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e-Health, including the use of mobile smartphone applications combined with interactive computerized programs, offers a new range of possibilities to improve secondary prevention after an acute myocardial infarction (MI). ASTERIA (improve real-life therapeutic follow-up through artificial intelligence) interventional study aims to assess the efficacy of a new web-based application (i.e., e-health BFC app) designed to improve the risk factors control and adherence recommended medications after MI, through kidney function, cholesterol and diabetes monitoring. From 1st June 2022 to 25th April 2024, the E-health app was proposed to all consecutive patients hospitalized for acute MI in intensive care unit in CHU de Dijon Bourgogne and able to handle the software on their smartphone (n = 1702). An automatic comparison between the initial and last biological values was made to detect any abnormality in kidney function through creatinine, K+ levels and to check if the LDL-cholesterol target was reached. Treatments decision algorithms to monitor patients'cholesterol and diabetes were created according to ESC recommendations. If biological abnormalities are detected, medical research team is alerted and can acts quickly. Renal function at one and four weeks, lipids at one and three months and HbA1c every three month after hospitalization were followed. Patients receive regular text messages reminding them to perform the blood tests and enter the biological results into the app. Among the 313 (19.8%) patients included, most (74%) completed their test results (weight, kalemia and creatinine) at one week, 74% at four weeks and 48% at 12 weeks after discharge. Alerts, automatically generated by the app, led to a new blood test prescription to assess kidney function for 12 (3.8%) patients and to adapt lipid-lowering treatment for 41 patients (41%). Results for algorithm-derived adaptation of diabetes treatment will be presented. The evaluation of the app by the patients raised a good feasibility and adherence level and showed that the majority (94.9%) thought that the app was useful to improve medical monitoring. Although only a few proportion of MI patients can benefit from this smartphone-based interventions (less than ¼), this innovative intervention could enhance self-management of risk factors and improve the link between the hospital and post discharge phases. [ABSTRACT FROM AUTHOR]

Harmful effects of some non-illicit substances including tobacco, alcohol and caffeine may evoke sudden death, myocardial infarction and severe arrhythmias. Exercising is a keystone of cardiovascular prevention; however, substance use may impair these beneficial effects. To analyse knowledge and behaviours regarding non-illicit substances among a regional sport population participating in the French rugby championship. From April 8th to July 3rd 2023, an anonymous online questionnaire was displayed to the 8368 players aged 12 y and more, the coaches and referees from the Bourgogne-Franche-Comté region. Among the respondents, 1061 were players, 195 coaches and 68 referees. Among the 1061 players respondents (13%), most were men (82.9%), median age was 22 (IQR 16–30) y. Women were younger than men (21y, IQR (16–29) vs 24 y (IQR 18–33), P = 0.017). Almost one third (32.1%) thought that sport cleans the smoker's lungs. Among the whole population, half (50.5%) have experienced tobacco smoking, including 18.1% of the younger players (< 18y). Since the beginning of the sport season, prevalence of cigarette smoking was high, at 29.1%, with 15.4% of daily consumption. These rates were similar in men and women. Almost one third (31.7%) of smokers were not aware of the risk of their cigarette consumption. Among referees and coaches, respectively 17.6% and 16.4% smoke within the 2 hours before and after a rugby session, i.e. often in the presence of players. Alcohol intake within one hour before a match was declared by 35.6% of alcohol drinkers, mostly among male (P < 0.0001); aim to performance enhancing was declared by 17.8% of them. Binge drinking was common, up to 81.3% of users, mostly among male. Energy drink during the season was declared by 20.7% of players, significantly more often among male (P < 0.001). Among them, more than 3 upon 4 declared an intake in the hour before the rugby session of whom almost 50% to enhance their performance. Non-illicit substance consumption remains common among rugby players of this French region. Consumption patterns in the setting of a sport session may increase CV risk; moreover, these behaviours concerning tobacco smoking may be harmful for their peers through second hand smoke, and can be an incentive to smoke. Our findings highlight the urgent need of health education and prevention addressing substances consumption in this population; these actions must include referees and coaches as relevant targets. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a highly heterogeneous entity, with multiple subgroups differing by clinic presentation, disease progression and risk of complications such as myocardial infarction (MI). A new T2DM phenotyping classification has been recently proposed to help to improve treatment tailoring and target early treatments. We aimed to identify the prevalence and characteristics of the new T2DM phenotypes in patients with acute MI. All consecutive adults with a history T2DM hospitalized in a French Coronary Intensive Care Unit for an acute MI between February 1st, 2021 and January 31st, 2023 were included. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance). We stratified patients into five subgroups: 1/SAID = severe autoimmune diabetes; 2/SIDD = severe insulin-deficient diabetes; 3/SIRD = severe insulin-resistant diabetes; 4/MOD = mild obesity-related diabetes; and 5/MARD = mild age-related diabetes. Among the 266 patients included, characteristics according to diabetes phenotypes are summarized in Table 1. Our prospective study showed that in real-world T2DM patients with acute MI, unclassical phenotypes, i.e. hyperinsulinaemic and insulinopaenic were common. Given the large discrepancies in characteristics, our findings suggest the relevance of the new substratification. However, its clinical utility and translation in tailored treatment strategies and prognosis remains to be determined. [ABSTRACT FROM AUTHOR]

A significant rate of patients admitted for acute myocardial infarction (MI) are under chronic treatment with non-vitamin K antagonist oral anticoagulants (NOACs). Their initial anticoagulant management should be limited to an unfractionated heparin bolus during percutaneous coronary angiography (PCI), according to the new ESC guidelines. However, level of anticoagulants through standard laboratory tests or specific dosages could provide important information to adapt anticoagulation therapy and limit the early bleeding risk. We aimed to investigate the levels of NOACs in patients admitted for an acute MI. Between February 1st, 2021 and January 31st, 2023, all consecutive adults admitted in coronary care unit for an acute MI and chronically treated with NOACs were prospectively included. Blood sampling was made on admission for anticoagulant assessment. NOAC concentrations (expressed in ng/mL) were measured using Liquid anti-Xa (Stago, Asnières sur Seine, France) for rivaroxaban and apixaban, and ECA-2 (Stago, Asnières sur Seine, France) for dabigatran, with specific set-up tests, according to the manufacturer's recommendations. Calibrations were performed using rivaroxaban, apixaban, dabigatran plasma calibrators (Stago, Asnières sur Seine, France). Patients were divided into 3 ranges according to levels of NOAC (Group 1: < 50 ng/mL, Group 2: 50–100 ng/mL, Group 3: > 100 ng/mL) taking account the haemostatic threshold of 50 ng/mL for surgery (except neurosurgery) or use of antidote and the through concentration of 100 ng/mL observed before next dose of twice-daily treatments. Rate of MI patients under chronic NOAC was 8,5% (n = 155). Their median (IQR) anticoagulant concentration was at 98 (51–179) ng/mL and the time from the last dose of NOACs was 495 (240–660) min. The main indication for chronic NOAC was atrial fibrillation. Among the 155 patients, 39 (25%), were in group 1, 42 (27%) in group 2 and 74 (48%) in group 3. Baseline characteristics were similar for the 3 groups (Table 1), including age, risk factors, type of NOAC and rate of PCI. However, there was a trend toward a higher rate of ST segment elevation MI in patients with elevated levels of anticoagulant. Our prospective pilot study suggests that the dosage of NOACs could be a relevant guiding tool for anticoagulant strategy in patients with acute MI. However, its clinical utility and prognosis value remains to be determined in larger prospective multicentric studies. [ABSTRACT FROM AUTHOR]

Exercise is a keystone of cardiovascular prevention; however, it is also a powerful trigger of acute cardiovascular events including sudden cardiac arrest and acute myocardial infarction. Contemporary studies addressing these sport-related myocardial infarctions (SR-MI) are scarce. To describe clinical characteristics and follow-up of SR-MI. We conducted a regional multicentre prospective survey addressing patients admitted for a SR-MI in 2 intensive coronary units. SR-MI was defined as MI onset occurring during sport or within the 1st hour of recovery. A one-year follow-up was performed by phone call. From April 1st 2018 to February 23th 2023, 155 SRMI were included, of whom 13 (8.4%) were female, median age was 61-y (IQR 54–66) (Table 1). Cycling was the most frequent sport (32.5%) followed by fitness and hiking (12.6% each) then jogging (11.3%). Most were ST elevation MI (68.8%). The main risk factors were dyslipidaemia (33.8%), hypertension (27.3%) and tobacco smoking (24.5%). No cardiovascular risk factors other than age were identified in 38 patients (25.7%). Prodromal symptoms were reported by 66 subjects (42.6%). SR-MI occurred mostly during exercise (60.6%). Out of hospital cardiac arrest (OHCA) occurred in 20 (12.6%) patients, more commonly among patients with prior coronary artery disease (CAD) (P = 0.02) and tobacco smoking (P = 0.047). A significant single vessel disease was observed in 67 patients (43.2%); stenting was performed by stenting in 134 patients (86.5%) and surgery in 11 (7.1%). In-hospital death occurred in 4 patients and was associated to OHCA (P = 0.007). Among the 151 survivors at discharge, 141 were eligible to follow-up, none was lost: one patient died suddenly at home, one experienced a recurrent MI and one a cardioversion from his implantable cardioverter defibrillator (ICD); an ICD was implanted in 4 subjects. A cardiovascular rehabilitation was performed in 101 patients (65.2%); from the 30 smokers at the time of SRMI, 26 quitted. Among patients admitted for a SR-MI, prodromal symptoms were common and OHCA occurred in 1 patient out of 8, associated with history of CAD, tobacco smoking and in-hospital death. Such findings highlight the need for mass education to adopt safer behaviours, especially while exercising. In this population, rehabilitation rate was high and quitting tobacco was commonly achieved. [ABSTRACT FROM AUTHOR]

Background: Type I Congenital Disorders of Glycosylation (CDG-I) are inherited diseases presenting deficits in protein N-glycosylation involving either the biosynthesis of the lipid-linked oligosaccharide Glc 3 Man 9 GlcNAc 2 -PP-dolichol or transfer of its oligosaccharide to protein., Results: We describe a patient harbouring hypoglycosylated transferrin, a characteristic of CDG-I. NGS revealed a homozygous RFT1 (c.16G > T p.Val6Leu) variant of unknown significance that is predicted to be benign. Metabolic radiolabelling of the patient's fibroblasts did not reveal the accumulation of truncated Man 5 GlcNAc 2 -PP-dolichol expected of RFT1-CDG but rather an accumulation of Man 7 GlcNAc 2 -PP-dolichol, characteristic of ALG12-CDG. Revaluation of the NGS data revealed a homozygous (22&#95;50311909A&#95;G, c.-79 + 2 T > C) variant that modifies the second nucleotide of the first intron of the ALG12 gene upstream of the first coding exon (exon 2). Sequencing of ALG12 cDNA revealed a 4-base insertion between exon 1 and exon 2 suggesting a shift in mRNA splicing in this intron to a putative new GU donor site. The patient's fibroblasts display 3% of control ALG12 mRNA levels., Conclusion: This is the first description of a pathogenic intronic ALG12 variant upstream of the first coding exon. The modification of the splicing process between intron 1 and exon 2, the very low transcript level and the absence of other mutations in the patient's ALG12 gene lead us to conclude that this ALG12 variant is a predicted Loss of Function (pLOF) variant., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval was from the Comité de protection des personnes (CPP) de l'Université Paris Descartes. For gene studies, signed informed consent protocols were obtained from the parents. Consent for publication: SV, TD, TA, VD, DC, SM, IC: Final approval of the version to be published. Competing interests: The authors declare no conflicts of interest., (© 2025. The Author(s).)

Background: The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear., Methods: We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023. We integrated clinical and pathological data to classify biopsy specimens according to the 2022 Banff Classification of Renal Allograft Pathology, which includes two new diagnostic categories: probable antibody-mediated rejection and microvascular inflammation without evidence of an antibody-mediated response. We then assessed the association between the newly recognized microvascular inflammation phenotypes and allograft survival and disease progression., Results: A total of 16,293 kidney-transplant biopsy specimens from 6798 patients were assessed. We identified the newly recognized microvascular inflammation phenotypes in 788 specimens, of which 641 were previously categorized as specimens with no evidence of rejection. As compared with patients without rejection, the hazard ratio for graft loss was 2.1 (95% confidence interval [CI], 1.5 to 3.1) among patients with microvascular inflammation without evidence of an antibody-mediated response and 2.7 (95% CI, 2.2 to 3.3) among patients with antibody-mediated rejection. Patients with a diagnosis of probable antibody-mediated rejection had a higher risk of graft failure beyond year 5 after biopsy than those without rejection (hazard ratio, 1.7; 95% CI, 0.8 to 3.5). Patients with a diagnosis of either newly recognized microvascular inflammation phenotype had a higher risk of progression of transplant glomerulopathy during follow-up than patients without microvascular inflammation., Conclusions: Microvascular inflammation in kidney allografts includes distinct phenotypes, with various disease progression and allograft outcomes. Our findings support the clinical use of additional rejection phenotypes to standardize diagnostics for kidney allografts. (Funded by OrganX. ClinicalTrials.gov number, NCT06496269.)., (Copyright © 2024 Massachusetts Medical Society.)

Introduction: Tissue defects (TD) at the nasal tip, dorsum, and alar regions can result from surgical excisions of cancerous skin lesions, congenital malformations, immunological diseases, trauma, or vascular anomalies. The ideal reconstruction should aim to restore the aesthetic subunits of the nose while minimizing donor site morbidity. Among the available techniques, the plicated paramedian frontal flaps (PPFF), combined with internal mucosal flaps, have proven particularly effective for extensive nasal pyramid tissue defects. This article presents our experience with a three-stage reconstruction technique using the PPFF combined with a mucosal flap for major tissue losses affecting the nasal tip and alar regions., Materials and Methods: This monocentric retrospective study reviewed 52 cases of nasal reconstructions performed between January 2019 and January 2024, of which 37 were treated with PPFF alone and 6 with combined mucosal flaps. All patients provided informed consent, and the study was approved by the ethics committee. The parameters analyzed included the types of tissue defects, the type of reconstruction, and aesthetic outcomes. A satisfaction survey was conducted six months postoperatively., Results: Among the six cases of reconstruction using the combined PPFF and mucosal flap, no cases of necrosis were observed. The average size of the tissue defects was 4cm, with a functional satisfaction rate of 92% and an aesthetic satisfaction rate of 96%. Partial necrosis of the skin graft was noted in 16.5% of cases, but it did not affect the overall result. Donor site scars were well accepted by patients., Conclusion: The three-stage PPFF reconstruction technique is recommended for complex nasal tissue defects, offering excellent aesthetic and functional outcomes with low donor site morbidity. It simplifies the process by reducing the need for additional mucosal flaps, thus limiting complications and associated complexities., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

Introduction: Deep sternal wound infection after cardiac surgery remains a serious complication associated with a poor prognosis. Deep sternal wound infection is classified by the Centers for Disease Control and Prevention as deep incisional surgical site-infection and mediastinitis. This study aims to describe the incidence, perioperative characteristics, and outcomes of deep sternal wound infection on the basis of clinical presentations., Methods: This monocentric retrospective study included all consecutive patients who underwent cardiac surgery with cardiopulmonary bypass between 2006 and 2019 in a tertiary teaching hospital. The primary outcome was 90-day mortality, and the main secondary outcome was a landmark analysis of 90-day mortality, excluding patients who died within the first 28 days., Results: Among the 14,850 patients included in this study, deep sternal wound infection occurred in 542 (3.6%) patients: 390 (72%) presented with deep incisional surgical site-infection and 152 (28%) presented mediastinitis. Patients with deep sternal wound infection had a lower 90-day survival than patients without deep sternal wound infection; in particular, patients with mediastinitis had the lowest survival rate compared to deep incisional surgical site-infection- and deep sternal wound infection -free patients (82% vs 94% vs 95%, respectively; both comparisons P < .001), and mediastinitis was an independent risk factor for 90-day mortality. No difference in 90-day survival was observed between patients without deep sternal wound infection and patients with deep incisional surgical site-infection (P = .378). However, in the landmark analysis, both deep incisional surgical site-infection and mediastinitis were associated with lower survival compared with patients without deep sternal wound infection and were independent risk factors for mortality., Conclusion: Deep incisional surgical site-infection and mediastinitis exhibited distinct incidences, bacterial characteristics, and prognoses, with mediastinitis being associated with the poorest prognosis. However, when the competing risk of death was considered, deep incisional surgical-site infection diSSI also emerged as an independent risk factor for 90-day mortality., Competing Interests: Conflict of Interest/Disclosure The authors declare no conflicts of interest in association with the present study., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The efficacy of icosapent ethyl among patients with very well-controlled baseline low-density lipoprotein cholesterol (LDL-C) is unknown., Methods: In this post hoc analysis of the REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) randomized clinical trial, statin-treated patients with high cardiovascular risk, elevated triglycerides (135-499 mg/dL), and baseline LDL-C of 41 to 100 mg/dL were included. Patients were randomized to icosapent ethyl (2 g twice daily) or placebo and then post hoc stratified by baseline LDL-C (<55 mg/dL versus ≥55 mg/dL). The primary composite end point included cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina., Results: Among 8175 patients with baseline LDL-C data, 7117 (87.1%) had LDL-C ≥55 mg/dL and 1058 (12.9%) had LDL-C <55 mg/dL. In patients with LDL-C <55 mg/dL, the rate of the primary composite end point was lower in the icosapent ethyl group (16.2% versus 22.8%) than in the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50-0.87]; absolute risk reduction, 6.6%; P =0.003). Among patients with LDL-C ≥55 mg/dL, a primary composite end point event occurred in a lower proportion of patients in the icosapent ethyl group (17.4% versus 21.9%) than in the placebo group (HR, 0.76 [95% CI, 0.69-0.85]; absolute risk reduction, 4.5%; P <0.0001). No significant interaction was observed between baseline LDL-C and treatment group ( P for interaction=0.40). Findings were consistent among secondary cardiovascular end points and in sensitivity analyses., Conclusions: Among statin-treated patients with elevated triglycerides and high cardiovascular risk, icosapent ethyl reduced the rate of cardiovascular end points irrespective of baseline LDL-C, including among eligible patients with optimal LDL-C control., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Background: Fibrillatory wave amplitude (fWA) on 12-lead ECG predicts the outcome of ablation in atrial fibrillation (AF). We hypothesized that changes in fWA following wide circumferential isolation of pulmonary veins (WPVI) in persistent AF (peAF) is a better predictor of ablation outcome compared to baseline fWA., Methods: Eighty-nine patients (sustained peAF 7 ± 7 months) underwent a first-time WPVI. Sixty-second ECG signals devoid of QRST waves were recorded at baseline and at the end of the WPVI (endWPVI). fWA for each ECG lead and mean fWA (meanfWA) across the 12-lead ECG were computed. Patients with recurrence after the index WPVI underwent a redo to ensure complete PVI. The primary endpoint was long-term AF freedom OFF antiarrhythmics drugs (AADs) after one or two WPVI (SUCCESS group). The FAILURE group was defined as AF recurrence post-redo., Results: Over a mean follow-up of 35 ± 10 months, freedom from AF OFF AADs was achieved in 61% (SUCCESS group), while 29% had AF recurrence after redo WPVI (FAILURE group). The SUCCESS group showed significantly higher fWA values in ECG leads V 1 , V 4 , and V 5 at baseline (p < 0.05), as well as in leads III, aVL, aVF, and V 4 , and in meanfWA at endWPVI (p < 0.05) compared to the FAILURE group. A baseline mean fWA ≥ 0.044 mV or a decrease in mean fWA ≤ 11% following WPVI predicted long-term sinus rhythm restoration with a sensitivity of 81% and a specificity of 69% (p < 0.05)., Conclusion: Low fWA values and a significant reduction in fWA following WPVI are associated with a high risk of AF recurrence in patients with peAF., Competing Interests: Declarations. Ethics approval: The study protocol was performed in line with the principles of the Declaration of Helsinki and approved by the local Human Research and Ethics Committees of Lausanne University. Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing interests: L. Roten has received research grants from Medtronic, the Swiss National Foundation, the Swiss Heart Foundation, the Immanuel and Ilse Straub Foundation, and the Sitem Insel Support Fund, all for work outside the submitted study. He has received speaker fees/honoraria from Biosense Webster, Boston Scientific, Abbott, and Medtronic. S. Knecht has received research grants from the Swiss Heart Foundation for work outside the submitted study. All remaining authors declare that they have no conflicts of interest, no relevant financial or non-financial interests to disclose related to the content of this manuscript., (© 2025. The Author(s).)

Advantages and disadvantages of intermittent versus daily vitamin D supplementation especially in adults with or at risk of osteoporosis are discussed by the Osteoporosis Research and Information Group (GRIO). The analysis of the literature suggests that intermittent long-term high doses vitamin D supplementation (such as 60,000 IU/month or more), may increase the risk of falls, fracture and premature death in certain populations, while daily doses of 800-1000 IU with calcium decrease falls and non-vertebral fractures in the elderly with vitamin D deficiency. In patients with or at risk of osteoporosis we hence recommend measuring the 25(OH)D concentration prior to supplementation and to provide vitamin D supplementation (with optimization of calcium intake if needed) to obtain a concentration between 30 and 60 ng/mL. We recommend the use of an initial loading dose, especially in those who need a quick repletion of vitamin D store (symptoms of osteomalacia and/or 25(OH)D concentration <12 ng/mL, patients eligible for treatment with potent antiresorptive therapy), followed by a maintenance dose. A daily supplementation should be the rule when possible. When daily forms are however not available or not reimbursed, we recommend, like other experts, to continue using intermittent dosing with the smallest available dose (≤ 50 000 IU) and the shortest interval between doses as a stopgap until reimbursement or adequate daily pharmaceutical forms (pills or soft capsules of 1000, 2000 IU) are available., (Copyright © 2025. Published by Elsevier Masson SAS.)

Purpose of Review: Differentiate between unipolar and bipolar depression through studies investigating objective sleep markers using polysomnography and actigraphy., Recent Findings: Studies comparing unipolar and bipolar depression using objective markers often lack power and present heterogeneous results. However, In a recent actigraphy study (1), which included 66 patients with unipolar depression and 24 with bipolar depression, notable and encouraging variations in sleep markers were found between the two disorders. Specifically, a decrease in sleep duration and efficiency was observed in people diagnosed with depression compared to those diagnosed with bipolar depression., Summary: Currently, there is a major challenge in distinguishing between unipolar and bipolar major depressive episodes. A significant body of research has been dedicated to identifying biomarkers that can aid in this differentiation due to its crucial implications, particularly for therapeutic and prognostic purposes. Among the biomarkers of interest, markers related to sleep and circadian rhythms show promise and could potentially aid in making this distinction. A few studies have evaluated these markers objectively, but they often lack power, or the results stay highly heterogeneous. We conducted a systematic review and meta-analysis of published studies comparing sleep disorders between unipolar or bipolar depression using PubMed, Cochrane Library, and Web of Science databases. Actigraphy, polysomnography, and nocturnal Electroencephalography (EEG) were considered. The qualitative analysis retained 11 original studies, including 666 participants (355 patients diagnosed with bipolar depression and 311 with unipolar depression) and 8 studies were included for the meta-analysis. Depression in unipolar disorder was associated with a shorter total sleep time (SMD -0.3539, [ CI: -0.5486 to -0.1592]; p <0.001; MD: -27.9592; I 2 = 0%) and a poorer sleep efficiency (SMD -0.3105, [95% CI: -0.5207 to -0.1003]; p = 0.004; MD: -0.3105; I 2 = 0%) than patients diagnosed with bipolar depression. There were no significant differences between the two groups in sleep onset latency, REM latency and REM % during the night. In summary, when examining objective sleep markers through polysomnography or actigraphy to distinguish between the two disorders, it appears that unipolar depressive disorder is associated with a reduced total sleep time and a poorer sleep efficiency than bipolar depressive disorder. These findings have substantial implications for identifying individuals with either unipolar or bipolar disorder using objective sleep markers, as well as for crafting tailored and effective therapeutic approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. Appendix Search on Pubmed used the following keywords equation: ("actigraphy" OR "accelerometer" OR "polysomnography" OR "sleep electroencephalography" OR "sleep") AND ("depression" OR "major depressive episode" OR “depressive episode" OR "major depressive disorder" OR "depression") AND ("bipolar"). Search on Cochrane used the following keywords equation: "actigraphy" OR "accelerometer" OR "polysomnography" OR "sleep electroencephalography" OR "sleep" AND "depression" OR "major depressive episode" OR “depressive episode" OR "major depressive disorder" OR "depression" AND "bipolar" Search on Web of Science used the following keywords equation: (ALL=(“actigraphy”) OR ALL¼(“accelerometer”) OR ALL¼(“polysomnography”) OR ALL¼(“sleep electroencephalography”) OR ALL¼(“sleep”) OR ALL¼(OR ALL¼(“sleep")) AND ((ALL¼(“depression”) OR ALL¼(“major depressive episode”) OR ALL¼(“ depressive episode”) OR ALL¼(“major depressive disorder”)) AND (ALL¼(“bipolar ”)., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Introduction: Sleep-disordered breathing (SDB) and the related clinical syndrome, sleep apnoea syndrome (SAS), are highly prevalent in patients with ischaemic heart disease and often remain undiagnosed. The AMI-Sleep study will describe its prevalence in patients with acute myocardial infarction (AMI) and assess the independent contribution of the type and severity of SDB/SAS to subsequent incident cardiovascular events and mortality., Methods and Analysis: This prospective study will include patients hospitalised for AMI enrolled in the multicentre nationwide prospective French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry. A nightly simplified polygraphy is performed before discharge from the index AMI admission, and participants complete two self-administered sleep questionnaires. Baseline data are obtained from the FRENCHIE registry. Each participant will be subsequently followed based on data from the National Health Data System (SNDS). Over a period of 4 years, the AMI-Sleep study is expected to recruit approximately 2000 participants. Assuming at least a 10% rate of incident cardiovascular events over 1 year, there would be an estimated 200 events during the first year of follow-up that would be sufficient in multivariable analysis. The primary objective is to describe the prevalence and severity of SDB in AMI and to analyse the association between the type and severity of SDB (based on the apnoea-hypopnoea index) and the occurrence of cardiovascular events (incident acute coronary syndrome, transient ischaemic attack, stroke) or all-cause death after AMI. Secondary objectives include determining the association between the presence of SAS and coronary artery disease severity, in-hospital mortality, morbidity events, healthcare consumption and related costs., Ethics and Dissemination: Eligible individuals are provided with information about the AMI-Sleep study and provided written informed consent. The protocol was approved by the regional Ethics Committee (CPP Ouest II - Angers, RCB N°2018-A00719-46) on 17 February 2019, is registered on ClinicalTrials.gov (NCT04064593) and started in January 2019 with the expected publication of primary outcome results in 2025., Trial Registration Number: ClinicalTrials.gov, NCT04064593., Competing Interests: Competing interests: PGS has received grants from Amarin, AstraZeneca, Bayer, Sanofi and Servier, consulting fees from Amgen, AstraZeneca, BMS/Myokarddia, Merck, Novo-Nordisk and Regeneron, Steering Comitee or Critical Event Committee from Amarin, AstraZeneca, Bayer, Boerhriger Ingelheim, BristolMyers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi and Servier, payments for lectures from AstraZeneca, Novartis and Novo-Nordisk, support for attending meetings from AstraZeneca and participation on a Data Safety Monitoring Board or Advisory Board from Servier, Sanofi, PHRI and Monash University and no other relationships or activities that could appear to have influenced the submitted work. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background and Objectives: Attention deficit hyperactivity disorder (ADHD) is one of the most frequent and disabling neurodevelopmental disorders. Recent research on cerebral blood flow (CBF) has enhanced understanding of the underlying pathophysiology in neuropsychiatric disorders. This systematic review aims to synthesize the existing literature on CBF anomalies among individuals with ADHD in comparison to controls., Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, a systematic literature search was conducted using PubMed, PsycInfo, and Web of Science to identify relevant studies on CBF in ADHD., Results: Twenty studies, encompassing a total of 1652 participants with ADHD and 580 controls, were included, employing measurements from SPECT (n = 9), ASL (n = 6), PET (n = 4), and BOLD-derived quantitative maps (n = 1). In individuals with ADHD during resting state, hypoperfusion was frequently observed in the right orbitofrontal gyrus, temporal cortex, basal ganglia and putamen. Conversely, hyperperfusion was noted in frontal lobes, left postcentral gyrus, and occipital lobes. During cognitive tasks, hyperperfusion was observed in frontal areas, temporal regions, cingulate cortex and the precuneus. Furthermore, the administration of methylphenidate was associated with increased CBF in striatal and posterior periventricular regions, the right thalamus, and the precentral gyrus., Conclusion: This review highlights diverse CBF anomalies in ADHD. The most consistently reported findings suggest hypoperfusion during resting state in prefrontal and temporal areas, along with the basal ganglia, while there is a hyperperfusion in frontal, parietal and occipital regions. Further research, including longitudinal studies, is essential to develop a comprehensive understanding of CBF implications in ADHD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Neutrophils are essential for host defense against infections, but they also play a key role in acute and chronic inflammation. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes the lymphoid-specific tyrosine phosphatase (Lyp) and a genetic single-nucleotide polymorphism of PTPN22 rs2476601 (R620W) has been associated with several human autoimmune diseases, including rheumatoid arthritis (RA). Here, we investigated the role of Lyp in TNFα-induced priming of neutrophil ROS production and in the development of arthritis using new selective Lyp inhibitors. Results show that Lyp-selective inhibitors (IC-11 and compound 8b), inhibited TNFα-induced priming of neutrophil superoxide anion production. TNFα induced an increase of Lyp protein expression in human neutrophils isolated from healthy donors. Key pathways involved in neutrophil priming were investigated. Lyp-selective inhibitors, inhibited TNFα-induced p47phox phosphorylation on Ser345, ERK1/2 phosphorylation and Pin1 activation. Interestingly, Lyp expression was increased in neutrophils isolated from synovial fluid of RA patients and Lyp inhibitors, I-C11 and compound 8b prevented superoxide anion production by endogenously primed neutrophils isolated from synovial fluid of RA. Moreover, IC-11 significantly prevented collagen antibody-induced arthritis in mice. These results show that Lyp expression is increased in inflammatory neutrophils, Lyp is involved in TNFα-induced excessive ROS production by neutrophils and its inhibition protected mice against arthritis. Inhibition of Lyp could be a therapeutic strategy in inflammatory arthritis., Competing Interests: Declaration of competing interest The authors declare no competing conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: After radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), prognosis is poor for high-risk patients. This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients., Patients and Methods: This phase II trial (NCT04617756) included patients with non-metastatic, high-grade UTUC, based on the ureteroscopic biopsy or urine cytology, and/or infiltrative aspect of the renal pelvis/ureteral wall by CT imaging. Before RNU, patients received durvalumab plus gemcitabine/cisplatin (cohort 1) or durvalumab plus gemcitabine/carboplatin (cohort 2) every 3 weeks for a total of four cycles (cohort choice based on the glomerular filtration rate). The primary objective was the pathological complete response (ypT0) rate in each cohort., Results: Fifty patients were enrolled between 2021 and 2024 (31 in cohort 1; 19 in cohort 2). Median age was 68 years (range 38-79), 59% were men. Forty-five patients received 4 cycles of treatment, three patients 3 cycles, and one patient 2 cycles. Five patients switched to carboplatin during treatment. At surgery (n=45 patients), rates of pT0 were 13% (4/29) in cohort 1 and 5% (1/19) in cohort 2. Fifty percent (15/29) of patients were pTa /pT1 in cohort 1, and 42% (8/19) in cohort 2. No severe immunotherapy-mediated toxicity was observed. Four patients had chemotherapy-related grade 3 neutropenia, one grade 4; one patient had grade 3 thrombopenia, one grade 4; four patients had grade 3 anemia., Conclusion: While our negative study did not meet its primary endpoint in either cohort, the combination of durvalumab and platin-based chemotherapy, especially cisplatin, showed promising results in terms of downstaging. The safety profile was good and the surgical risk was not increased.

Background: Sodium-glucose co-transporter (SGLT)-2 inhibitors have shown consistent benefit in improving heart failure-related outcomes but not ischaemic cardiovascular events such as myocardial infarction or stroke. We assessed if the dual SGLT1/2 inhibitor sotagliflozin improves ischaemic outcomes., Methods: We did a prespecified secondary analysis of the SCORED trial, which was a double-blind, placebo-controlled, randomised clinical trial enrolling patients (aged ≥18 years) with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate [eGFR] 25-60 mL/min per 1·73 m 2 ), and additional cardiovascular risk factors. Patients at 750 sites in 44 countries were randomly assigned (1:1) to oral sotagliflozin or placebo via an interactive response technology system (block size of four; stratified by heart failure-related criteria and geographical region), with participants, investigators, and study staff, including those who assessed outcomes, masked to group assignment. Sotagliflozin treatment was prescribed at 200 mg once a day, with the dose increased to 400 mg once a day within the first 6 months if tolerated. Matching placebo was prescribed at the same treatment frequency as the intervention regimen. A prespecified secondary outcome was total major adverse cardiovascular events (MACE), which was defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, assessed as first and subsequent events. Other outcomes included total myocardial infarction and total stroke (fatal and non-fatal events) as individual post-hoc endpoints. Outcomes were assessed by intention to treat with competing-risk proportional hazard models in the overall population, and, for total MACE, in prespecified subgroups stratified by baseline demographic and clinical features (sex, age, geographical region, heart failure-related criteria, eGFR, urine albumin-creatinine ratio, and cardiovascular disease history). The SCORED trial was registered at ClinicalTrials.gov, NCT03315143, and was ended early due to loss of funding., Findings: 10 584 patients were enrolled and randomly assigned to sotagliflozin (n=5292 [50·0%]) or placebo (n=5292 [50·0%]) between Dec 8, 2017 and Jan 20, 2020 (median age 69 years [IQR 63-74]; 4754 [44·9%] female patients and 5830 [55·1%] male patients). 5144 (48·6%) patients had a history of cardiovascular disease, of whom 2108 (19·9% of the total population) had a history of myocardial infarction, 946 (8·9%) had a history of stroke, and 2375 (22·4%) had a history of coronary revascularisation. Patients in the sotagliflozin group had a significantly lower rate of total MACE than those in the placebo group (4·8 events per 100 person-years vs 6·3 events per 100 person-years; hazard ratio [HR] 0·77 [95% CI 0·65-0·91]; p=0·0020). Interaction analyses suggested a consistent effect of sotagliflozin on total MACE among stratified subgroups without evidence of heterogeneity. Additionally, sotagliflozin significantly reduced the rate of myocardial infarction (1·8 events per 100 person-years vs 2·7 events per 100 person-years; HR 0·68 [0·52-0·89]; p=0·0041) and stroke (1·2 events per 100 person-years vs 1·8 events per 100 person-years; HR 0·66 [0·48-0·91]; p=0·012) compared with placebo., Interpretation: Sotagliflozin reduced MACE, with independent reductions in myocardial infarction and stroke, among patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk. The ischaemic benefit on both myocardial infarction and stroke has not been previously observed with other SGLT inhibitors and warrants investigation of combined SGLT1 and SGLT2 inhibition as a possible underlying mechanism., Funding: Lexicon Pharmaceuticals., Competing Interests: Declaration of interests RA is involved in research funded by the Bristol Myers Squibb–Pfizer alliance, Novartis, Amarin, and Lexicon Pharmaceuticals. He has previously served as a consultant for Lexicon. DLB receives research funding from Lexicon Pharmaceuticals paid to the Icahn School of Medicine at Mount Sinai for his role as Chair of the SCORED trial and discloses the following relationships: advisory board membership for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, E-Star Biotech, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors membership for the American Heart Association New York City, Angiowave, Bristol Myers Squibb, DRS.LINQ, and High Enroll (and holds stock or stock options with Angiowave, Bristol Myers Squibb, DRS.LINQ, and High Enroll); consulting for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; data monitoring committee participation for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2 trial), Duke Clinical Research Institute, Mayo Clinic, Icahn School of Medicine at Mount Sinai (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; and for the ALLAY-HF trial, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the MINT trial, funded by the US National Institutes of Health [NIH]); honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; and Chair, American College of Cardiology Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; for RE-DUAL PCI Clinical Trial Steering Committee membership funded by Boehringer Ingelheim; for AEGIS-II Executive Committee membership funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), the Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor, Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, the Population Health Research Institute (for the COMPASS Operations Committee, Publications Committee, Steering Committee, and US National Co-Leader, funded by Bayer), WebMD (continuing medical education steering committees), and Wiley (steering committee); other support from Clinical Cardiology (Deputy Editor); a patent for sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned the patent to Lexicon Pharmaceuticals; neither DLB nor Brigham and Women's Hospital receive any income from this patent); research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon Pharmaceuticals, Eli Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties from Elsevier (Editor, Braunwald's Heart Disease); a role as site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; a role as Trustee of the American College of Cardiology; and unfunded research with FlowCo. MS serves as a consultant for and/or has received research support from Lexicon Pharmaceuticals, Amarin, NewAmsterdam, Silence, Sanofi, Regeneron, and Tourmaline. MS also receives salary support from CPC, a non-profit academic research organisation affiliated with the University of Colorado, that receives or has received research grant or consulting funding between July, 2021 and July, 2024 from the following organisations: Abbott Laboratories, Agios Pharmaceuticals, Alexion Pharma Godo Kaisha, Amgen, Anthos Therapeutics, ARCA biopharma, Arrowhead Pharmaceuticals, AstraZeneca Pharma India, AstraZeneca UK, Bayer, Bayer Aktiengesellschaft, Bayer Pharma, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, Bristol Myers Squibb, Cleerly, Colorado Department of Public Health and Environment, Congress, Cook Regentec, CSL Behring, Eidos Therapeutics, EPG Communication Holdings, Esperion Therapeutics, Faraday Pharmaceuticals, HeartFlow, Insmed, Ionis Pharmaceuticals, IQVIA, Janssen Pharmaceuticals, Janssen Research & Development, Janssen Scientific Affairs, Lexicon Pharmaceuticals, Medpace, Medscape, Merck Sharp & Dohme, Nectero Medical, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, PPD Development, Prothena Biosciences, Regeneron, Regents of the University of Colorado (University of Colorado Denver), Sanifit Therapeutics, Sanofi, Silence Therapeutics, Stanford University, Stealth BioTherapeutics, Brigham and Women's Hospital, Thrombosis Research Institute, Tourmaline Bio, University of Colorado, University of Colorado Denver, University of Pittsburgh, VarmX, Verve Therapeutics, and WraSer. CPC has received research grants from Amgen, Better Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Merck, Novo Nordisk, and Pfizer; has received consulting fees from Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Eli Lilly, Janssen, Lexicon Pharmaceuticals, Merck, Pfizer, Rhoshan, and Sanofi; and has served on data and safety monitoring boards for Applied Therapeutics and Novo Nordisk. LAL has received research funding from, has provided continuing medical education on behalf of, and/or has acted an adviser to Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion, HLS Therapeutics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pfizer, and Sanofi. SEI has served as a consultant and member of clinical trial steering committees for Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Merck, Pfizer, and Bayer; and has delivered lectures sponsored by Boehringer Ingelheim and AstraZeneca. RDL has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received funding for educational activities or lectures from Pfizer, Bristol Myers Squibb, Novo Nordisk, and AstraZeneca; and has received funding for consulting from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Novo Nordisk, and AstraZeneca. DKM has received research support for clinical trials leadership from Boehringer Ingelheim, Merck, Pfizer, AstraZeneca, Novo Nordisk, Esperion, Eli Lilly, Lexicon Pharmaceuticals, CSL Behring, and NewAmsterdam Pharma; and has received honoraria for consultancy from Eli Lilly, Boehringer Ingelheim, Merck, Novo Nordisk, Applied Therapeutics, Altimmune, CSL Behring, Bayer, GlaxoSmithKline, and Intercept. JBL has received consultant fees from Sanofi. MCR has received honoraria for consulting from Adocia, Anji, Xeris, DalCor, and Theracos. MJD, AKC, and PB are employees of Lexicon Pharmaceuticals, and may hold stocks or stock options in the company. BAS reports institutional research grants to Brigham and Women's Hospital from Better Therapeutics, Merck, Novo Nordisk, and Pfizer; consulting fees from Allergan, Boehringer Ingelheim, Better Therapeutics, Elsevier Practice Update Cardiology, Esperion Therapeutics, Hanmi Pharmaceutical, Lexicon Pharmaceuticals, and Novo Nordisk; and equity in Health at Scale and Doximity. DZIC has received honoraria from Boehringer Ingelheim–Eli Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi Tanabe, AbbVie, Janssen, Amgen, Bayer, Prometic, Bristol Myers Squibb, Maze, Gilead, CSL Behring, Otsuka, Novartis, Youngene, Lexicon Pharmaceuticals, Inversago, GlaxoSmithKline, and Novo Nordisk, and has received operational funding for clinical trials from Boehringer Ingelheim–Eli Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL Behring, Novo Nordisk, and Bayer. SV holds a Tier 1 Canada Research Chair in Cardiovascular Surgery; and reports receiving grants and/or research support and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, the Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Humber River Health, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management, and Sanofi. JAU discloses advisory board roles for Boehringer Ingelheim, Novavax, Novo Nordisk, and Sanofi; speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, and Eli Lilly; and research funding to his institution from Amgen, Bayer, Boehringer Ingelheim, and Novartis. RPM has received research funding or consulting fees from Amarin, Lexicon Pharmaceuticals, Esperion, and HLS Therapeutics. BP has received consulting fees from Lexicon Pharmaceuticals, Bayer, AstraZeneca, Boehringer Ingelheim, Merck, and Phasebio; has received consulting fees from and/or holds stock options from Viror, KBP Biosciences, Cereno Scientific, Tricida, scPharmaceuticals, SQ Innovation, G-3 Pharmaceuticals, Protonintel, and Brainstorm Medical; and holds a US patent (number 9931412) on site-specific delivery of eplerenone to the myocardium and US patent, pending (number 63/045,783) on histone-modulating agents for the protection and treatment of organ damage. PGS has received research grants from Amarin, Bayer, Sanofi, and Servier; has received speaker or consultant fees from Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Kowa, Idorsia, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, and Servier; and is a Senior Associate Editor of Circulation. All other authors declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix., Competing Interests: Declaration of interests OAC declares grants from the German Federal Ministry of Education and Research (BMBF), Cidara, the German Center for Infection Research (DZIF), EU Directorate-General Research and Innovation, F2G, Gilead, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; consulting fees from AbbVie, AiCuris, Basilea, Biocon, Cidara, Seqirus, Gilead, GSK, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partner, MSGERC, Mundipharma, Noxxon, Octapharma, Pardes, Partner Therapeutics, Pfizer, PSI, Scynexis, and Seres; honoraria from Abbott, AbbVie, Akademie für Infektionsmedizin, Al-Jazeera Pharmaceuticals–Hikma, amedes, AstraZeneca, Deutscher Ärzteverlag, Gilead, GSK, Grupo Biotoscana–United Medical–Knight, Ipsen Pharma, Medscape–WebMD, MedUpdate, MSD, Moderna, Mundipharma, Noscendo, Paul-Martini-Stiftung, Pfizer, Sandoz, Seqirus, Shionogi, streamedup!, Touch Independent, and Vitis; payment for expert testimony from Cidara; and board participation from Boston Strategic Partners, Cidara, IQVIA, Janssen, MedPace, PSI, Pulmocide, Shionogi, The Prime Meridian Group, and Vedanta Biosciences. RS declares grants from DZIF and Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen; honoraria from Pfizer, Akademie für Infektionsmedizin, and Hikma; travel support from the European Confederation of Medical Mycology (ECMM), Pfizer, and Page Medical; and has board membership for Young ECMM. MB declares honoraria and board participation from Angelini, Cidara, Gilead, Menarini, MSD, Pfizer, Shionogi, and Mundipharma. SC-AC reports an untied educational grant from F2G, and travel support from the Asia Fungal Working Group and the International Society for Human & Animal Mycology (ISHAM). AHG declares a research grant paid to his institution from Gilead Sciences; consulting fees from Basilea, Pfizer, and Mundipharma; and honoraria from Gilead, MSD, Mundipharma, Basilea, and Pfizer. OK declares research grants from the EU, German Research Foundation (DFG), BMBF, and BMG; consulting fees paid to his institution from Mundipharma; honoraria paid to his institution from Gilead, Pfizer, and Fujifilm Wako; receipt of microbiology media for evaluation from Mast Diagnostika; and reports receipt of chemical substances (antifungal drugs) for susceptibility testing. CL-F declares grants paid to her institution from Gilead Sciences and Astellas Pharma; consulting fees from Merck Sharp and Dohme; honoraria from Gilead Sciences, Merck Sharp and Dohme, Pfizer, BioMerieux, F2G, Immy, and Shionogi; travel support from Gilead; and advisory board fees from Mundipharma. LO-Z declares grants paid to his institution from Scynexis, Pulmocide, Pfizer, Basilea, Eurofins Viracor, and T2 Biosystems; honoraria from Pfizer, Gilead, F2G, GSK, Melinta, Eurofins Viracor, and Knight–Biotoscana. RR-R declares support for this work by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre grant (NIHR203308). LPW declares a grant paid to his institution from F2G; consulting fees from Mundipharma, Pfizer, F2G, and Gilead; honoraria from Gilead, Mundipharma, and Pfizer; travel support from Mundipharma and Gilead; board participation from F2G, Mundipharma, Gilead, and Pfizer; and receipt of equipment from Launch Diagnostics for his institution. AA-I declares consulting fees from WHO; payments for educational talks from Gilead, Pfizer, and Mundipharma; travel support from Gilead; and has unpaid roles as President of the Asociación Española de Micología and as a member on the scientific advisory board of the Joint Programming Initiative on Antimicrobial Resistance. MCA declares research grants and contract work paid to her institution from Cidara–Mundipharma, F2G–Shionogi, and Scynexis; and speaker honoraria from Gilead and F2G–Shionogi. RB-A declares participation for the MSD advisory board and GSK advisory board. AJB declares grant funding paid to his institution from the Foundation for Innovative New Diagnostics and the Global Antibiotic Research and Development Partnership. JG declares grants paid to his institution from Fondo de Investigación Sanitaria, Gilead, Cidara, F2G, Scynexis, and Mundipharma; honoraria from Gilead, Pfizer, MSD, and Mundipharma; and travel support from Gilead and Scynexis. FH declares travel support from ISHAM; has unpaid roles as Treasurer for the Netherlands Society for Medical Mycology, Vice-President of ISHAM, and chair of the Division of Microbial Genomics of the Royal Netherlands Society for Microbiology; reports receipt of reduced price or free diagnostic reagents and kits to run validation tests from CHROMagar, Bruker MDx, Pathonostics, OLM Diagnostics, and Altona Diagnostics. MH declares grants from Astellas, Scynexis, Gilead, IMMY, MSD, Pfizer, Euroimmun, Mundipharma, Melinta, and Pulmocide; and research funding from Gilead Sciences, Astellas, Mundipharma, Euroimmun, MSD, GSK, Basilea, Pulmocide, Scynexis, AiCuris, Melinta, Partner, F2G, Shionogi, Stendahl, and Pfizer. SH declares grants paid to his institution from Merck, Pfizer, Cidara, Avir Pharma, Sunovion, F2G, and Pulmocide; and consulting fees from TFF and Takeda. SSK declares speaker honoraria from Pfizer, MSD, Basilea, Gilead, and Hikma; payments for advisory board member meetings from Menari and MSD; and has roles as President-elect of the International Society of Antimicrobial Chemotherapy and President of the Lebanese Society for Infectious Diseases and Clinical Microbiology. PK declares grants paid to his institution from BMBF, the B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung), NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network), NUM (Netzwerk Universitätsmedizin, Network of University Medicine), and the State of North Rine-Westphalia, Germany; consulting fees from Ambu, Gilead Sciences, Munipharma, Noxxon, and Pfizer; honoraria from Akademie für Infektionsmedizin, Ambu, Astellas Pharma, BioRad Laboratories, Datamed, ECMM, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken, Jazz Pharmaceuticals Germany, medupdate, MedMedia, MSD, Pfizer, Scilink Comunicación Científica, streamedup!, University Hospital and LMU Munich, and Vitis; a German patent application (DE 10 2021 113 007.7) has been filed by the University of Cologne (Cologne, Germany), listing PK as one of three inventors; board participation from Ambu, Gilead Sciences, Pfizer Pharma, Mundipharma, and Noxxon; honoraria for reviews and royalties from book authorships from Elsevier; and an unpaid role of Editor for Mycoses (Wiley) and Annals of Medicine (Taylor & Francis online). TL declares consulting fees from Gilead, Merck/MSD, Roche, Recordati, Mundipharma, and Pharming; and honoraria from Merck/MSD, AstraZeneca, Pfizer, Mundipharma, Gilead, Sanofi Pasteur, and Recordati. REL declares royalties from UptoDate; consulting fees from Basilea, F2G, and Gilead; and honoraria from Basilea, Gilead, Avir, and Pfizer. MHN declares consulting fees from Basilea; and was one of the authors of the Infectious Diseases Society of America (IDSA) guideline for aspergillosis. DS declares lecture fees from Pfizer and Hikma. TT declares honoraria from Asahikasei Pharma Japan, Pfizer Japan, MSD Japan, and Sumitomo Pharma Japan. DCV declares a grant from the senior clinician and senior scientist research scholar programme of the Fonds de Recherche du Québec–Santé; grants paid to his institution for clinical trial support from Cidara therapeutics, Janssen Pharmaceuticals, and Moderna; further grants paid to his institution from the Public Health Agency of Canada (COVID Immunity Task Force: DISCoVER project, UNCoVER project, and VISID project), the Jeffrey Modell Foundation, and the Canadian Institutes of Health Research; consulting fees from AstraZeneca, CSL Behring, Merck Canada, Moderna, Novartis Canada, Qu Biologics, and Shire (Takeda); honoraria from CSL Behring; travel support from the Association of Medical Microbiology and Infectious Disease (AMMI) Canada; has a patent pending (Electronic Filing System ID: 40101099); has unpaid roles as Chair of the AMMI Canada Guidelines Committee, member of the Clinical Immunology Society Education Committee and Continuing Education Committee, patient advocate of the Medical Committees of the Association des patients immunodéficients du Québec and the Canadian Immunodeficiency Patient Organization, patient advocate as medical advisor to the Regroupement Trisomie 21 and the Leukemia & Lymphoma Society of Canada; and reports receipt of equipment to his institution from the McGill University Health Centre Foundation and the Montreal General Hospital Foundation. JA declares research grants from Pfizer, Gilead, and Knight; and honoraria from Knight and Gilead. FC declares honoraria from Pfizer, Knight, and Sandoz; travel support from Pfizer and Mundipharma; and board participation from Pfizer and Sandoz. LYAC declares honoraria from Pfizer paid to her institution, and board participation from CIDARA Therapeutics (paid to her institution). ALC declares a grant from Knight–United Medical; honoraria from Mundipharma, Sandoz, and Knight–United Medical; travel support from Mundipharma and Knight–United Medical; and advisory board membership from Mundipharma and Sandoz. ACo declares fees for lectures from Gilead, Pfizer, and Mundipharma; and advisory board fees from Gilead, MSD, Mundipharma, and Pfizer. DECL declares a Biotechnology and Biological Sciences Research Council–US National Science Foundation project grant (BB/W002760/1) held by Elizabeth Ballou; honoraria from Gilead; and travel support from a project grant (BB/W002760/1). LD declares payment for lectures from Pfizer. SG declares a grant from the NIHR Manchester Biomedical Research Centre Dowager Countess Eleanor Peel Trust. RK declares a grant from Pfizer for support of investigator-initiated research; and payments for lectures from Pfizer, Mundipharma, and Gilead. KL declares a grant from TECOmedical paid to her institution; consulting fees from Mundipharma paid to her institution; payments for lectures and presentations from Gilead and Pfizer, paid to herself, and Mundipharma and FUJIFILM Wako Chemicals Europe, paid to her institution; travel support from Gilead, Pfizer, and AstraZeneca; and payment for board participation from Pfizer paid to her institution. MSL declares funding from the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. MKM declares consulting fees from GenMark Diagnostics, NED Biosystems, and Vericel; honoraria from Thermofisher Scientific; payment for expert testimony; a patent for neutrophil therapeutic; and board participation from Karius. JM declares grants from Gilead, Mundipharma, and VIRCELL; and honoraria and travel grants from Gilead, all paid to his institution. SCM declares grants from DZIF and the University of Cologne (Cologne, Germany); consulting fees from Octapharma; honoraria from Pfizer; and board participation from Octapharma. MMi declares a grant from Gilead paid to her institution; honoraria from AstraZeneca, Gilead, Janssen, Mundipharma, and Pfizer; and board participation from Allovir, Moderna, Mundipharma, and Shionogi. PM declares consulting fees and honoraria from Menarin, Pfizer, MSD, Viatris, and Mundipharma. VO declares role and stock options from Volumeer. PP declares grants from F2G, Melinta, Scynexis, and Astellas; and board participation from F2G, Basilea, Scynexis, Melinta, and ISHA Pharmaceuticals. TFP declares grants from Cidara, F2G, and Scynexis paid to his institution; board participation from Gilead, Scynexis, and Basilea; and roles as Treasurer (past) of the Immunocompromised Host Society, Treasurer (past) and IDSA liaison (current) of the Texas Infectious Diseases Society, and member of the board of directors of the Mycoses Study Group Education and Research Consortium. PP-A declares grants paid to his institution from Instituto de Salud Carlos III and Gilead; honoraria from Gilead, Pfizer, and MSD; and board participation from Gilead. ER declares research grants from Merck, AbbVie, Shionogi, Cidara Therapeutics, Melinta, and Pfizer paid to his institution; payments as scientific advisor and member of the speaker bureau from Gilead, Merck, Shionogi, Mundipharma, and Pfizer, paid to his institution. CR declares grants and research support paid to his institution from Chimerix, Cidara, and Scynexis; consulting fees from Avir Pharma, Merck Canada, and Pfizer Canada; and honoraria from Avir Pharma, Merck Canada, and Sunovion Pharmaceuticals Canada. TR declares speaker fees from Hikma, and lecture fees from Akademie für Infektionsmedizin. RSa declares honoraria from Pfizer. JS-G declares honoraria from Gilead, Menarini, and Pfizer; travel support from AstraZeneca; and board participation from Pfizer. JSi declares honoraria and travel support from Pfizer, MSD, and Gilead. RSo declares honoraria for lectures from Pfizer, MSD, Mylan, Cipla, and Glenmark; and advisory board fees from Pfizer, MSD, Mylan, Cipla, Glenmark, and Hoffmann la Roche. AS declares grants from Astellas and Mayne, and consulting fees from GSK. JStei declares a grant from Pfizer, and honoraria from Pfizer and Gilead. JStem declares grants paid to his institution from the German Federal Ministry of Education and Research, the Medical Faculty of the University of Cologne (Cologne, Germany), Basilea Pharmaceuticals, and Noscendo; consulting fees from Gilead, Micron Research, and Alvea; and honoraria from AbbVie, Gilead, Hikma, and Pfizer. AFT declares grants from the UK–Ireland Fellowship, Gilead Sciences, and Associates of Cape Cod (Fungitell). GRT declares grants and consulting fees from Astellas, Basilea, Cidara, F2G, Mundipharma and Melinta; and board participation from Pfizer. NW declares grants from bioMerieux, Bruker, F2G, Mycovia, Sfunga, and Scynexis; honoraria from the American Society for Microbiology and the American College of Veterinary Internal Medicine; travel support from the Clinical and Laboratory Standards Institute, Page Medical, and the American College of Veterinary Internal Medicine; has roles within the Clinical and Laboratory Standards Institute, the American Society for Microbiology, and the British Society for Antimicrobial Chemotherapy; and reports receipt of drugs (drug powder) from Scynexis, Basilea, Cidara, F2G, and Mycovia. BWi declares a grant from Schülke & Mayr paid to her institution; and honoraria from Mundipharma, bioMérieux, BD, CapeCod, and Schülke & Mayr. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Study Objectives: This multi-center comparative cross-sectional study aimed to describe educational and occupational pathways, quantify effort/reward imbalance at work and identify factors associated with professional prognosis in patients with narcolepsy type 1 (NT1)., Methods: Adult patients with NT1 and controls answered online questionnaires (Epworth sleepiness Scale, Beck Depression Inventory II, Siegrist questionnaire, Adult Self-Report, and a questionnaire on academic and professional trajectories) and were compared using sex- and age-adjusted logistic regressions. Clinical, demographic and psycho-social factors associated with patients' professional prognosis, as assessed by a composite score based on occupational-related outcomes, were explored with a generalized linear model., Results: We included 235 patients (63.8% women, 36.4±14.7 years, 86.5% treated, 66.4% with childhood onset) and 166 controls (69.9% women, 40.3±14.4 years). No difference was observed between patients and controls for graduation, but patients reported more interruptions, absenteeism and lateness during schooling. No difference was observed for employment rate (69.5% vs 77.0%), but income was lower in patients who reported more unwanted changes in position and part-time work, with increased effort-reward imbalance (OR=2.28 95%CI[1.20-4.33], p=0.01). Impaired professional prognosis was associated with depression (p<0.0001) and attention disorders (p=0.03), while being narcoleptic during schooling was a protective factor (p=0.02)., Conclusions: Most patients with NT1 manage to achieve their careers goals, but at the cost of an effort/reward imbalance. Early diagnosis might allow a better adjustment to the disease. The strong impact of psycho-cognitive comorbidities on professional outcomes stresses the need to consider psycho-cognitivo-social dimensions in patient care., Clinical Trial Registration: Registry: ClinicalTrials.gov; Identifier: NCT03765892., (© 2025 American Academy of Sleep Medicine.)

The combination of aztreonam (ATM) and avibactam (AVI) is an attractive option to treat infections caused by extended spectrum β-lactamase plus NDM-1-producing Enterobacteriaceae . Since ATM activity was shown to be severely impacted by an increase in the inoculum size in vitro , we wondered whether ATM-AVI activity could be impaired in high-inoculum infections. We analyzed the impact of the inoculum size on ATM-AVI activity in vitro and in a murine model of peritonitis due to susceptible Escherichia coli CFT073-pTOPO and its isogenic derivatives producing NDM-1 ( E. coli CFT073-NDM1) and CTX-M-15 plus NDM-1 ( E. coli CFT073-CTXM15-NDM1). The impact of the inoculum size on bacterial morphology was studied by microscopic examination. In vitro , at standard (10 5 ) inoculum, E. coli CFT073-CTXM15-NDM1 was resistant to ATM but susceptible to the ATM-AVI combination. At high (10 7 ) inoculum, MICs of ATM alone and of the ATM-AVI combination reached >512 and 64 mg/L, respectively, against all tested strains. ATM led to bacterial filamentation when active against the bacteria, i.e., in monotherapy or in combination with AVI against susceptible E. coli CFT073-pTOPO and only in combination with AVI against E. coli CFT073-CTXM15-NDM1. In vivo , increase in the inoculum led to a drastic decrease in the activity of ATM alone against E. coli CFT073-pTOPO and ATM-AVI against E. coli CFT073-CTXM15-NDM1. Our results suggest a high in vivo impact of the inoculum increase on the activity of ATM alone against ATM-susceptible E. coli and of ATM-AVI against CTX-M-15 plus NDM-1 producing E. coli . Clinicians must be aware of the risk of failures when using ATM-AVI in high-inoculum infections., Competing Interests: The authors declare no conflict of interest.

Background: Interstitial lung disease is rarer in children than adults, but, with increasing diagnostic awareness, more cases are being discovered. The prognosis of childhood interstitial lung disease is often poor, but increasing numbers are now surviving into adulthood., Aim: To characterise childhood interstitial lung disease survivors and identify their impact on adult interstitial lung disease centres., Methods: This was a European study (34 adult and childhood interstitial lung disease centres) reporting incident/prevalent cases of childhood interstitial lung disease survivors from January to July 2023. Epidemiological, clinical, physiological and genetic data were collected., Results: 244 patients were identified with a median (interquartile range) age at diagnosis of 12.5 years (6-16 years) and age at study inclusion of 25 years (22-33 years), with 51% male, 86% nonsmokers and a median (interquartile range) % predicted forced vital capacity of 70% (47-89%) and diffusing capacity of the lungs for carbon monoxide of 48% (32-75%). 32% were prescribed long-term oxygen and 227 (93%) were followed up in adult centres whereas 17 (7%) never transitioned. The commonest diagnoses (82%) were childhood interstitial lung disease category B1 (sarcoidosis, hemosiderosis, connective tissue disorders, vasculitis) at 35%, A4 (surfactant-related) at 21%, B2 (bronchiolitis obliterans, hypersensitivity pneumonitis) at 14% and Bz (unclassified interstitial lung disease) at 13%. Bz patients had the worst functional status. 60% of all patients were still being prescribed corticosteroids. Re-specification of diagnosis and treatment were made after transition for 9.8% and 16% of patients, respectively. Not all childhood interstitial lung disease diagnoses were recognised in adult interstitial lung disease classifications., Conclusion: Childhood interstitial lung disease survivors are seen in most adult interstitial lung disease centres and only a minority continue follow-up in paediatric centres. Survivors have a significant loss of lung function. The heterogeneity of their aetiologies and therapeutic requirements has a real impact on adult interstitial lung disease centres. Re-specification of diagnosis and treatment may contribute to precision and personalisation of management., Competing Interests: Conflict of interest: E.D. Manali reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, CSL Behring and Hoffman-La Roche; support for attending meetings and/or travel from Boehringer Ingelheim, CSL Behring, Hoffman-La Roche and Elpen; and leadership as Chair in the ERS task force for transition of chILD. M. Griese reports consulting fees and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim. N. Nathan reports grants from CORTICONEHI for the clinical trial “Efficacy of methylprednisolone pulses in neuroendocrine cells hyperplasia of infancy”, the Million Dollar Bike Ride project for Neuroendocrine Cell Hyperplasia of Infancy, the Chancellerie des Universités, RespiFIL for the development of an e-learning module for CT-scan in childhood interstitial lung diseases and RespiFIL for the development of an online platform for rare lung disease quality of life and transition questionnaires; payment or honoraria for lectures, presentations, manuscript writing or educational events from La Lettre du Pneumologue; and support for attending meetings from the ERS. Y. Uzunhan reports grants from Oxyvie; consulting fees from Boehringer Ingelheim and Pfizer; payment or honoraria for lectures, presentations, manuscript writing or educational events from Sanofi, CSL Vifor and Boehringer Ingelheim; support for attending meetings and/or travel from Boehringer Ingelheim and Oxyvie; and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim. R. Borie reports consulting fees from Boehringer Ingelheim, Ferrer and Sanofi; payment or honoraria for lectures, presentations; and educational events from Boehringer Ingelheim; and support for attending meetings from Boehringer Ingelheim. N. Schwerk reports consulting fees from Boehringer Ingelheim for consultancy work; paid lectures, publications and advisory board participation; and a leadership role as President-elect of the German Society for Paediatric Pneumology. C. McCarthy reports support for the present manuscript from Savara Inc.; grants from Health Research Board (Ireland), Enterprise Ireland and The LAM Foundation; consultancy fees from Savara Inc., AI Therapeutics, and Theravance Inc.; support for attending meetings from Boehringer Ingelheim; and participation on a data safety monitoring board or advisory board with Savara Inc. M. Koziar Vasakova reports consulting fees from Boehringer Ingelheim and Roche; payment or honoraria for lectures, presentations and educational events from Boehringer Ingelheim and Roche; support for attending meetings from Roche and Boehringer Ingelheim; and participation on a data safety monitoring board or advisory board with MSD and Boehringer Ingelheim. M. Molina-Molina reports grants from Boehringer Ingelheim and Roche; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, Ferrer and Veracyte. C.H.M. van Moorsel reports grants from Boehringer Ingelheim for research support in digital auscultation for ILD, payment or honoraria for lectures from Boehringer Ingelheim and a leadership role as Co-chair of the ClinGen ILD Gene Curation Expert Panel. I. Campo reports consulting fees from Partner Therapeutics for a paid interview and participation on a data safety monitoring board or advisory board with Savara as a member of the advisory board for molgramostim. E. Bendstrup reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim and Daichii Sankyo; support for attending meetings from Boehringer Ingelheim; and participation on a data safety monitoring board or advisory board with Simbec-Orion for Molecure DSMB. T.S. Prior reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim; and support for attending meetings from Boehringer Ingelheim. F. Bonella reports consulting fees from Boehringer Ingelheim, Sanofi, BMS and CSL-Behring; payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and Sanofi; support for attending meetings from Boehringer Ingelheim, AstraZeneca and Atyr; and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim, Sanofi and BMS. R. Diesler reports grants from CSL Behring, Fondation du Souffle and Fondation pour la Recherche Médicale, and support for attending meetings from Asdia. A. Froidure reports consulting fees from Boehringer Ingelheim; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, AstraZeneca and GSK. F. Jeny reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim; and support for attending meetings from Oxyvie (travel for a French congress). N. Ocal reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, Nobel and Humanis. B. Crestani reports grants from Boehringer Ingelheim; consultancy fees from BMS, Boehringer Ingelheim, Chiesi, GSK and Sanofi; payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, BMS, Boehringer Ingelheim, GSK, Novartis, Roche and Sanofi; support for attending meetings from AstraZeneca, BMS, Boehringer Ingelheim, Roche and Sanofi; participation on a data safety monitoring board or advisory board with BMS, Boehringer Ingelheim, Horizon and Sanofi; and a leadership role as President of the board of trustees of the Fondation du Souffle (a French charity). P. Pohunek reports support for the present study from the ERS Task Force TF2021-14 (payment for the librarian); consulting fees from AstraZeneca and GSK; payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK and AstraZeneca (personal), and Chiesi, AstraZeneca and GSK (institutional); support for attending meetings from GSK and AstraZeneca; and participation on a data safety monitoring board or advisory board with GSK and AstraZeneca. S.A. Papiris reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and Hoffman La Roche; support for attending meetings from Boehringer Ingelheim, Hoffman La Roche and Elpen; and leadership or fiduciary role as a member in the ERS Task Force for the transition of chILD. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2025. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Loiasis is endemic in Central Africa. Despite evidence of clinical complications and increased mortality, it remains excluded from the list of neglected tropical diseases. The main manifestations are Calabar swellings (CS), Eyeworm (EW) and non-specific general symptoms such arthralgia and pruritus. We calculated incidence rates for clinical manifestations of loiasis from a 13-month study on clinical manifestations in 991 individuals living in Loa loa-endemic areas in the Republic of Congo., Methodology: From September 2022 to September 2023, community health workers collected weekly symptoms from cohort participants. Detailed data on symptom duration, intensity, associated pruritus, and impact on sleep were recorded. Laboratory procedures included thick blood smear for L. loa microfilaremia measurement, creatininemia measurement and eosinophilia counts. We used multiple failure analysis and frailty models to calculate incidence rates of EW, CS, arthralgia, pruritus and absence from work (AfW) and to analyses factors associated with increased incidence of each symptom. The population-attributable fractions (PAFs) associated with loiasis were also calculated for pruritus, AfW and arthralgia., Principal Findings: Among the studied manifestations, arthralgia had the highest incidence rate at 555.2 cases per 1000 Person-Year (PY), followed by pruritus (332.3 cases/1000 PY), AfW (298.6/1000 PY), EW (266.4/1000 PY), and CS (213.8/1000 PY). Notably, the incidence rates of CS, pruritus, arthralgia, and AfW were statistically significantly higher in the subgroup of individuals who experienced at least one episode of EW during the follow-up period. EW occurrence is more frequent when microfilaremia is present. The PAFs of AfW, pruritus and arthralgia, associated with loiasis was 18.0% [07.3-27.6], 20.8% [11.6-29.1] and 12.1% [3.1-20.1], respectively., Conclusion/significance: This is the first study to provide incidence rates for the clinical manifestations of loiasis. These estimates are crucial for assessing the burden of loiasis. The findings highlight the disease's impact on quality of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Campillo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Sotorasib has shown efficacy in a phase 3 trial compared to docetaxel among previously treated non-small cell lung cancer (NSCLC) patients with a KRAS G12C mutation. However, its real-world effectiveness and tolerance, especially post-immunotherapy, remain debated., Methods: This French retrospective multicentre study analysed NSCLC patients receiving at least one dose of sotorasib as part of early access program The main objective was to assess real-world progression-free survival (rwPFS), and secondary objectives included assessment of overall survival (rwOS) and sotorasib-related hepatotoxicity., Results: 458 patients from 76 centres were analysed, with a median age 65.8. Among them, 43.4 % were female, 28.3 % had performance status ≥ 2, 95.4 % were active/former smokers, and 38.0 % had brain metastases with 55.2 % in progression at sotorasib initiation. PD-L1 expression was < 1 %, ≥ 1-49 %, ≥ 50 %, and unknown in 35.1 %, 34.1 %, 23.4 %, and 7.4 % of patients, respectively. Most patients had received prior treatments (96.7 %), including immunotherapy (54.9 %). Median (95 % confidence interval [CI]) rwPFS and rwOS were 3.5 (3.1-4.2) and 8.3 (7.5-9.3) months, with a median (95 % CI) follow-up of 15.8 (13.9-17.3) and 16.4 (15.5-17.3) months, respectively. The real-world objective response rate (rwORR) was 33.2 % and disease control rate (rwDCR) was 63.2 %. In patients with brain metastases, cerebral rwORR and rwDCR were 20.1 % and 66.9 %, respectively. Grade 3-4 adverse events related to hepatotoxicity occurred in 5.2 % of patients. Sotorasib was discontinued for toxicity in 16.5 % of patients., Conclusion: This study gave insights into effectiveness and safety of sotorasib in a real-world setting, in advanced or metastatic KRAS G12C-mutated non-squamous NSCLC., Competing Interests: Declaration of Competing Interest M. Wislez: Amgen, Roche, BMS, MSD, Astra-Zeneca, Sanofi, Novartis, Lilly, Takeda, Kephren, Amgen, Janssen. C. Mascaux: Amgen, AstraZeneca, BMS, MSD, Lilly, Novartis, Pfizer, Roche, Sanofi, Takeda, Kephren, Janssen. J. Cadranel: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Daiichi Sankyo, MSD, Lilly, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Takeda. Q. D. Thomas: Amgen, AstraZeneca, Sanofi. A. Swalduz: AstraZeneca, Janssen, Roche, Amgen, BMS, Pfizer, Lilly. E. Pichon: BMS, AstraZeneca, Takeda, Janssen, BeiGene. R. Veillon: Janssen, BMS, Takeda, Amgen, Sanofi, Roche, AstraZeneca, Abbvie, GSK, Novartis, Merck KGaA, Pfizer. V. Gounant: BMS, AstraZeneca, Takeda, Sanofi, Pfizer. G. Rousseau-Bussac: AstraZeneca, Takeda, BMS, Boehringer, Sanofi, Lilly, Pfizer. A. Madroszyk: AstraZeneca, Roche, Pfizer. C. Daniel: AstraZeneca, MSD, Amgen, Sanofi. P. Fournel: Amgen, AstraZeneca, BMS, Janssen, MSD, Sanofi, Takeda, Ipsen. F. Guisier: Amgen, AstraZeneca, BMS, Janssen, MSD, Pfizer, Roche, Sanofi, Takeda. V. Westeel: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Pfizer, Janssen, Ipsen. All the other authors declare that they have no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) tumor interpatient heterogeneity has been well described with two major prognostic subtypes (classical and basal-like). An important intrapatient heterogeneity has been reported but has not yet been studied extensively due to the lack of standardized, reproducible, and easily accessible high-throughput methods. We built an immunohistochemical (IHC) tool capable of differentiating RNA-defined classical and basal-like tumors by selecting relevant antibodies using a multistep process. The successive stages of (i) an in silico selection from a literature review and a bulk transcriptome analysis of 309 PDACs, (ii) a tumor-specific selection from 30 patient-derived xenografts and single-cell data, followed by (iii) the validation on tissue microarrays in 50 PDAC were conducted. We used our final IHC panel on two independent cohorts of resected PDAC (n = 95, whole-slide, n = 148, tissue microarrays) for external validation. After digitization and registration of pathology slides, we performed a tile-based analysis in tumor areas to identify relevant marker combinations. Sequential marker selection led to the following panel: GATA6, CLDN18, TFF1, MUC16, S100A2, KRT17, PanBasal. Four different phenotypes were identified: one classical, one intermediate (KRT17+), and two basal-like (MUC16+ versus S100A2+) with specific biological properties. The presence of a minor basal contingent drastically reduced overall survival [hazard ratio (HR) = 1.90, p = 0.03], even in classical predominant PDACs. Analysis of preneoplastic lesions suggested that pancreatic carcinogenesis might follow a progressive evolution from classical toward a basal through an early intermediate phenotype. In conclusion, our IHC panel redefined and easily assessed the high degree of intra- and intertumoral heterogeneity of PDAC. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

GRASP65 is a Golgi-associated peripheral protein encoded by the GORASP1 gene and required for Golgi cisternal stacking in vitro. A key role of GRASP65 in the regulation of cell division has also been suggested. However, depletion of GRASP65 in mice has little effect on the Golgi structure and the gene has not been associated with any human phenotype to date. Here, we report the identification of the first human pathogenic variant of GORASP1 (c.1170&#95;1171del; p.Asp390Glufs*18) in a patient combining a neurodevelopmental disorder with neurosensory, neuromuscular, and skeletal abnormalities. Functional analysis revealed that the variant leads to a total absence of GRASP65. The structure of the Golgi apparatus did not show fragmentation, but glycosylation anomalies such as hyposialylation were detected. Mitosis analyses revealed an excess of prometaphases and metaphases with polar chromosomes, suggesting a delay in the cell cycle. These phenotypes were recapitulated in RPE cells in which a similar mutation was introduced by CRISPR/Cas9. These results indicate that loss of GRASP65 in humans causes a novel Golgipathy associated with defects in glycosylation and mitotic progression., (© 2025 Lebon et al.)

Background and Aims: Rheumatic heart disease is the commonest acquired cardiovascular disease worldwide. About 20 years have elapsed since the original Euro Heart Survey on valvular heart disease (VHD) was conducted with multiple changes in practice due to advances in treatment techniques. In this study, we aimed to analyse the management of patients with severe native valve disease or those with previous valvular intervention in comparison with existing European Society of Cardiology guidelines., Methods: The European Society of Cardiology VHD II registry is an international, prospective, longitudinal multicentre, observational study, which was conducted in 222 centres. The registry included patients with severe native VHD or with previous valvular intervention. Follow-up was undertaken at 6 months at the investigating centre or by telephone., Results: Amongst patients recruited in the European Society of Cardiology VHD II registry, 470 had severe rheumatic mitral valve disease and 332 had previous rheumatic mitral valve intervention. Amongst the patients with Class I recommendation for intervention, it was undertaken in only 70%. Adherence to guideline recommendations was more in patients with native VHD than in those with previous intervention. Total mortality was 1.5% in hospital and 3.5% at 6 months follow-up. Independent predictors of death at 6 months were age, chronic pulmonary disease, New York Heart Association Classes III and IV at presentation, liver dysfunction, and previous myocardial infarction., Conclusions: Compliance with guideline recommendations for intervention is poor overall in patients with rheumatic valve disease. Concerted educational efforts are needed to improve the management of this vulnerable patient cohort., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: The objective was to investigate the efficacy and safety of clopidogrel-aspirin versus aspirin alone in patients after ischemic stroke by glycemic status using data from the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial., Methods: Patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) were randomized to clopidogrel-aspirin or aspirin alone. They were categorized into 3 subgroups according to glycemic status based on medical history and diagnosis by a clinician during hospitalization: without type 2 diabetes mellitus, with newly diagnosed type 2 diabetes, and with a history of type 2 diabetes mellitus. The primary efficacy and safety outcomes were new stroke and moderate-to-severe bleeding risk within 90-day follow-up., Results: A total of 6,100 patients were enrolled (3,050 in each arm), with a median age of 65 years (interquartile range [IQR], 57-71) and 2,185 female (35.8%). Clopidogrel-aspirin treatment was associated with a reduction in recurrent stroke compared with aspirin alone in patients without type 2 diabetes mellitus (6.3% vs 8.4%; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59-0.94; p = 0.01) and those with newly diagnosed type 2 diabetes mellitus (5.8% vs 13.0%; HR, 0.30; 95% CI, 0.14-0.66; p = 0.002), but not in those with a history of type 2 diabetes mellitus (10.0% vs 9.9%; HR, 0.98; 95% CI, 0.72-1.33; p = 0.88) (p for interaction = 0.03). Moderate-to-severe bleeding events did not differ significantly by treatment across glycemic subgroups., Interpretation: In the INSPIRES trial, patients without or with type 2 diabetes mellitus derived greater benefit from clopidogrel-aspirin than those with a history of type 2 diabetes mellitus after mild ischemic stroke or high-risk TIA., Trial Registration: INSPIRES, NCT03635749. Registered 15 August 2018, https://clinicaltrials.gov/search?cond=NCT03635749. ANN NEUROL 2025., (© 2025 American Neurological Association.)

Background: Accurate bleeding risk stratification after percutaneous coronary intervention is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of patients at high bleeding risk. We derived and validated a novel bleeding risk score by augmenting the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria., Methods: The derivation cohort comprised 29 188 patients undergoing percutaneous coronary intervention, of whom 1136 (3.9%) had Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from 4 contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis ( P <0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) and 5970 patients from the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy-2) total cohort., Results: The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white blood cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in STOPDAPT-2, with superior discrimination compared with PRECISE-DAPT (cross-validation: ΔAUC, 0.01; P =0.02; MASTER DAPT: ΔAUC, 0.05; P =0.004; STOPDAPT-2: ΔAUC, 0.02; P =0.20) and other risk scores. In the derivation cohort, a cutoff of 23 points identified 11 414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white blood cell count, showed similar predictive ability., Conclusions: The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after percutaneous coronary intervention, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice., Competing Interests: Dr Valgimigli reports grants and personal fees from Terumo and personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, IDORSIA PHARMACEUTICALS LTD, Universität Basel, Department Klinische Forschung, Bristol Myers Squib SA, Medscape, Biotronik, and Novartis, outside the submitted work. Dr Gragnano reports personal fees from SANOFI for advisory board outside the submitted work. Dr Heg is affiliated with the Department of Clinical Research (DCR), University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. DCR Bern is involved in the design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. Pharmaceutical and medical device companies provide direct funding to some of these studies. Dr Räber reports grants or contracts from Abbott, Biotronik, BostonScientific, Heartfolow, Sanofi, and Regeneron; consulting fees from Canon; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbott, Amgen, Sanofi, and Occlutech; and participation on a data safety monitoring board or advisory board for Abbott, Amgen, NovoNordisk, Medtronic, and Sanofi outside the submitted work. Dr ten Berg reports support by an institutional research grant from AstraZeneca for the present article. Dr Bär reports grants or contracts from Medis Medical Imaging Systems, Abbott, Bangerter-Rhyner Stiftung, and Swiss National Science Foundation, outside the submitted work. Dr Kimura reports research grants from Abbott and Boston Scientific, outside the submitted work. Dr Leonardi reports grants from AstraZeneca and consulting fees from AstraZeneca, Daiichi Sankyo, Bayer, Pfizer/BMS, ICON, Chiesi, and Novo Nordisk, outside the submitted work. Dr Bhatt reports the following relationships outside the submitted work: Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association, New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; data monitoring committee: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT Trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC accreditation oversight committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, which assigned to Lexicon; neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo. Dr Urban reports consulting fees from Biosensors and MedAlliance; support for attending meetings and/or travel from MedAlliance; and stock or stock options for MedAlliance and CERC, outside the submitted work. Dr Windecker reports research, travel, or educational grants to the institution from Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave. He serves as Advisory Board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis, with payments to the institution but no personal payments. He is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. The other authors report no conflicts.

Background: Currently, diagnosis of bacterial infections is based on culture, possibly followed by the amplification and sequencing (Sanger method) of the 16S rDNA - encoding gene when cultures are negative. Clinical metagenomics (CMg), i.e. the sequencing of a sample's entire nucleic acids, may allow for the identification of bacteria not detected by conventional methods. Here, we tested the performance of CMg compared to 16S rDNA sequencing (Sanger) in 50 patients with suspected bacterial infection but negative cultures., Methods: This is a prospective cohort study. Fifty patients (73 samples) with negative culture and a 16S rDNA sequencing demand (Sanger) were recruited from two sites. On the same samples, CMg (Illumina NextSeq) was also performed and compared to 16S rDNA Sanger sequencing. Bacteria were identified using MetaPhlAn4., Results: Among the 73 samples, 20 (27 %, 17 patients) had a clinically relevant 16S rDNA Sanger sequencing result (used for patient management) while 11 (15 %, 9 patients) were considered contaminants. At the patient level, the sensitivity of CMg was 70 % (12/17) compared to 16S rDNA. In samples negative for 16S rDNA Sanger sequencing (n = 53), CMg identified clinically-relevant bacteria in 10 samples (19 %, 10 patients) with 14 additional bacteria., Conclusions: CMg was not 100 % sensitive when compared to 16S, supporting that it may not be a suitable replacement. However, CMg did find additional bacteria in samples negative for 16S rDNA Sanger. CMg could therefore be positioned as a complementary to 16S rDNA Sanger sequencing., Competing Interests: Conflict of interest None., (Copyright © 2025 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Introduction: Until recently there was no recommended adjuvant therapy for patients with lymph nodes metastasis (ypN+) following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of the study was to describe the oncological outcomes of ypN+ patients following NAC and RC for MIBC., Methods: This collaborative retrospective study included 195 patients with ypN+ disease after NAC followed by RC and bilateral pelvic lymph node dissection for MIBC between 2000 and 2019 in seven centers. Patients' demographics, clinical and pathological features were collected. Survival analyses were carried out with Kaplan-Meier estimates and a Cox model was generated., Results: A total of 120 patients (62%) were pN1, 51 pN2 (26%) and 24 pN3 (12%). Adjuvant radiation therapy was performed in 18 (9%), adjuvant chemotherapy in 40 (21%) and the remaining 137 (70%) patients were observed. The median follow-up time was 51 months (95%CI 44-62). Median times for recurrence-free survival, cancer-specific survival and overall survival (OS) were 18 months (95%CI 16-21), 47 months (95%CI 31-70) and 28 months (95%CI 22-34) respectively. On multivariable analysis, female gender (HR = 1.5, 95%CI 1.002-2.21, p = 0.049) and positive surgical margins (HR = 1.6, 95%CI 1.06-2.38, p = 0.026) were the only independent predictor of OS. The type of adjuvant therapy did not impact OS (adjuvant chemotherapy, p = 0.44; adjuvant radiotherapy p = 0.40)., Conclusion: MIBC patients with residual node positive disease following NAC and RC have poor survival outcomes. Females and patients with positive margin status at RC carry a poorer prognosis. These results may be beneficial for clinical trial design., Competing Interests: Declaration of competing interest No conflict of interest for all authors., (Copyright © 2025. Published by Elsevier España, S.L.U.)

Background: One anastomosis gastric bypass (OAGB) currently stands as the third most common metabolic and bariatric surgical procedure with increasing popularity worldwide. Iron deficiency anemia (IDA) is the most prevalent anemia observed after gastric bypass procedures., Methods: This systematic review and meta-analysis aimed to assess the overall incidence of IDA and identify the effect of biliopancreatic limb (BPL) length on the incidence of IDA in patients undergoing OAGB by a systematic literature search in PubMed, Web of Sciences, and Scopus., Results: Twenty-six studies including 11,015 patients were finally included for review. The mean age and mean BPL lengths were 40.1 ± 7.2 years and 190.4 ± 29.2 cm respectively. The IDA prevalence after OAGB was 16% and BPL length was shown to predict IDA rates after OAGB (p = 0.042). Specifically, 8% of patients with a BPL length of 150-179 cm, 12% of patients with a BPL length of 180-199 cm, and 9% of patients with a BPL length of ≥ 200 cm experienced IDA., Conclusion: Despite the promising trends of performed OAGB worldwide, further studies are required to ascertain the risks related to this procedure and refine the surgical techniques., Competing Interests: Declarations. Disclosures: Drs Mohammad Kermansaravi, Masoumeh Shahsavan, Karl Hage, Halit Eren Taskin, Shahab ShahabiShahmiri, Tigran Poghosyan, Amir Hossein Davarpanah Jazi, Clement Baratte, Rohollah Valizadeh, Jean-Marc Chevallier, and Omar M. Ghanem have no conflicts of interest or financial ties to disclose., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: While difficult-to-treat multidrug-resistant Gram-negative bacteria infections increase over time, the real-world effectiveness, use, and safety of ceftazidime-avibactam (CAZ-AVI) for treating hospitalized patients was assessed in 41 French centers., Procedures: OZAVIE was a prospective, multicenter, observational study conducted between March 2019 and November 2021. Hospitalized adult patients having initiated CAZ-AVI for infections within 14 days before enrolment were eligible. Demographic, clinical, microbiological, and therapeutic data were collected. Outcome was categorized as "failure" if the patient died from the initial infection, or if the infections persisted and required another antibiotic or surgery, or if CAZ-AVI was discontinued due to intolerance, and as "global success" otherwise. Patients whose outcome was not "failure", did not die and required no other antibiotics during the index hospitalization were categorized as "therapeutic success"., Results: 257 patients were enrolled: 76 females/181 males, mean age 58.4 years, with diabetes (30.0 %), chronic renal failure (25.7 %), end-stage liver disease (9.3 %) and/or immunocompromised (31.1 %). CAZ-AVI was prescribed for nosocomial pneumonia (34.2 %), complicated urinary tract infections (17.5 %), complicated intra-abdominal infections (14.8 %) and other specified sites (27.6 %). The main pathogens were Pseudomonas aeruginosa (52.4 %), Klebsiella spp. (34.9 %), Enterobacter spp. (18.4 %). Global and therapeutic successes were observed in 79.0 % and 63.4 % of patients, respectively, and 28-day mortality was 20.2 %. Overall, adverse events possibly related to CAZ-AVI were reported in 17.4 % of patients, including serious AEs in 6.2 %., Conclusions: CAZ-AVI is effective and well tolerated for treating various infections - including difficult-to-treat infection sites - and for treating various infections strains, including Pseudomonas aeruginosa and Enterobacter spp., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Masson SAS.)

Ojective: We aim to describe a large, multicenter cohort of patients with bloodstream infection (BSI) acquired during extracorporeal membrane oxygenation (ECMO) support., Methods: We conducted a retrospective observational study in 12 Europeans ICUs. Only patients who developed a BSI of unknown source during ECMO support were included in the present analysis. Primary aim was to describe BSI epidemiology in patients with ECMO support. Secondary objectives were to describe antimicrobial susceptibility of incriminated micro-organisms., Results: One hundred and eighty-two patients were included. Main reason for ECMO support was ARDS, followed by cardiogenic shock and post-cardiotomy. Half of the patients (51.9%) received early antimicrobial therapy. Main incriminated microorganisms were Enterococcus sp. (37.4%), Enterobacterales (26.9%), coagulase negative Staphylococci (15.9%) and Gram negative bacilli (11.5%). Multi drug resistant organisms (MDRO) were incriminated in 26 (14.3%) BSI and were mainly extended spectrum producing-Enterobacterales (17/26). Antimicrobial therapy was considered as appropriate in 130 patients (71.4%). Patients who received inappropriate antimicrobial therapy were more frequently infected with MDRO. Only 59 (32.4%) of cases were susceptible to 3rd generation cephalosporin while association of piperacillin/tazobactam with vancomycin was considered appropriate in 155 cases (85.2%) as compared with 168 cases (92.3%) for carbapenems combined with vancomycin., Conclusion: Enterococcus sp. was incriminated in about a third of BSI among patients with ECMO support. High appropriateness would only be obtained with piperacilline/tazobactam or carbapenems in association with vancomycin while 3rd generation cephalosporin would have failed in the majority of BSI cases., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval: In accordance with the declaration of Helsinki, the protocol was submitted and then approved by the ethics committee of the Société de Réanimation de Langue Française (registration no. CE-SRLF-22–074) and the database is registered by the Commission Nationale de l’Informatique et des Libertés (CNIL, registration no 2228484v 0). Consent to participate: In accordance with current French law, informed written consent for demographic, physiologic and hospital-outcome data analyses was waived because this observational study did not modify existing diagnostic or therapeutic strategies. Nonetheless, patients and/or relatives were informed about the anonymous data collection and told that they could decline inclusion. Competing interests: The authors declare no competing interests. Contributors: Groupe Hospitalier Pitié-Salpêtrière, Paris, France: Juliette Chommeloux, Guillaume Hékimian, Alain Combes, Nima Djavidi, Aymeric Lancelot, Pauline Dureau, Guillaume Lebreton. CH de Saint-Brieuc, France: Pierre Fillâtre. Centre Hospitalier Universitaire de La Réunion, Saint Denis, France: Laura Rivoire, Nicolas Allou, Radj Cally. Hôpital Bichat-Claude Bernard, Paris, France: Hermann Do Rego, Mariem Dlela, Marc Doman. Centre Hospitalier universitaire de Rennes: Christophe Camus, Erwan Flecher, Alexandre Mansour. Hôpital Louis Pradel, Lyon, France: Jean-Luc Fellahi, Matteo Pozzi, Matthias Jacquet-Lagreze. Hôpitaux Universitaires de Genève, Genève, Switzerland: Raphaël Giraud, Karim Bendjelid. Hôpital Henri Mondor, Créteil, France: Keyvan Razazi, Armand Mekontso-Dessap. Hôpital universitaire de Lille, Lille, France: Anahita Rouzé, Saad Nseir, Thibault Duburcq. Hôpital Nord, Marseille, France: Christophe Guervilly, Jean-Marie Forel. Hôpital Haut Leveque, Pessac, France: Eline Bonnardel. Hôpital Universitaire de Bruxelles, Brussels, Belgium: Fabio S Taccone. Central message: Among ECMO patients with bloodstream infection, incriminated microorganisms were dominated by Enterococcus sp., Enterobacterales and coagulase negative Staphylococci. Mortality was high (50%). Perspective statement: Base on observed microbiology, high appropriateness would only be obtained with piperacilline/tazobactam or carbapenems in association with vancomycin. Future trial evaluating empirical therapy in this setting are needed., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Data suggest excess mortality is associated with loiasis, which is endemic to Central Africa, although the underlying mechanisms remain unknown. We hypothesized that there could be an association between Loa loa microfilarial densities (MFD) and lower spleen volume (SV) due to micro-obstruction linked to circulating microfilariae (mf). This could result in functional hyposplenia and a higher burden of infections. Our objective was to investigate the impact of L. loa MFD and malaria on spleen's bi-dimensional dimensions, volume, and parenchymal lesions., Methods: We included 981 participants aged 18-88 years in a cross-sectional study conducted in May-June 2022 in the Republic of the Congo. Centralized ultrasonographic examination was performed. The primary outcomes included SV, splenomegaly (cranio-caudal-distance ≥ 13 cm), and anatomical hyposplenia (AH) (SV ≤ 80, ≤ 110 or ≤ 150 cm 3 ). Blood samples were analyzed for L. loa MFD, Plasmodium-PCR, Anti-Plasmodium falciparum-IgG, total IgM, sickle-cell disease status, and hematological abnormalities. Linear and logistic regressions were used to assess these associations., Results: Among 981 participants, 139 (14.1%) had splenomegaly, and 26 (2.7%) and 175 (17.8%) had SV ≤ 80 and ≤ 150 cm 3 , respectively. L. loa microfilariae were detected in 353 (35.6%) participants. A gradient effect was observed in each model, with the highest MFD (> 30,000 mf/ml) having the highest adjusted odds ratio of 17.94 (95% CI: 2.91-110.76, P = 0.002), 5.94 (95% CI: 1.40-25.17, P = 0.016), and 5.77 (95% CI: 1.95-17.12, P = 0.002) for SV ≤ 80, 110, and 150 cm 3 , respectively. Anti-P. falciparum-IgG levels were gradually associated with splenomegaly. Fourteen participants met the criterion for hyper-reactive malarial splenomegaly (HMS). Conversely, higher L. loa MFD was correlated with AH, with an attributable fraction of 25%, and the presence of splenic parenchymal lesions., Conclusions: This study provides a detailed description of spleen morphology and the factors influencing its size in a rural central African population. It demonstrates a strong association between L. loa MFD and reduced SV, suggesting that loiasis may lead to AH, and potentially to functional hyposplenia, with consequences such as increased susceptibility to bacterial infections. Malaria was associated with splenomegaly, with a figure of HMS consistent with estimates from other African countries., Competing Interests: Declarations. Ethics approval and consent to participate: Participation in the study was contingent upon informed consent. All participants provided written informed consent. If a treatable condition was identified, participants in the study were offered free treatment, and they were referred to the local hospital if appropriate. The study was approved by the Ethics Committee of the Congolese Foundation for Medical Research (036/CIE/FCRM/2022) and by the national administrative authorities of Congo (376/MSP/CAB/UCPP-21). Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Aims: Apolipoprotein (Apo) C3 has been associated with incident coronary heart disease and major adverse cardiovascular events (MACE). Whether ApoC3 levels predict risk in patients with acute coronary syndrome (ACS) on optimized statin treatment is unknown., Methods: ApoC3 was measured by mass spectrometry at baseline (n=11,956) and after 4 months' treatment (M4; n=11 176) with alirocumab or placebo in the ODYSSEY OUTCOMES trial. Patients with fasting triglycerides >400 mg/dL were excluded. The association of baseline ApoC3 with risk of MACE or death was assessed in post hoc adjusted Cox regression models and spline analyses adjusted for treatment and ApoB. In adjusted models in the alirocumab group we determined association of ApoC3 change from baseline to M4 with subsequent risk of MACE and death., Results: Median (Q1, Q3) baseline ApoC3 concentration was 85 (65, 113) mg/L. With adjustment for ApoB, baseline ApoC3 showed no clinically meaningful relationship to risk of MACE or death in spline analyses and no association with MACE (P=0.89) or death (P=0.70) in Cox regression analyses. Alirocumab reduced ApoC3 modestly by median -10 (-27, -5) mg/L (P<0.0001) and reduced MACE (10.1% vs 12.1%; P=0.0006) and death (3.5% vs 4.2%; P=0.045) versus placebo. However, the change in ApoC3 on alirocumab did not predict subsequent MACE or death., Conclusion: In patients with recent ACS on optimized statins without severe hypertriglyceridemia, neither baseline ApoC3 (accounting for ApoB) nor ApoC3 change with alirocumab predicted MACE or death. It is uncertain whether targeted therapies producing larger reductions in ApoC3 from higher baseline levels will affect cardiovascular risk., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

In pancreatic ductal adenocarcinoma (PDAC), fibroblast activation leads to excessive secretion of extracellular matrix (ECM) and soluble factors that regulate tumor progression, prompting investigation into endoplasmic reticulum (ER)-resident proteins that may support this activation. We identified FKBP7, a peptidyl-prolyl isomerase in the ER, as overexpressed in PDAC stroma compared to cancer cells, and in patients with favorable prognosis. Analysis of single-cell RNA sequencing databases revealed FKBP7 expression in pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs). When analyzed by immunohistochemistry on PDAC patient tissues, FKBP7 emerged as an early activation marker in the preneoplastic stroma, preceding αSMA expression, and responding to FAK- and TGFβ-induced stiffening and pro-fibrotic programs in PSCs. Functional analyses revealed that FKBP7 knockdown in PSCs enhanced contractility, Rho/FAK signaling, and secretion of pro-inflammatory cytokines as well as remodeling of type I collagen, promoting an activated phenotype and accelerating tumor growth in vivo. Conversely, FKBP7 expression supported a tumor-restraining (i.e. encapsulating) ECM characterized by type IV collagen. Mechanistically, FKBP7 interacts with BiP, and blocking this interaction instead leads to increased PSC secretion of type I collagen. Thus, FKBP7 serves as a novel PSC marker and ER regulator in a complex with BiP of the secretion of specific collagen subtypes, highlighting its potential to mediate ECM normalization and constrain PDAC tumorigenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. I, Corinne Bousquet and Corresponding Author for this manuscript, certify in the name of my co-Authors that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched QISAR, a web-based data acquisition and reporting system, which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Objective: Previous genetic and clinical analyses have associated lower lipoprotein(a) and LDL cholesterol (LDL-C) with greater risk of new-onset type 2 diabetes (NOD). However, PCSK9 inhibitors such as alirocumab lower both lipoprotein(a) and LDL-C without effect on NOD., Research Design and Methods: In a post hoc analysis of the ODYSSEY OUTCOMES trial (NCT01663402), we examined the joint prediction of NOD by baseline lipoprotein(a), LDL-C, and insulin (or HOMA-insulin resistance [HOMA-IR]) and their changes with alirocumab treatment. Analyses included 8,107 patients with recent acute coronary syndrome on optimized statin therapy, without diabetes at baseline, assigned to alirocumab or placebo with median follow-up 2.4 years. Splines were estimated from logistic regression models., Results: Lower baseline lipoprotein(a) and higher baseline insulin or HOMA-IR independently predicted 782 cases of NOD; baseline LDL-C did not predict NOD. Alirocumab reduced lipoprotein(a) and LDL-C without affecting insulin or NOD risk (odds ratio [OR] vs. placebo 0.998; 95% CI 0.860-1.158). However, in logistic regression, decreased lipoprotein(a) and LDL-C on alirocumab were independent, opposite predictors of NOD. OR for NOD for 25% and 50% lipoprotein(a) reductions on alirocumab were 1.12 (95% CI 1.01-1.23) and 1.24 (1.02-1.52). OR for NOD for 25% and 50% LDL-C reductions on alirocumab were 0.88 (95% CI 0.80-0.97) and 0.77 (0.64-0.94)., Conclusions: Baseline lipoprotein(a) was inversely associated with risk of NOD. Alirocumab-induced reductions of lipoprotein(a) and LDL-C were associated with increased and decreased risk of NOD, respectively, without net effect on NOD. Ongoing trials will determine the impact of larger and longer lipoprotein(a) reductions on NOD., (© 2025 by the American Diabetes Association.)

Background: Recurrent respiratory papillomatosis (RRP) is a rare respiratory disease primarily caused by chronic human papillomavirus (HPV) infection of serotypes 6 and 11. It manifests in childhood (juvenile-onset recurrent respiratory papillomatosis [JoRRP]) and adulthood (adult-onset recurrent respiratory papillomatosis [AoRRP]), leading to progressive obstruction by papillomas in the upper airway and occasionally in the lower respiratory tract (LRT), including the lungs, with a potential for malignant transformation. This study aimed to delineate the characteristics of JoRRP and AoRRP with LRT involvement in adulthood., Methods: A multicenter French-speaking cohort study was conducted, coupled with a comprehensive literature review of clinical, histological, therapeutic, and prognostic features associated with RRP-LRT., Results: Among the 122 with LRT involvement with LRT involvement analyzed, 55 (45%) had JoRRP and 67 (55%) had AoRRP. The mean age at diagnosis was 4 years for JoRRP and 54 years for AoRRP. Ear, nose, and throat involvement was observed in all JoRRP cases and in 34 AoRRP cases (51%). Lung involvement occurred in 47 JoRRP cases (85%) and in ten AoRRP cases (15%). Malignant transformation to squamous cell carcinoma in the trachea (n=6) or lung (n=36) was observed in 42 patients (34%). Factors associated with lung involvement included JoRRP, repeated debulking, and malignant transformation; the only factor associated with malignant transformation was lung involvement. Overall mortality was 16%, with JoRRP, lung involvement, and malignant transformation identified as risk factors for death., Conclusion: This study highlights the prevalence of lung involvement and malignant transformation in RRP with LRT and advocates for targeted screening measures and preventive therapeutic strategies., (Copyright ©The authors 2025. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (-DTG) as human immunodeficiencyvirus (HIV) treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents., Methods: A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-generation sequencing of protease, reverse transcriptase (RT), and integrase was performed on all samples with viral loads >200 copies/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm., Results: 264 participants were enrolled (median age, 17 years); 226 received a DTG-based regimen for a median of 20.5 months. Among them, there was virological suppression at the 200-copies/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (ie, >640 ng/mL), suboptimal, and below the limit of quantification in 74.1%, 6.7%, and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of nucleoside RT inhibitors, non-NRTIs, and protease inhibitors were found in 52%, 66%, and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n = 3/32; R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 copies/mL., Conclusions: These first findings in a large series of adolescents in a low-income country showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Osteoporosis and fragility fractures are frequent complications of lung transplantation patients. Among 131 patients included, 35 (26.5%) patients had a diagnosis of fractures after transplantation. Low bone mineral density was associated with fractures. Fractures post transplantation were identified as an independent risk factor for overall mortality., Introduction: The prevalence of osteoporosis among lung transplant candidates has been estimated at 31% to 46%, and significant bone loss occurs after lung transplantation, predominantly in the first year, with increased risk of incident fractures. This study aimed to evaluate the prevalence of fragility fractures in a population of lung transplant recipients and the associated risk factors as well as mortality after a fragility fracture., Patients and Methods: This was a cross-sectional monocentric study that included patients with lung transplantation occurring < 10 years and > 1 year who were undergoing lung transplantation monitoring. All patients underwent bone mineral density evaluation by dual-energy X-ray absorptiometry and radiography to establish the presence of vertebral fractures. Mortality was assessed 2 years after the last inclusion., Results: We included 131 patients (82 men, 62.6%), with mean age 56.8 ± 10.8 years. The mean time from lung transplantation to inclusion was 3.5 ± 3.5 years. Overall, 35 (26.5%) patients had a diagnosis of fractures after transplantation; 67 fractures were confirmed (average of 2 per patient), including 48 (71.6%) vertebral fractures. Odds of low bone mineral density at the femoral neck, total hip and spine was associated with fracture: odds ratio 0.007 [0.0002-0.3], 0.001 [0.0002-0.05], and 0.03 [0.001-0.6], respectively. Fracture post transplantation was significantly associated with death (hazard ratio 2.32 [1.01-5.33])., Conclusion: This study confirmed a high prevalence of vertebral fracture in lung transplant patients. Fracture after lung transplant was associated with mortality. Bone fragility needs more attention to reduce the fracture risk., Competing Interests: Declarations. Conflicts of interest: None. Statements of human rights: The institutional review board (No. 12–011) of Paris North Hospitals approved this study. Written informed consent was obtained from all participants in agreement with French bioethics laws., (© 2025. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)