Karolinska University Hospital

• Stakeholders identified five themes for home-based stroke rehabilitation. • Patient involvement and staff competence were both rated feasible and important. • The physical home environment and social networks were rated as important, yet less feasible to implement. • A gap was found between policy ambitions and real-world rehabilitation delivery. • Concept mapping enabled stakeholder-driven priorities in care development. Despite growing emphasis on home-based rehabilitation following stroke, there remains limited understanding of how to effectively tailor services to individual needs. This study employed concept mapping to explore diverse stakeholder perspectives on adapting home-based rehabilitation to better support the recovery process after stroke. Through this mixed-methods participatory approach, we engaged 89 stakeholders, including stroke survivors, significant others, healthcare professionals, managers, and architects. Participants generated, sorted, and rated statements about what matters most in home-based stroke rehabilitation. A hierarchical cluster analysis was conducted to organize the data into concepts. Five clusters were identified: 1) social support at home and beyond; 2) professional competence; 3) supportive home environment; 4) teamwork and resources; and 5) patient involvement. Patient involvement was rated highest for importance and feasibility, followed by professional competence. Specifically, stakeholders emphasized that rehabilitation should feel meaningful and be tailored to the patient's needs. No generated ideas from the cluster “supportive home environment” were found in the go-zone, and adapting rehabilitation to diverse home environments was recognized as crucial but hard to implement. The findings underscore the need for individualized, context-sensitive approaches and suggest that strengthening professional competence, particularly in navigating diverse environments and engaging support networks, will be essential to translating person-centered principles into everyday rehabilitation practice.

Diagnostic delay is common in pediatric inflammatory bowel disease (PIBD), and fecal calprotectin (FCP) is often limited by challenges with sample collection. Therefore, we aimed to identify and validate a blood-based diagnostic protein signature of PIBD. Proteins were analyzed using proximity extension assay in plasma samples from treatment-naïve pediatric patients in a Swedish inception cohort referred for suspected inflammatory bowel disease (IBD) and validated in an independent Norwegian population-based pediatric inception cohort. Diagnostic performance was estimated by the area under the curve (AUC) with 95% confidence intervals (CIs). The discovery cohort included 58 patients with PIBD and 36 symptomatic controls without evidence of IBD, while the validation cohort consisted of 79 patients with PIBD and 37 symptomatic controls. In total, 154 proteins were examined. Univariable analyses identified 26 differentially regulated proteins for PIBD versus symptomatic controls in the discovery cohort (q < 0.05), whereas 29 proteins were differentially regulated in the validation cohort. Using regularized logistic regression, we identified a diagnostic model of 31 proteins that differentiated PIBD from symptomatic controls in the discovery cohort (AUC = 0.83; 95% CI: 0.74-0.90). The protein signature was further reduced to a clinically relevant biomarker consisting of high-sensitivity C-reactive protein (hsCRP) and seven other proteins with diagnostic capacity (AUC = 0.85, 95% CI: 0.78-0.92) outperforming hsCRP in the validation cohort (p = 0.006). We identified and validated a blood-based protein signature for PIBD with superior diagnostic performance compared to hsCRP. Given the challenges of fecal sample collection, further assay development may enable integration of these biomarkers into diagnostic pathways for PIBD. ClinicalTrials.gov identifier: NCT02727959.

The aim of this study was to identify biological processes associated with neuroaxonal degeneration in multiple sclerosis (MS) by analyzing protein patterns linked to neurofilament light (NfL) protein in CSF and serum samples. The highly sensitive proximity extension assay technology was used to quantify protein levels in paired CSF and serum samples from treatment-naïve, early-stage active MS patients (n = 114). The cohort was stratified into above and below median of CSF-NfL level. A discovery phase identified proteins upregulated in CSF, and a validation cohort (n = 128) confirmed findings in a more clinically diverse MS population, including patients receiving disease-modifying therapies. In the discovery cohort, 13 proteins were upregulated in CSF (leukocyte immunoglobulin like receptor B4, CXCL6, CXCL5, cluster of differentiation 38, CCL19, CXCL11, IMPA1, macrophage scavenger receptor 1 (MSR1), CXCL10, monocyte chemotactic protein 2, ITM2A, TNFRSF12A, and CCL23). It is important to note that associations with CCL19, CXCL11, MSR1, CXCL10, TNFRSF12A, and CCL23 were replicated in a validation MS cohort. By contrast, no consistent serum protein profiles associated with serum levels of NfL could be discerned in this group-based analysis. Furthermore, 75 CSF proteins showed a positive adjusted linear association with CSF-NfL, whereas no such significant association remained in the corresponding analysis in serum. The identified and replicated CSF protein profile indicates distinct inflammatory processes associated with ongoing neuroaxonal degeneration. All of these most robust 6 proinflammatory markers-CCL19, CXCL11, MSR1, CXCL10, TNFRSF12A, and CCL23-independently replicated and were individually observed to be relevant in the context of MS. These findings may further elucidate the immunologic pathways underlying disease processes leading to neuroaxonal degeneration.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Hemodynamic instability is a highly prevalent, complex and life-threatening condition in critically ill patients. Its multifactorial nature and patient-specific variability challenge standardised treatment approaches. Computational physiological models (CPMs) offer a promising solution by simulating cardiovascular dynamics to guide individualised hemodynamic management. This systematic review evaluates the current landscape of cardiovascular CPMs, focusing on their design, credibility, and clinical readiness. A systematic search was conducted in MEDLINE ALL, Embase, Scopus, and Web of Science. Original research articles describing zero-dimensional, closed-loop cardiovascular models with (potential) applications in critical care were included. Data were extracted on context of use, model design, and validation. Model credibility was assessed using a risk-based framework and clinical readiness using a nine-level technology maturity scale. Out of 10,704 screened articles, 183 were included. Direct clinical applications were described in 50% of these studies, including diagnosis, decision support, and closed-loop control. Fluid management was the most common application domain (30%). Personalisation of model parameters was reported in 25% of the articles. While 66% of the articles presented model validation, only 21% achieved moderate credibility scores. Reporting of model characteristics was consistently (100%) insufficient. Most models (75%) were at clinical readiness level 3-4 (model prototyping and development), with four studies reaching clinical testing (level 6-8). A substantial body of cardiovascular CPMs exists with promising prospects for relevant applications in critical care, while a large part is currently confined to pre-clinical research settings. Advancing clinical integration requires leveraging existing models, improving transparency in verification and validation, and establishing robust personalisation strategies. PROSPERO - CRD42022300137, registered on February 11, 2022.