Filetype
BACKGROUND: Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.METHODS: Patients with TRK fusion-positive primary C
PURPOSE: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblin
PURPOSE: To determine the impact of the implementation of novel systemic regimens and locoregional treatment modalities on survival at population level in colorectal cancer (CRC) patients presenting with peritoneal metastases (PMs).METHODS: All consecutive CRC patients with synchronous PM (<3 months) between 1995 and 2014 were extracted from the Eindhoven area of the Netherlands Cancer Registry. T
PURPOSE: Primary cytoreductive surgery (CRS) and peri-operative intraperitoneal chemotherapy (PIC) is the only curative option for patients with colorectal cancer peritoneal carcinomatosis (PC). A significant proportion of patients develop peritoneal recurrence. Outcomes of patients undergoing secondary CRS and PIC for recurrent PC were examined.METHODS: All patients undergoing second procedures w
BACKGROUND AND OBJECTIVES: Failure to respond to systemic chemotherapy is considered an exclusion criterion by some institutions for treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). However, it is unknown if these patients benefit from HIPEC treatment. This study aimed to report on outcomes of HIPEC in patients who failed to respond to adjuvant systemic c
Background: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality. Methods: Prospective, observational, cohort study in patients ≥
Background: Outcome of patients operated for anorectal malformation (ARM) type rectovestibular fistula (RVF) is generally considered to be good. However, large multi-center studies are scarce, mostly describing pooled outcome of different ARM-types, in adult patients. Therefore, counseling parents concerning the bowel function at early age is challenging. Aim of this study was to evaluate bowel fu
Economic analysis has produced ample insights on how international trade and climate policy interact. Trade presents both opportunities and obstacles, and invites the question of how domestic climate policies can be effective in a global economy integrated through international trade. Particularly problematic is the potential relocation of production to regions with low climate standards. Measures
Understanding how hematopoietic stem and progenitor cells (HSPCs) are regulated is of central importance for the development of new therapies for blood disorders and stem cell transplantation. To date, HSPC regulation has been extensively studied in vitro and in animal models, but less is known about the mechanisms in vivo in humans. Here, in a genome-wide association study on 13,167 individuals,
In cancer, the primary tumour's organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mu
The 19th World Rural Health Conference, hosted in rural Ireland and the University of Limerick, with over 650 participants coming from 40 countries and an additional 1600 engaging online, has carefully considered how best rural communities can be empowered to improve their own health and the health of those around them. The conference also considered the role of national health systems and all sta
OBJECTIVE: To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial.STUDY DESIGN: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy popul
Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard (Podarcis muralis), which differ in orange and yellow pigmentation and in their ecology and behavior, are vi
Objectives: The aim of this study was to evaluate the effect of fractional flow reserve (FFR)–guided revascularization compared with culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) on infarct size, left ventricular (LV), function, LV remodeling, and the presence of nonculprit infarctions. Background: Patients with STEMI with
Type 2 diabetes (T2DM) is associated with pancreatic islet dysfunction. Loss of β-cell identity has been implicated via dedifferentiation or conversion to other pancreatic endocrine cell types. How these transitions contribute to the onset and progression of T2DM in vivo is unknown. The aims of this study were to determine the degree of epithelial-to-mesenchymal transition occurring in α and β cel
PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic mutations in these genes cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, and cancer predisposition (BRCA2/FANCD1 and PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without bone
The Transiting Exoplanet Survey Satellite (TESS) will provide high-precision time series photometry for millions of stars with at least a half-hour cadence. Of particular interest are the circular regions of 12° radius centred around the ecliptic poles that will be observed continuously for a full year. Spectroscopic stellar parameters are desirable to characterize and select suitable targets for
Background: There is uncertainty whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) should be used in older patients with cardiopulmonary failure after cardiac surgery. Methods: This was a retrospective multicenter study of 781 patients who required postcardiotomy VA-ECMO for cardiopulmonary failure after adult cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. A para
