Abstract Background and Aims Hydralazine-isosorbide dinitrate (H-ISDN) has shown benefit in earlier randomized trials of patients with reduced left ventricular ejection fraction (LVEF) and chronic heart failure. This trial tested if H-ISDN could reduce worsening heart failure or mortality in patients with chronic heart failure with reduced ejection fraction (HFrEF) receiving contemporary treatment. Methods The Hydralazine-Isosorbide Dinitrate in Patients With Chronic Heart Failure Trial (H-HeFT) was a multicentre, randomized (1:1), double-blind, placebo-controlled trial in patients with HFrEF at 23 Danish hospitals (New York Heart Association class II–IV, elevated N-terminal pro-B-type natriuretic peptide and LVEF ≤40%). Target treatment was hydralazine 75 mg/isosorbide dinitrate 40 mg three times a day (t.i.d). The primary endpoint was a composite of hospitalization with worsening heart failure, an urgent outpatient visit resulting in intravenous/metolazone therapy for heart failure, heart transplantation, left ventricular assist device implantation, or death. Secondary endpoints included components of the primary outcome. Results Overall, 592 predominantly White patients (median age 72 years, 18% women) were randomized with a mean follow-up of 3.7 years. The primary outcome occurred in 90 of 294 patients (30.6%) in the H-ISDN group and in 91 of 298 patients (30.5%) in the placebo group [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.67–1.21; P = .48]. There were 57 deaths in the H-ISDN group vs 72 in the placebo group (HR 0.72; 95% CI 0.51–1.02); worsening heart failure events occurred in 52 vs 47 patients (HR 1.01; 95% CI 0.68–1.50). Conclusions Hydralazine-isosorbide dinitrate did not change the incidence of the composite endpoint of heart failure events or death in patients with heart failure and LVEF ≤40%.
Background Hospitalisations represent major clinical events in cirrhosis, yet prediction based on clinical variables alone remains limited.Objective Given the role of the gut microbiome in disease progression, we evaluated whether gut metagenomic profiles are associated with 90-day hospitalisation and provide additional prognostic information beyond clinical features in a multinational outpatient cirrhosis cohort.Design We enrolled 679 outpatients with cirrhosis from seven countries and performed stool metagenomic profiling, including taxonomic, functional pathway and antibiotic resistance gene (ARG) analyses, with 90-day follow-up. Machine learning models were developed using clinical and microbiome features for predicting non-elective hospitalisations.Results 25% of patients required hospitalisation within 90 days. Hospitalised patients had more advanced cirrhosis, lower microbial diversity which was consistent across countries despite marked variation in microbial composition. Diet had a modest influence on microbiome structure. After adjustment for country, disease severity, cirrhosis aetiology and treatment, 19 bacterial species remained independently associated with hospitalisation, including enrichment of Enterococcus faecium and Veillonella rogosae and depletion of multiple commensal taxa. Functional profiling demonstrated coordinated taxonomic-functional alterations focusing on complex carbohydrate degradation pathways, glycan biosynthesis, lipid and nucleotide salvage pathways and association with antimicrobial resistance mechanisms. The combined clinical-microbiome model significantly outperformed both the clinical-only (area under the curve (AUC) 0.79) and microbiome-only (AUC 0.74) models, achieving an AUC of 0.84.Conclusion Gut microbiome composition and function are associated with short-term hospitalisation risk and provide additional prognostic information beyond clinical variables in a multicountry cohort. Hospitalisation, regardless of country, is characterised by loss of short-chain fatty acid-producing taxa, functional shifts, ARG and pathway changes.
Frailty is common in multiple myeloma (MM) and is associated with inferior outcomes. Knowledge on quality of life (QoL) primarily originates from clinical trials, where frail patients are often not included. In this nationwide, longitudinal observational study, QoL was assessed in 681 Danish patients with newly diagnosed MM (NDMM) or relapsed or refractory MM (RRMM) with symptomatic disease using patient-reported outcomes collected over 2 years of follow-up between 2017 and 2021. Patients were categorized as fit, intermediate-fit or frail according to the International Myeloma Working Group (IMWG) frailty score. Preselected QoL domains from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30), the Chemotherapy-Induced Peripheral Neuropathy module (EORTC QLQ-CIPN20) and the Short-form health survey (SF12) questionnaires were analysed using linear mixed models and interpreted in terms of clinical relevance. At inclusion, frail patients reported clinically relevant lower global QoL and physical functioning, and more fatigue compared to fit patients. Frail NDMM patients reported improvement in global QoL and pain during follow-up, whereas physical functioning and fatigue remained unchanged. Frail RRMM patients reported unchanged global QoL and fatigue, and deterioration in physical functioning and more pain during follow-up. Our results based on a real-world population show that QoL findings from clinical trial populations cannot directly be applied to frail patients.
BackgroundNear-infrared autofluorescence (NIRAF) has been introduced as an adjunct to improve parathyroid gland (PG) identification during thyroid surgery. The extent to which its intraoperative application is influenced by a learning curve remains unclear. This study aimed to evaluate and quantify a potential learning curve in NIRAF-guided thyroid surgery.Materials and methodsWe conducted a retrospective cohort study including all consecutive patients undergoing image-based NIRAF-guided thyroid surgery between 2021 and 2023 at two Danish ENT departments. After each procedure, all surgeons completed a standardized form detailing the manner in which NIRAF was applied. The primary outcome was the minimum number of procedures per surgeon needed to achieve consistent surgical behavior, defined as systematic use of NIRAF or a stable pattern of PG autotransplantation.ResultsA total of 130 patients underwent NIRAF-guided thyroid surgery, performed by two surgeons. Near-infrared autofluorescence was most often utilized on the removed specimen (94.6%), before dissection of the lower thyroid pole (93.1%) and before latero-posterior dissection (88.5%). It was less likely to be utilized before upper thyroid pole dissection (62.3%). For both surgeons, NIRAF application was not systematic in the early phase but became increasingly consistent over time (α = 11,0 (95% CI: 3,5-18,6), p=0,013 and α = 5,6 (95% CI: 0,03-11,2), p=0.049, respectively). Initially, both surgeons demonstrated remarkably high PG autotransplantation rates, which declined over time (α= -3,9 (95% CI: -7,9 - 0,07), p=0,053 and α =-4,8 (95% CI: -8,1 - (-1,6)), p=0.01, respectively). Surgeon no. 1 adopted systematic NIRAF use after a minimum of 30 procedures, while surgeon no. 2 displayed consistent behavior with regard to PG autotransplantation after a minimum of 30 procedures.ConclusionsThis study demonstrates a clear learning curve in NIRAF-guided thyroid surgery. A minimum of 30 procedures per surgeon was required to establish consistent surgical practice, either in terms of systematic NIRAF application or a stable pattern of PG autotransplantation. These findings underscore the importance of structured implementation strategies and targeted training when integrating the NIRAF technology into routine surgical practice.
Background Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease, but its relationship with aortic valve calcification (AVC) remains unclear.Objective The present study aims to investigate whether the presence of DM is associated with a higher prevalence of AVC.Methods This cross-sectional study combines two large multicentre cohorts: Steno INTEN-CT (EUCT2022-500143-21-01) and DANCAVAS (NCT03946410). Participants with available AVC scores assessed by cardiac CT were included in the present study. Propensity score matching was performed to compare participants with DM to those without DM. AVC was analysed as a binary outcome (0 vs >0) using logistic regression with clustering by matched pairs.Results After propensity matching of participants with and without DM, 14 182 participants (7091 matched pairs) were included. Mean age was 67±4 years in the no-DM group compared with 66±4 years in the DM group, p<0.001. AVC was present in 54% and 52% of individuals without and with DM, respectively (p=0.003). In a multivariate logistic regression analysis, DM was not associated with higher AVC prevalence (OR=0.88, 95%CI 0.80–0.96, p=0.004) while male sex, older age, higher body mass index, hypertension, smoking, higher low density lipoprotein cholesterol and statin use remained independently associated with higher prevalence of AVC. An interaction between statin use and DM was found in the association with AVC (p for interaction 0.018), suggesting a potentially stronger association between statin use and AVC among individuals without DM.Conclusion In this large cross-sectional cohort of 14,182 individuals without known cardiovascular disease, the presence of DM was not associated with higher prevalence of AVC. Instead, higher prevalence of AVC was independently associated with cardiovascular risk factors that frequently coexist with DM. These findings suggest that the previously reported relationship between DM and AVC may, at least partly, be related to accompanying cardiovascular risk factors rather than DM per se.
