Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure.

Background: Little is known about the associations between choline metabolites (total choline, phosphatidylcholine, and glycine) and the incidence of heart failure (HF).

Objectives: The purpose of this study was to assess the associations of choline metabolites with incident HF and examine the effect modification by genetic susceptibility.

Methods: This prospective cohort study followed 245,072 participants from the UK Biobank from baseline (2006-2010) until March 30, 2023.

Improved outcomes after groin hernia surgery in Sweden between 1992 and 2021: Swedish Hernia Register.

Purpose: Surgery for groin hernia is one of the most common operations in the world. Therefore, research concerning the outcomes of groin hernia surgery is extremely important both for the individual patient as well as for those providing the healthcare funding. The aim of this study is to evaluate the outcomes of hernia surgery in Sweden over a 30 year time period, from 1992 to 2021.

Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.

Biomarkers.

Background: Peak-width of skeletonized mean diffusivity (PSMD) is an emerging biomarker of cerebral small vessel disease (cSVD)-related vascular contributions to cognitive impairment and dementia (VCID). Higher PSMD values reflect greater white matter microstructural damage, and prior research has related PSMD to sporadic and monogenic forms of cSVD and worse cognitive function. Therefore, we proposed PSMD as a risk stratification biomarker for VCID.

1-year data on patient-reported outcome is enough after surgery for degenerative cervical myelopathy: a cohort study from the Swedish Spine register.

Background And Purpose:  Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adults. Repeated follow-ups after surgery are resource consuming. The aim was to examine whether patient-reported outcome measures (PROMs) change after the first year.

Biomarkers.

Background: [F]FDG PET is essential since it allows us to differentiate between different dementia disorders/types, revealing distinct neurodegenerative patterns in those predisposed to the condition. Individuals with Autosomal Dominant Alzheimer's Disease (ADAD) have a predictable age of onset, enabling the study of cognitive and pathological changes before clinical manifestation. Our objective was to investigate temporal course and regional links between cognition and glucose metabolism as a measure of early synaptic impairment in ADAD.

Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS.

Background: The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established.

Determinants of growth differentiation factor 15 plasma levels in outpatients with peripheral arterial disease.

Background: Growth differentiation factor 15 (GDF-15) is a robust prognostic biomarker in patients with cardiovascular (CV) disease, and a better understanding of its clinical determinants is desirable. We aimed to study the associations between GDF-15 levels and in outpatients with peripheral arterial disease (PAD).

Methods: An explorative cross-sectional study (Study of Atherosclerosis in Vastmanland, Västerås, Sweden) included 439 outpatients with carotid or lower extremity PAD.

Efficacy and safety of the PHIL embolic agent in the treatment of intracranial dural arteriovenous fistulas: results of the PHIL-dAVF study.

Background And Purpose: Embolization is the first-line treatment for dural arteriovenous fistulas (dAVF). The precipitating hydrophobic injectable liquid (PHIL) embolic agent is a non-adhesive copolymer with specific features and endovascular behavior. This study assessed its safety and efficacy in a prospective real-life cohort.

Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting.

Purpose: We aimed to characterize genomic alterations with potential prognostic or predictive significance in patients with metastatic triple-negative breast cancer (mTNBC) treated with chemotherapy in a real-world setting.

Patients And Methods: Next-generation sequencing with FoundationOne® CDx was conducted primarily on primary tumor tissue from 112 consecutive patients with mTNBC. Genomic alterations were subdivided into canonical oncogenic pathways and noted for their involvement in homologous recombination deficiency (HRD).

Have People Treated With Antihypertensives Been Diagnosed With Hypertension? A Cross-Sectional Study in Stockholm, Sweden.

Purpose: Studies on antihypertensive treatment are important, as hypertension remains the major risk factor for cardiovascular morbidity and premature death. However, antihypertensive medicines are also used for other conditions, and the use of these medicines as a proxy for a diagnosis of hypertension might lead to misclassification in pharmacoepidemiological studies. This study aimed to investigate to what extent people dispensed antihypertensive medicines have been diagnosed with hypertension.

Pelvic Organ Prolapse Repair Using Robotic-Assisted Sacral Hysterocolpopexy vs Vaginal Surgery with the Uphold™ System: 1-Year Clinical Outcomes.

Introduction And Hypothesis: The aim of the study was to compare clinical outcomes when using robotic-assisted sacral hysterocolpopexy (RASC) and vaginal surgery using the Uphold™ Vaginal Support System mesh for pelvic organ prolapse repair.

Methods: This was a nonrandomized, prospective, multicenter study in which 72 women underwent RASC, and 73 Uphold™ surgery, for apical prolapse (POP-Q C ≥ stage II). Anatomical outcomes were assessed using the Pelvic Organ Prolapse Quantification (POP-Q) system.

What are the important risk factors for excessive daytime sleepiness in a population-based cohort?

Excessive daytime sleepiness (EDS) is a common complaint in the general population and is associated with cardiovascular disease and increased mortality. We aimed to investigate whether sleep duration is related to excessive daytime sleepiness in the general population, both in itself and in combination with other factors. We performed a cross-sectional analysis in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort (n = 27,976; 14,436 females; aged 50-64 years) to assess how sleep-related factors along with anthropometric, lifestyle, socioeconomic factors as well as somatic disease and psychological distress, were related with EDS assessed by the Epworth sleepiness scale (ESS).

Adherence to guidelines for incidental pulmonary nodules: insights from a Nordic survey.

Background And Purpose: There is limited data on the real-world management of incidental pulmonary nodules (IPN). In this article, we review current practices and adherence to international guidelines in the Nordic countries.

Materials And Methods: This non-interventional, observational survey study based on an online survey consisting of 13 questions.

Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations.

The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells.

Completion of registration of risk factor variables during telephone vs on-site follow-up after myocardial infarction: a nationwide observational study in 101 199 patients from contemporary clinical practice in Sweden.

Objectives: The objective of this study was to assess the completeness of registration of secondary preventive variables comparing on-site visits with telephone consultations during follow-up after myocardial infarction.

Design: This was an observational study based on the Swedish quality registry SWEDEHEART.

Setting And Outcome Measures: We analysed the proportion of missing values for major secondary preventive target data registered at the 2-month and 1-year follow-up visits, during 2006-2022 (n=101 199).

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study.

Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan.

Ligand and Residue Free Energy Perturbations Solve the Dual Binding Mode Proposal for an AAR Partial Agonist.

Adenosine receptors, particularly AAR, are gaining attention for their role in pathological conditions such as cancer immunotherapy, prompting the exploration for promising therapeutic applications. Despite numerous selective AAR antagonists, the lack of selective full agonists makes the partial agonist BAY60-6583 one of the most interesting activators of this receptor. Recent cryo-EM structures have univocally revealed the binding mode of nonselective ribosidic agonists such as adenosine and its derivative NECA to AAR; however, two independent structures with BAY60-6583 show alternative binding orientations, raising the question of which is the physiologically relevant binding mode.

Infrared Spectroscopic Electronic Noses: An Innovative Approach for Exhaled Breath Sensing.

Gastric cancer remains a leading cause of cancer-related mortality, requiring the urgent development of innovative diagnostic tools for early detection. This study presents an integrated infrared spectroscopic electronic nose system, a novel device that combines infrared (IR) spectroscopy and electronic nose (eNose) concepts for analyzing volatile organic compounds (VOCs) in exhaled breath. This system was calibrated using relevant gas mixtures and then tested during a feasibility study involving 26 gastric cancer patients and 32 healthy controls using chemometric analyses to distinguish between exhaled breath profiles.

Myocardial Fibroblast Activation After Acute Myocardial Infarction: A Positron Emission Tomography and Magnetic Resonance Study.

Background: Myocardial fibrosis is a key healing response after myocardial infarction driven by activated fibroblasts. Gallium-68-labeled fibroblast activation protein inhibitor ([Ga]-FAPI) is a novel positron-emitting radiotracer that binds activated fibroblasts.

Objectives: The aim of this study was to investigate the intensity, distribution, and time-course of fibroblast activation after acute myocardial infarction.

Swedish Genome-Wide Haplotype Association Analysis Suggests Breast Cancer Loci with Varying Risk-Modifying Effects.

To find support for risk-modifying genes in breast cancer, a haplotype GWAS in sporadic breast cancer cases was undertaken. The results were compared with the results from previous analyses in familial cases and all cases from the same Swedish cohort. In total, 2550 women with sporadic invasive breast cancer and 5021 healthy controls were included in a sliding-window haplotype GWAS using PLINK 1.

DHODH Inhibition Suppresses and Inhibits the Growth of Medulloblastoma in a Novel In Vivo Zebrafish Model.

Background/objectives: Medulloblastoma (MB) is the most common high-grade paediatric brain tumour, with group 3 MB patients having the worst prognosis. A high prevalence of group 3 tumours shows overexpression of the oncogene, making it a potential therapeutic target. However, attempts to directly inhibit have so far demonstrated limited success.