Odense 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.

Intracranial calcifications are commonly found in adults and may represent either benign or pathological lesions. Conventional imaging modalities detect static macrocalcifications but do not capture molecular microcalcification. In this study, we used 18 F-sodium fluoride (NaF) PET/computed tomography (CT) to idetect intracranial molecular microcalcification. A total of 127 subjects underwent 18 F-NaF PET/CT 90 min following radiotracer injection. Artificial intelligence-based quantification was performed to obtain regions of interest for the brainstem, basal ganglia (caudate and lentiform nuclei), insula, thalamus, and ventricles. Linear regression models were used to correlate NaF mean standardized uptake value (SUV mean ) with various clinical factors. NaF SUV mean was highest in the insula (0.8 ± 0.4) and brainstem (0.8 ± 0.3), while uptake was lowest in the caudate nucleus (0.1 ± 0.1). No differences were found in NaF SUV mean between healthy volunteers and at-risk patients. On multivariate regression, NaF SUV mean directly correlated with age in the brainstem ( β = 0.01, P = 0.01), lentiform nucleus ( β < 0.01, P = 0.02), and ventricles ( β < 0.01, P < 0.01). Male sex inversely correlated with NaF SUV mean in the insula ( β = -0.30, P < 0.01). There was an association between NaF SUV mean and BMI in the brainstem, caudate nucleus, lentiform nucleus, thalamus, and ventricles ( β ≤ 0.01, P < 0.01 in all regions). Thalamic and ventricular NaF SUV mean directly correlated with hypertension on univariate but not multivariate analysis. NaF PET/CT detects intracranial molecular microcalcification that is not visible on conventional CT and may provide insight into pathology associated with this biological process.

People with schizophrenia experience markedly reduced health-related quality of life (QoL), partly driven by obesity and metabolic dysregulation. Glucagon-like peptide-1 receptor agonists such as semaglutide induce substantial weight loss in the general population and in patients receiving antipsychotic medication. However, the extent to which semaglutide-associated weight loss mediates changes in QoL and symptom severity in schizophrenia remains unclear. This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity. Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30weeks. Outcomes were the SF-36v2 Physical and Mental Component Summary scores (PCS, MCS) and the Positive and Negative Syndrome Scale, 6-item version (PANSS-6). Causal mediation analyses estimated natural direct and indirect effects of semaglutide via weight loss at weeks 15 and 30. Semaglutide improved PCS at weeks 15 and 30, with effect sizes exceeding the minimally important difference. Indirect effects via weight loss were positive but not statistically significant, although at week 30 approximately half of the total PCS effect was estimated to be mediated through weight change. No total or mediated effects were found for MCS. For PANSS-6, no meaningful mediation was observed. Semaglutide improved physical QoL in patients with schizophrenia, and weight loss may partially contribute to this effect. Longer-term studies are needed to determine whether mental QoL or symptom effects emerge beyond 30weeks.

Robot-assisted microsurgery may improve supermicrosurgical procedures, including lymphatic reconstruction mitigating fatigue and tremor. It remains unclear whether robot-assisted supermicrosurgery, using the Symani Surgical System(Medical Microinstruments, Calci, Italy) or the MUSA(MicroSure, Eindhoven, Netherlands), surpasses conventional surgery.1

The efficacy of anti-CD20 therapies in multiple sclerosis (MS) has been recognized since 2008. Since then, three anti-CD20 monoclonal antibodies - ocrelizumab, ofatumumab, and ublituximab - have been developed and approved for MS treatment, whereas rituximab, the first monoclonal antibody shown to be effective, remains an off-label therapy in this indication. Anti-CD20 antibodies deplete B cells primarily through two mechanisms: complement-dependent cytotoxicity (CDC) and natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). The relative contribution of these mechanisms differs among individual antiCD20 antibodies. NK cell-mediated ADCC is modulated by the glycosylation state of the antibody Fc region as well as by genetic polymorphisms in FcγRIIIa, the Fc receptor on NK cells responsible for Fc binding. Fc engineering can enhance ADCC and partially overcome the functional consequences of FcγRIIIa polymorphisms. This article reviews the structure and mechanisms of action of immunoglobulins and anti-CD20 antibodies; outlines the development of antibody humanization and Fc engineering to enhance efficacy and tolerability; presents clinical data from ublituximab treatment; and discusses additional strategies for achieving effective B-cell depletion.

Background/Objectives: To prevent surgical site infections, it is important to consider the concentration of the administered antibiotic in the target compartment. We measured the concentrations of cefuroxime and metronidazole in peritoneal fluid with the microdialysis technique in patients undergoing surgery for secondary peritonitis (7 patients) and for inflammatory bowel disease (11 patients). Methods: All patients received 1.5 g of cefuroxime and 0.5 g of metronidazole every 8 h during the postoperative period for at least 72 h. Microdialysates covering 8-h intervals were collected, and the concentration of cefuroxime and metronidazole was measured using liquid chromatography-mass spectrometry. Results: For metronidazole, a concentration of ≥4 μg/mL was reached in all but one sample, corresponding to the minimal inhibitory concentration (MIC) for most anaerobic bacteria strains. For cefuroxime, a value of ≥4 μg/mL was reached in 88% and 93% of the samples in the peritonitis group and the IBD group, respectively, corresponding to the MIC values for most Gram-negative bacteria, and a value of ≥16 μg/mL, corresponding to the MIC value for more resistant bacteria, was reached in only 40% and 23% of the samples, respectively. Conclusions: Our results show that the peritoneal microdialysis method is feasible for studying the diffusion of antibiotics into the peritoneal cavity. Measuring the accumulative concentration of antibiotics in the peritoneal fluid corresponding to the drug administration interval may provide important information to consider alongside traditional pharmacodynamic parameters and may be relevant to achieving an optimal therapeutic effect.

Abstract Background The glymphatic system supports brain homeostasis by clearing interstitial solutes via perivascular pathways. Alterations in glymphatic function have been linked to neurodevelopmental and neurodegenerative disorders, but its role in autism spectrum disorder (ASD) remains unclear. Methods We analyzed diffusion tensor imaging (DTI) magnetic resonance imaging data from five cohorts in the Autism Brain Imaging Data Exchange (ABIDE) project. Glymphatic function was estimated using the DTI analysis along the perivascular space (ALPS) index. ASD diagnoses were confirmed according to DSM-IV-TR or DSM-5 criteria, and neurotypical (NT) participants had no history of neurological, psychiatric, or developmental disorders. Results The final sample comprised 250 participants (128 ASD, mean age = 18.57 ± 13.81; 122 NT, mean age = 21.32 ± 14.37). Two-way analysis of variance (ANOVA) revealed a significant main effect of diagnosis, F(1, 246) = 10.44, p = 0.0014, with lower ALPS-indices in ASD. A diagnosis-by-age interaction was also observed, F(1, 246) = 4.71, p = 0.031. Post hoc tests demonstrated that autistic adults (≥ 18 years) had significantly lower ALPS-indices than NT adults (p = 0.0004), whereas no group differences were demonstrated between younger ASD and NT (&lt; 18 years). In ASD adults, the ALPS-index correlated negatively with depressive symptoms (r = − 0.489, p = 0.013), but not with IQ or autistic traits. Conclusions These findings suggest that glymphatic dysfunction in ASD may follow a developmental trajectory, with alterations becoming most evident in adulthood, potentially contributing to an increased risk of developing neurodegenerative disorder in autistic individuals.