St Olav's University Hospital

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.

Schizophrenia patho-etiology may involve endothelial inflammation and blood-brain barrier (BBB) dysregulation with cellular adhesion molecules (CAMs) as important mediators. CAMs are essential for cellular integrity but can show increased levels in inflammation. Cognitive dysfunction precedes and exists independently of psychotic symptoms in schizophrenia patients. CAMs could impact cognition through influence on BBB integrity. To gain insights into disease mechanisms and potential therapeutic targets, we explored the relationship between CAMs protein levels and neurocognitive tests in schizophrenia-spectrum disorders in the BeSt InTro study. Seventy-one in- and out-patients underwent CAMs measurements and neuropsychological testing on a minimum of one time point: baseline, 6, 26, or 52weeks. Cognitive domains included working memory, processing speed, verbal abilities, executive functions, and overall cognition. CAMs analyzed were neural CAMs: junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD); vascular CAMs: intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), and platelet (P)-selectin from fasting blood samples. Linear mixed effects models, adjusted for age, sex, body mass index, smoking, education, and drug naivety, estimated CAMs effect on cognitive outcome measures. N-CAD levels correlated positively with overall cognition (p=0.002), working memory (p=0.034), and executive functions (p=0.0011). ICAM-1 levels correlated positively with overall cognition (p=0.037). Conversely, JAM-A levels correlated negatively with executive functions (p=0.021). Associations between CAMs (N-CAD, ICAM-1, JAM-A) and neurocognitive tests suggest CAMs may impact cognition in schizophrenia. Contrary to our hypothesis, most associations between CAMs levels and cognitive tests were positive. Future research on mechanisms is mandatory.

Impaired clinical insight is common in schizophrenia spectrum disorders (SSDs) and predicts poor treatment adherence and outcomes. It is linked to disorganised, positive, negative, and hostility symptoms. However, few studies repeatedly assess insight after antipsychotic initiation while comparing pharmacologically distinct agents. This study examined how symptom levels and changes predict the development and endpoint of clinical insight over 6 weeks, contrasting the partial dopamine agonist aripiprazole (PDA) with two dopamine antagonists (DAs). Data from 144 SSD patients in the Bergen-Stavanger-Innsbruck-Trondheim (BeSt InTro) trial, a pragmatic, semi-randomised study of amisulpride, aripiprazole, and olanzapine, were analysed using latent growth curve models. Insight was measured by PANSS Item G12; symptom factors (positive, negative, hostility, cognitive/disorganised) were derived from PANSS. Lower baseline symptoms and greater improvement between weeks 3 and 6 predicted better insight at 6 weeks across all factors. For positive symptoms, improvement between weeks 1 and 3 (b = 0.57, p = 0.009) also predicted better insight. Patients on aripiprazole showed less improvement in insight, though some findings lost significance after correction. Symptom reduction is associated with improved insight, with early changes in positive symptoms exerting the fastest effect. Despite symptom improvement, aripiprazole PDA treatment was linked to less insight gain than DA treatment. These preliminary findings warrant further study.

Collaboration between healthcare services is essential for the quality and continuity of care for persons with chronic pain. Collaboration meetings using digital solutions can be useful in overcoming collaboration challenges. However, there is a scarcity of studies on conducting digital collaboration meetings across services, particularly across healthcare levels for patients with chronic pain. Therefore, the aim of the study was to develop recommendations for how to plan and conduct digital collaboration meetings across care levels and services for patients with chronic pain. A qualitative study collecting data from a development process for digital collaboration meeting recommendations was conducted between October 2022 and June 2023. Data were collected at workshops, discussions in the clinic and research group meetings. The analysis focused on topics that generated the most discussions during the development process. The discussions leading to the recommendations were categorised into three themes: ‘Patient-centeredness in the digital collaboration meeting’, ‘A common action plan’ and ‘Good meeting climate’. The main discussions included what it meant to place the patient at the centre of the activities, whether the patient should be present when professionals discussed the interprofessional assessments, whether clinical notes and suggestions for action should be distributed before the digital collaboration meeting, and how to ensure well-led meetings with clear agendas. A set of recommendations for how to plan and conduct digital collaboration meetings across care levels and services for patients with chronic pain was developed. Due to practical issues and differing opinions, the final recommendations offer flexible approaches to meet different levels of preparedness before the meeting. The recommendations are ready to be further tested as collaboration meetings are implemented more widely.

Abstract Background and Aim Socioeconomically disadvantaged people are more likely to have high body mass index (BMI). However whether socioeconomic position moderates genetic susceptibility to high BMI, and whether this effect differs by sex, remains unclear. We aimed to investigate whether educational attainment (EA) moderates the association between genetic liability for high BMI and BMI trajectories across adulthood in females and males. Methods We analyzed data from 69,314 participants in the Trøndelag Health Study (HUNT), a population-based cohort with genotyping and repeated BMI measures. A polygenic index for BMI (BMI PGI) was calculated, and participants were categorized by EA level. Using linear mixed-effects models stratified by sex, we tested the interaction between BMI PGI, EA, and age on BMI trajectories. Results The relationship between BMI PGI and BMI was non-linear, showing a steeper slope in the upper deciles, and was modified by sex ( p &lt;0.001). Sex-stratified analysis showed that EA moderated the effect of BMI PGI on BMI in females ( p =0.003) but not in males ( p =0.089). Among highly educated females, the BMI difference between the top and bottom BMI PGI deciles was-0.99 kg/m² [95%CI: -1.67 to -0.30] smaller than among those with low education. In males, the corresponding difference was -0.16 kg/m² [-0.71 to 0.39]. Genetic influences on BMI trajectories showed consistent age-dependent patterns across all educational groups, though trajectories differed by sex. Females experienced a steady increase in BMI until age 60, after which it declined. Males had an early rapid increase, then stabilization, followed by a slight late-life decline. Conclusion Higher EA consistently moderates the effect of genetic liability for high BMI in females throughout adulthood, but this protective effect is absent in males. This sex difference suggests that gender-related socioeconomic factors may modulate the expression of BMI-related genetic variants, warranting further investigation into the underlying mechanisms.

In this proof-of-concept study, we evaluated the feasibility of non-invasive estimation of cardiac power metrics-total power, steady power, oscillatory power, and oscillatory power fraction-and compared the prognostic and diagnostic value with established echocardiographic metrics. We prospectively included 29 patients (mean age 76 ± 13 years, 24% women) hospitalized with decompensated heart failure. Left ventricular outflow tract flow waveforms were derived from Doppler echocardiography and synchronized with a continuous arterial pressure waveform from a finger-volume-clamp device (INL382, Finapres Medical Systems B.V., Amsterdam, Netherlands). Total power was computed as the integral of the instantaneous pressure-flow product per second, steady power as mean arterial pressure multiplied by mean flow, and oscillatory power as their difference. All measures were calculated from the same consecutive heartbeats covering three respiratory cycles. The feasibility of obtaining cardiac power metrics was 91%. Total, steady, and oscillatory power predicted short-term all-cause mortality (log rank p < 0.015), whereas left ventricular ejection fraction, global longitudinal strain, and myocardial work indices did not. These findings suggest that cardiac power metrics may be useful in risk stratification and warrant validation in larger cohorts.

Meningiomas are heterogeneous tumors and studies suggest that meningiomas might be part of MEN1 syndrome. The tumors express somatostatin receptors (SSTRs) comparable to that seen in neuroendocrine neoplasms. We aimed to explore neuroendocrine differentiation in meningiomas by investigating the following neuroendocrine markers: neural cell adhesion molecule (CD56/NCAM), chromogranin A, chromogranin B, chromogranin C, neuron-specific enolase (NSE), secretagogin, and synaptophysin. Our findings were related to WHO grade, tumor subtype, and SSTR2 immunoreactivity. Tissue microarrays from 162 patients with intracranial meningioma underwent immunohistochemical analyses. Immunoreactivity was assessed with manual and digital analyses. Transmission electron microscopy (TEM) was used to detect secretory granules in one tumor specimen. NSE, CD56, and chromogranin B were detected in 91%, 44%, and 16% of meningiomas, respectively. The other neuroendocrine markers were mostly negative. NSE immunoreactivity was higher in WHO grade 2 tumors (p = 0.027) and differed among subtypes with highest and lowest immunoreactivity in meningothelial and fibrous subtypes, respectively. Chromogranin B (p = 0.006) and NSE (p = 0.003) were positively correlated to SSTR2 immunoreactivity. No secretory granules were detected. Manual and digital evaluation showed excellent agreement. Our study does not support the hypothesis of neuroendocrine differentiation in meningiomas, as chromogranin A and synaptophysin were mostly absent.