Clonazepam repurposing in patients through conventional RCT and N-of-1 trials: an experimental strategy for orphan disease development.

Background: Clinical trials for rare disorders have unique challenges due to low prevalence, patient phenotype variability and high expectations. These challenges are highlighted by our study on clonazepam in patients, a common cause of intellectual disability. Previous studies on Arid1b-haploinsufficient mice showed positive effects of clonazepam on various cognitive aspects.

Prognostic value of toe pressure measurements in patients with diabetic foot ulcers and medial arterial calcification.

Objectives: Diabetic foot ulcers (DFU) are one of the most serious chronic diabetes related complications. Since medial arterial calcification (MAC) can be present in patients with a DFU, toe pressure (TP) measurements are advised to grade potential ischemia. However, the value of TP to predict clinical outcomes in this group of patients is poorly understood.

Guselkumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients: results of the phase 3, randomized, placebo-controlled PROTOSTAR study.

Background: No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis.

Objective: PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis.

Enteropathy-associated T-cell lymphoma: A population-based cohort study on incidence, treatment, and outcome in the Netherlands.

Introduction: Enteropathy-associated T-cell lymphoma (EATL) is a peripheral T-cell lymphoma (PTCL) with a poor prognosis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide consolidated by autologous stem cell transplantation (ASCT) are recommended for fit PTCL patients. The role of etoposide and ASCT in EATL is unclear.

The crisis of the third day in intracranial pressure dynamics following traumatic brain injury, fact or fiction?

Introduction: In 1960, Lazorthes and Campman introduced the concept of a which gained prominence in the field of traumatic brain injury (TBI), where it relates to neurological deterioration on the third day after injury. However, evidence regarding this phenomenon remains scarce.

Research Question: This study aimed to analyze posttraumatic intracranial pressure (ICP) patterns in a large European cohort to investigate the existence of a third-day crisis and its impact on 12-month functional outcomes.

Validation of the GCS-Pupil Scale in Traumatic Brain Injury: Incremental Prognostic Value of Pupillary Reactivity with GCS in the Prospective Observational Cohorts CENTER-TBI and TRACK-TBI.

To compare the incremental prognostic value of pupillary reactivity captured as part of the Glasgow Coma Scale-Pupils (GCS-P) score or added as separate variable to the GCS+P, in traumatic brain injury (TBI). We analyzed patients enrolled between 2014 and 2018 in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI, = 3521) and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI, = 1439) cohorts. Logistic regression was utilized to quantify the prognostic performances of GCS-P (GCS minus number of unreactive pupils) and GCS+P versus GCS alone according to Nagelkerke's .

Effect of fluid and driving pressure on cyclical "on-off" flow of pulmonary microcirculation during mechanical ventilation.

Objectives: This study aimed to identify the cyclical "on-off" flow of pulmonary microcirculation during inspiration and expiration by sidestream dark field imaging (SDF) technology in vivo and investigate the effects of volume status and driving pressure on cyclical "on-off" flow of microcirculation.

Methods: 24 ARDS-modeled rabbits were randomly divided into high-driving pressure group (HDP group) and low-driving pressure group (LDP group). Lung microcirculation measurements were performed using the SDF microscope at two timepoints (T1 CVP 2-4 mmHg, T2 CVP 8-10 mmHg).

Characteristics of Patients With Asymptomatic Atrial Fibrillation and Ischemic Stroke-Insights From the GLORIA-AF Registry (Phase 2).

Background: Asymptomatic nonvalvular atrial fibrillation is often suspected in patients with cryptogenic stroke which constitute 20%-30% of ischemic strokes. Detection of atrial fibrillation (AF) and treatment with anticoagulation can reduce the risk of stroke. We sought to investigate the prevalence of asymptomatic atrial fibrillation (aAF) in patients with a history of stroke or an acute stroke on admission.

External validation of EuroSCORE I and II in patients with infective endocarditis: results from a nationwide prospective registry.

Objectives: The primary objective was to externally validate EuroSCORE I and II in surgically treated endocarditis patients. The secondary objective was to assess the predictive performance of both models across sex, redo surgery, age, and urgency.

Methods: Data were retrieved from the Netherlands Heart Registration.

Targeted antimicrobial regimens for Gram-negative prosthetic joint infections: a prospective multicenter study.

Fluoroquinolones (FQs) are considered the most effective antimicrobial treatment for Gram-negative prosthetic joint infection (GN-PJI). Alternatives are needed due to increasing FQ resistance and side effects. We aimed to compare different targeted antimicrobial strategies for GN-PJI managed by debridement, antibiotics, and implant retention (DAIR) or one-stage revision surgery (1SR) and to review the literature of oral treatment options for GN-PJI.

A Molecular Urine Assay to Detect Recurrences During Surveillance of High-Risk Non-Muscle Invasive Bladder Cancer.

Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) patients require long-term surveillance with cystoscopies, cytology and upper tract imaging. Previously, we developed a genomic urine assay for surveillance of HR-NMIBC patients with high sensitivity and anticipatory value.

Objective: We aimed to validate the performance of the assay in an unselected prospectively collected cohort of HR-NMIBC patients under surveillance.

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies.

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m/cycle) were included.

A systematic review evaluating the association of atherosclerosis and lumbar degenerative disc disease.

Introduction: Lumbar disc herniation (LDH) and disc degeneration (DD) are associated with low back pain (LBP) and sciatica, which are common health problems. Emerging evidence suggests a link between vascular health, specifically abdominal aortic calcification (AAC) and systemic lipid profiles, and these spinal conditions.

Research Question: This study investigates the associations between AAC, systemic lipid profiles, lumbar Modic Changes (MC), DD/LDH, and the occurrence of LBP or sciatica.

Development and Portability of a Text Mining Algorithm for Capturing Disease Progression in Electronic Health Records of Patients With Stage IV Non-Small Cell Lung Cancer.

Purpose: The objective was to develop and evaluate the portability of a text mining algorithm for prospectively capturing disease progression in electronic health record (EHR) data of patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunochemotherapy.

Methods: This study used EHR data from patients with mNSCLC receiving immunochemotherapy (between October 1, 2018, and December 31, 2022) in four Dutch hospitals. A text mining algorithm for capturing disease progression was developed in hospitals 1 and 2 and then transferred to hospitals 3 and 4 to evaluate portability.

How well does the academic performance of Ethiopian anaesthetists predict their National Licensing Examination scores: a cross-sectional study.

Objectives: This study assessed the relationship between academic performance and National Licensing Examination (NLE) scores of Ethiopian anaesthetists and proposed academic performance thresholds that predict failing the NLE.

Design: A retrospective cross-sectional study.

Setting: Academic performance measures were collected from eight universities and matched to total and subdomain NLE scores for anaesthetists.

Impact of comorbidity on health-related quality of life in newly diagnosed patients with lymphoma or multiple myeloma: results from the PROFILES-registry.

With the increasing prevalence of comorbidity in an ageing population, it is crucial to better understand the impact of comorbidity on health-related quality of life (HRQoL) after lymphoma or multiple myeloma (MM) diagnosis. We included 261 newly diagnosed patients (67% response rate) diagnosed with lymphoma or MM between October 2020 and March 2023 in a longitudinal survey. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires were used to measure generic and disease-specific HRQoL.

Real-world overall survival after alternative dosing for pembrolizumab in the treatment of non-small cell lung cancer: A nationwide retrospective cohort study with a non-inferiority primary objective.

Background: High and increasing expenses on pembrolizumab ask for more cost-effective and sustainable treatment strategies to improve affordability of healthcare. Therefore, a part of the Dutch hospitals implemented an alternative, partially lower, weight-based dosing protocol for pembrolizumab. This provided the unique opportunity to compare the overall survival (OS) of the alternative pembrolizumab dosing protocol to standard dosing using a nationwide registry in non-small cell lung cancer (NSCLC) patients.

Rate of nosocomial MRSA transmission evaluated via contact screening.

Background: The prevention of methicillin-resistant S. aureus (MRSA) transmission in the healthcare setting is a priority in Infection Control practices. A cornerstone of this policy is contact tracing of nosocomial contacts after an unexpected MRSA finding.