Herlev Hospital

The systematic review evaluates the impact of indocyanine green fluorescence angiography (ICG-FA) on surgical decisions, postoperative complications, and mortality in acute bowel ischemia. Studies were included if they met the following criteria: patients ≥18 y undergoing ICG-FA for perfusion assessment in all-cause acute bowel ischemia; if they were human clinical studies with original data (n ≥ 5); and if they were published in English, Latin, or Nordic languages. The primary outcome was change of strategy; secondary outcomes included postoperative complications and mortality. Studies were excluded if they were reviews or meta-analyses, animal studies, or papers without original empirical data. Risk of bias was assessed with the Risk of Bias In Non-randomized Studies - of Interventions (ROBINS-I Tool). Outcomes were presented narratively, given the high clinical and methodological heterogeneity across studies. Seven studies met the following inclusion criteria: five retrospective cohort studies and two case series. No randomized trials were identified. A total of 356 patients undergoing fluorescence-guided surgery for suspected or confirmed acute bowel ischemia were included. Across studies, the reported change in surgical strategy ranged from 29% to 67%, postoperative complications from 0% to 24%, and mortality from 0% to 64%. Our findings suggest that ICG-FA may influence surgical decision-making in acute bowel ischemia by guiding resection strategy, but no clinical benefit in regard to postoperative outcomes was shown. However, the evidence is limited to small, retrospective studies with significant risk of bias and low quality of evidence.

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.

Endotrophin is a matrikine released from the C-terminus of the alpha-3 chain of type VI collagen, gaining increasing attention both as a biomarker and as a therapeutic target in the cardiometabolic space. So far, it has been quantified in circulation by the PRO-C6 assay, which detects different-sized proteolytic fragments of the C-terminus, including endotrophin. Here, we developed and evaluated a novel immunoassay targeting the full-length endotrophin, explored its biological relevance in two clinical cohorts of HFpEF, and investigated its potential as a prognostic biomarker. Increased circulating Endotrophin levels were associated with cardiovascular and all-cause mortality in both cohorts. When adjusting for relevant confounders, Endotrophin remained independently associated with both endpoints only in cohort 1. This work emphasizes the importance of the extracellular matrix in disease, confirms the prognostic value of endotrophin, and provides a novel tool for further exploration of its biological role.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment and are increasingly used in the adjuvant and neoadjuvant setting for malignancies such as melanoma, which often affect younger adults. With improving survival, concerns about long-term safety, including potential effects on fertility, are growing. We conducted a national, multicenter, prospective observational study of female patients < 45 years treated with adjuvant anti-PD-1 therapy for resectable stage III-IV melanoma from 2018 to 2024. Ovarian function was assessed at baseline and at 3, 6, 12, and 18 months after treatment initiation. Each visit included transvaginal ultrasound for antral follicle count (AFC) and serum analysis of anti-Müllerian hormone (AMH), estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and inhibin-B. Seventeen female patients were enrolled (mean age 28.9 years, range 17-38). Median follow-up was 5.1 years. Ovarian morphology and AFC remained normal and stable at all time points. No decline in AMH was observed during or after treatment. FSH, LH, estradiol, progesterone, and inhibin-B levels fluctuated within physiological ranges consistent with normal menstrual cycling. After completing adjuvant therapy, five patients had at least one child, and one was pregnant at data cut-off. Two patients developed endocrine immune-related toxicity (type 1 diabetes and hypophysitis); both conceived post-treatment. This prospective evaluation of ovarian function during and after adjuvant anti-PD-1 therapy in melanoma found no evidence of treatment-related ovarian insufficiency, including in patients with endocrine toxicities. These findings are important for counseling young patients receiving adjuvant therapy who may wish to conceive in the future.

This presentation introduces fast simulation methods for assessing harmonic compliance of inverter-based resource (IBR) plants that is necessary for receiving an energization (EON), interim (ION), and finale (FON), operational notification, for grid-connection of the IBR plants to the transmission grid. Generally, the harmonic compliance shall be proven by simulation studies applying harmonic impedance envelopes representing various operation regimes of the meshed transmission grid and provided by the grid operator. The harmonic impedance envelopes may range from tens ohms up to several thousand ohms with a step by one ohm for each relevant integer harmonic and interharmonic order. Such studies shall be fully completed and approved by the grid operator prior to granting operational notifications. Fastest-possible completion of the harmonic compliance studies and high accuracy of the results are essential for the IBR plant developers to obtain the operation notifications. The first presented fast method allows expediting the simulation time by omitting slow processes by many repeated, embedded, load-flow and harmonic load-flow commands on large harmonic impedance envelopes with a required resolution. The method applies fast arithmetical operations on independent variables to identify the area within the harmonic impedance envelope with the largest harmonic voltages and then, reduce the number of the embedded commands to be executed. The first method reduces the simulation time up to 65 times with the largest benefit for the largest envelopes. The second fast method applies interpolation through critical points within the envelope to calculate the largest harmonic voltage. The second method simulates up to 20 times faster than the first method. The third fast method combines the two first methods. This presentation will demonstrate the three methods using anonymized, real-life, examples and propose possible areas of applications.

Renal cell carcinoma (RCC) primarily affects older adults who often present with frailty, increasing their risk of surgical complications and delayed recovery. Prehabilitation, incorporating exercise, nutrition, and psychological support, may improve postoperative outcomes. However, no studies have investigated prehabilitation prior to surgery for RCC. The aim is to assess whether a one-month multimodal prehabilitation program including geriatric interventions improves recovery in patients with frailty undergoing surgery for localized RCC≤7cm. 60 patients, aged ≥65, with a Clinical Frailty Scale (CFS) score of 3-6 are randomized 1:1 to standard care or prehabilitation involving home-based exercise, geriatric assessment with tailored interventions, and smoking cessation support. The primary outcome is change in Quality of Recovery-15 (QoR-15) 21days postoperatively. Secondary outcomes include changes in QoR-15, health-related quality of life (EQ-5D-5L) and physical performance (30-s chair-stand test, handgrip strength) assessed preoperatively, 1, 21 and 90days postoperatively. Postoperative complications will be evaluated using the Clavien-Dindo classification, alongside a cost-effectiveness analysis. Long-term outcomes include 1- and 5-year recurrence-free, cancer-specific, and overall survival. Pre-KiT explores if a pragmatic geriatric prehabilitation strategy is effective and feasible for older frail patients with RCC. The intervention is designed for easy implementation in clinical practice: administered by a single healthcare professional, requiring only one additional hospital visit, and consists of home-based exercises. This low-resource approach also aims to minimize financial costs, which is of importance for implementation possibilities. If successful, it could improve standard care and outcomes after surgery. ClinicalTrials.gov ID: NCT06745609. Prospectively registered December 12th, 2024.

Kidney transplant recipients face a high risk of adverse events, including fractures. Reported fracture rates post-transplant vary widely and may have changed over time. The consequences of a fracture, especially subsequent fractures, remain under-investigated. This study examined the risk and prognosis of fractures after kidney transplantation in the current era. This retrospective cohort study included all adults who received a first single-organ kidney transplant between 2000 and 2022 in Denmark. Nationwide healthcare registries were utilized to identify the study population and provide demographic data, diagnostic and procedural codes, and prescription data. Cumulative incidence (risk) of both first fracture and subsequent fracture was computed, treating death as a competing risk. Crude, and sex- and age-standardized incidence rates were estimated for different time periods. The study included 3977 first kidney transplant recipients, of whom 788 sustained any post-transplant fracture. The 10-year risk of fracture was 21% (95% confidence interval 20-23). Crude incidence rates of any fracture remained unchanged over time, while standardized estimates showed a slight decline. Fractures were primarily located at the peripheral skeleton. Twenty-eight percent of patients with a fracture sustained a subsequent fracture, with the highest incidence at 6-12 months following the first event. Kidney transplant recipients remain at high fracture risk, with unchanged fracture rates over the past 20 years. The imminent fracture risk following a first fracture is high and largely unaddressed. Although formal guidelines have yet to be established, this knowledge should urge clinicians to perform risk assessment and consider intervention following a post-transplant fracture.

Despite advancements in surgical patient care, postoperative pulmonary complications (PPCs) following emergency abdominal surgery remain common and are linked to increased morbidity, mortality, and healthcare costs. This study aims to identify the incidence and risk factors of PPCs following major emergency abdominal surgery. This is a single-center observational study including patients undergoing major emergency abdominal surgery between January 1, 2021, and December 31, 2023, collecting pre-, intra-, and postoperative variables. The primary outcome was the occurrence of PPCs, and the secondary outcomes were risk factors for PPCs and 30-day mortality rates following PPCs. Multivariable logistic regression was used to identify perioperative risk factors associated with PPCs. The same analysis was used on a subgroup of patients with 'severe' PPCs. Of 1080 patients included in the study, 431 (39.9%) had at least one PPC, and 150 (13.9%) had at least one 'severe' PPC. Multivariable logistic regression identified several risk factors for developing PPCs: an increased ARISCAT score, a history of pulmonary disease, hypertension, a history of cerebral disease, increased Clinical Frailty Scale, preoperative admission to the intensive care unit, a CDC grade IV contaminated wound, intraoperative findings of perforated stomach or duodenal ulcer, need for subsequent reoperations, and protracted postoperative ileus. Patients with PPCs had a 30-day mortality rate of 21.0%, while those with 'severe' PPCs had a 30-day mortality rate of 46.3%. Several independent risk factors, beyond those already established, were associated with an increased risk of PPCs.

To assess whether menopausal hormone therapy increases the risk of all cause mortality. Nationwide, registry based cohort study. Denmark. Danish women born between 1950 and 1977 and alive at 45 years. Follow-up began on each woman's 45th birthday and ended on 31 July 2023. Of 969 424 eligible women, 92 619 were excluded because of thrombophilia, liver disease, arterial thrombosis or venous thrombosis, breast cancer, endometrial cancer, ovarian cancer, previous use of menopausal hormone therapy, or previous bilateral oophorectomy. Systemic menopausal hormone therapy was the intervention of interest. Death as registered in the Central Persons Register. Secondary outcomes were cause specific mortality registered in the cause of death register (cardiovascular, cancer, or other mortality). Hazard ratios were estimated using Cox regression, adjusted for age, calendar year, parity, educational degree, income group quarter (based on quartiles), country of birth, diabetes, hypercholesterolemia, hypertension, atrial fibrillation, valvular disease, heart failure, and three or more hospital contacts between 44 and 45 years of age. Of 876 805 women, 104 086 (11.9%) redeemed a prescription for menopausal hormone therapy, and 47 594 (5.4%) died, with a median follow-up time of 14.3 years (interquartile range (IQR) 7.9-21.0 years). Women who used menopausal hormone therapy had an incidence rate of 54.9 deaths per 10 000 person years compared to 35.5 per 10 000 person years in the unexposed group, corresponding to an adjusted hazard ratio of 0.96 (95% confidence interval (CI) 0.93 to 0.98). Stratifying this by cumulative duration of menopausal hormone therapy use gave an adjusted hazard ratio after <1 years of menopausal hormone therapy of 1.01 (95% CI 0.98 to 1.05), after 1-2.9 years of use 0.94 (0.89 to 0.98), 3-4.9 years of use 0.90 (0.84 to 0.95), 5-9.9 years of use 0.89 (0.84 to 0.95), and over ≥10 years of use 0.98 (0.90 to 1.07). No unequivocal differences in cause-specific mortality were found between groups. Among the 703 women who underwent bilateral oophorectomy between 45-54 years, those who used menopausal hormone therapy experienced a 27-34% lower mortality hazard as compared to women who did not (median age at death for those who had taken menopausal hormone therapy 60.9 years (IQR 55.3-66.6 years) v 56.6 years (52.9-62.0 years) for those who had not). This nationwide cohort study did not find menopausal hormone therapy was associated with increased mortality.