Aarhus University Hospital Research Articles

Right ventricular to pulmonary artery coupling in chronic thromboembolic pulmonary hypertension

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is characterized by increased pulmonary vascular resistance (PVR) and pressure and right ventricular (RV) dysfunction. We aimed to evaluate the correlation of RV to pulmonary artery coupling, measured as the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and invasive hemodynamic measurements, and to assess the changes in this ratio following CTEPH treatment. MethodsWe conducted a retrospective cohort study of CTEPH patients treated at Aarhus University Hospital with pulmonary angioplasty (BPA), pulmonary endarterectomy (PEA), and or medical therapy only. Patients underwent transthoracic echocardiography and right heart catheterization at baseline and follow-up. The primary endpoint was the association between TAPSE/PASP and PVR. Secondary endpoints included other hemodynamic and functional parameters. ResultsThe study included 139 patients. Mean TAPSE/PASP at baseline was 0.22 [0.16, 0.29] mm/mmHg. An exponential decay correlation was found between TAPSE/PASP and PVR (correlation coefficient − 0.67, p < 0.001). The TAPSE/PASP ratio improved from 0.23 [0.18; 0.29] to 0.33 [0.26; 0.46] mm/mmHg, p < 0.0001, following BPA, and from 0.20 [0.15;0.27] to 0.35 [0.21;0.41] mm/mmHg, p = 0.0007 following PEA, indicating enhanced RV to pulmonary artery coupling. ConclusionIn patients with CTEPH, the echocardiographic TAPSE/PASP ratio as a measure of RV-PA coupling correlates well with invasively measured pulmonary vascular resistance. The TAPSE/PASP ratio improved after BPA or PEA treatments suggesting a potential use for monitoring patient outcomes. Further prospective studies are warranted to establish the prognostic value of the TAPSE/PASP ratio and ability to guide treatment decisions.

The impact of social restrictions on the incidence and microbiology of severe acute tonsillitis.

We aimed to explore the impact of social distancing on the incidence, severity and microbiology of patients with acute tonsillitis (AT). In this single-centre study, we retrospectively included all patients with AT referred to the Ear-Nose-Throat Department, Aarhus University Hospital, Denmark, in the two years preceding versus the two years after the COVID-19 lockdown in Denmark (11 March 2020). In total, 425 patients were included. The incidence of AT was significantly lower in the post-lockdown period (n = 128) than in the pre-lockdown period (n = 297) (p less-than 0.001). Reduced incidence was observed across all age groups. No significant differences were found in patient characteristics between periods. The proportion of hospitalised patients was significantly lower in the post- than in the pre-lockdown period (36% versus 25%, p = 0.032). Prevalent culture findings were Streptococcus pyogenes (15%), S. anginosus group (11%) and Fusobacterium necrophorum (5%). No statistically significant differences in the relative prevalence of individual bacteria were found between periods. The incidence of patients with AT referred to hospital decreased by 57% in the two-year period after the COVID-19 lockdown compared with the period leading up to the lockdown. Our findings suggest that this decrease mirrored a general decline in AT incidence rather than altered referral patterns. None. The study was approved by the Danish Data Protection Agency (#1-16-02-134-23) and the Danish Patient Safety Authority (#1-45-70-41-23).

Phenotypes, Genetics, and Estimated Prevalence of Focal Dermal Hypoplasia (Goltz Syndrome): A Single-Center Report.

Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is a rare ectodermal dysplasia that primarily affects the skin, skeleton, and eyes. It is an X-linked dominant disorder, predominantly seen in females, caused by pathogenic variants in PORCN. We characterized a case series of four genetically confirmed FDH patients (three females, one male) at Aarhus University Hospital, Denmark. We estimated the FDH prevalence from our local cohort and nationwide registry data. Three patients had characteristic dermatological findings suspicious for FDH and confirmed by targeted PORCN analysis. One patient had an atypical presentation with several malformations but only subtle skin changes and was diagnosed following trio exome-sequencing analysis. Skin atrophy with fat herniations and telangiectasias were typical cutaneous findings. Limb malformations included oligodactyly (cleft foot), syndactyly, and polydactyly. Eye abnormalities included coloboma and microphthalmos. Facial dysmorphology was defined by asymmetry, thin upper lip, and malformed ears. One patient developed a giant cell bone tumor, which is a rare feature of FDH. Dental findings included enamel hypoplasia with vertical grooving and irregular crowns. Four PORCN variants were identified, including three not previously reported in the literature.We estimated a regional point prevalence in Western Denmark of 1.6 cases per million population (95% confidence intervals (CI): 0.7-3.7 per million) and a nationwide registry-based point prevalence of 1.2 cases per million population (95% CI: 0.6-2.4 per million). FDH is an extremely rare and complex multisystem disorder of variable presentation, which requires close multidisciplinary collaboration for diagnosis and patient care.

Surgical instrument tray optimization process at a university hospital: A comprehensive overview

ObjectiveThis study presents the results of a surgical instrument tray optimization process implemented across all surgical specialties within the largest university hospital in Denmark. MethodsData was extracted from a comprehensive instrument optimization process including all Operating Rooms at Aarhus University Hospital. Adopting a holistic perspective, the optimization process, involved aligning instrument trays across various surgical specialties. This included: a) Reduction in number of instruments, b) Consolidation or separation of trays, c) Modularization - introducing modular trays for specific purposes, and d) Standardization - standardizing commonly used instruments across specialties. Instruments per tray, total number of instruments, and changes in the number of trays were compared against existing tray contents to identify discipline-specific changes. ResultsSome specialties made substantial alterations to tray structures, while others primarily reduced number of instruments in existing trays. Across all specialties, optimization resulted in 17 % decrease in number of tray types (p = 0.01, 95%CI:1.0–6.8), 1 % increase in total number of trays (p = 0.36, 95%CI:-11.9–4.8), 18 % decrease in number of instruments per tray (p = 0.0002, 95%CI: 3.2–7.6) and 16 % reduction in total number of instruments for all specialties (p < 0.0001, 95%CI:404–758). ConclusionThis study underscores complexity of instrument tray design. The approach employed at Aarhus University Hospital, involving interdisciplinary experts in an iterative design process, demonstrated the feasibility of redesigning instrument trays with significant reduction in content. Additionally, data suggests that reducing the number of instruments could lead to a decrease in workload within the Central Sterile Supply Specialty. This presents opportunity to minimize wasted resources and streamlining cleaning processes for unused instruments.

Recurrent Ischemic Stroke/Transient Ischemic Attack After Patent Foramen Ovale Closure: A cohort study.

Patent foramen ovale (PFO) has been associated with ischemic stroke and transient ischemic attack (TIA). Guidelines recommend PFO closure for stroke prevention in selected patients, but the risk of recurrent stroke remains high compared to the background population. We aimed to evaluate the causes of recurrent stroke/TIA and post-interventional complications in patients after PFO closure. Patients from the Central Denmark Region who underwent PFO closure at Aarhus University Hospital between November 5, 2018, and May 12, 2023, following an ischemic stroke, TIA, amaurosis fugax or retinal emboli were included. Data on patient demographics, risk factors, procedural details, post-interventional complications and recurrent stroke/TIA were collected from electronic medical records. PFO closure was performed in 310 patients (median age: 49 years). During a median follow-up of 2.6 years (interquartile range: 1.5-3.6, 814 total patient years), recurrent stroke/TIA was observed in 8 patients (2.6%) or 0.98 recurrent strokes per 100 patient years. Recurrent stroke/TIA was more frequent in patients with hypertension (50.0% vs 16.9%, p = 0.039). Recurrent stroke/TIA was related to thrombophilia or haematological conditions entailing hypercoagulability in 62.5% of patients. New-onset atrial fibrillation was observed in 9.4% of patients within 45 days after the procedure. None of these patients subsequently developed an ischemic event. Other adverse outcomes were uncommon. Rates of recurrent ischaemic stroke/TIA after PFO closure were comparable to findings in previous trials. Pre-existing vascular risk factors (hypertension), and a hypercoagulable state were associated with recurrent ischaemic stroke/TIA.

Anifrolumab treatment improves patient-reported quality of life and decreases disease activity and corticosteroid use in patients with systemic lupus erythematosus: A qualitative study in Denmark.

Anifrolumab is a new therapeutic approach for individuals with systemic lupus erythematosus (SLE) directed at blocking the type 1 interferon pathway. Despite the expanding body of literature on Anifrolumab, an essential aspect remains absent: the subjective patient experience of treatment effects and implications on patients' health-related quality of life (HRQoL). The present study aimed to fill this void by elucidating the nuanced perspectives of SLE patients receiving Anifrolumab treatment by conducting qualitative in-depth interviews (IDIs). SLE patients at Aarhus University Hospital who had received at least three infusions of Anifrolumab were approached for inclusion in the study, which comprised two main elements: (1) qualitative IDIs and (2) collection of patient data from electronic medical records (EMRs). The IDIs were semi-structured and based on a discussion guide that included open-ended and close-ended questions. Verbatim transcripts were coded and analysed using qualitative software to understand concepts important to patients and to understand patients' own experiences before and after Anifrolumab therapy. A clinical chart review was conducted using EMR data at baseline, 3months, and 6months after Anifrolumab initiation. IDIs were completed with 14 patients, and EMR data was collected from 16 patients (treatment days range: 62-474). Of the 23 symptoms spontaneously reported by patients prior to Anifrolumab treatment, fatigue, joint pain, sun sensitivity, joint stiffness, skin rashes, and hair loss were the most common. Most symptoms improved, and none worsened during treatment. Patients reported significant impacts of disease on daily life before treatment: day-to-day activities, social life, emotional aspects, physical activity, concentration/memory, work/employment, and family/romantic relationships. Patients reported improvements in all aspects after treatment but were still impacted. From the EMR data, we observed a fall in disease activity after treatment initiation with a concomitant reduction in the use of corticosteroids. This study provides valuable insights into the subjective experiences of SLE patients treated with Anifrolumab, and the findings collectively contribute to a comprehensive understanding of the treatment's efficacy from the patients' perspective and its tangible effects on both subjective and objective parameters in SLE patients.

The effect of twin pregnancy in intrahepatic cholestasis of pregnancy: A case control study.

Intrahepatic cholestasis of pregnancy (ICP) is one of the most common hepatic disorders during pregnancy, and the etiology is thought to be multifactorial including both environmental and hormonal contributions. In twin pregnancies, the fetal and placental mass is generally greater than in singleton pregnancies, and is, theoretically, likely to have a greater influence upon the maternal hepatic metabolism compared to singleton pregnancy. The aim of this study was to compare ICP in twin and singleton pregnancies according to ICP characteristics, time of diagnosis, serum bile acid levels, pharmacological treatment, and pregnancy outcomes. This case control study was undertaken at Aarhus University Hospital, Denmark, from 2012 to 2019. The study comprised 51 women with twin pregnancies and ICP. These women were matched with 153 women with twin pregnancies without ICP and 153 women with singleton pregnancies with ICP, respectively. Three controls were matched per case, and data obtained from medical records and Danish obstetrical databases were compared. We found a significantly lower gestational age at ICP diagnosis in twin pregnancies (227 vs. 242 days for singleton pregnancies; p = 0.002). Bile acids reached significantly higher maximum blood levels in twin pregnancies (32.9 vs. 22.2 μmol/L; p = 0.012), and at a lower gestational age (gestational age maximum bile acids: 235 vs. 250 days; p < 0.001). No difference in pharmacological treatment was observed between the groups. Twin pregnancies with and without ICP had comparable pregnancy outcomes; however, ICP pregnancies had a higher incidence of gestational diabetes mellitus (15.7% vs. 5.2%; p = 0.03). In repeat pregnancies, ICP was diagnosed earlier in the twin pregnancy (p = 0.006). Compared to singleton pregnancies, twin pregnant women with ICP have an earlier diagnosis of ICP, and levels of bile acids are higher. Compared to twin pregnancies without ICP, the pregnancy outcomes are comparable.

Exploring tonsillar cancer associations in patients with base of tongue cancer: insights from a single-center study

PurposeTo explore the prevalence of synchronous and metachronous tonsillar cancer in patients with base of tongue cancer, as well as identifying potential risk factors linked to these secondary malignancies. We aim to answer the following question: Should bilateral tonsillectomy be recommended to patients diagnosed with base of tongue cancer?MethodsA case-series study was conducted at Aarhus University Hospital, including all patients with histologically confirmed base of tongue squamous cell carcinoma treated between January 2012 and December 2021. Data from electronic patient records, including diagnosis of prior, synchronous or metachronous tonsillar cancer, demographics, and clinical features were analysed. Fisher’s exact test was performed to assess factors associated with synchronous and metachronous tonsillar cancer.ResultsAmong 198 patients with base of tongue cancer, 5.6% had a history of tonsillar cancer, either prior to (4.5%), synchronous (0.5%), or metachronous (0.5%) to the base of tongue diagnosis. The prevalence of synchronous or metachronous tonsillar cancer among patients without previous bilateral tonsillectomy was 1.2%. Patients with tonsillar cancer were older, had heavier smoking histories, and exhibited less frequent P16-overexpression.ConclusionOur findings deepen understanding of tonsillar cancer in patients with base of tongue cancer. The prevalence of synchronous or metachronous tonsillar cancer was found to be relatively low, suggesting that routine tonsillectomy for all base of tongue cancer patients is not warranted.

The Effectiveness and Safety of Romosozumab and Teriparatide in Postmenopausal Women with Osteoporosis.

The purpose of this observational study was to investigate the effectiveness and safety of romosozumab (ROMO) and teriparatide (TPTD) in a clinical setting. 315 postmenopausal women were included based on the reimbursement criteria for ROMO and TPTD at the Department of Endocrinology at Aarhus University Hospital. ROMO: Bone Mineral Density (BMD) T-score <-2.5 (femoral neck (FN), total hip (TH), or lumbar spine (LS)) + a fragility fracture (hip, spine, pelvis, distal forearm, or proximal humerus) within 3 years. TPTD: Within 3 years ≥2 vertebral fractures or 1 vertebral fracture + BMD T-score (FN, TH, or LS) <-3. Data was collected from medical records. The primary end point was percentage change from baseline in BMD (FN, TH, and LS) at month 12. BMD was measured by DXA. At month 12 ROMO led to significantly (p<0.001) larger increases than TPTD in BMD (FN: 4.8% vs. 0.2%, TH: 5.7% vs. 0.3%, and LS: 13.7% vs. 9.3%). Discontinuation rate was lower with ROMO than with TPTD. Lower incidence of cardiovascular adverse events was observed with ROMO compared to TPTD. Treatment-naïve patients had non-significantly higher BMD increases compared to previously treated patients with both ROMO and TPTD. Treatment with romosozumab yields larger increases in bone mineral density than teriparatide after 12 months and a higher rate of completion.

Exercise Hemodynamics and Mitochondrial Oxidative Capacity in Disease Stages of Wild-Type Transthyretin Amyloid Cardiomyopathy.

Wild-type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients. The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (NAC I-L, n=14), NAC I with high levels NT-proBNP (NAC I-H, n=20), and NAC II-III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I-L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I-H (Diff. -2.4, 95% CI (-4.2: -0.7), P=0.00) and the NAC II-III group (Diff: -3.1 L/min, 95% CI (-5.2: -1.1), P=0.00) compared with the NAC I-L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I-L and NAC II-III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3, P=0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity. An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early-stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure-flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt.

Changes in experienced quality of oncological cancer care during the COVID-19 pandemic based on patient reported outcomes - a cross-sectional study.

The study aims to investigate the impact of the COVID-19 pandemic on cancer patients' perceptions of the quality of their oncological treatment and care. The COVID-19 pandemic disrupted healthcare delivery and oncological resources were repurposed, potentially leading to prolonged treatment and reduced access to innovative therapies and clinical trials. Still, little is known about how patients perceived the quality of their treatment. A cross-sectional study was conducted in the spring of 2020 among cancer patients at the Department of Oncology, Aarhus University Hospital and Rigshospitalet, Denmark. Patients were invited to complete an online questionnaire on clinical, socioeconomic, emotional, behavioural, and quality-related aspects of oncological cancer care. Patients who experienced reduced treatment quality and those who reported no or slight reductions were compared using multiple logistic regression, exploring the associations with patient characteristics, behaviours, and fear of cancer progression or recurrence. A total of 2,040/5,372 patients experienced changes in their treatment plans during the pandemic, and 1,570/5,372 patients experienced reduced treatment quality, with 236 reporting a high degree of reduction. Patients with breast, head and neck, and upper gastrointestinal cancers were more likely to experience reduced treatment quality. Altered interactions with healthcare providers, along with isolation, lack of social support, and heightened fear of cancer progression, were significant risk factors for experiencing reduced cancer care quality. We identified subgroups of cancer patients needing targeted communication and care during health crises affecting cancer treatment. The findings underscore the importance of safeguarding the needs of vulnerable patient populations in future healthcare emergencies.

Effect of gestational diabetes on fetal growth rate and later overweight in the offspring.

Children of women with gestational diabetes (GDM) are often born with a higher birthweight and have an increased risk of overweight during childhood. High fetal growth rate is also associated with being overweight in childhood. To examine excessive fetal growth rate as a mediator between GDM and overweight in the offspring. This was a longitudinal cohort study, using routinely collected data on children born 2008-2014 in Aarhus, Denmark. Fetal biometrics were extracted from the patient records at Aarhus University Hospital and childhood weight from the health records at Aarhus Municipality Healthcare Service. We calculated growth trajectories for fetuses affected by GDM and for unaffected fetuses using cubic mixed model regression. We extracted individual fetal growth rate and estimated the contributing effect of fetal growth rate on the risk of being overweight in the 5-9 year-old offspring. We included 6794 mother-child pairs, 295 with GDM. Fetal growth was higher in women with GDM from week 25, and the offspring had an increased risk of being overweight (OR: 2.02 (95%CI: 1.44 - 2.84)). When adjusting for fetal growth rate in week 28 the effect attenuated by 15%, and to 1.10 (95%CI: 0.76 - 1.60) when further adjusting for pre-pregnancy BMI. Pregnancies affected by GDM had higher fetal growth rate and the offspring had a higher risk of being overweight at 5-9 years. Fetal growth rate in early third trimester was a mediator of up to 15% of this association, but pre-pregnancy BMI contributed strongly as well.

Long-term cardiac computed tomography follow-up after left atrial appendage occlusion.

Left atrial appendage occlusion (LAAO) is performed increasingly, but long-term follow-up imaging data are lacking. The aim of this study was to evaluate the safety and durability of the Amplatzer Amulet device >4 years after LAAO. This was a prospective observational cohort study including 52 patients implanted with the Amplatzer Amulet device at Aarhus University Hospital, Denmark. A >4-year follow-up cardiac computed tomography (CT) scan after LAAO was performed and compared with the results from the 2-month and 12-month scans. The primary outcome was left atrial appendage (LAA) sealing based on distal LAA contrast patency and peridevice leakage (PDL), stratified into complete occlusion (grade 0 [G0]) and grade 1-3 leakage (G1-3), respectively. Secondary outcomes were low- and high-grade hypoattenuated thickening (HAT), device-related thrombosis (DRT) and device durability. The median (interquartile range [IQR]) follow-up time from LAAO to the latest CT scan was 5.8 years (4.5; 6.3). At 2-month (n=52), 12-month (n=27) and >4-year CT follow-ups (n=52), rates of both complete occlusion (33%, 37%, 35%) and G2 leaks (52%, 52%, 48%) remained stable. Rates of G1 leaks varied (14%, 4%, 6%) and G3 leaks rose (2%, 7%, 12%) from earliest to latest follow-up. The median left atrial (LA) volume increased from 127 mL (96; 176) to 144 mL (108; 182) and 147 mL (107; 193). No DRT was found. The structural device integrity was preserved. This study indicates a stable LAA sealing status throughout the follow-up period, emphasising the importance of the procedural result in avoiding PDL. Few patients displayed PDL progression, which might partly be related to LA remodelling with increasing volume. The long-term device durability appears excellent. Larger studies are warranted to confirm these findings.

Validation of the Bethesda System for Reporting Thyroid Cytopathology in a Danish tertiary centre.

The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) is used to categorise thyroid fine-needle aspiration (FNA). The aim of this study was to validate the BSRTC in a consecutive cohort and to evaluate the derived management in terms of performing repeat FNA or thyroid surgery. Results of thyroid FNAs assessed at the Department of Pathology, Aarhus University Hospital, in the period 2016-2019 were retrieved from The Danish Pathology Registry. FNA category according to the BSRTC along with the histological diagnosis (if available) were linked to the individual patient. In total, 3,669 biopsies were included from 2,873 thyroid nodules in 2,547 patients. Repeat FNA was performed in 23.6% of nodules. The majority of primary FNAs were Benign (BSRTC II; 52.4%). Non-diagnostic (ND) (BSRTC I) was found in 26.3% and BSRTC III-VI were found in 3.6-7.5%. Compared with the first with the last FNA, the frequency of Benign (BSRTC II) increased (61.3%), whereas the frequency of ND (BSRTC I) decreased (14.8%). Surgery was performed in 38.2% (n = 1,097) of nodules. The malignancy rate of 11.5% correlated positively with the BSRTC category, being 2.8% in Benign (BSRTC II) and 95.7% in Malignant (BSRTC VI). The malignancy rates in the BSRTC categories were in accordance with reports from other countries. Since the BSRTC ensures a standardised and concise communication of cytopathology assessments, application of the BSRTC for thyroid nodule management in a Danish setting is recommended. None. Not relevant.

Respiratory Depression Following Intraoperative Methadone: A Retrospective Cohort Study.

Methadone is used as a perioperative analgesic in the management of postoperative pain. Despite positive outcomes from randomized trials favoring methadone, concerns about its safety persist, particularly regarding respiratory depression (RD) and excessive sedation. In this study, we compared the incidence of naloxone administration between patients administered intraoperative methadone and those administered intraoperative morphine as a measure of severe RD. Time spent at the postanesthesia care unit (PACU) was used as a proxy variable for excessive sedation. This was a retrospective cohort study including all patients aged ≥18 years who underwent surgery between March 2019 and March 2023 at Aarhus University Hospital, Denmark. We assessed the association between intraoperative administration of either methadone or morphine and postoperative naloxone administration within the first 24 hours using logistic regression (primary outcome). An analogous linear regression model was used for the secondary outcome of time spent in the PACU after surgery. Patients were weighted using propensity scores to adjust for potential confounding variables. A total of 14,522 patients were included in the analysis. Among the 2437 patients who received intraoperative methadone, 15 (0.62%) patients received naloxone within the first 24 hours after surgery compared to 68 of 12,0885 (0.56%) who received intraoperative morphine. No statistical difference was observed in the odds of naloxone administration between patients administered methadone or morphine (adjusted odds ratio 95% confidence interval [CI], 1.21 [0.40-2.02]). Patients who were administered intraoperative methadone had a mean PACU length of stay (LOS) of 334 minutes (standard deviation [SD], 382) compared to 195 minutes (SD, 228) for those administered intraoperative morphine. The adjusted PACU LOS of patients administered intraoperative methadone was 26% longer compared to those administered intraoperative morphine (adjusted ratio of the geometric means 95% CI, 1.26 [1.22-1.31]). The incidence of naloxone administration to treat severe RD was low. No difference was observed in the odds of naloxone administration to treat severe RD between patients administered intraoperative methadone or intraoperative morphine. Intraoperative methadone was associated with longer stays at the PACU; however, this result should be interpreted with care. Our findings suggest that intraoperative methadone has a safety profile comparable to that of morphine with regard to severe RD.

Association between socioeconomic position and discontinuation of pharmacotherapy for heart failure after cardiac resynchronization therapy.

Pharmacological therapy remains a cornerstone in heart failure (HF) treatment despite implantation of a cardiac resynchronization therapy (CRT) device. The aim of this study was to investigate the association between 1) drug discontinuation, and 2) long-term adherence to HF pharmacotherapy after CRT implantation and socioeconomic position and multimorbidity. We conducted a registry-based cohort study including all patients who underwent a first-time CRT implantation at Aarhus University Hospital from 2000-2017. HF pharmacotherapy included beta blockers (BBs), renin angiotensin system inhibitors (ACEI/ARB), and mineralocorticoid receptor antagonists (MRAs). Patients were identified using the Danish Pacemaker and ICD Registry, and information about medication and comorbidities was obtained through linkage to the Danish health registries. We identified 2,007 patients of whom 1,880 (94%) were eligible for inclusion. The cumulative incidence of drug discontinuation at 10 years was 6% (95% confidence interval [CI] 5-8%) for BB, 10% (95% CI 9-12%) for ACEI/ARB, and 24% (95% CI 20-27%) for MRAs. Living alone was associated with higher BB discontinuation rates (hazard ratio [HR] 1.83, 95%CI 1.20-2.79), whereas patients with multimorbidity were more likely to discontinue ACEI/ARB- (HR 1.92, 95%CI 1.33-2.80) and MRA therapy (HR 1.51, 95% CI 1.10-2.09). Income- and educational level did not influence drug discontinuation rates, and similar adherence patterns were observed across all strata of socioeconomic position and multimorbidity. In patients with CRTs, drug discontinuation rates were low, and adherence to HF pharmacotherapy was comparable regardless of socioeconomic position. Living alone and multimorbidity were associated with discontinuation of specific HF drugs.

#153 The risk of post-transplant recurrent immunoglobulin A nephropathy: the association with post-transplant steroid use

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common cause of kidney failure among glomerulopathies worldwide and it is reported that approximately 6-7% of all kidney transplantation is due to IgAN. It is well known that IgAN can recur in the kidney allograft and previous studies suggest that recurrent IgAN is the third most common cause of graft loss in patients with IgAN as primary disease. There is currently no effective treatment for recurrent IgAN, and the main goal is therefore to prevent recurrence in the allograft. Post-transplant steroid therapy is a cornerstone in many immunosuppressive regimens, but steroid treatment also come with several side effects leading to the use of steroid-free protocols. Controversy remains as to whether the use of steroid affects the risk of recurrent IgAN. Previous, retrospective studies report widely divergent associations between the use of steroids and the risk of recurrent IgAN and thus, more research on the association between steroid use and the risk of recurrent IgAN is warranted. We examined this by taking advantage of the fact that two different standard immunosuppression protocols have been employed at two Danish transplantation centers, of which one included steroids and the other did not. The patients treated at the two transplantations centers were otherwise similar with respect to ethnicity, socio-economic status and other aspects of treatment differing only by regional residency. This provided a unique opportunity to compare the association between steroid use, recurrence rate and graft survival. We furthermore aimed to identify potential risk factors for recurrent IgAN. Method A retrospective cohort study including all adult patients (age ≥ 18 years) with biopsy-proven IgAN and a first-time kidney-only transplantation from 1990 to 2020 at either Aarhus University Hospital or Odense University Hospital using a steroid containing or a steroid free post-transplant immunosuppressive protocol, respectively. Renal transplant patients with IgAN were identified from the Danish Nephrology Registry and data on medical treatment, graft survival and histopathological evidence of recurrent IgAN were extracted from electronic medical journals. Data is presented by Aalen-Johansen and Kaplan-Meier plot, and associations between risk factors for recurrent IgAN were analyzed by cox-regression. Results A total of 120 first-time kidney recipients were included in the study. Biopsy-proven, recurrent IgAN was identified in 17 (14.2%) recipients. The median time from transplantation to recurrence was 2.91 years (IQR 0.89−5.60). Only one of 18 (15%) recipients adhering to steroid-free protocol was diagnosed with recurrent IgAN during the study period. The accumulated use of steroid as part of the immunosuppression regime was not associated with the risk of recurrent IgAN (unadjusted HR (95% CI) =1.02 (0.94−1.12)). Transplantation with genetically related living donor was associated with a greater risk of recurrent IgAN compared with non-genetically related ((unadjusted HR (95% CI) = 3.90 (1.37−11.10)) and recipients with recurrent IgAN were more likely to be younger at time of been diagnosed with IgAN and had a shorter time from being diagnosed to kidney failure when compared to recipients with non-recurrent IgAN. There were no associations between the risk of recurrent IgAN and induction therapy or HLA-mismatches. The 10-year death censored graft survival was 45% for recipients with recurrent IgAN, compared to 80% for recipients with non-recurrent IgAN. Conclusion The risk of recurrent IgAN after kidney transplantation was not associated with the use of steroids as part of the immunosuppression protocol, whereas recipients receiving a kidney from a genetic related donor appeared to have a higher risk of recurrent IgAN.

Changes in exercise capacity in people with Cystic Fibrosis after one year of Elexacaftor/Tezacaftor/Ivacaftor treatment – A Danish prospective cohort

BackgroundCystic Fibrosis (CF) is an inherited multiorgan disease that causes lung damage and early death. People with CF (pwCF) experience diminished exercise capacity compared to the general population. This is due to an accelerated decline in lung function resulting from recurrent lung infections, declining lung function and nutritional challenges. Since 2020 the CFTR-modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved for pwCF aged 12 and above in Denmark. Initial experiences with the medication have shown promising results, including improved lung function and disease stability. To date a limited number of studies have evaluated the impact of CFTR-modulators on exercise capacity in pwCF. ObjectiveThe study aims to assess the impact of one year of ETI treatment, without any further intervention, on exercise capacity measured through cardiopulmonary exercise test (CPET) in pwCF aged 12 years and above. MethodsA Danish prospective registry cohort study including pwCF from CF-Center Copenhagen, Copenhagen University Hospital and CF-Center Aarhus, Aarhus University Hospital. Participants underwent CPET before initiating ETI and at follow up one year later. Primary outcomes were VO₂ peak (ml/kg/min), secondary outcomes were VO2 peak (ml/min), VO2 peak (% pred), watt-max, HR-max and saturation at max. The difference between baseline and follow-up was assessed using a paired-sample t-test and regression analyses were applied to relevant outcomes. ResultsWe included 229 pwCF in the analyses. An increase in oxygen uptake, VO₂ peak (ml/kg/min) from baseline to follow-up was observed; 0.6, 95% CI [0.06; 1.09] p = 0.03. Moreover, significant increase was noted for all other CPET outcomes. Regression analysis showed that changes in FEV₁% pred and BMI could explain some of the differences, 0.05 ml/kg/min, 95% CI [0.01, 0.1] p = 0.02 and -0.5 ml/kg/min, 95% CI [-0.8, -0.2] p = 0.002 respectively. ConclusionAmong Danish pwCF we found a significant, but not clinically relevant, increase in oxygen uptake, after one year of ETI treatment.

Seven percent of primary anterior crucial ligament reconstruction patients have arthroscopic resection of cyclops lesions within 2 years: A cohort study of 2556 patients.

After anterior cruciate ligament reconstruction (ACL-R), a localised scar tissue called cyclops lesion may develop anterior to the graft causing knee extension deficits, pain, oedema, clicking and reduced knee function. This study determined the incidence of arthroscopic resection of a cyclops lesion within 2 years after ACL-R and investigated the associations of patient characteristics and surgical techniques with the need for arthroscopic resection of a cyclops lesion. This study included patients who underwent primary ACL-R with adult surgical technique from 2005 to 2019 at Aarhus University Hospital, Denmark. The cohort was identified in a national registry. To identify patients who had resected a cyclops lesion within the first 2 years after ACL-R, patients' surgical records were reviewed. In 2005-2019, 2556 patients underwent primary ACL-R; 176 developed cyclops lesions that were resected within 2 years, equivalent to an incidence of 6.9% (95% confidence interval [CI]: 5.9-7.9). When stratified by the femoral drilling technique used, this incidence was 8.9% (95% CI: 7.7-10.3) with the anteromedial technique and 1.9% (95% CI: 1.0-3.1) with the transtibial technique. The incidence was 8.5% (95% CI: 6.8-10.3) in women and 5.7% (95% CI: 4.6-7.1) in men. Age, graft choice and the presence of cartilage or meniscal lesions did not affect the incidence. The overall incidence of a cyclops lesion removal within 2 years post-ACL-R was 6.9%. This was five times higher with the anteromedial femoral drilling technique than with the transtibial technique. Women had a 47% higher incidence of cyclops lesion removal than men. This is relevant for the surgeon when planning an ACL-R. Level II.

Percutaneous intramedullary screw or rush pin fixation of unstable ankle fractures in patients with fragile soft tissue – retrospective study of 80 cases

IntroductionThe standard surgical procedure for unstable ankle fractures is fixation of the lateral malleolus with a plate and screws. This method has a high risk of complications, especially among patients with fragile skin conditions. The aim of this study was to estimate the re-operation rates and identify complications in patients with an unstable ankle fracture, surgically treated with an intramedullary screw or rush pin.Materials and methodsWe identified all patients who were surgically treated with either a 3.5-mm screw or rush pin at Aarhus University Hospital, Denmark, from 2012 to 2018. Major complications were re-operations within three months. We included 80 patients, of which 55 (69%) were treated with a 3.5-mm intramedullary screw and 25 (31%) with a rush pin. The majority of the study population was female (59) and the mean age was 75 (range 24 to 100) years. Of the 80 patients included, 41 patients had more than 2 comorbidities.ResultsThree patients underwent re-operation within three months due to either fracture displacement or hardware cutout. Radiographs obtained after six weeks showed that nine patients had loss of reduction. Additionally, four patients had superficial wound infections and six patients had delayed wound healing.ConclusionsIntramedullary fixation of distal fibula fractures with either a screw or rush pin has low re-operation rates. However, the high proportion of patients with radiological loss of reduction is concerning.