University of Copenhagen

There is limited data regarding the rare and aggressive colorectal neuroendocrine carcinoma (CR-NEC). In this large prospective study, molecular-clinical characteristics and treatment outcomes following palliative chemotherapy are reported for 163 metastatic CR-NEC patients, with a comparison to a population-based prospective cohort of 263 metastatic colorectal adenocarcinoma (CR-AC) patients. Eighty-three percent of CR-NEC received first-line platinum-etoposide, while 98% of CR-AC patients received first-line fluorouracil-based chemotherapy. Disease control rate across all first-line regimens in CR-NEC and CR-AC was 43% vs. 74%, immediate progressive disease 46% vs. 15%, progression-free survival 2.4 months (m) (95% CI 2.1-3.3) vs. 7.7 m (95% CI 6.9-8.5), and overall survival 6.7 m (95% CI 5.6-8.8) vs. 16.8 m (95% CI 13.7-20.3), all, p < .001. CR-NEC more often had synchronous metastases, worse performance status, and symptom burden at treatment initiation than CR-AC (all, p < .001). Two-year survival was 9% vs. 37% in CR-NEC and CR-AC (p < .001). BRAF mutations were frequent in CR-NEC and CR-AC (26% vs. 20%, p = .153) and associated with shorter OS in CR-NEC and CR-AC (p = .025 and p = .003). KRAS mutations were less frequent in CR-NEC than CR-AC (34% vs. 45%, p = .041), but only associated with shorter OS in rectal NEC (p = .04). The frequencies of APC and TP53 mutations were similar between the cohorts and did not impact survival. Metastatic CR-NEC and CR-AC are clinically distinct, with NEC demonstrating more aggressive features, limited treatment effect, and worse prognosis. Although they share important driver mutations, the underlying reason for their marked clinical differences remains unclear.

Timely discharge of patients who are clinically ready to be discharged from hospitals to the next point of care is a common health system challenge. Ensuring safe and effective discharge holds new urgency, given the backlogs and increased waiting times for inpatient services in many countries after the COVID-19 pandemic. The study aimed to identify policy options for addressing delayed discharges in six European countries (Denmark, France, Germany, the Netherlands, Norway, and Sweden), and to summarise available evidence on their effectiveness. Experts from the Health Systems and Policy Monitor (HSPM) network of the European Observatory on Health Systems and Policies and additional country experts identified relevant policies and initiatives up to November 2023. When evaluations were available, the experts also provided information on their findings. The data collection was followed by a qualitative, cross-country comparative analysis. A total of 17 policies or initiatives were identified in the study countries. Hospital-based initiatives included discharge planning and transitional care. Community and home care initiatives included municipal emergency beds, intensive home rehabilitation, and assisted discharge. Cross-sectoral initiatives ranged from coordination efforts at the regional and municipal levels to decision support systems and financial incentives. Several common factors or principles underpin many of the identified policies and initiatives. These include clarity of responsibility, effective planning and communication, resourcing of community-based capacity, possible unintended consequences of financial penalties, and the need to adopt a systemic approach.

Virtual reality-based cognitive remediation therapy (VR-CRT) offers an ecologically valid approach to enhance real-world cognitive functioning in mood disorders (MD) or schizophrenia spectrum disorders (SSD). This study investigated baseline cognitive, clinical, and neural predictors of VR-CRT response in MD and SSD. Sixty-two MD and SSD participants were randomized to receive four-week VR-CRT or control with assessments at baseline, treatment completion (week 5), and follow-up (week 17). Univariate general linear models examined predictors of VR-CRT improvement on daily-life cognitive skills, assessed using the Cognition Assessment in Virtual Reality (CAVIR). Predictors included age, diagnosis, baseline cognition, IQ-cognition discrepancy, dorsal prefrontal cortex (dPFC) activation during a working memory task, functional connectivity within the dorsal attention (DAN) and salience (SAL) networks, subjective cognition, and technological acceptance. Higher IQ-cognition discrepancy at baseline (i.e., better cognitive performance than expected from premorbid IQ) predicted greater treatment efficacy at treatment completion (β=0.17, p=0.045) and follow-up (β=0.21, p=0.008), while baseline cognition was not associated with treatment response (ps≥0.15). Higher baseline dPFC activity predicted more improvements at both times (β=2.27 p=0.03; β=1.82; p=0.048, respectively). Higher DAN-SAL connectivity predicted improvements at treatment completion (β=2.81 p=0.047), but not at follow-up (p=0.38). Age, sex, diagnosis, subjective cognition, and technological acceptance were not associated with cognitive change. Better cognitive performance than expected based on IQ, possibly reflecting higher cognitive fitness, and greater task-related engagement of dPFC may enhance VR-CRT responsiveness. This profile may indicate greater readiness for change and propensity to translate cognitive strategies into daily life.

Perfluoroalkyl substances (PFAS) have been linked to immunotoxic effects in children, and the consequences of immune suppression could be particularly severe for children in low-income settings. We thus aimed to investigate associations between infant and maternal PFAS exposure and infant vaccine antibody concentrations in Burkina Faso. Infants (n = 200) were vaccinated against measles at baseline (age 4-7 months) and/or at 9 months. Associations between maternal and infant PFAS concentrations (quantified in serum collected at baseline) and infant measles antibody concentrations before and after vaccination were assessed in confounder-adjusted linear regression models. Influential observations were excluded in sensitivity analyses. Infant PFAS exposure was positively associated with pre-vaccination antibody concentrations, but associations were largely driven by a few influential observations. Maternal and infant PFAS concentrations were not consistently associated with infant measles antibody concentrations after one or two vaccinations. Thus, these results from a low-exposed population did not confirm findings from previous studies.

High entropy materials (HEMs) have emerged as a promising new class of electrocatalysts distinguished by their immense compositional flexibility and structural complexity, which can give rise to unprecedented catalytic properties and open new avenues for fundamental insight into catalysis. Realizing the potential of HEM electrocatalysts is dependent on building a deep understanding of structure-property relationships, based on nuanced characterization of both structural and electrochemical properties. This critical review navigates the current landscape of HEMs in electrocatalysis, exploring the evolving nomenclature and conceptual frameworks that shape how these materials are described and understood across the literature. We consider the diverse characterization techniques used to investigate the structure of HEMs, discussing the length scales and chemical contrasts they provide as well as the challenges associated with characterizing highly complex, multielement systems. Building on this foundation, we highlight key studies of HEMs in electrocatalysis, including those focused on screening the vast compositional space of HEMs to identify new electrocatalysts, or else examining the activity and stability of HEM electrocatalysts in detail, drawing insights into the factors that govern their performance. This critical review also emphasizes emerging research directions and strategies where advanced characterization and design approaches may help unlock the full potential of HEMs in electrocatalytic applications.