Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

Episiotomies and obstetric anal sphincter injuries following a restrictive episiotomy policy in France: An analysis of the 2010, 2016, and 2021 National Perinatal Surveys.

Background: The French guidelines have recommended a restrictive policy of episiotomy since 2005. We aimed to assess variations in the prevalence of both episiotomy and obstetric anal sphincter injury (OASI) from the 2010, 2016, and 2021 National Perinatal Surveys.

Methods And Findings: A total of 29,750 women who had given birth to a live infant by vaginal delivery were included.

Supraglottoplasty outcomes and peri-operative care in congenital laryngomalacia.

Objectives: This study aimed to identify factors predicting postoperative ICU admission, the need for orotracheal intubation (OTI), and the occurrence of supraglottic stenosis in children undergoing supraglottoplasty for laryngomalacia.

Methods: A retrospective analysis was conducted on 31 children (Dear Reviewer, we would have greatly preferred to include a larger sample size. However, as you know, this type of management is rare, and we deliberately selected a 7-year period to ensure a minimum of 30 children while avoiding significant differences in management guidelines over time.

A Machine Learning Model Using Cardiac CT and MRI Data Predicts Cardiovascular Events in Obstructive Coronary Artery Disease.

Background Multimodality imaging is essential for personalized prognostic stratification in suspected coronary artery disease (CAD). Machine learning (ML) methods can help address this complexity by incorporating a broader spectrum of variables. Purpose To investigate the performance of an ML model that uses both stress cardiac MRI and coronary CT angiography (CCTA) data to predict major adverse cardiovascular events (MACE) in patients with newly diagnosed CAD.

Stanniocalcin 1 in patients with refractory colorectal cancer treated with regorafenib: A post-hoc biomarker analysis of the TEXCAN and CORRECT trials.

Biomarkers for anti-angiogenic drugs in chemo-refractory metastatic colorectal cancer (mCRC) are lacking. We investigated the relationship between stanniocalcin 1 (STC1) and outcomes in patients treated with regorafenib in the TEXCAN and CORRECT trials. Baseline plasma STC1 protein levels were measured by ELISA from patients with chemo-refractory mCRC enrolled in TEXCAN (regorafenib n=48) and CORRECT (placebo n=211; regorafenib n=435).

Tenascin-X deficiency causing classical-like Ehlers Danlos syndrome type 1 in humans is a significant risk factor for GI and tracheal ruptures.

Background: Classical-like Ehlers Danlos Syndrome type 1 (clEDS1) is a very rare form of Ehlers Danlos Syndrome (EDS) caused by tenascin-X (TNX) deficiency, with only 56 individuals reported. TNX is an extracellular matrix protein needed for collagen stability. Previous publications propose that individuals with clEDS1 might be at risk for gastrointestinal (GI) tract perforations and/or tracheal ruptures.

Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010-2021.

Background And Purpose: Clinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance-reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under-diagnosed in Japan since diagnostic tests are not readily available.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.

Vascular ageing manifestations and hypertension in the community.

Objective: To investigate the association between joint manifestations of vascular ageing (VA) and hypertension.

Methods: We used baseline (2008-2012) and follow-up data (up to 2024) from the Paris Prospective Study III, a French cohort of 10,157 participants. Prevalent and incident hypertension were determined at baseline (blood pressure ≥140/90 mmHg or on medication) and at 2, 4, 6, 8 and 10 years of follow-up (self-reported antihypertensive treatment).

Do national cancer control plans address care and research for children, adolescents, and young adults? A review of status, priorities, and recommendations across 41 European countries.

Paediatric cancers, although rare, are the leading cause of disease-related mortality in European children above one year. A key pillar of the European Health Union, Europe's Beating Cancer Plan (EBCP) puts a spotlight on childhood cancer. National Cancer Control Plans (NCCPs) have a key role but did not address childhood cancers sufficiently previously.

Birth defects reporting and the use of dydrogesterone: a disproportionality analysis from the World Health Organization pharmacovigilance database (VigiBase).

Study Question: Is there an association between dydrogesterone exposure during early pregnancy and the reporting of birth defects?

Summary Answer: This observational analysis based on global safety data showed an increased reporting of birth defects, mainly hypospadias and congenital heart defects (CHD), in pregnancies exposed to dydrogesterone, especially when comparing to progesterone.

What Is Known Already: Intravaginal administration of progesterone is the standard of care to overcome luteal phase progesterone deficiency induced by ovarian stimulation in ART. In recent years, randomized controlled clinical trials demonstrated that oral dydrogesterone was non-inferior for pregnancy rate at 12 weeks of gestation and could be an alternative to micronized vaginal progesterone.

Exploration of interprofessional collaboration for the diagnosis of infections and antibiotic prescription in nursing homes using multiple case study observational research.

Background: Antibiotic resistance in nursing homes (NHs) is inconsistently tackled by antimicrobial stewardship programmes. The literature on individual determinants of antibiotic prescriptions (APs) in NHs is extensive. However, less is known about the structural determinants of AP in NHs.

Association of a remote monitoring programme with all-cause mortality and hospitalizations in patients with heart failure: National-scale, real-world evidence from a 3-year propensity score analysis of the TELESAT-HF study.

Aims: To examine the association of a remote monitoring programme (RMP) with all-cause mortality and hospital admissions for heart failure (HF) within the French healthcare system.

Methods And Results: A national-scale, real-world, propensity-weighted cohort study was conducted using the SNDS French database from August 2018 to December 2022 (NCT06312501). Patients receiving standard of care (SoC) were compared with those receiving RMP (Satelia® Cardio, NP Medical).

Impacts of immersive 3D videos on students' surgical learning compared to 2D videos: a randomized controlled trial.

Background: Unlike other medical specialties, surgery is primarily learned through apprenticeship, by observing surgeons in action during operations. However, the increasing number of medical students and work-hour restrictions limit opportunities for learning in the operating room (OR). These circumstances call for novel technologies, such as immersive video.

Cohort profile: the potentially preventable burden of community-acquired pneumonia in South African adults in the era of widespread PCV13 immunisation and antiretroviral therapy roll-out, before and during the COVID-19 pandemic - the multicentre, multimethod PotPrev Study.

Purpose: In the setting of an established childhood pneumococcal vaccination programme with immediate initiation and treatment of antiretroviral therapy (ART) for people living with HIV (PLWH), the risk of adult pneumococcal community-acquired pneumonia (CAP) is not recently described. We aimed to investigate CAP incidence, recurrence, mortality, risk factors and microbiology before and during the COVID-19 pandemic.

Participants: Adults aged ≥18 years were enrolled in three South African provinces from March 2019 to October 2021, with a brief halt during the initial COVID-19 lockdown.

Impact of alternative diagnostic labels for melanoma in situ on management choices and psychological outcomes: protocol for an online randomised study.

Introduction: A diagnosis of melanoma in situ presents negligible risk to a person's lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients' management choices and anxiety levels.

Methods And Analysis: This study is a between-subjects randomised online experiment, using hypothetical scenarios.

PAK3 pathogenic variant associated with sleep-related hypermotor epilepsy in a family with parental mosaicism.

Protein-activated kinases mediate spine morphogenesis and synaptic plasticity. PAK3 is part of the p21-activated kinases (PAKs) family of Ras-signaling serine/threonine kinases. Pathogenic variants in the X-linked gene PAK3 have been described in patients with neurodevelopmental syndromes.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Factors affecting communication time in an emergency medical communication centers.

Background: Emergency Medical Communication Centres (EMCCs) play a crucial role in emergency care by ensuring timely responses through telephone triage. However, extended communication times can impede accessibility, patient triage, and decision-making. Identifying the factors influencing communication duration is essential for improving EMCC efficiency.

Laparoscopic pancreatic enucleation: how far should we go for parenchyma preservation? A study by the French National Association of Surgery.

Background: Pancreatic enucleation is indicated for selected patients and tumours with very low oncological risk to preserve a maximum of healthy pancreatic parenchyma. Minimally invasive pancreatic enucleation (MIPE) is increasingly performed. This study aims to assess the impact of tumor location and center experience on textbook outcomes (TBO) in patients undergoing MIPE.

Genome-wide association study unravels mechanisms of brain glymphatic activity.

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets.

[Recommendations for clinical practice: Prevention and management of varicella zoster virus (VZV) infection during pregnancy and the perinatal period (extended version)].

The Société de Pathologie Infectieuse de Langue Française released in 2024 a new national recommendation for clinical practice on the prevention and management of varicella zoster virus (VZV) infection during pregnancy and the perinatal period. The previous recommendation was issued in 1998, at a time of anti-VZV immunoglobulins shortage; it has hence become obsolete. This recommendation is a formalized expert consensus focusing on infectious diseases management; it is drawn up by a multidisciplinary working group (infectiologists, obstetricians, pediatricians, microbiologists, midwives, hygienists).

Biomechanical assessment of ligament maturation after arthroscopic ligament reconstruction of the anterior talofibular ligament.

Background: Many techniques have been described for lateral ankle ligament reconstruction. Although the biomechanical properties of gracilis tendons are different from those of ligaments, the use of a gracilis tendon autograft is a popular option for anatomical reconstruction. Graft maturation and the biomechanical processes over time remain unclear.