Gentofte Hospital

The efficacy and safety of monopolar biphasic focal pulsed field ablation (F-PFA) in close proximity to the atrioventricular (AV) node remain unknown. This study aimed to describe the effect of direct or indirect F-PFA application at the AV junction. In pigs, F-PFA (Centauri, CardioFocus) was applied directly at the AV junction (n = 3) and indirectly from within the aortic noncoronary cusp (NCC) (n = 5), followed by macroscopic gross and histologic analysis. In 5 patients planned for a pace-and-ablate strategy, F-PFA was applied at the AV junction. In 1 patient with recurrent para-Hisian atrial tachycardia and previously failed ablation, F-PFA was applied from within the NCC. In pigs, direct F-PFA applications at the AV junction were associated with junctional beats and resulted in complete AV block after 2-3 F-PFA applications. Tissue histology revealed a lesion depth of approximately 8 mm with minor hemorrhage and leukocyte infiltration. F-PFA from within the NCC resulted in a transient increase in the AV node's Wenckebach cycle length and 1 pig had transient AV block, which recovered within 10 minutes. In 5 patients undergoing pace-and-ablate strategy, F-PFA applications at the AV junction resulted in sustained AV block. In 1 patient, application of F-PFA from within the NCC resulted in termination and noninducibility of a recurrent incessant para-Hisian atrial tachycardia without AV block. There were no immediate or long-term complications. F-PFA directly at the AV junction results in nonreversible AV block. F-PFA from within the NCC may represent a promising strategy for treating para-Hisian arrhythmias while preserving AV conduction.

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality globally. Low-density lipoprotein cholesterol is a causal risk factor for atherosclerotic cardiovascular disease, with multiple classes of cholesterol-lowering therapies effective at reducing atherosclerotic cardiovascular disease risk. Despite robust efficacy data from randomized trials, real-world implementation of guideline-recommended lipid-lowering therapies is suboptimal. Barriers to the implementation of guideline lipid-lowering therapy recommendations exist at the healthcare systems level, the medical therapy level, and the patient level. A combination of strategies, including the incorporation of quality improvement and cost-effectiveness analysis among payers, pharmacist-based educational initiatives, digital health tools directed towards patients, the simplification of drug regimens via polypill, and emerging novel therapies, including PCSK9 gene silencing and editing technologies, may bridge these implementation gaps. This review highlights challenges and solutions to alleviating barriers to optimal implementation of guideline-recommended lipid-lowering therapies.

Left ventricular diastolic dysfunction (LVDD) is common in chronic kidney disease (CKD) and is suggested to be linked to worse renal prognosis. We investigated the associations between both the ratio of early mitral inflow velocity to early diastolic tissue velocity (E/e') and LVDD grades with the risk of end-stage kidney disease (ESKD). This prospective cohort study included individuals with non-dialysis-dependent CKD from the nephrology outpatient clinics at Rigshospitalet and Herlev-Gentofte hospital, Copenhagen. All participants underwent a thorough, protocolized echocardiographic examination. The outcome was time to ESKD (defined as dialysis treatment or kidney transplantation). A total of 731 participants were included. Mean age was 57 ± 13 years and 39% were female. During a median follow-up of 3.8 years (IQR: 3.3;4.5), 102 individuals reached ESKD. In multivariable Cox regression models, both increasing continuous E/e' (HR = 1.09 [95%CI:1.03;1.15], P = 0.004, per 1 unit increase) and E/e' > 14 (HR = 3.44 [95%CI:1.44;8.26], P = 0.005) (reference E/e' < 8) were associated with ESKD, while E/e' 8-14 was not. Compared with no or indeterminate LVDD, LVDD grades 2 or 3 were associated with ESKD (HR = 2.92 [95% CI:1.44;5.94], P = 0.003), while LVDD grade 1 was not. E/e' > 14 and LVDD grade 2 or 3 demonstrated similar predictive accuracy with excellent specificity and negative predictive values, but poor positive predictive values and sensitivity. Prominent LVDD assessed by E/e' and LVDD grades was independently associated with worse renal prognosis and had similar predictive accuracy in patients with non-dialysis dependent CKD.

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk.

Irreparable rotator cuff tears show increasing incidence with age. In symptomatic cases, first-line therapy should be a minimum of six months of physical training, as many improve over time. Reparability is evaluated clinically and by MRI - assessing tendon retraction, fatty infiltration, and muscle atrophy. If symptoms persist, surgical treatment is considered: reverse shoulder arthroplasty is generally offered to older patients (> 60 years), while joint-preserving procedures such as tendon transfer or superior capsular reconstruction may be suitable for younger patients (less-than 60 years), as argued in this review.

Sepsis and septic shock remain major causes of morbidity and mortality worldwide, and management is largely based on source control, antimicrobial therapy, and supportive care. Despite limited high-quality evidence, adjunctive therapies targeting the dysregulated host response involving immune dysfunction, coagulopathy, and endothelial injury, steroids, vasopressors, and adjunctive therapies are frequently used in clinical practice. This survey aimed to describe real-world patterns of sepsis therapy across Europe. We conducted an open, web-based, multinational survey endorsed by the European Society of Intensive Care Medicine (ESICM) and the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). The survey was distributed through professional mailing lists, newsletters, and national society networks. A structured 30-item questionnaire collected information on respondent demographics, ICU characteristics, availability of adjunctive therapies, clinical indications, triggers for initiation, and duration of treatment. Participation was voluntary and anonymous. A total of 442 physicians completed the survey. Data were analyzed descriptively and are presented as proportions and frequencies. More than 80% of respondents reported use of at least one adjunctive therapy for septic shock within the previous year. Corticosteroids were used by over 90% of clinicians, predominantly hydrocortisone for septic shock. Considerable variability was observed regarding indications, timing of initiation, and duration of therapy. Extracorporeal blood purification techniques were used by approximately 75% of respondents, most frequently hemoadsorption in patients with refractory shock; high cost and limited availability were the main barriers to broader implementation. Intravenous immunoglobulins were used by approximately one-third of clinicians, often guided by measured immunoglobulin levels or perceived immune dysfunction. Additional vasoactive and inotropic agents, including levosimendan, methylene blue, and beta-blockers, were employed in selected cases. In contrast, specific immunomodulatory therapies such as interleukin (IL)-1receptor antibodies were rarely used. Across all adjunctive strategies, marked heterogeneity in practice patterns was evident. Adjunctive therapies are widely used in European ICUs, particularly in patients with severe or refractory sepsis, despite limited supporting evidence. The substantial variability in practice highlights ongoing clinical uncertainty and underscores the need for well-designed randomized trials to inform evidence-based and individualized treatment strategies.

Physical inactivity is a major stroke risk factor. In 2016, over one-third of adults in high-income countries did not fulfil the World Health Organization recommendations for physical activity. Evidence on pre-stroke physical activity is limited and inconsistent. We sought to assess pre-stroke physical activity in patients with stroke and its associations with medical conditions and sociodemographic variables. This project was a cross-sectional study of patients hospitalised with stroke. Pre-stroke physical activity was assessed using the Physical Activity Scale-2, to identify whether the World Health Organization recommendations were fulfilled. Patients were stratified into the following: none, 1 to 149 minutes, or ≥150 minutes of moderate- or vigorous-intensity physical activity per week. Crude and age-adjusted logistic regressions were performed to identify associations. Among 122 patients (mean age 71 years (standard deviation = 11.8), 40% women, 70% with a mild stroke), 55% did not fulfil the World Health Organization recommendations. Nonfulfilment was associated with age >75 years (odds ratio [OR] = 0.36; 95% confidence interval [CI], 0.15-0.89), smoking (OR = 0.25; 95% CI, 0.08-0.77), and use of mobility aid (OR = 0.18; 95% CI, 0.05-0.68). Thirty-four per cent reported no moderate- or vigorous-intensity physical activity. Fifty-five per cent of the patients did not fulfil the World Health Organization recommendations before stroke, and one-third did not engage in moderate- or vigorous-intensity activity. Fulfilling the recommendations was linked to older age, smoking, and use of mobility aids.