The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.

Purpose: Unfortunately, treatment of patients with uveal melanoma (UM) with metastatic disease is limited. Twenty percent of patients with UM harbor a mutation in the splicing factor gene SF3B1, suggesting that aberrant spliceosome function plays a vital role in tumorigenesis. Splicing inhibitors exploit the preferential sensitivity of spliceosome-compromised leukemic cells to these compounds.

8q Gain Has No Additional Predictive Value in Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with Uveal Melanoma.

Purpose: Gain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in the absolute number of 8q-copies correlated with an even shorter survival. Splicing factor 3b subunit 1 ()-mutated () tumors display structural chromosomal anomalies and frequently show a partial gain of chromosome 8qter. A recent subset of UM with early-onset metastases has been identified, prompting the investigation of the relationship between survival, 8q gain, and UM.

Acetabular dysplasia and the risk of developing hip osteoarthritis at 2,5,8, and 10 years follow-up in a prospective nationwide cohort study (CHECK).

Objective: To assess the relationship between acetabular dysplasia (AD) and the risk of incident and end-stage radiographic hip osteoarthritis (RHOA) over 2,5,8 and 10 years.

Design: Individuals (n = 1002) aged between 45 and 65 from the prospective Cohort Hip and Cohort Knee (CHECK) were studied. Anteroposterior pelvic radiographs were obtained at baseline and 2,5,8, and 10-years follow-up.

Emulator-based Bayesian calibration of the CISNET colorectal cancer models.

Purpose: To calibrate Cancer Intervention and Surveillance Modeling Network (CISNET) 's SimCRC, MISCAN-Colon, and CRC-SPIN simulation models of the natural history colorectal cancer (CRC) with an emulator-based Bayesian algorithm and internally validate the model-predicted outcomes to calibration targets.

Methods: We used Latin hypercube sampling to sample up to 50,000 parameter sets for each CISNET-CRC model and generated the corresponding outputs. We trained multilayer perceptron artificial neural networks (ANN) as emulators using the input and output samples for each CISNET-CRC model.

Analysis of the challenges in implementing guidelines to prevent the spread of multidrug-resistant gram-negatives in Europe.

Objective: The main objective of the study was to investigate major differences among European countries in implementing infection prevention and control (IPC) measures and reasons for reduced compliance.

Design: An online survey including experts in IPC and a gap analysis were conducted to identify major limitations in implementing IPC guidelines.

Setting: Europe.

Chronic Hepatitis E in Rheumatology and Internal Medicine Patients: A Retrospective Multicenter European Cohort Study.

Hepatitis E virus (HEV) infection is a pandemic with regional outbreaks, including in industrialized countries. HEV infection is usually self-limiting but can progress to chronic hepatitis E in transplant recipients and HIV-infected patients. Whether other immunocompromised hosts, including rheumatology and internal medicine patients, are at risk of developing chronic HEV infection is unclear.

Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer.

With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age.