Skåne 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.

Sepsis-induced coagulopathy (SIC) is a scoring system developed for early detection of coagulopathy in sepsis and selection of patients for interventional studies. Our aim was to define the prevalence of SIC in a critically ill population and investigate if SIC at intensive care unit (ICU) admission is associated with morbidity and mortality. Patients admitted with septic shock between 2011, and March 2024 were propensity matched into 2 groups (control and SIC). Primary outcome was 28-day mortality. Other outcomes were 90-, 180-day and ICU-mortality, days alive and free of vasopressors, mechanical ventilation and renal replacement therapy (RRT) along with the use of RRT, number of critical bleeding events and red blood cell transfusion. 1367 patients with septic shock were identified, 422 (31%) had SIC at ICU admission. Propensity matching resulted in 340 patients in each group. SIC was not associated with higher 28-day mortality (44% versus 37%, p=0.091). ICU-mortality was higher in the SIC group (30% versus 22%, p=0.016) and it had fewer median days alive and free of vasopressors (20 versus 22, p=0.046). Incidence of critical bleeding events was higher in the SIC group (17% versus 10%, p=0.009). More patients in the SIC group required red blood cell transfusion (63% versus 53%, p=0.009). There was no significant difference in other outcomes. SIC was prevalent in 31% of patients at ICU admission and was associated with higher ICU-mortality, fewer days alive and free of vasopressors, more critical bleeding events and more red blood cell transfusions.

Abstract Acute myeloid leukemia (AML) is an aggressive hematologic cancer characterized by proliferation of immature myeloblasts 1 . It shows profound molecular heterogeneity, which has been primarily studied through genetic abnormalities, providing the basis for disease classification, prognostication, and therapeutic choice 2–8 . However, genetic factors alone may not fully explain AML pathogenesis and diversity, while leaving the role of abnormal epigenome, particularly chromatin state, largely unexplored in a large cohort of patients. Here we show that AML is classified into 16 subgroups with distinct chromatin accessibility profiles based on ATAC-seq in 1,563 AML cases, derived from the encyclopedia of chromatin in AML (eCHROMA AML) dataset, including novel AML subgroups not previously recognized in conventional genomic classifications. By integrating multi-omics analyses of genome, transcriptome, and major histone marks, we show that these epigenetic subgroups exhibit unique features in clinical presentation, gene mutations, differentiation states, gene expression, and super-enhancer profiles, which are validated across independent cohorts. Single-cell sequencing demonstrates the presence of subgroup-specific ATAC signatures that are shared by all leukemic cells, confirming the key role of the epigenome in the ATAC-based classification. Mechanistically, each subgroup is associated with a distinct gene regulatory network centered on key transcription factors, where subgroup-specific super-enhancers play a pivotal role. These ATAC subgroups also have prognostic significance independent of genomic classification, and help reveal unexpected drug sensitivities. In summary, ATAC-based chromatin profiling in this large sample set, combined with multi-omics data, provides new insights into AML pathogenesis beyond genomic profiling and also serves as an invaluable resource for AML research.

ObjectiveTo compare longitudinal speech outcomes at ages 5 and 10 years in foreign-born and Swedish-born children with cleft palate with or without cleft lip (CP ± L), and assess impact of cleft type, additional diagnosed conditions, sex, and age at completed primary palatal surgery.DesignLongitudinal, registry-based cohort study.SettingRegional public care university hospitals in Sweden.Participants723 children (143 foreign-born, 580 Swedish-born) with CP ± L.InterventionsPrimary and secondary palatal surgery, and speech-language therapy.Main outcome measuresDichotomized outcomes of velopharyngeal competence (VPC), percentage of consonants correct (PCC), and non-oral speech errors, and received secondary palatal surgery and speech-language therapy.ResultsA significantly lower proportion of foreign-born than Swedish-born 5-year-olds had VPC (75% vs. 85%, p = .007), age-appropriate consonant production (25% vs. 57% p < .001), and no non-oral speech errors (67% vs. 84%, p < .001). Speech improved longitudinally, yet a significantly lower proportion of foreign-born children had VPC (86% vs. 94%, p = .002), age-appropriate consonant production (52% vs. 76%, p < .001), and no non-oral errors (82% vs. 93%, p < .001) at 10 years. The difference in VPC at age 5 and in all speech outcomes at age 10 was associated with higher age at primary surgery in foreign-born children. They also had higher rates of secondary palatal surgery (p < .001) and speech-language therapy (p < .001) than Swedish-born peers.ConclusionsLater primary palatal surgery in foreign-born children was associated with poorer speech outcomes at 10 years. Early primary palatal surgery and continued follow-up are essential to optimize speech development.

Alzheimer’s disease (AD) is the most common cause of dementia and a growing healthcare challenge. Amyloid-targeting therapies (ATT) may slow progression, but implementation is limited by logistical and economic barriers. As primary care is the first contact for most patients with cognitive concerns, quantifying treatment eligibility in this setting is essential. The purpose of this study was to estimate the proportion of primary care patients presenting with cognitive symptoms who are eligible for ATT. This cohort study included patients presenting with cognitive symptoms in primary care across the region Skåne, in southern Sweden, recruited between January 2020 and April 2025. Stepwise exclusion criteria based on clinical diagnosis, comorbidities, and treatment contraindications were applied, in alignment with appropriate use recommendations for lecanemab and donanemab, respectively. Eligibility was further refined using CSF biomarkers (Aβ42/40 ratio), cognitive performance, and MRI findings. In a full diagnostic work-up of 607 patients with sequential exclusions, 86 patients (14.2%) and 78 patients (12.8%) ultimately met the eligibility criteria for lecanemab and donanemab, respectively. Due to comorbidities, medication use, and age/BMI, around 1/3 of the original population was excluded. Most ineligible patients met more than one exclusion criterion. The eligible population was 63% female, mean age 77 years. Around 65% of the individuals had mild cognitive impairment (MCI), and 35% mild dementia. About 13-14% of primary care patients evaluated for cognitive complaints were eligible for ATT. Compared with clinical trials, the eligible population was older and consisted of more women. BioFINDERPrimary Care study (NCT06120361, Registration date 2 November 2023 https//biofinder.se).

To explore the meaning of lived experiences of women with a hereditary risk of breast cancer who participate in surveillance of their breasts with magnetic resonance imaging. Hermeneutic phenomenology. Interviews on two occasions were made with 14 women in the surveillance programme. The verbatim transcripts were analysed according to van Manen. The analysis was an insightful iterative process and provided a sensitive understanding of the meaning of lived experiences. Women's lived experiences were that surveillance was constantly present in their lives. Their experiences implied 'needing to put on a mantle', 'not wanting to go through this alone' and 'wanting to keep their breasts'. The women created an invisible mantle that they put on when necessary to protect themselves. They wished to be open about their experiences and longed to be truly listened to. The women needed confirmation that they had the ethical right to their values and the choice they had made to participate in the programme. They were aware of the consequences of their decision, but they valued their breasts as a part of their identity and wanted to keep their breasts to remain who they were. The understanding of the meaning of lived experiences of women in surveillance is vital for the development of person-centred care practice. Person-centredness should be integrated in the surveillance programme guidelines. The study provides an understanding of the meaning of surveillance from the perspective of women. The evidence that women want to keep their breasts to preserve themselves as a person questions the norm of prioritising the bio-medical perspective in women's care. COREQ. No patient or public contribution.

Abstract All animals age. However, aging is a heterogeneous process and individual organisms age differently. Moreover, within the same organism, cells or organs do not age at the same time or speed. For instance, although neurodegeneration is a key trait of aging, neurological symptoms normally manifest long after multiple indicators of aging in peripheral tissues. The genetic determinants of aging remain poorly understood. Mutations in leucine-rich repeat kinase 2 (LRRK2) are major genetic risk factors for Parkinson’s disease (PD). By analyzing PD patients and mice with LRRK2 gain of function mutation (LRRK2 GoF ), we demonstrate that PD is an accelerated aging disease characterized by systemic low-grade STING-dependent inflammation (inflammaging) that first manifests in the periphery then disrupts the blood brain barrier and progresses to the brain resulting in neurodegeneration. Mechanistically, we demonstrate that a primary consequence of aging or Lrrk2 GoF is endolysosomal decline. This results in the cytosolic build-up of extraneous self-DNA and subsequent shedding of DNA-containing extracellular vesicles thereby triggering the cGAS- STING pathway cell-intrinsically and intercellularly in distant host cells. This study unveils the cGAS-STING pathway and LRRK2 GoF as key determinants and potential targets for preventive or therapeutic strategies against accelerated aging, inflammaging and neurodegeneration.

Incretins such as glucagon-like-peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play crucial roles in postprandial glucose management. GLP-1 and GIP stimulate insulin release in conjunction with meals and are responsible for up to 75% of the insulin secretion. Incretins are therefore very important for maintenance of normal blood glucose levels. Dairy foods are crucial for adequate nutrition at a young age, and skim milk powder in infant formula is frequently used. However, stored skim milk powder has been found to reduce the islet cell mass of the pancreas in experimental studies. The aim of this study was to investigate the potential effect of stored skim milk powder on incretin release from intestinal cells. Intestinal endocrine cells (STC-1 cells) were incubated with fresh and stored skim milk powder, the latter containing 70-fold higher amounts of Maillard reactants. The cells' viability, proliferation, and release of incretins were measured after 24 h. Both the viability and proliferation of the STC-1 cells decreased significantly during incubation with stored skim milk powder. The release of GLP-1 and GIP was suppressed in a dose-dependent manner by stored skim milk powder compared with fresh milk powder. The clinical significance for the development of diabetes and obesity, due to this observed weak release of incretins induced by stored skim milk powder containing high amount of Maillard reactants, requires further studies.

Individuals affected with a psychiatric disorder typically have elevated genetic risks for other mental disorders beyond the one from which they are currently suffering. From this observation it is possible to develop the concept of genetic specificity , defined in a cohort of affected individuals, as the proportion of the genetic risk for a set of psychiatric conditions due specifically to the disorder from which they are affected. To investigate this phenomenon, we studied all Swedish individuals born 1950 to 1995 with one of nine disorders ascertained from national registers: schizophrenia (SZ), bipolar disorder (BD), alcohol use disorder (AUD), ADHD, Autism spectrum disorder (ASD), PTSD, major depression (MD), anxiety disorder (AD) and drug use disorder (DUD). Genetic liabilities were calculated from family genetic risk scores. Specificity of genetic risk was defined as the proportion of genetic risk to all nine disorders due to genetic risk to the diagnosed disorder. The specificity of genetic risk varied from 29.5% for DUD to 73.1% for SZ. With increasing age at onset (AAO), genetic specificity decreased for BD and increased for PTSD. Higher levels of recurrence increased genetic specificity for all disorders with the largest effects on BD and ADHD. Genetic specificity was highest with hospitalized cases for BD while for PTSD, AD and MD, specificity was highest in primary care cases. Common psychiatric disorders differ widely in their degrees of genetic specificity. The genetic specificity for many disorders can vary substantially as a function of AAO, level of recurrence, and site of treatment.