Cathinone metabolism and biliary excretion in an ex-vivo pig liver model: Example of 4-Cl-PVP and eutylone.

Objective: Recently, the pig liver model perfused ex vivo using a normothermic machine perfusion (NMP) has been proposed as a suitable model to study xenobiotic metabolism and biliary excretion. The aim of our study is to describe the metabolism of NPS such as cathinones (with a focus on 4-Cl-PVP and eutylone) in blood and bile, using a normothermic perfused pig liver model.

Methods: Livers (n = 4) from male large white pigs, 3-4 months of age and weighing approximately 75-80 kg, were harvested and reperfused onto an NMP (LiverAssist®, XVIVO) using autologous whole blood at 38 °C.

How to facilitate the wider use of pharmacogenetic tests?

4P medicine (personalized, preventive, predictive, and participatory) is experiencing a remarkable rise, and pharmacogenetics is an essential part of it. However, several obstacles are hindering its deployment. This round table brought together a group of experts to take stock of the situation, reflecting on ways to facilitate the prescription of these tests and the dissemination of the results on a national scale.

Investigating 3-CMC metabolism: Insights from liver microsomes and postmortem biological matrix.

3-Chloromethcathinone (3-CMC) is a synthetic cathinone that has been identified as a new psychoactive substance (NPS) by the European Monitoring Centre for Drugs and Drug Addiction. Despite its increasing prevalence in the recreational drug market since 2014, scientific literature on 3-CMC remains limited. This study employed a multi-step approach to investigate 3-CMC metabolism.

Physiologically Based Pharmacokinetic Model of Cefotaxime in Patients with Impaired Renal Function.

Background: Cefotaxime is a widely prescribed cephalosporin antibiotic used to treat various infections. It is mainly eliminated unchanged by the kidney through tubular secretion and glomerular filtration. Therefore, a reduction of kidney function may increase exposure to the drug and induce toxic side effects.

Recurrences and rechallenges of suspected drugs in epidermal necrolysis patients.

Background: Epidermal necrolysis (EN) is a rare and severe condition, characterized by a diffuse skin and mucosal detachment and mainly induced by drugs. Literature is scarce regarding the rate of recurrences and culprit drug re-exposure.

Objectives: To assess the rate of EN recurrences as well as high notoriety drugs re-exposures in patients with EN.

Trends of Publication of Negative Trials Over Time.

Studies with negative results are less likely to be published than others, potentially leading to publication bias. Introduced in 2000, trial registration could have participated in decreasing the proportion of unpublished studies. We assessed the proportion of negative randomized controlled trials (RCT) over the last 20 years.

Lateral decubitus: its influence on hemodynamic and respiratory function during retroperitoneal robotic assisted laparoscopic pyeloplasty (R-RALP) in children.

Retroperitoneal robotic-assisted laparoscopic pyeloplasty (R-RALP) is the commonest urologic procedure performed in children, entailing retroperitoneal CO2 insufflation and lateral decubitus, whose effects on cardiopulmonary variables are poorly known. We, therefore, studied hemodynamic and respiratory changes due to CO2 insufflation and lateral decubitus in children undergoing R-RALP and their effects on regional tissue oxygenation. Between 1/2021 and 7/2024, children affected by ureteropelvic joint obstruction (UPJO) underwent a pyeloplasty by R-RALP at Necker Enfants Malades Hospital (Paris, France), using a standardized surgical technique and a lung-protecting anesthetic protocol aimed to prevent hypercarbia.

Exposure to childhood maltreatment is associated with specific epigenetic patterns in sperm.

Childhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual. Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven epigenetic changes in the germ line. Here we investigated the associated between early life stress on the epigenome of sperm in humans with history of CME.

DPYD genotype should be extended to rare variants: report on two cases of phenotype / genotype discrepancy.

The enzyme dihydropyrimidine dehydrogenase (DPD) is the primary catabolic pathway of fluoropyrimidines including 5 fluorouracil (5FU) and capecitabine. Cases of lethal toxicity have been reported in cancer patients with complete DPD deficiency receiving standard dose of 5FU or capecitabine. DPD is encoded by the pharmacogene DPYD in which more than 200 variants have been identified.

Interest and limits of using pharmacogenetics in MDMA-related fatalities: A case report.

Interpreting postmortem concentrations of 3,4-Methylenedioxymethamphetamine (MDMA) remains challenging due to the wide range of reported results and the potential idiosyncratic nature of MDMA toxicity. Consequently, forensic pathologists often rely on a body of evidence to establish conclusions regarding the cause and the manner of death in death involving MDMA. Given these issues, implementing pharmacogenetics' (PGx)' testing may be beneficial.

Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation.

Multiciliated cells (MCCs) ensure fluid circulation in various organs. Their differentiation is marked by the amplification of cilia-nucleating centrioles, driven by a genuine cell-cycle variant, which is characterized by wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients with CCNO mutations exhibit a subtype of primary ciliary dyskinesia called reduced generation of motile cilia (RGMC).

Lack of fibro-inflammatory response in human mammary adipose tissue in obesity.

Background: Understanding how obesity impacts human mammary adipose tissue (MAT) biology is crucial for deciphering its role in mammary epithelium during both physiological and pathophysiological processes, including breast cancer. Hypertrophic mammary adipocytes and Crown-Like Structures are present in MAT of patients with obesity but whether these changes initiate a fibro-inflammatory response at the tissue level remains insufficiently explored.

Objective: We investigated the markers of adipose tissue dysfunction (immune cell infiltration, secretion pattern and fibrosis) in tumor-free MAT of patients with obesity versus patients who are lean.

Rapid Selection of HIV-2 Capsid Mutations in Salvage Therapy with Lenacapavir-Containing Regimen.

Lenacapavir is the first capsid inhibitor, its use is currently approved for multidrug resistant HIV-1 infection. We report that, despite an initial efficacy of a LEN-containing regimen in patients with multi-drug resistant HIV-2 viruses, virological suppression was not achieved after a year and most patients selected capsid drug-resistance associated mutations.

CLEC12B regulates melanocyte immunity and homeostasis in the skin through the STAT1/IRF1 axis.

CLEC12B is a C-type lectin receptor involved in the inhibition of natural killers-mediated cytotoxicity. We have previously shown that CLEC12B is predominantly expressed on melanocytes, inhibits melanin production and pigmentation as well as proliferation of melanoma. To date, the role of CLEC12B in skin immunity is unknown.

Population pharmacokinetics and dosing simulations of temocillin in liver transplanted paediatric patients: a prospective, open-label, non-randomized study.

Objectives: Temocillin is a β-lactam antibiotic used for preventing or treating bacterial infections in liver-transplanted children. We characterized its pharmacokinetics in plasma and ascitic fluid and proposed dosing regimens that maximize achievement of effective drug exposures in this patient group.

Methods: Patients aged 6-36 months received 25 mg/kg/12h (n=14) or 25 mg/kg/8h (n=23).

Predictors of return to work after multidisciplinary rehabilitation program for patients with chronic low back pain.

Introduction: Patients with chronic low back pain face functional, psychological, social and professional difficulties. Multidisciplinary Rehabilitation Programs (MRP) can be an effective treatment to help these patients to improve their condition and return to work.

Objective: To determine baseline predictors for return to work after an MRP for patients with chronic low back pain struggling to maintain their job.

A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging.

Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance.

Restrictive versus Liberal Transfusion in Myocardial Infarction - A Patient-Level Meta-Analysis.

Background: Clinical guidelines have concluded that there are insufficient data to provide recommendations for the hemoglobin threshold for the use of red cell transfusion in patients with acute myocardial infarction (MI) and anemia. After the recent publication of the Myocardial Infarction and Transfusion (MINT) trial, we performed an individual patient-level data meta-analysis to evaluate the effect of restrictive versus liberal blood transfusion strategies.

Methods: We conducted searches in major databases.

Monitoring opioid analgesic misuse, abuse and dependence: What to the data from addictovigilance tell us about the situation in France?

The opioid epidemic has emerged in the USA in the late 1990s and widespread to Canada, Australia, and the UK to a lesser extent in the more recent years. At the European level, several studies performed in different European countries have highlighted that prescription opioid use increased substantially over the last decade, and several proxies for misuse show a parallel increasing trend. The French addictovigilance experience on opioid analgesics is a good example of a specific dedicated monitoring, taking into account in a global and multisource perspective, patterns of utilization, population involved in problematic use, ways of acquisition and health complications.

Investigation of choroid plexus variability in schizophrenia-spectrum disorders-insights from a multimodal study.

Previous studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) and is associated with peripheral inflammation. However, it is unclear whether such an enlargement delineates a biologically defined subgroup of SSD. Moreover, it remains elusive how ChP is linked to brain regions associated with peripheral inflammation in SSD.

Shaping the future of pharmacoepidemiology in France: Recommendations from the SFPT Pharmacoepidemiology Working Group.

The drug authorization process is shifting towards a policy aimed at shortening time-to-market. While this policy facilitates early access to new treatments, it can also result in potentially insufficient knowledge of both efficacy and safety at the time of marketing. The latter is particularly true for long-term outcomes or in specific populations (e.