Design, development and implementation of a national faculty development program to promote CBME in graduate medical education in Switzerland.

Background: Competency Based Medical Education (CBME) is a global movement in graduate medical training but implementation on a national scale is challenging. One crucial element of fostering CBME is to establish faculty development. We report the design of a national program, the process of implementation, and the results of the first two years.

Multicenter Evaluation of the QIAstat-Dx and the BioFire Multiplex Panel Tests for the Detection of Respiratory Pathogens.

Syndromic multiplex panel testing enables simultaneous detection of multiple respiratory pathogens, but limited data is available on the comparative diagnostic performance of different testing systems. In this multicenter prospective study, we aimed to compare the QIAstat-Dx Respiratory Panel 2.0 (QIAstat-Dx-RP2.

Tumour purity assessment with deep learning in colorectal cancer and impact on molecular analysis.

Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation.

Hyperreflective material evolution patterns during long term anti-VEGF therapy in neovascular age-related macular degeneration.

This retrospective, real-life cohort was analyzed to detect the frequency of different HRM evolution patterns and their correlation with MNV types, morphological and functional changes in exudative nAMD under long-term anti-VEGF therapy. We evaluated optical coherence tomography (OCT) volume scans in 143 eyes of 94 nAMD patients (start of anti-VEGF therapy 2009-2018, therapy until the last visit) and recorded the VA at all visits. HRM evolution patterns were differentiated: pattern 1 = no HRM, pattern 2 = subretinal HRM resolved during follow-up, pattern 3 = persistent subretinal HRM with new HRM-boundary remodeling [BR], pattern 4 = persistent subretinal HRM without HRM-BR.

Contextual modulation emerges by integrating feedforward and feedback processing in mouse visual cortex.

Sensory systems use context to infer meaning. Accordingly, context profoundly influences neural responses to sensory stimuli. However, a cohesive understanding of the circuit mechanisms governing contextual effects across different stimulus conditions is still lacking.

ExerG - an exergame-based training device for the rehabilitation of older adults: a functional model usability study.

Background: Exergames are interactive technology-based exercise programs. By combining physical and cognitive training components, they aim to preserve independence in older adults and reduce their risk of falling. This study explored whether primary end users (PEU, healthy older adults and patients with neurological and geriatric diagnoses) and secondary end users (SEU, health professionals) evaluated the ExerG functional model to be usable, providing a positive experience and therefore acceptable.

Epstein-Barr virus hijacks B cell metabolism to establish persistent infection and drive pathogenesis.

When B cells engage in an immune response, metabolic reprogramming is key to meeting cellular energetic and biosynthetic demands. Epstein-Barr virus (EBV) is a highly prevalent gamma-herpesvirus, latently infecting B cells for the human host's lifetime. By hijacking signaling pathways of T cell-dependent humoral immunity, EBV activates B cells in a T cell-independent manner, forcing lymphoblastoid transformation.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

Emerging clinical evidence of a dual role for Ang-2 and VEGF-A blockade with faricimab in retinal diseases.

Anti-vascular endothelial growth factor (VEGF) therapies have transformed the treatment of retinal diseases. However, VEGF signaling is only one component of the complex, multifactorial pathophysiology of retinal diseases, and many patients have residual disease activity despite ongoing anti-VEGF treatment. The angiopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor receptor-2 (Ang/Tie2) signaling pathway is critical to endothelial cell homeostasis, survival, integrity, and vascular stability.

The Long-Term Cost-Effectiveness of Tirzepatide 5 mg versus Dulaglutide 0.75 mg for the Treatment of People with Type 2 Diabetes in Japan.

Introduction: This analysis aimed to evaluate the long-term cost-effectiveness of tirzepatide 5 mg versus dulaglutide 0.75 mg (both administered once weekly) in people not achieving glycemic control on metformin, based on the results of the head-to-head SURPASS J-mono trial from a Japanese healthcare payer perspective.

Methods: A cost-utility analysis was performed over a 50-year time horizon using an implementation of the UKPDS Outcomes Model 2 developed in Microsoft Excel.

Genetic basis of resistance in hosts facing alternative infection strategies by a virulent bacterial pathogen.

Having alternative infection routes is thought to help parasites circumvent host resistance, provided that these routes are associated with different host resistance loci. This study tests this postulate by examining whether alternate infection routes of the parasite Pasteuria ramosa are linked to distinct resistance loci in its crustacean host, Daphnia magna. We focus on the P.

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Clinical Applications of Bone Marrow CD34 Immunohistochemistry (BM CD34 IHC) Assay: International Council for Standardization in Hematology (ICSH) Guidelines.

Introduction: Investigation of bone marrow (BM) trephine biopsies and/or clot sections by CD34 immunohistochemistry (IHC) testing has been used by pathologists for several decades, and its clinical value has been well established with QBEND10 being the most frequently used primary antibody (Ab) clone. However, most other parameters related to the IHC protocol as well as the readout vary widely between clinical laboratories and in the published literature. The ICSH Working Group having reviewed the published evidence has established guidelines that will help to harmonize performance and reporting of CD34 IHC on BM biopsies.

Investigational Use of Real-World Data as a Hybrid Control in Pancreatic Ductal Adenocarcinoma from the Randomized Phase Ib/II MORPHEUS Trial.

Enrolling adequate numbers of patients into the control arm of randomized controlled trials (RCTs) often presents barriers. There is interest in leveraging real-world data (RWD) from electronic health records (EHRs) to construct external control (EC) arms to supplement RCT control arms and form hybrid control (HC) arms. This investigation showed the use of an HC arm in second-line metastatic pancreatic ductal adenocarcinoma (PDAC).

Evaluation of Exomass-Related Artefacts Caused by Dental Implants of Different Materials in Cone-Beam Computed Tomography Scans: An Ex Vivo Study.

Objectives: To evaluate the influence of different dental implant materials within the exomass on the image quality in cone-beam computed tomography (CBCT).

Material And Methods: Five pig jaws were scanned using four CBCT devices, first without any dental implants, followed by scans with three dental implants of the same material-pure titanium, titanium-zirconium alloy, and zirconium dioxide. Two fields of view (FOVs) were used for each device to position the implants in the exomass of a small FOV and within a large FOV.

Characterizing the Clinical Trajectory and Predicting Persistence and Deterioration of Attenuated Psychotic Symptoms in Ultra-High-Risk Individuals.

Background: Almost 40% of individuals at ultra-high risk (UHR) for psychosis experience persistent attenuated psychotic symptoms (APS) yet it is unclear (1) whether they share overlapping clinical and functional outcomes compared to individuals who transition to psychosis, (2) when symptom and functioning trajectories begin to diverge between UHR individuals with different clinical outcomes, and (3) whether non-remission (persistent APS or transition) can be predicted using baseline and/or longitudinal data.

Study Design: Participants were drawn from 2 randomized clinical trials: Neurapro (n = 220; discovery sample) and STEP (n = 180; external validation sample). First, 12-24 month symptoms and functioning were compared between UHR individuals with persistent APS, sustained remission, or transition to psychosis.

Biologically defined neuronal synuclein disease as a tool to advance drug development.

In a recent Viewpoint article (. 2024;81:789‒90), Okubadejo et al. raised concerns regarding two recent proposals for biological definitions and staging systems for synucleinopathies (the Neuronal Synuclein Disease Integrated Staging System and SynNeurGe system).

Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomised, double-blind, multicentre, placebo-controlled, phase 2b trial.

Background: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury.

Schistosomiasis status and health impact in preschool-aged children in hard-to-reach areas and populations of Homa Bay County, Kenya.

Pediatric schistosomiasis in hard-to-reach communities is poorly understood, hampering tailored interventions. This study investigated the prevalence, intensity, health impact, and risk factors for schistosomiasis in preschool-aged children (PSAC) residing in hard-to-reach areas and populations of Homa Bay County, Kenya. A cross-sectional study was conducted among 476 PSAC aged 2-5 years across 6 islands in Lake Victoria, Homa Bay County, Kenya.

Methods for Diagnosing Proteinuria: When to Use Which Test, and Why.

Proteinuria plays a central role in the diagnosis of kidney disease and has a high prognostic value. The test methods used differ considerably regarding impact on test accuracy, sensitivity, and specificity. Therefore, knowledge of the methodology is crucial for the interpretation of the results.

[A comparison of direct admissions to inpatient-equivalent home treatment with transfers from psychiatric wards].

Aim: Different access routes to inpatient-equivalent home treatment (IEHT) were examined.

Methods: Baseline differences were examined using exploratory group comparisons, treatment effects by type of admission using regression analysis.

Results: Of 200 StäB users, 144 (72%) were admitted directly to IEHT, while 56 (28%) were transferred.

GRADE-based procalcitonin guideline for emergency departments.

Procalcitonin is a useful biomarker for infection. Over the past two decades, there has been much research on the clinical applications of procalcitonin, yet the majority of these studies have been conducted in the intensive care setting. Despite the extensive use of procalcitonin in emergency departments, there have been no guidelines focusing specifically on these clinical settings.

Neurofilament Light Chain as a Discriminator of Disease Activity Status in MOG Antibody-Associated Disease.

Background And Objectives: In patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), acute disease activity is generally identified through medical history, neurologic examination, and imaging. However, these may be insufficient for detecting disease activity in specific conditions. This study aimed to investigate the dynamics of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) after clinical attacks and to assess their utility in discriminating attacks from remission in patients with MOGAD.

Viral suppression and adherence in adolescents living with HIV in rural Tanzania.

Background: Adolescents living with HIV (ALHIV) in sub-Saharan Africa are affected by poor treatment outcomes, likely a consequence of poor adherence.

Objectives: To assess viral suppression rates and evaluate factors associated with achieving viral suppression and maintaining treatment adherence among ALHIV in rural Tanzania.

Methods: Cross-sectional analysis of data from the Kilombero and Ulanga Antiretroviral Cohort in Ifakara, Tanzania, including adolescents aged 10-19 years on antiretroviral treatment (ART) ≥6 months at the time point of their first viral load (VL) measurement after implementation of routine VL testing from August 2017 through December 2023.