Novel Phenotypes and Genotype-Phenotype Correlations in a Large Clinical Cohort of Patients With Kleefstra Syndrome.

Kleefstra syndrome (KLEFS) is a genetic neurodevelopmental disorder caused by haploinsufficiency of EHMT1. The full spectrum of clinical features and genotype-phenotype correlations is currently not fully understood. We performed a retrospective chart review of patients with KLEFS evaluated at the Boston Children's Hospital Kleefstra Clinic.

The role of the axonal guidance cue Semaphorin3A in innervation of the postnatal heart in health and disease.

During cardiac development the heart is innervated by the autonomous nervous system. After development, neurons of the autonomic nervous system have limited capacity for growth and regeneration. However, in the past decades, it has become clear that cardiac nerves can regenerate after cardiac damage.

Family screening for hypertrophic cardiomyopathy: Initial cardiologic assessment, and long-term follow-up of genotype-positive phenotype-negative individuals.

Aims: (i) Investigate the prevalence of hypertrophic cardiomyopathy (HCM) in individuals with pathogenic/likely pathogenic (P/LP) gene variants detected through family cascade testing in relatives, and (ii) evaluate phenotypic progression in genotype-positive phenotype-negative (G+/P-) individuals during follow-up.

Results: From 2000 to 2023, 273 individuals underwent cardiologic evaluation following P/LP variant detection through family screening. Upon initial evaluation, HCM was diagnosed in 128 (47 %) individuals.

Exploring Motives Behind Ideal Melanoma Survivorship Care Plans With Multiple Stakeholders: A Cocreation Study.

Background: Survivorship care plans (SCPs), ie, personalized health care plans for cancer survivors, can be used to support the growing group of melanoma survivors throughout their disease trajectory. However, implementation and effectiveness of SCPs are suboptimal and could benefit from the involvement of stakeholders in developing a user-centered design.

Objective: The aim of this study was to identify the ideal SCP for patients with melanoma in terms of functions and features to be included according to different stakeholders and to explore their underlying motives.

How and where Effectively Apply Cerebellum Stimulation: The frequency-dependent Modulation of Cerebellar Output by Transcranial Alternating Current Stimulation.

As brain-machine interfaces (BMI) are growingly used in clinical settings, understanding how to apply brain stimulation is increasingly important. Despite the emergence of optogenetic techniques, ethical and medical concerns suggest that interventions that are safe and non-invasive, such as Transcranial Alternating Current Stimulation (tACS), are more likely to be employed in human in the near future. Consequently, the question of how and where to apply current stimulation is becoming increasingly important for the efficient neuromodulation of both neurological and psychiatric disorders.

Vacuolar H-ATPase and Megalin-Mediated Prorenin Uptake: Focus on Elements Beyond the (Pro)Renin Receptor.

Megalin is a multiple-ligand receptor that contributes to protein reabsorption in the kidney. Recently, megalin was found to act as a novel endocytic receptor for prorenin. Internalization depended on the (pro)renin receptor.

Understanding Noninferiority Trials: What Stroke Specialists Should Know.

Noninferiority trials aim to prove that the efficacy, defined in terms of a key clinical outcome, of a new treatment is not meaningfully worse than that of an established active control. Noninferiority trials are important when other aspects of care can be improved, such as convenience, toxicity, costs, and safety (nonefficacy benefits). While the motivation for a noninferiority trial is straightforward, the design, execution, and interpretation of these trials is not a trivial task.

Antiplatelet Prophylaxis Reduces the Risk of Early Hepatic Artery Thrombosis Following Liver Transplantation in High-Risk Patients.

The prevention of hepatic artery thrombosis (HAT) is pivotal for graft survival immediately after liver transplantation (LT). This study aimed to identify risk factors (RF) for early HAT (eHAT) and assess the benefit of antiplatelet prophylaxis (AP). This retrospective single-center study included 836 adult patients who underwent LT between 2007 and 2022.

Jugular Vascular Closure and Scar Formation after Leadless Pacemaker Implantation.

Background: Achieving hemostasis of large bore venous access sites can be challenging and time consuming. Closure devices have proven to be superior in achieving hemostasis, reducing time to ambulation and improving patient comfort, compared to manual hemostasis techniques after femoral venous and arterial access. The closure of the jugular vein following large bore access has not been investigated in previous studies.

Novel Dolutegravir and Lenacapavir Resistance Patterns in Human Immunodeficiency Virus Type 2 Infection: A Case Report.

Background: The treatment management of human immunodeficiency virus (HIV)-2 infection presents greater challenges compared to HIV-1 infection, primarily because of inherent resistance against non-nucleoside reverse transcriptase inhibitors. Integrase strand transfer inhibitors, particularly dolutegravir, have improved treatment outcomes for people with HIV-2. Lenacapavir, a novel and potent antiretroviral capsid inhibitor, offers additional therapeutic options.

Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group.

Objective: We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC).

Methods: The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE.

Tackling the primary healthcare workforce crisis: time to talk about health systems and governance-a comparative assessment of nine countries in the WHO European region.

Background: Primary healthcare has emerged as a powerful global concept, but little attention has been directed towards the pivotal role of the healthcare workforce and the diverse institutional setting in which they work. This study aims to bridge the gap between the primary healthcare policy and the ongoing healthcare workforce crisis debate by introducing a health system and governance approach to identify capacities that may help respond effectively to the HCWF crisis in health system contexts.

Methods: A qualitative comparative methodology was employed, and a rapid assessment of the primary healthcare workforce was conducted across nine countries: Denmark, Germany, Kazakhstan, Netherlands, Portugal, Romania, Serbia, Switzerland, and the United Kingdom/ England.

Incidence and Outcomes of Patients With Mismatch Repair Deficient Rectal Cancer Operated in 2016: A Nationwide Cohort From The Netherlands.

Introduction: Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients.

Method: A retrospective cross-sectional cohort study was conducted in 67 Dutch centers.

Reorganizing medical care for older persons in times of scarcity: A cybernetics analysis of work pressure and organizational change.

Capacity problems in healthcare lead organizations to seek new and fluid ways of organizing care to safeguard access to services. Task reallocation, triage and stepped care models are increasingly foregrounded as promising interventions that enhance the capacity, efficiency, and resilience of medical services and through which access can be maintained for a growing client base. In this paper, we argue that interventions meant to enhance capacity and increase efficiency have their limits in a system that is already under strain.

A Prospective Non-interventional Real-World Study of cabozantinib in Pretreated Patients With Advanced Renal Cell Carcinoma Refractory to Vascular Endothelial Growth Factor-Targeted Therapy (CASSIOPE).

Background: There is a lack of published data on real-world cabozantinib use in patients with advanced renal cell carcinoma after prior vascular endothelial growth factor (VEGF)-targeted therapy.

Methods: CASSIOPE was a real-world, prospective, multicenter, non-interventional postauthorization safety study of cabozantinib in adult patients with advanced renal cell carcinoma in Europe following prior VEGF-targeted treatment (NCT03419572). Endpoints included cabozantinib utilization (dose modifications due to adverse events [AEs; primary endpoint], dose, dose modifications, and treatment duration), safety, effectiveness (progression-free survival [PFS], overall survival [OS], best overall response [BOR]), and healthcare resource utilization.