 0.046; r = 0.491). HCV-specific CD4+ T-cells distinguished from other antigenic specificities (e.g., Cytomegalovirus) by a CCR5+ (HIV-1 co-receptor), CXCR6+ (liver-homing marker) and CCR6+ (Th17 marker) phenotype and supported productive HIV-1 infection in vitro. In the HCV+ HIV+ subject, HCV-specific CD4+ T-cells carried replication-competent reservoir during acute HCV reinfection, with integrated HIV-DNA persisting in these cells upon HCV clearance. We provide evidence that HCV-specific CD4+ T-cells are targets of integrative HIV-1 infection and carry proviruses that persist during ART despite HCV resolution. Canadian Institutes of Health Research (CIHR) (PJT-173467, PJT-153052, PJT-178127, PJT-195736, HB2-164064, BR4-197730, MOP135260, FDN-143270, CTN222 and NHC142832), the National Institutes of Health (NIH) (U19AI159819), and Fonds de recherche du Québec-Santé (FRQS)-Réseau SIDA/maladies infectieuses.
Nano-rare diseases, affecting fewer than 30 individuals worldwide, are mostly genetic and severe, with no effective treatments available. Nucleic acid-based therapies, such as antisense oligonucleotides, allow for the targeted modulation of gene expression. Successes like nusinersen and ultrapersonalized treatments (for example, Milasen) highlight their potential. Other approaches, including viral gene therapy and CRISPR-Cas9, enable the addition or correction of genes. However, major challenges remain, including high costs, difficulties in conducting clinical trials, and inadequate regulatory frameworks, especially for "N-of-1" therapies. International initiatives are emerging to facilitate access to these innovative treatments in Europe and Switzerland. Les maladies nanorares, touchant moins de 30 personnes dans le monde, sont majoritairement génétiques, graves et sans traitement. Les thérapies basées sur les acides nucléiques, comme les oligonucléotides antisens, offrent des approches ciblées capables de moduler l’expression des gènes. Des succès comme le nusinersen et des traitements ultrapersonnalisés (par exemple, milasen) illustrent ce potentiel. D’autres technologies, telles que les vecteurs viraux et la CRISPR-Cas9, permettent d’ajouter ou de corriger des gènes. Cependant, ces innovations soulèvent des défis majeurs : coûts élevés, essais cliniques difficiles et cadres réglementaires inadaptés, notamment pour les approches « N-of-1 ». Des initiatives internationales visent à améliorer l’accès à ces thérapies en Europe et en Suisse.
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The Republic of Guinea has faced an important challenge with human African trypanosomiasis (HAT), which was endemic over the last century. After initial control in the 1960s-1970s, HAT resurged in the 1990s along the Guinean coast, driven by economic and demographic pressures on the mangrove ecosystem. In response, the Guinean government established a national control program in 2002, focusing on medical mass screenings. In 2012, vector control using tiny targets was introduced in the East Boffa focus to reduce fly density and human-vector contact. However, the Ebola epidemic from 2013 to 2016 disrupted these efforts, leading to a reliance on passive screening. Resuming screenings in 2016-2017 revealed increased cases in all foci except the East Boffa area, where vector control had been effective. Vector control continued during the SARS-CoV2 pandemic and at the same time targeted door-to-door screenings were introduced to target high-risk individuals. Since 2018, around 30,000 at-risk individuals have been screened annually. These strategies reduced the total number of new cases below 1 per 10,000 inhabitants in endemic areas over the period 2019-2023, allowing to validate the elimination of HAT as a public health problem. The Guinean team and partners then focused on systematic spatial monitoring of patients and community engagement in vector control. The program also integrates control of other neglected tropical diseases and addresses new research questions, especially about anatomical and animal reservoirs for parasites. These efforts, combined with implementation of improved diagnostic tests and new oral treatments, through active involvement in multiple clinical trials and studies, now aim to interrupt HAT transmission by 2030.
The association of erythrocytosis, splenomegaly, and iron overload represents a complex diagnostic situation that may reveal hereditary stomatocytosis related to a PIEZO1 mutation. We report the case of a 76-year-old patient presenting with erythrocytosis, iron overload, and splenomegaly. The initial etiological workup was unremarkable. The identification of chronic hemolysis, associated with a decreased oxygen partial pressure at which 50% of haemoglobin is saturated with oxygen (venous P50) and abnormalities in erythrocyte deformability, guided further molecular investigations. Next-generation sequencing (NGS) identified a heterozygous pathogenic PIEZO1 mutation, confirming the diagnosis of stomatocytosis. This case highlights a misleading presentation of chronic hemolysis masked by polycythemia. Venous P50 appears to be a key discriminating marker. An integrated approach combining biological and molecular analyses is essential to avoid diagnostic delay.
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Relapsing polychondritis (RP) is a rare, multisystem inflammatory disease characterized by heterogeneous clinical manifestations and a substantial impact on patients' daily functioning and well-being. Health-related quality of life (HR-QoL) in RP remains insufficiently characterized, and no disease-specific measurement tool is available so far. This study aimed to develop and validate the RP-QoL, a multilingual, patient-reported outcome instrument specifically designed to assess HR-QoL in individuals with RP. The RP-QoL was developed within the European Reference Network ReCONNET using a structured four-step approach: (1) identification of relevant HR-QoL domains through systematic literature review, an international patient survey, and expert consensus; (2) item generation; (3) pilot testing including cognitive debriefing; and (4) comprehensive psychometric validation. Validation analyses included assessment of internal consistency, structural validity, construct validity, convergent validity with the SF-36, and criterion-related validity. Domain identification incorporated input from 274 patients across 22 countries, leading to a 31-item pilot questionnaire with a 28-day recall period and 5-point response scale. Cognitive debriefing confirmed clarity, relevance, and feasibility. Validation in 239 patients from 19 countries (median age 55 years; 80% female) demonstrated excellent internal consistency (Cronbach's α = 0.96). Exploratory factor analysis supported near-unidimensionality, with the first factor explaining 46.6% of variance. RP-QoL scores correlated strongly with disease impact (ρ = -0.62, p< 0.0001) and SF-36 physical (ρ = 0.65) and mental (ρ = 0.55, p< 0.0001) components (both p< 0.0001, p< 0.0001). Discriminative ability was high (AUC = 0.87). The RP-QoL is the first validated, disease-specific HR-QoL instrument for RP, with robust psychometric performance and applicability in both clinical practice and research.
Multidrug-resistant (MDR) Klebsiella pneumoniae is an increasingly important cause of recurrent urinary tract infections (UTIs). As bacteriophage therapy represents a promising alternative, we aimed to isolate and characterize bacteriophages targeting a clinical MDR K. pneumoniae strain causing recurrent UTI and evaluate their activity under urinary conditions. Three bacteriophages targeting an ESBL-producing K. pneumoniae clinical isolate were obtained and characterized by genome sequencing, electron microscopy, stability assays, one-step growth curves, and host-range analysis across 79 UTI isolates. Phage activity was quantified in LB medium and human urine. Three lytic phages (EDIRA083, EDIRA088, and EDIRA092) belonging to distinct genera were identified. Absence of lysogeny-associated, virulence, or antibiotic-resistance genes was confirmed. Capsule, LPS and maltoporin LamB were identified as receptors for EDIRA083 and EDIRA092. Host-range analysis revealed narrow activity for EDIRA083 and EDIRA088, whereas EDIRA092 infected 29% of the panel strains. In liquid phage infection assays, overall lytic activity was consistently higher and more sustained in human urine than in LB. These results identify three genetically distinct lytic phages targeting MDR K. pneumoniae. Their activity in urine supports further evaluation of these phages as candidates for therapeutic development against MDR Klebsiella UTI.
There is no consensus on functional imaging modalities for lesion assessment in medullary thyroid carcinoma. The aim of this single-center retrospective study was to analyze the performance of [18F]F-DOPA-PET/CT, [18F]F-FDG-PET/CT and morphologic imaging in a cohort of patients with medullary thyroid carcinoma and extrathyroidal lesions. Forty-three patients (10 women and 33 men; median age, 62.8 years), including 28 with RET mutation (germline: n=13, somatic: n=15), all with extrathyroidal morphological lesions, underwent conventional imaging, plus [18F]F-DOPA-PET/CT with early and late acquisitions (n=40), [18F]F-FDG-PET/CT (n=29) or both (n=26), for initial staging or follow-up. PET/CT scans were analyzed visually and semi-quantitatively (SUVmax of the hottest lesion). The gold-standard was based on histology and imaging follow-up. According to the gold-standard, a median 2 extrathyroidal regions were involved per patient. Per-patient sensitivity was 95.0% (38/40) for [18F]F-DOPA-PET/CT, 93.1% (27/29) for [18F]F-FDG-PET/CT, and 76.9% (30/39) for morphologic imaging. [18F]F-DOPA-PET/CT identified more hepatic and osteomedullary involvement than did [18F]F-FDG-PET/CT. The combination of both PET modalities detected at least 1 additional metastatic site in 10/26 patients (38.5%). [18F]F-DOPA SUVmax was significantly higher on early than late acquisitions (p = 0.0001) and correlated positively with blood calcitonin (p = 0.0069). [18F]F-FDG SUVmax correlated with shorter calcitonin doubling time (p = 0.0203). SUVmax and RET status did not correlate. Our results provide insight into the complementary role of [18F]F-DOPA and [18F]F-FDG PET/CT in a high-risk population with morphologically proven metastatic disease.
Data on acute respiratory distress syndrome (ARDS) are scarce in patients with cirrhosis admitted to the intensive care unit (ICU). This study aimed to assess 28-day mortality among ventilated patients with cirrhosis presenting with ARDS and identify associated factors. We conducted a retrospective observational cohort study of consecutive mechanically ventilated patients with cirrhosis admitted to two ICUs between 1 February 2007 and 31 December 2021 and fulfilling ARDS criteria during ICU stay. Demographic, clinical, and biological data were collected, and factors associated with 28-day mortality were identified using multivariable logistic regression. Among 621 patients with cirrhosis requiring mechanical ventilation, 165 (26.6%) met ARDS criteria during their stay. Reasons for ICU admission included acute respiratory failure (52.1%), gastrointestinal bleeding with shock (18.2%), and septic shock (15.8%). The median Model for End-Stage Liver Disease score on admission was 29 (interquartile range [IQR]: 23-36) and Simplified Acute Physiologic Score II was 60 (IQR: 44-72). ARDS developed a median of 2 (IQR: 1-5) days after ICU admission, with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio of 118 mmHg. Twenty-eight-day mortality was 75.2% and did not change over the study period (80.9% in 2007-2014 vs. 68.4% in 2015-2021, P=0.064). On multivariate analysis, factors associated with 28-day mortality were MELD score (odds ratio [OR]=2.31, 95% confidence interval [CI]: 1.48 to 3.80; P <0.001), PaO2/FiO2 ratio at ARDS onset (OR=0.49, 95% CI: 0.24 to 0.97; P=0.039) and ICU admission for acute respiratory failure (OR=0.44, 95% CI: 0.19 to 0.97; P=0.047). ARDS is common among patients with cirrhosis admitted to the ICU. Mortality remains high and has not improved over the past decade. Identifying factors associated with mortality may help guide treatment intensity in this population.
Khat (Catha edulis) is widely consumed in parts of East Africa and the Arabian Peninsula. Although khat-related liver injury has been described, data on the clinical presentation of cirrhosis in patients with chronic khat exposure remain limited. We aimed to describe the clinical characteristics of patients with suspected khat-associated cirrhosis in a khat-endemic region. We conducted a retrospective case series at a tertiary referral center in southern Saudi Arabia between January 2020 and December 2024. Adult patients with confirmed cirrhosis and documented chronic khat use, in the absence of an alternative dominant etiology, were included. Demographic data, comorbidities, laboratory findings, liver disease severity scores, and cirrhosis-related complications were analyzed descriptively. Twenty-eight patients met the inclusion criteria. The median age was 37 years (interquartile range [IQR] 32-41), and 85.7% were male. Diabetes mellitus and hypertension were present in 14.3% and 10.7%, respectively. The median Model for End-Stage Liver Disease score was 18 (IQR: 11-23), and 82.1% of patients were classified as Child-Pugh class B or C. Cirrhosis-related complications were common: ascites was present in 32.1%, hepatic encephalopathy in 28.6%, gastroesophageal varices in 35.7%, and variceal bleeding in 25.0%. Hepatocellular carcinoma was identified in 7.1% of cases. In this case series from a khat-endemic region, suspected khat-associated cirrhosis predominantly affected younger males and frequently presented with clinically significant decompensation. These findings are descriptive and hypothesis-generating and highlight the need for prospective studies with standardized exposure assessment and diagnostic criteria. Résumé Contexte:Le khat (Catha edulis) est largement consommé dans certaines régions d’Afrique de l’Est et de la péninsule Arabique. Bien que des lésions hépatiques liées au khat aient été décrites, les données concernant la présentation clinique de la cirrhose chez les patients exposés chroniquement au khat restent limitées. Nous avons cherché à décrire les caractéristiques cliniques des patients présentant une cirrhose suspectée associée au khat dans une région endémique.Matériels et Méthodes:Nous avons réalisé une série rétrospective de cas dans un centre tertiaire du sud de l’Arabie saoudite entre janvier 2020 et décembre 2024. Les patients adultes atteints de cirrhose confirmée et présentant une consommation chronique documentée de khat, sans autre étiologie dominante identifiée, ont été inclus.Résultats:Vingt-huit patients répondaient aux critères d’inclusion. L’âge médian était de 37 ans (IQR 32–41) et 85,7 % étaient des hommes. Les complications liées à la cirrhose comprenaient l’ascite, l’encéphalopathie hépatique, les varices gastro-œsophagiennes et le carcinome hépatocellulaire.Conclusion:Cette série de cas suggère que la cirrhose associée au khat pourrait représenter une cause sous-reconnue de maladie hépatique chronique dans les régions endémiques et souligne la nécessité d’études prospectives supplémentaires.
The emergence of antigenically distinct SARS-CoV-2 variants increases the risk of immune escape and requires continually updated vaccines. In addition, short-lived specific immunity is a limitation faced by current COVID-19 mRNA vaccines against Sarbecoviruses. This underscores the need for new vaccine approaches providing lasting immunity against SARS-CoV-2. Here, we demonstrate the capacity of two non-adjuvanted subunit vaccines to induce long-lasting and protective immunity against SARS-CoV-2 variants in macaques. We designed antibody-mediated vaccines (AMV) leveraging an anti-CD40 monoclonal antibody to enhance immune responses by targeting selected antigens to antigen-presenting cells through the CD40 receptor. The CD40.RBDv vaccine targets sequences from the original Wuhan RBD and a mutated RBD, while CD40.Pan.CoV incorporates a conserved nucleocapsid sequence and a mutated RBD region. We show that both adjuvant-free vaccines induce robust and durable systemic and mucosal anti-RBD antibody responses that neutralise multiple SARS-CoV-2 variants in naive and SARS-CoV-2 convalescent animals, including recent variants such as XFG. In convalescents, mathematical modelling predicted persistence of vaccine-induced antibody for decades. Additionally, the vaccines boost immune responses in mRNA-vaccinated animals, demonstrating the efficiency of CD40-based vaccines as boosters. Both vaccines protect animals against B.1.617.2 Delta and BA.1 Omicron challenges. Viral control correlates with vaccine-induced systemic and mucosal antibody levels and T-cell responses. These findings support the ability of AMV targeting CD40 to induce strong, long-lasting responses against adapted antigens and broad protection against evolving SARS-CoV-2 variants without requiring adjuvant. These two vaccine candidates are currently under clinical testing. The Investissements d'Avenir program (ANR-10-LABX-77-01 and ANR-11-INBS-0008), the PSPC COVID-19 - Project EVIDENCE.
Hypoalbuminemia has been repeatedly linked to increased non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT); a recent analysis also suggested an association with relapse risk. To evaluate the relationship between hypoalbuminemia, NRM, and relapse, we assessed its prognostic role in 1258 adults with MDS (myelodysplastic neoplasm)/AML or AML allografted while in remission between 2006 and 2023. After multivariable adjustment, low pre-HCT serum albumin levels were statistically significantly associated with NRM (hazard ratio [HR] = 0.67, p = 0.028), relapse-free survival (RFS; HR = 0.73, p = 0.005), and overall survival (OS; HR = 0.72, p = 0.007) but not relapse (HR = 0.77, p = 0.070). A day-28 landmark analysis showed day +28 hypoalbuminemia to be associated with NRM (HR = 0.31, p < 0.001), RFS (HR = 0.67, p < 0.001), and OS (HR = 0.52, p < 0.001) but not relapse (HR = 1.08, p = 0.6). Together, our data indicate that pre- and post-HCT serum albumin levels are independently associated with NRM and survival in AML patients undergoing allogeneic HCT.
Globally, chronic obstructive pulmonary disease (COPD) ranks third in terms of morbidity and mortality. Chronic obstructive lung disease is a respiratory illness caused by partial or complete obstruction of the airflow. It is one of the joint conditions that can be treated, and it is marked by tissue degradation and a progressive restriction of airflow. It was linked to structural alterations in the lungs brought on by long-term inflammation caused by exposure to harmful particles or gases. To determine the sputum bacteriology in Exacerbations of hospitalized COPD patients and assess their antibiogram and their correlation with inflammatory markers, clinical and functional profile. This cross-sectional study was conducted in the Department of Respiratory Medicine in a tertiary care center in Tamil Nadu, India. The study was conducted for a period of 18 months. A total of 104 patients with acute exacerbation of COPD aged more than 40 years were included in the study. After the initial assessment, a sputum examination was performed, followed by culture sensitivity, a spirometry evaluation, and the determination of the oxygen saturation in all the patients. One hundred four patients diagnosed with the acute exacerbation of COPD participated in the study. Sputum production is the most common symptom encountered in patients, followed by breathlessness. Purulent or mucopurulent sputum was noted in 57.6% of patients, sputum culture positivity in 62.5% of patients, and Klebsiella pneumoniae is the most common organism encountered in the sputum. Elevated C-reactive protein (CRP) levels and reduced Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) were noted in 85.6% of patients. Moreover, the study showed a significant association with age (P < 0.001), gender (P = 0.002), locality (P = 0.003), smoking (P < 0.001), alcohol (P = 0.004), exposure to indoor smoke (P = 0.001), type 2 diabetes mellitus (P < 0.001), coronary artery disease (P = 0.001), nature of sputum (P = 0.001), culture positivity (P = 0.001), spirometry (P = 0.025), and DLCO (P = 0.024) with elevated CRP levels and also with the all the clinical, spirometry, and saturation parameters with the culture positiveness. Numerous bacterial infections have been linked to the acute exacerbation of COPD; moreover, the bacterial infection profile differs depending on the geographic location. It is vital to periodically evaluate the patient's bacteriological profile to make sure it matches the organism's pattern of antibiotic resistance in order to lower the morbidity and mortality of the patient experiencing an acute exacerbation. Résumé Introduction:La maladie pulmonaire obstructive chronique (MPOC) est l’une des principales causes de morbidité et de mortalité dans le monde. Elle se caractérise par une inflammation chronique des voies respiratoires entraînant une limitation progressive du flux aérien. Les infections bactériennes constituent un facteur majeur des exacerbations aiguës de la MPOC et influencent l’évolution clinique de la maladie.But (Aim):Déterminer la bactériologie de l’expectoration chez les patients hospitalisés pour une exacerbation aiguë de la MPOC, évaluer leur profil de sensibilité aux antibiotiques (antibiogramme) et étudier la corrélation avec les marqueurs inflammatoires ainsi qu’avec les profils clinique et fonctionnel.Matériels et Méthodes:Une étude transversale a été menée pendant 18 mois auprès de 104 patients âgés de plus de 40 ans présentant une exacerbation aiguë de la MPOC dans un centre tertiaire de soins en Inde. Tous les patients ont bénéficié d’un examen de l’expectoration comprenant la culture bactérienne et l’étude de la sensibilité aux antibiotiques, d’une évaluation spirométrique ainsi que de la mesure de la saturation en oxygène.Résultats:Parmi les échantillons d’expectoration analysés, 62,5 % étaient positifs à la culture bactérienne. Klebsiella pneumoniae était l’agent pathogène le plus fréquemment isolé. Un taux élevé de protéine C-réactive (CRP) a été observé chez 85,6 % des patients, tandis qu’une diminution de la capacité de diffusion pulmonaire du monoxyde de carbone (DLCO) a été retrouvée chez la même proportion de patients. Des associations statistiquement significatives ont été mises en évidence entre le taux de CRP et plusieurs paramètres cliniques, fonctionnels et bactériologiques.Conclusion:Les infections bactériennes jouent un rôle important dans les exacerbations aiguës de la MPOC. Une surveillance régulière de la flore bactérienne et de son profil de résistance aux antibiotiques est essentielle pour optimiser la prise en charge thérapeutique et réduire la mortalité associée à cette pathologie.
EHMT1 and EHMT2 genes encode human euchromatin histone lysine methyltransferase 1 and 2 (EHMT1 alias GLP; EHMT2 alias G9a) that form heteromeric GLP/G9a complexes with essential roles in epigenetic regulation of gene expression. While EHMT1 haploinsufficiency has been established as the cause of Kleefstra syndrome 1, the pathogenesis of G9a dysfunction in human disease remains largely unknown. We identified seven de novo EHMT2 variants in patients with clinical presentation, episignatures, histone modifications and transcriptomic profiles similar to those of Kleefstra syndrome 1. In vitro studies reveal that these variants encode for structurally stable G9a proteins that are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. Heterozygous mice carrying a patient-derived variant exhibit growth retardation, facial/skull dysmorphia and aberrant behavior. Here we report pathogenic EHMT2 variants that likely exert dominant-negative effect on GLP/G9a complexes and thus genocopy the EHMT1 haploinsufficiency via a distinct molecular mechanism, defining an autosomal dominant EHMT2-related Kleefstra syndrome.
β-lactam antibiotics are the most commonly used antibiotics to treat infection in critically-ill patients. The modalities of antibiotics reconstitution/preparation for continuous infusion are elaborated according to drug stability. In between 2 periods, a sustainable protocol for 4 common β-lactam antibiotics administration was implemented, consisting of preparing the highest stable concentration for continuous administration through a 50 mL syringe. Overall, 418 patients were treated (202 in 2024 and 216 in 2025), age, and SAPSII did not differed between both periods. A sustainable protocol implementation reduced the greenhouse gas emission (GHG) by 52% from 2760 [1380-4968]g to 1380 [552-2208]g/treatment, p < 0.0001. The global reduction of plastic consumed (syringes, tubing, solution bags, blister packs) was - 48% (-61 kg), and treatment cost was also reduced by 48% (-1324 €). The total nursing time for preparation was 145 h shorter during the second 6 months period. These results showed that implementation of a sustainable protocol for continuous β-lactam antibiotics can significantly reduce the environmental impact of antibiotic administration. A careful prescription of drug dilution, if continuous infusion of β-lactam antibiotics is used, can be efficient in reducing GHG emissions, consumables, waste, and costs.
Herbal remedies such as Terminalia arjuna have been explored as adjuncts to conventional therapies for heart failure because of their potential cardioprotective properties attributed to bioactive compounds including flavonoids, glycosides, and triterpenoids. This systematic review and meta-analysis synthesized evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of T. arjuna in adults with heart failure. This systematic review and meta-analysis was conducted following PROSPERO registration. PubMed, Cochrane Library, Scopus, and Web of Science databases were searched for comparative studies published up to December 2025 evaluating Terminalia arjuna for improving cardiac function in adults with heart failure. Data were analyzed using RevMan software. Nine studies involving 537 patients were included in the meta-analysis. Terminalia arjuna significantly reduced left ventricular mass (mean difference [MD]: -44.32; P = 0.0001) with no heterogeneity, suggesting potential favorable effects on cardiac remodeling. Left ventricular ejection fraction showed a modest but non-significant improvement (MD: 1.85; P = 0.1). High-density lipoprotein levels increased significantly (MD: 3.53; P = 0.0006), whereas blood pressure, triglycerides, and low-density lipoprotein levels showed no significant changes. Terminalia arjuna may serve as a potential adjunctive therapy in heart failure, demonstrating reductions in left ventricular mass and improvement in high-density lipoprotein levels. However, inconsistent effects on ejection fraction and other cardiovascular parameters underscore the need for larger, high-quality trials to confirm its efficacy and safety. Résumé Introduction:Les remèdes à base de plantes tels que Terminalia arjuna ont été explorés comme adjuvants aux traitements conventionnels de l’insuffisance cardiaque en raison de leurs propriétés cardioprotectrices potentielles attribuées à des composés bioactifs, notamment les flavonoïdes, les glycosides et les triterpénoïdes. Cette revue systématique et méta-analyse a synthétisé les données probantes issues d’essais contrôlés randomisés (ECR) afin d’évaluer l’efficacité et la sécurité de T. arjuna chez les adultes atteints d’insuffisance cardiaque.Méthodes:Cette revue systématique et méta-analyse a été réalisée conformément à l’enregistrement PROSPERO. Les bases de données PubMed, Cochrane Library, Scopus et Web of Science ont été consultées afin d’identifier des études comparatives publiées jusqu’en décembre 2025 évaluant Terminalia arjuna pour l’amélioration de la fonction cardiaque chez des adultes atteints d’insuffisance cardiaque. Les données ont été analysées à l’aide du logiciel RevMan.Résultats:Neuf études impliquant 537 patients ont été incluses dans la méta-analyse. Terminalia arjuna a réduit de manière significative la masse ventriculaire gauche (différence moyenne [DM] : −44,32 ;P = 0,0001) sans hétérogénéité, suggérant des effets favorables potentiels sur le remodelage cardiaque. La fraction d’éjection ventriculaire gauche a montré une amélioration modeste mais non significative (DM : 1,85 ; P = 0,1). Les niveaux de lipoprotéines de haute densité ont augmenté de manière significative (DM : 3,53 ; P= 0,0006), tandis que la pression artérielle, les triglycérides et les niveaux de lipoprotéines de basse densité n’ont montré aucun changement significatif.Conclusion:Terminalia arjuna pourrait servir de traitement adjuvant potentiel dans l’insuffisance cardiaque, démontrant une réduction de la masse ventriculaire gauche et une amélioration des niveaux de lipoprotéines de haute densité. Cependant, les effets incohérents sur la fraction d’éjection et d’autres paramètres cardiovasculaires soulignent la nécessité d’essais plus vastes et de haute qualité afin de confirmer son efficacité et sa sécurité.
Albinism is characterized by generalized hypopigmentation and ocular features resulting from impaired melanin biosynthesis. Most known pathogenic variants are rare (MAF < 0.001) and found in coding regions. The role of non-coding variants, especially those with higher allele frequencies, is generally not investigated. Our next generation sequencing panel that includes the entire sequence of five major albinism genes (TYR, OCA2, SLC45A2, GPR143 and HPS1) identified compound OCA2 heterozygosity in a patient with a rare (MAF:0,0003) coding variant, NM_000275.3:c.1025 A > G;p.(Tyr342Cys) and a more common intronic variant, NM_000275.3:c.574-19 A > G (MAF:0,0087, with 80 homozygotes in the control population GnomADv4.1.0). In silico prediction tools indicated that this intronic variant could alter splicing. RT-PCR analysis on RNA extracted from the patient's blood revealed the skipping of exons 6 and 7, which resulted in the in-frame deletion of 78 amino acids. Protein modelling suggested that this deletion disrupts the GOLD-like domain and leads to the loss of conserved N-glycosylation sites, likely impairing protein folding and intracellular trafficking. These findings provided strong evidence for a deleterious effect on OCA2 function. Therefore, the variant was classified as likely pathogenic, allowing to establish the diagnosis in the patient. The relatively high allele frequency of this variant suggests that it behaves as a hypomorphic allele leading to disease in a compound heterozygous state. This underscores that intronic variants outside the canonical splice sites must be taken in consideration and functionally tested, and that common variants should not be systematically discarded in the diagnosis of albinism, and, similarly, of other rare diseases.
Healthcare workers (HCW) have been at the frontline during the COVID-19 pandemic, with an increased risk of infection, particularly due to the emergence of the omicron variant. This study aims to assess risk factors for omicron acquisition among vaccinated HCW, comparing hybrid immunity (previous infection and vaccination) to vaccine-induced immunity alone. We took advantage of the COVID-HOP prospective cohort, which includes vaccinated HCW followed over several months, collecting detailed data on demographic characteristics, comorbidities, and professional and personal exposures to COVID-19. We analyzed factors associated with omicron acquisition after January 2022, with a focus on immunization scheme (hybrid or vaccine-induced immunity). Out of 698 HCW analyzed, 298 acquired the omicron variant. In the multivariable analysis (taking into account comorbidities, professional/personal exposure and lifestyle), the two independent factors associated with an increased risk of infection were: younger age (P = 0.005) and immunization scheme (OR associated with vaccine-induced immunity alone: 2.43 [95% Confidence Interval: 1.64-3.60]) with hybrid immunity as reference). HCW with hybrid immunity have a reduced risk of acquiring omicron compared to those with vaccine-induced immunity alone. These findings emphasize the importance of a combined vaccination strategy to better protect HCW against emerging variants, and to vaccine HCW who experienced previous COVID-19 episodes.