Rigshospitalet

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.

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.

Integrated genomic surveillance, combining whole genome sequencing (WGS) of bacterial isolates with patient movement data, promises improved detection and prevention of pathogen transmission. However, evidence on its cost-effectiveness and clinical utility remains limited, not least because the full extent of transmission in hospital settings is difficult to capture. We conducted a 28-month observational study at Rigshospitalet, Copenhagen, collecting patient movement data and sequencing 18 438 bacterial isolates from 7398 patients across diverse species, infection sites, and resistance profiles. We estimated the hypothetical benefits of implementing integrative WGS surveillance, assuming that continued transmission could be prevented when WGS information was acted upon immediately. We found that 1975 of 7398 of culture-positive hospitalized patients (26.7%) harboured a pathogen genetically related to another patient's isolate. Of those, 1359 (68.8%) had an epidemiological link in the hospital, with Enterococcus faecium by far being the most prevalent bacteria involved in transmissions. WGS-informed prevention could hypothetically generate a net savings of €1.35 million annually if transmission was stopped once a clonal isolate was detected in a second patient. Furthermore, this approach could potentially have prevented an estimated 1284 hospital-acquired infections over the 28-month study period, including 94 cases characterized by the recovery of bloodstream isolates. Our integrated genomic surveillance approach reveals previously unexplored transmission landscapes. We discovered that transmission is widespread, varies between species, and is not limited to resistant isolates. Our results emphasize the potential of integrated genomic surveillance, the identification of local transmission hotspots, potential for greater savings by including susceptible isolates, and an incremental cost-effectiveness ratio classification by pathogen species.

Obstructive Sleep Apnoea (OSA) is a highly prevalent disease often treated with CPAP therapy, but long-term adherence remains a challenge. This study aimed to explore which phenotypes of OSA patients are more or less likely to achieve high adherence to CPAP therapy, based on pre-treatment characteristics. We analysed demographic, socioeconomic, and clinical characteristics across predefined CPAP adherence groups (high, low, and no adherence) in a multicentre cohort of newly diagnosed OSA patients. Multivariate logistic regression was used to assess predictive accuracy, and observed patterns were synthesised into rule-based clinical phenotypes. Among 2845 patients, 41% were highly adherent, 20% had low adherence, and 39% were non-adherent after one year. High adherence was associated with cohabitation, higher education, employment, and greater disease severity. Low or no adherence was linked to comorbidity burden and social vulnerability. The predictive model yielded an accuracy of 60%. Based on group-level differences and model outputs, three clinically reasoned phenotypes were identified: (1) Symptomatic severe OSA with social support, (2) Multimorbidity-dominated, and (3) Non-employed working-age adults. Distinct demographic, socioeconomic, and clinical profiles were associated with CPAP adherence. The identified phenotypes offer a practical framework for understanding adherence variation and may support more individualised approaches to treatment and follow-up.

Patient-reported pain during intravitreal injection (IVI) may vary by injection quadrant and influence adherence to repeated treatments. Hence, this study aimed to quantify whether patient-reported pain differs by IVI quadrant and identify the least-painful approach. We searched 13 literature databases on 15 October 2025 for clinical studies reporting patient-reported IVI pain stratified by injection quadrant (superotemporal [ST], superonasal [SN], inferotemporal [IT], inferonasal [IN]). Random-effects meta-analyses synthesized mean differences (MD) in 0-10 visual analogue scale (VAS) pain across all six pairwise quadrant contrasts. All eligible studies were included for a qualitative review and a meta-analysis. The review was prospectively registered (PROSPERO CRD420251164189). Seven studies comprising 2048 IVI were included (ST 611, SN 469, IT 556, IN 412). Most injections involved anti-VEGF agents. All injections were performed under topical anesthesia (100%; drops or gel), with no subconjunctival anesthesia reported (0%), and pain was recorded immediately post-procedure using VAS-derived scales. Across all six pairwise contrasts, pooled mean differences between quadrants were small (typically < 1 VAS unit on a 0-10 scale), and all 95% confidence intervals crossed zero. Across quadrant comparisons, pooled pain differences were small and inconsistent; none of the pairwise pooled estimates demonstrated a statistically consistent difference, and between-study heterogeneity was substantial to considerable (I2 generally > 80%). Current evidence does not demonstrate a clearly less painful quadrant for intravitreal injections. Estimates varied across studies and heterogeneity was substantial, limiting confidence in any single average quadrant effect. Efforts to minimize IVI-related pain should prioritize optimized anesthesia protocols, communication, and injection technique, while future studies should standardize pain measurement and quadrant allocation to clarify whether subtle quadrant effects exist. PROSPERO registration:CRD420251164189.

The efficacy and safety of monopolar biphasic focal pulsed field ablation (F-PFA) in close proximity to the atrioventricular (AV) node remain unknown. This study aimed to describe the effect of direct or indirect F-PFA application at the AV junction. In pigs, F-PFA (Centauri, CardioFocus) was applied directly at the AV junction (n = 3) and indirectly from within the aortic noncoronary cusp (NCC) (n = 5), followed by macroscopic gross and histologic analysis. In 5 patients planned for a pace-and-ablate strategy, F-PFA was applied at the AV junction. In 1 patient with recurrent para-Hisian atrial tachycardia and previously failed ablation, F-PFA was applied from within the NCC. In pigs, direct F-PFA applications at the AV junction were associated with junctional beats and resulted in complete AV block after 2-3 F-PFA applications. Tissue histology revealed a lesion depth of approximately 8 mm with minor hemorrhage and leukocyte infiltration. F-PFA from within the NCC resulted in a transient increase in the AV node's Wenckebach cycle length and 1 pig had transient AV block, which recovered within 10 minutes. In 5 patients undergoing pace-and-ablate strategy, F-PFA applications at the AV junction resulted in sustained AV block. In 1 patient, application of F-PFA from within the NCC resulted in termination and noninducibility of a recurrent incessant para-Hisian atrial tachycardia without AV block. There were no immediate or long-term complications. F-PFA directly at the AV junction results in nonreversible AV block. F-PFA from within the NCC may represent a promising strategy for treating para-Hisian arrhythmias while preserving AV conduction.

Left ventricular diastolic dysfunction (LVDD) is common in chronic kidney disease (CKD) and is suggested to be linked to worse renal prognosis. We investigated the associations between both the ratio of early mitral inflow velocity to early diastolic tissue velocity (E/e') and LVDD grades with the risk of end-stage kidney disease (ESKD). This prospective cohort study included individuals with non-dialysis-dependent CKD from the nephrology outpatient clinics at Rigshospitalet and Herlev-Gentofte hospital, Copenhagen. All participants underwent a thorough, protocolized echocardiographic examination. The outcome was time to ESKD (defined as dialysis treatment or kidney transplantation). A total of 731 participants were included. Mean age was 57 ± 13 years and 39% were female. During a median follow-up of 3.8 years (IQR: 3.3;4.5), 102 individuals reached ESKD. In multivariable Cox regression models, both increasing continuous E/e' (HR = 1.09 [95%CI:1.03;1.15], P = 0.004, per 1 unit increase) and E/e' > 14 (HR = 3.44 [95%CI:1.44;8.26], P = 0.005) (reference E/e' < 8) were associated with ESKD, while E/e' 8-14 was not. Compared with no or indeterminate LVDD, LVDD grades 2 or 3 were associated with ESKD (HR = 2.92 [95% CI:1.44;5.94], P = 0.003), while LVDD grade 1 was not. E/e' > 14 and LVDD grade 2 or 3 demonstrated similar predictive accuracy with excellent specificity and negative predictive values, but poor positive predictive values and sensitivity. Prominent LVDD assessed by E/e' and LVDD grades was independently associated with worse renal prognosis and had similar predictive accuracy in patients with non-dialysis dependent CKD.

Older people with dementia are frequently prescribed opioids, but little is known about adverse events associated with opioid use in this population. The aim was to investigate whether opioid use was associated with an increased risk of hospitalization in older people with dementia. Matched cohort study using Danish nationwide registries. All Danish residents (≥ 65 years) diagnosed with dementia between 2008 and 2018 were included. Individuals with opioid use in the year prior to dementia diagnosis were excluded. Exposure was first redeemed opioid prescription after dementia diagnosis. Persons exposed to opioids were matched with up to two unexposed persons on age and sex. Outcome was all-cause 180-days hospitalization. Cox proportional hazards models compared rates of hospitalization within 180 days between the exposed and unexposed and adjusted for potential confounders. Forty-two percent (31,619/75,471) of older people with dementia redeemed an opioid prescription after diagnosis. Among exposed, 7,356 (23.3%) were hospitalized within 180 days, compared with 7,618 (12.1%) of unexposed, and opioid use was associated with a 4-fold increased risk of hospitalization (fully adjusted hazard ratio: 3.86 (95% confidence interval, 3.72–4.01)), and 8-fold within the first 14 days ((7.77 (7.15–8.45)). Exposed were more often admitted due to fractures, infections, and cardiovascular events. Opioid use was associated with increased risk of hospitalization, which may be due to the opioid, the indication, or both. This observation calls for further research into potential harmful effects associated with opioid use as it can have important implications for patient safety.