Linköping University Hospital (Swedish: Universitetssjukhuset i Linköping; abbreviated US in Sweden) is a university hospital in Linköping, Sweden, operated by Östergötland County. Its scientific activities are integrated into the medical faculty (Hälsouniversitet) of Linköping University.The hospital has all specializations except organ transplantation. Excellent areas are, for example, burn care, where the hospital together with Uppsala University Hospital is responsible for national care (rikssjukvård). It has been ranked three times as "best hospital" in Sweden by the journal Dagens Medicin, and in 2019 was listed as the third best Swedish university hospital.The hospital has about 4,900 employees and 600 care places.
MGMT promoter methylation is a key predictive biomarker for response to alkylating agents in glioblastoma. However, there is no consensus regarding optimal analytical method or cut-off. This study aimed to define a clinically relevant survival-based cut-off value for MGMT using a standardized pyrosequencing assay. Patients from five Swedish university hospitals with MGMT promoter methylation status analyzed using the Therascreen MGMT Pyro Kit, investigating CpGs 76–79, were identified. Glioblastoma patients treated with radiotherapy and concomitant temozolomide were selected from the Swedish CNS Tumor Registry. Quantitative MGMT status, both mean value and percentage of methylation for each individual CpG, was analyzed using an unsupervised bimodal normal mixture model and a survival-informed approach adjusted for established prognostic factors. A total of 451 patients were included. The unsupervised model identified a cut-off at ≥ 11
BACKGROUND:HYPO-RT-PC is a phase 3 trial comparing ultra-hypofractionated and conventionally fractionated radiotherapy in intermediate-to-high-risk localised prostate cancer. This 10-year update reports long-term efficacy and toxicity outcomes. METHODS:In this open-label, randomised, phase 3, non-inferiority trial done in ten centres in Sweden and two in Denmark, we recruited men aged 75 years or younger with intermediate-risk or high-risk prostate cancer and a WHO performance status between 0 and 2. Previous or current androgen deprivation therapy was not permitted. Patients were randomly assigned (1:1) to ultra-hypofractionated radiotherapy (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventionally fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). Randomisation was performed with a minimisation algorithm balancing T stage, Gleason score, prostate-specific antigen, and trial centre. The primary endpoint was failure-free survival, defined as time from randomisation to the first occurrence of biochemical failure, evidence of clinical progression, initiation of androgen deprivation therapy, or death from prostate cancer, analysed in the per-protocol population. The non-inferiority margin was 4% at 5 years and had previously been met, corresponding to a critical hazard ratio (HR) limit of 1·338. Toxicity was assessed using the Radiation Therapy Oncology Group morbidity scale. Here, we report long-term efficacy and safety results at 10 years. The trial is registered with the ISRCTN registry, ISRCTN45905321, and is closed. FINDINGS:Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionated radiotherapy (n=602) or ultra-hypofractionated radiotherapy (n=598). Ten patients withdrew consent, eight were found to be ineligible, and two died of reasons unrelated to prostate cancer. 1180 patients constituted the per-protocol population (591 in the conventional fractionation group and 589 in the ultra-hypofractionation group). After a median follow-up of 10·6 years (IQR 9·0-13·0) in the conventional fractionation group and 10·7 years (9·1-12·7) in the ultra-hypofractionation group, 205 and 178 primary events were observed, respectively. 10-year failure-free survival was 65% (95% CI 61-69) in the conventionally fractionated group and 72% (68-76) in the ultra-hypofractionated group. The adjusted HR for the primary endpoint was 0·84 (95% CI 0·69-1·03; Cox regression analysis), confirming non-inferiority. The 10-year cumulative incidence of late grade 2 or worse genitourinary toxic effects was 30% (95% CI 26-34) in the conventional fractionation group and 28% (24-32) in the ultra-hypofractionated group (HR 1·01, 95% CI 0·81-1·25; p=0·95). For late grade 2 or worse gastrointestinal toxic effects, the corresponding figures were 14% (95% CI 11-18) and 14% (11-17; HR 0·94, 95% CI 0·70-1·28; p=0·72). INTERPRETATION:This 10-year follow-up confirms the non-inferiority of the ultra-hypofractionated radiotherapy regimen compared with the conventionally fractionated, with similar toxicity profiles. The findings support the seven-fraction schedule as a safe, effective, and practical standard-of-care option for patients with intermediate-risk prostate cancer. FUNDING:The Nordic Cancer Union, the Swedish Cancer Society, the Swedish Research Council, the Swedish Prostate Cancer Association, and Cancerforskningsfonden i Norrland.
Importance:Elevated blood pressure (BP) in adolescence has been linked to higher risk of cardiovascular disease mortality, as well as surrogate markers of atherosclerosis, such as carotid intima-media thickness and coronary artery calcification. However, these markers do not fully capture the complex spectrum of subclinical atherosclerotic cardiovascular disease. Objective:To examine the association between systolic and diastolic BP in adolescence and atherosclerosis in middle age, measured by coronary computed tomography angiography (CCTA). Design, Setting, and Participants:This population-based cohort study conducted in Sweden linked BP data from the Swedish Military Conscription Register (1972-1987) during adolescence to atherosclerosis data from the Swedish Cardiopulmonary Bioimage Study (2013-2018) during middle age. Data analyses were performed in May 2025. Exposure:Adolescent BP was categorized according to the 2025 American College of Cardiology/American Heart Association (ACC/AHA) and the 2024 European Society of Cardiology (ESC) guidelines. Main Outcomes and Measures:The primary outcome was coronary atherosclerosis, evaluated via CCTA stenosis. The associations were analyzed using multinomial logistic regression, adjusted (marginal) prevalences, and restricted cubic splines. Results:A total of 10 222 men with mean (SD) age of 18.3 (0.5) years at baseline and median (IQR) age of 57.8 (53.4-61.2) years at follow-up were included. At baseline, mean (SD) systolic BP (SBP) and diastolic BP (DBP) were 127.6 (10.7) mm Hg and 68.3 (9.5) mm Hg, respectively. After a median (IQR) follow-up of 39.5 (35.2-42.8) years, 4159 participants (45.7%) had 1% to 49% coronary stenosis and 784 (8.6%) had 50% or greater coronary stenosis. Elevated BP in adolescence was associated with coronary stenosis in a dose-response fashion. Adolescents with stage 2 hypertension had a higher risk of severe coronary stenosis (≥50%), with an odds ratio of 1.84 (95% CI, 1.40-2.42) and an adjusted prevalence of 10.1% (95% CI, 8.6%-11.5%) compared to those with normal BP (adjusted prevalence, 6.9%; 95% CI, 5.7%-8.1%). Elevated BP categories according to the 2025 ACC/AHA (120-129/<80 mm Hg) and the 2024 ESC (120-139/70-89 mm Hg) were associated with severe coronary atherosclerosis in middle age. The association was stronger for SBP than for DBP. Conclusions and Relevance:In this population-based cohort study, higher BP levels in adolescence were associated with a dose-dependent higher risk for atherosclerosis in middle age, particularly for severe coronary atherosclerosis. Excess risks of atherosclerosis were even evident in the elevated BP range in adolescence as defined by the 2025 ACC/AHA and 2024 ESC BP guidelines.
Acute myeloid leukaemia (AML) is an aggressive blood cancer characterized by the unregulated proliferation of immature myeloblasts. Gene mutations have been shown to have a large effect on pathogenesis, inter-tumour heterogeneity and clinical outcomes in AML1-8; however, the role of epigenetic alterations in these respects has been investigated less extensively. Here we use ATAC-seq (assay for transposase-accessible chromatin with sequencing) in a cohort of 1,563 individuals with a recent diagnosis of AML (the 'eCHROMA' cohort) to show that AML can be classified into 16 subgroups on the basis of chromatin accessibility profiles. Multiomics analyses of gene mutations, the transcriptome, DNA methylation and histone marks show that these ATAC subgroups exhibit distinct driver mutations, differentiation states, gene expression, DNA methylation and super-enhancer profiles, and are also associated with clinical outcomes. These findings were validated in independent cohorts. Single-cell ATAC sequencing reveals that all leukaemic cells in each subgroup share a common chromatin accessibility profile, which suggests that subgroup-specific epigenomic fingerprints underlie the ATAC-based classification. Mechanistically, the subgroups have distinct gene-regulatory networks that are driven by the activities of key transcription factors in haematopoiesis, and in which subgroup-specific super-enhancers have a pivotal role. Multiomics single-cell analysis further reveals deregulated trajectories of differentiation coupled with chromatin accessibility and gene expression. Notably, ATAC subgroups have an independent prognostic effect, compared with genomic classification, and are associated with particular drug sensitivities. In summary, ATAC-based chromatin profiling, combined with multiomics data, provides insights into AML pathogenesis beyond genomics and constitutes a valuable resource for AML research.
Introduction:Treatment of chronic type B aortic dissection associated aneurysms where key vessels originate from both the true and false lumens is technically challenging. Further aneurysm formation may require new interventions after initial treatment. Innovative endovascular techniques can lead to successful treatment. Report:A 74 year old man with a type B dissection was treated with an urgent femorofemoral crossover bypass (in 2001) and surgical graft in the thoracic aorta (in 2003). Due to the combination of a chronic type B dissection and a right sided common iliac artery aneurysm, he was subsequently treated with two separate Nellix endoprotheses (Endologix Inc., Irvine, CA, USA) in the infrarenal aorta. The Nellix endoprotheses were deployed in the true and the false lumens (in 2015). Eight years later, he required another intervention due of progressive enlargement of the thoracic aorta between the surgical graft and Nellix endoprotheses. The chosen treatment was a customised two inner branch thoracic endovascular aortic repair (TEVAR) and four inner branch endovascular aortic repairs, in combination with long Viabahn stent grafts from the TEVAR to the old Nellix endoprothesis in the false lumen (in 2021). All stent grafts were patent at three years of follow up. Discussion:This case report presents a patient in whom former techniques were used as an initial treatment for a chronic type B dissection with aneurysm formation complicating further treatment. This report highlights what can be achieved with careful planning in combination with new available devices, resulting in a good individual outcome.
