Multicenter In-House Evaluation of an Amplicon-Based Next-Generation Sequencing Panel for Comprehensive Molecular Profiling.

Background: Predicting response to targeted cancer therapies increasingly relies on both simple and complex genetic biomarkers. Comprehensive genomic profiling using high-throughput assays must be evaluated for reproducibility and accuracy compared with existing methods.

Methods: This study is a multicenter evaluation of the Oncomine™ Comprehensive Assay Plus (OCA Plus) Pan-Cancer Research Panel for comprehensive genomic profiling of solid tumors.

Automatic 4D mitral valve segmentation from transesophageal echocardiography: a semi-supervised learning approach.

Performing automatic and standardized 4D TEE segmentation and mitral valve analysis is challenging due to the limitations of echocardiography and the scarcity of manually annotated 4D images. This work proposes a semi-supervised training strategy using pseudo labelling for MV segmentation in 4D TEE; it employs a Teacher-Student framework to ensure reliable pseudo-label generation. 120 4D TEE recordings from 60 candidates for MV repair are used.

Allocation of Semaglutide According to Coronary Artery Calcium and BMI: Applying the SELECT Trial to MESA.

Background: Implementation of semaglutide weight loss therapy has been challenging due to drug supply and cost, underscoring a need to identify those who derive the greatest absolute benefit.

Objectives: Allocation of semaglutide was modeled according to coronary artery calcium (CAC) among individuals without diabetes or established atherosclerotic cardiovascular disease (CVD).

Methods: In this analysis, 3,129 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) without diabetes or clinical CVD met body mass index criteria for semaglutide and underwent CAC scoring on noncontrast cardiac computed tomography.

Quantifying DNA Lesions and Circulating Free DNA: Diagnostic Marker for Electropathology and Clinical Stage of AF.

Background: Atrial fibrillation (AF) persistence is associated with molecular remodeling that fuels electrical conduction abnormalities in atrial tissue. Previous research revealed DNA damage as a molecular driver of AF.

Objectives: This study sought to explore the diagnostic value of DNA damage in atrial tissue and blood samples as an indicator of the prevalence of electrical conduction abnormalities and stage of AF.

Digital Solutions for the Optimization of Pharmacologic Therapy for Heart Failure.

Data from large-scale, randomized, controlled trials demonstrate that contemporary treatments for heart failure (HF) can substantially improve morbidity and mortality. Despite this, observed outcomes for patients living with HF are poor, and they have not improved over time. The are many potential reasons for this important problem, but inadequate use of optimal medical therapy for patients with HF, an important component of guideline-directed medical therapy, in routine practice is a principal and modifiable contributor.

Value-based healthcare for social insurance medicine: key enablers for adoption in practice.

Background: Driven by rising retirement age and increasing prevalence of chronic diseases impacting work participation, there is an increasing need for quality and efficiency improvement in social insurance medicine (SIM). SIM provides guidance to individuals facing long-term work disability, assess their functional abilities and eligibility for long-term disability benefits. Value-based healthcare (VBHC) targets quality and efficiency improvements in healthcare by placing a priority on improving patient value.

Pediatric Brain Tumors in Western Kenya: Patient Outcomes and Healthcare Providers' Perspectives.

Background: Pediatric brain tumors are understudied compared to other pediatric malignancies in low- and middle-income countries. Care delivery is inherently dependent on collaboration between multiple departments. This study aimed to present baseline data of pediatric neuro-oncology care in Western Kenya and illustrate barriers and facilitators of multidisciplinary care.

The Impact of Diabetes Mellitus and Metformin Use on Outcomes After Endovascular Aneurysm Repair.

: To study the influence of diabetes mellitus (DM) and metformin treatment on aneurysm sac remodeling after endovascular aneurysm repair (EVAR). : A retrospective single-center cohort analysis was conducted on consecutive patients who underwent elective EVAR for an infrarenal abdominal aortic aneurysm (AAA) between January 2011 and December 2021. Differences between study groups were analyzed and Kaplan-Meier analysis were employed to describe overall and reintervention-free survival.

Effects of Automated Versus Conventional Ventilation on Quality of Oxygenation-A Substudy of a Randomized Crossover Clinical Trial.

: Attaining adequate oxygenation in critically ill patients undergoing invasive ventilation necessitates intense monitoring through pulse oximetry (SpO) and frequent manual adjustments of ventilator settings like the fraction of inspired oxygen (FiO) and the level of positive end-expiratory pressure (PEEP). Our aim was to compare the quality of oxygenation with the use of automated ventilation provided by INTELLiVENT-Adaptive Support Ventilation (ASV) vs. ventilation that is not automated, i.

Primary Mediastinal Ewing's Sarcoma: Post Hoc Analysis from Two International Multicenter Prospective Randomized Trials.

Objective: Ewing sarcoma (EWS) of the mediastinum is extremely rare, with only a few cases reported in the literature. We aimed to gain a better understanding of primary mediastinal EWS, describing patients treated within two international, multicenter, prospective, randomized EWS trials.

Methods: Data from patients with primary mediastinal EWS were retrieved from the database of the EURO-E.

Impact of the Number of Positive Pelvic Lymph Nodes on Risk of Para-Aortic Recurrence in Patients with Clinically Early Cervical Cancer Treated by a Radical Hysterectomy and Pelvic Lymphadenectomy.

Background: Guidelines recommend the extension of the pelvic radiotherapy volume to the para-aortic region in locally advanced cervical cancer and ≥3 suspicious pelvic lymph nodes (PLN) on imaging. Whether this recommendation is also valid for clinically early stages is uncertain. The objective of this study was to investigate the para-aortic (PAO) lymph node recurrence rate in patients with early-stage cervical cancer, ≥3 metastatic PLN, and negative common iliac nodes after a radical hysterectomy followed by pelvic (chemo)radiotherapy without extension to the PAO region.

Generation of Bona Fide Human Induced Trophoblast Stem Cells by Direct Reprogramming of Term Umbilical Cord Cells.

Placentation disorders, including severe preeclampsia and fetal growth restriction, have their origins in early pregnancy, whereas symptoms typically present later on. To investigate the pathogenesis of these diseases, there is a need for a reliable in vitro model system of early placenta development with known pregnancy outcomes. Therefore, we optimized the generation of human induced trophoblast stem cells (iTSCs) from term umbilical cord, enabling non-invasive collection of patient-derived material immediately after birth.

Conventional and Tropism-Modified High-Capacity Adenoviral Vectors Exhibit Similar Transduction Profiles in Human iPSC-Derived Retinal Organoids.

Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences.

The Accuracy of the Passive Leg Raising Test Using the Perfusion Index to Identify Preload Responsiveness-A Single Center Study in a Resource-Limited Setting.

We investigated the accuracy of predicting preload responsiveness by means of a passive leg raising test (PLR) using the perfusion index (PI) in critically ill patients showing signs of hypoperfusion in a resource-limited setting. We carried out a prospective observational single center study in patients admitted for sepsis or severe malaria with signs of hypoperfusion in Chattogram, Bangladesh. A PLR was performed at baseline, and at 6, 24, 48, and 72 h.

Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes.

Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei profiles from 391 disease-case and control brains, we report 13,939 genes whose expression correlated with genetic variation, of which 16.7-40.

Typing of feces-derived Candida albicans strains using a novel seven-locus microsatellite panel reveals associations with yeast phenotype in individuals with inflammatory bowel disease.

Inflammatory diseases of the human gastrointestinal tract are affected by the microbes that reside in the mucosal surfaces. Patients with inflammatory bowel diseases (IBD) have altered bacterial and fungal intestinal compositions, including higher levels of fecal Candida yeasts. Ongoing research indicates that genetic and phenotypic diversity of Candida albicans may be linked with disease severity.

Dent disease: Clinical Practice Recommendations.

Dent disease is a rare X-linked tubulopathy that is characterized by low-molecular-weight (LMW) proteinuria associated with hypercalciuria, which may lead to nephrolithiasis, nephrocalcinosis, and kidney failure between the 3rd and the 5th decades of life in 30-80% of affected males. The disease is most often associated with various manifestations of proximal tubular dysfunction. Affected individuals may present nephrotic range proteinuria which may be misinterpreted and cause diagnostic delay.

Robot-assisted Kidney Transplantation: The 8-year European Experience.

Background And Objective: Evidence regarding perioperative results and long-term functional outcomes of robotic-assisted kidney transplantation (RAKT) is limited. We evaluated perioperative surgical results and long-term functional outcomes of RAKT in patients receiving kidney transplants from living donors.

Methods: This retrospective analysis is based on a prospective multicenter cohort study conducted from July 2015 to October 2023 across ten European centers.

Single-cell Rapid Capture Hybridization sequencing to reliably detect isoform usage and coding mutations in targeted genes.

Single-cell long-read sequencing has transformed our understanding of isoform usage and the mutation heterogeneity between cells. Despite unbiased in-depth analysis, the low sequencing throughput often results in insufficient read coverage thereby limiting our ability to perform mutation calling for specific genes. Here, we developed a single-cell Rapid Capture Hybridization sequencing (scRaCH-seq) method that demonstrated high specificity and efficiency in capturing targeted transcripts using long-read sequencing, allowing an in-depth analysis of mutation status and transcript usage for genes of interest.

Cyclophosphamide is not associated with clinically relevant late pulmonary dysfunction in Dutch survivors of childhood cancer - the DCCSS-LATER 2 PULM sub-study.

Background: Treatment for childhood cancer may increase the risk of long-term pulmonary complications and dysfunction. Pulmonary surveillance is recommended after established pulmonary toxic exposures, including bleomycin, busulfan, carmustine (BCNU), lomustine (CCNU), radiotherapy to a field exposing the lungs, and pulmonary surgery. However, the role of cyclophosphamide as a pulmonary toxic agent is debated.

Radiation doses to the breast and predicted breast cancer risk among patients treated for Hodgkin lymphoma with modern radiotherapy.

Purpose: To contrast breast radiation exposure from chest radiotherapy in 2006-2021 with 1965-1997, and to compare breast cancer (BC) risk 25 years after treatment predicted by two models.

Methods: Radiation dose distributions to the breast from 101 chest radiotherapies given 2006-2021 for Hodgkin lymphoma (HL) or other lymphoma in one German and two Dutch hospitals were compared with doses received by 505 Dutch HL patients treated 1965-1997 and sampled into a nested case-control study, weighted to represent a HL patient cohort. Dose-volume histograms, mean dose and doses to 10 breast segments were evaluated.

Tamuzimod in patients with moderately-to-severely active ulcerative colitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 induction trial.

Background: Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.

Methods: This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America.