Aarhus University Research Articles

Jonas Thorup Thomsen, Danish Clergymen and their Book Collections: An investigation into Clerical Libraries, Book Distribution, and Knowledge Circulation in Denmark, c. 1685–1810 (Aarhus: Aarhus University, 2022). 272 s.

Jonas Thorup Thomsen, Danish Clergymen and their Book Collections: An investigation into Clerical Libraries, Book Distribution, and Knowledge Circulation in Denmark, c. 1685–1810 (Aarhus: Aarhus University, 2022). 272 s.

Are orofacial pain and xerostomia associated with differences in diet, sensory perception, appetite and enjoyment of eating?-An explorative study.

Orofacial function is believed to influence an individual's diet. knowledge on appetite and enjoyment of eating in orofacially impaired individuals is scarce. We aimed to explore potential associations between impaired orofacial function, that is, orofacial pain, jaw function limitation and xerostomia, respectively, and diet, appetite, taste perception, as well as the enjoyment of eating. An online questionnaire was shared among Aarhus University's dental patients and through social media. A convenience sample of 351 individuals responded (97 men, 254 women, aged 18-86 years). Participants were divided into groups with and without orofacial pain or xerostomia based on responses. Questions about food intake, appetite, meal-related well-being and oral/general health were included. Data were analysed using Mann Whitney U tests, Spearman's correlation, Chi-square tests, and t-tests. Participants with (n = 123) and without (n = 228) orofacial pain differed significantly regarding age, perceived oral/general health, frequency of consumption of for example cooked vegetables and raw whole fruit, perception of sourness, chewiness, and nausea/pain when eating (p ≤ .031). Participants with (n = 101) and without (n = 250) xerostomia differed significantly regarding perceived oral/general health, intake of prepared fruit, alcohol, ice cream/mousse/pudding, general appetite, intake of breakfast and liquid snacks, nausea/pain when eating, taste and chewiness of food (p ≤ .038). Diet, appetite, taste and sensory perception, as well as enjoyment of eating of individuals reporting orofacial pain and/or xerostomia differed slightly to that of individuals free of such symptoms. However, due to the explorative nature of this study, the results should be interpreted with caution pending further research on potential long-term effects on nutritional status and well-being.

CO2 laser deroofing technique: A robust and effective treatment for hidradenitis suppurativa regardless of comorbidities (a retrospective study of 334 lesions in 130 treated patients)

AbstractBackgroundHidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects the terminal hair follicles in areas rich in apocrine glands. The condition most commonly manifests in the axillae, inframammary areas and genitofemoral region. Prevalence rates range between 1% and 4%. The management of HS encompasses both medical and surgical treatments, with surgical options including wide excision and carbon dioxide (CO2) laser‐assisted deroofing.ObjectivesThe aim of this study is to characterize patients with HS and to evaluate the efficacy of CO2 laser‐assisted deroofing technique in the treatment of chronic HS lesions with a particular focus on recurrence rates.MethodsThis retrospective study included a cohort of 130 Danish patients treated at the Department of Dermatology, Aarhus University Hospital, Denmark, over a 4‐year period. All participants met the established criteria for HS and were treated using the deroofing technique. Data were manually extracted from the electronic patient record and subjected to statistical analysis using Microsoft Excel 2016 and STATA version 15. Kaplan−Meier survival curves were generated, and comparisons were made using the Log‐rank test.ResultsA total of 334 lesions were treated using the deroofing technique; 15.4% had Hurley stage I, 56.9% had Hurley stage II and 27.7% Hurley stage III. Recurrence was seen in 59 of 334 lesions (17.7%), affecting a total of 47 patients. Risk of recurrence was highest during the first 20 months.ConclusionsThis study confirms that CO2 laser deroofing is an effective treatment for chronic HS elements, demonstrating a low recurrence rate. Results showed that factors such as age, sex, diabetes, smoking habits, location of the treated area and lesion size did not significantly influence the risk of recurrence. However, patients with a body mass index greater than 25 showed a borderline significant increased risk of recurrence. The deroofing technique is robust and serves as an important tool in the surgeon's armamentarium.

Efficacy and Safety of the Heat Shock Protein 90 Inhibitor RGRN-305 in Hidradenitis Suppurativa

Hidradenitis suppurativa is a painful immune-mediated disorder with limited treatment options; hence, a need exists for new treatments. To evaluate the feasibility of heat shock protein 90 inhibition by RGRN-305 as a novel mechanism of action in treating moderate to severe hidradenitis suppurativa. This was a parallel-design, double-blind, proof-of-concept, placebo-controlled randomized clinical trial conducted between September 22, 2021, and August 29, 2022, at the Department of Dermatology, Aarhus University Hospital in Denmark. The study included a 1- to 30-day screening period, a 16-week treatment period, and a 4-week follow-up period. Eligibility criteria included age 18 years or older and moderate to severe hidradenitis suppurativa with 6 or more inflammatory nodules or abscesses in at least 2 distinct anatomic regions. Of 19 patients screened, 15 patients were enrolled in the study. Intention-to-treat analysis was performed. Patients were randomly assigned (2:1) to receive oral RGRN-305, 250-mg tablet, or matching placebo once daily for 16 weeks. The primary efficacy end point was the percentage of patients achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR-50) at week 16. Secondary efficacy end points included HiSCR-75 or HiSCR-90, Hidradenitis Suppurativa Physician's Global Assessment, Dermatology Life Quality Index scores, and a pain numeric rating scale. Safety was assessed by adverse events, physical examinations, clinical laboratory measurements, and electrocardiograms. A total of 15 patients were enrolled, completed the study, and were included in all analyses (10 [67%] female; median age, 29 [IQR, 23-41] years). The primary end point HiSCR-50 at week 16 was achieved by a higher percentage in the RGRN-305 group (60% [6 of 10]) than in the placebo group (20% [1 of 5]). Improvements were also observed across all secondary end points at week 16, including higher rates of the harder-to-reach HiSCR levels; 50% (5 of 10) achieved HiSCR-75 and 30% (3 of 10) achieved HiSCR-90, whereas none of the placebo-treated patients achieved HiSCR-75 or HiSCR-90. RGRN-305 was well tolerated, with no deaths or serious adverse events, and treatment-emergent adverse events were similarly frequent between the RGRN-305 and placebo groups. The findings of this trial suggest that heat shock protein 90 inhibition by RGRN-305 offers a novel mechanism of action in treating hidradenitis suppurativa, warranting further evaluation in larger trials. ClinicalTrials.gov Identifier: NCT05286567.

Workplace intervention among pregnant hospital employees – A protocol of a cluster randomized trial

BackgroundSick leave during pregnancy is frequent and 36 % of Danish pregnant employees are on sick leave > 14 days. Health care professionals are considered a risk population. This intervention applies preventive sessions including the pregnant employee, her manager and a midwife in addition to usual practiceat Aarhus University Hospital, Denmark (AUH). It is hypothesised that pregnant employees who participate in preventive sessions will have less sick leave and report better wellbeing compared to the reference group. MethodsAll departments at AUHare cluster randomized. A total of 25 and 24 departments are allocated to the intervention and reference group, respectively. The intervention is protocolled with preventive sessions in addition to usual practice. The reference group receives usual practice. The primary outcome is mean number of days on sick leave during pregnancy. Secondary outcomes are wellbeing measured as physical and mental health, general work ability, work-life balance, manager support, and completed work adjustments during pregnancy. Data on sick leave will be collected from the hospital payment system and survey data will be collected at inclusion and follow-up. DiscussionThis study will contribute to limited experimental research aimed to reduce sickness leave during pregnancy. The overall strength is the study design with easy access to study participants within a large hospital. The main limitation of the study is the high complexity of the study. Trial registrationThe trial is registered in ClinicalTrials.gov with ID number 29-2019-03.

Preface

Proceedings of NSB 2023: 13th Nordic Symposium on Building Physics 12th to 14th of June 2023 Aalborg, Denmark The 13th Nordic Symposium on Building Physics (NSB 2023) took place at Aalborg University in the city of Aalborg, Denmark, from the 12th to the 14th of June, 2023. This conference was organised by the Department of the Built Environment of Aalborg University, with the help of fellow researchers from Aarhus University, the University of Southern Denmark and the Technical University of Denmark.NSB is a renowned international conference series in Building Physics, held every three years since 1987. Although organised in Nordic countries, the conference is in English and is not limited to cold climates. It has grown to attract participants worldwide, to the point that more than half of the participants have been from other countries.This symposium is intended to be a forum for scientists, practitioners, PhD students and other building professionals to share new research results, demonstrate innovative and sustainable building technologies, and discuss current and future challenges and solutions within building physics, heat, air and moisture transfer in buildings, and on aspects of moisture problems in the built environment, energy performance and indoor environmental quality. The NSB 2023 central theme is “Building physics as a key player for the sustainable built environment”. The conference focus is primarily on the following aspects that all require a throughout understanding of building physics:• Heat, air and moisture transport• Measurement and modelling techniques• Material properties• Contaminant transfer (gas phase, airborne pollutants)• Outdoor and indoor climate for building physics analysis• Hygrothermal performance of building envelope• Advanced building envelope systems• Air-tightness, air movement inside and around the buildings• Building materials and components• Facades• Climate change and climate adaptation of buildings• Moisture and mould problems• Investigation methods of moisture and microbial damages• Moisture safety in design, construction, and maintenance• Durability of materials and structures• Repair methods• Architectural design integration• Interaction with HVAC systems and solar shading• Indoor environmental quality: air quality, daylight, thermal comfort and acoustics• Passive, active and low-energy buildings, zero-emission buildings• Retrofitting and conservation of buildings, including historical buildings• Building sustainability and circularity• Integrated BIM solutions for building physics, energy performance and indoor environmental quality• Education about building physics: innovative tools and methodsThe 250 participants of NSB 2023 attended a total of 3 keynotes, 186 paper presentations (149 Scientific Papers and 37 Technical Papers) and one workshop over 3 days and 34 sessions. The Scientific Papers (6-8 pages) are published in the present IOP Journal of Physics: Conference Series proceedings. The Technical Papers (1-6°pages) are published by Aalborg University in a dedicated book of technical papers. All papers presented at NSB 2023 and published in the proceedings or book of technical papers went through a 3-stage double-blind peer-review process: review and acceptance of the abstract, first round of review for the full paper, second round of review of the revised paper, final decision on the paper. All reviews were conducted by the 124 members of the scientific community.List of Conference organising committee, Scientific Committee are available in this Pdf.

Soundscape improvement of 45 Danish nursing homes

This paper describes an analysis of Danish nursing home soundscapes and the subsequent attempt at implementing incremental interventions aiming to improve the soundscapes. Danish nursing homes are challenged by simultaneously being a home, workplace, and institution. Staff and residents will invariably encounter the conflicting environmental characteristics of these disparate functions, including the sound environment. In 2020, Aarhus Municipality launched a project in collaboration with Aarhus University. In the first phase, the authors conducted a soundscape analysis in five nursing homes in Aarhus. This resulted in a report containing recommendations for improving the nursing home soundscape. In the second phase initiated in 2022, soundscape screenings in all 45 nursing homes in Aarhus was conducted, the purpose of which was the mapping of existing sound sources and how staff and residents perceived them. The results of the screenings confirmed the findings in the report with certain local differences. As of May 2023, various soundscape interventions are being tested in several nursing homes. As this process is still ongoing, this paper will review the results and experiences collected so far. As part of this long-term project, the authors wish to address the gap between soundscape analysis and practical soundscape interventions.

Prevalence of Resistance-Associated Bruton Tyrosine Kinase (BTK) C481 Mutations By Prior Treatment Status Among Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): A Real-World Observational Study

Introduction: BTK mutations, particularly at C481, are an important cause of acquired resistance to covalent BTK inhibitors (BTKi) among pts with CLL/SLL. Almost two-thirds of pts whose disease progresses on a covalent BTKi have a BTK C481 mutation detectable at progression. Furthermore, BTK C481 mutations have been detected up to 28 mo before progression among pts with CLL/SLL treated with a covalent BTKi. The early identification of pts who are at risk for developing covalent BTKi resistance is critical to optimize clinical treatment of pts with CLL/SLL. In this cross-sectional study, the prevalence of BTK C481 mutations was evaluated in a real-world population of patients with CLL/SLL. Methods: Patients with CLL/SLL undergoing standard-of-care treatment at Aarhus University Hospital and Gødstrup Hospital in Denmark were recruited. Eligible patients were ≥18 y old, had a confirmed diagnosis of CLL/SLL, provided a whole blood sample during their clinical visit, and had CLL cells detectable by flow cytometry. DNA was assayed from newly collected blood samples for 6 BTK C481 mutations known to confer resistance to covalent BTKi (c.1442G>C, c.1441T>A, c.1442_1443delinsCT, c.1442G>T, c.1441T>C, c.1442G>A), using droplet digital polymerase chain reaction with assay sensitivities of 0.1% variant allele frequency or less depending on the variant. A patient was considered to have a BTK C481 mutation “detected” if any of the variants were present above the limit of detection. Demographic, clinical, and treatment characteristics were extracted from medical records. Patients were grouped by treatment status at the time of blood collection: treatment naive (group 1), treated with therapies other than a BTKi (BTKi naive; group 2), and previously treated with or currently receiving a covalent BTKi (BTKi experienced; group 3). The primary objectives were to determine the presence of BTK C481 mutations in pts who had not received prior BTKi and the natural history of BTK C481 mutations in BTKi-experienced pts with CLL/SLL. Demographic and clinical variables were summarized descriptively. The prevalence of BTK C481 mutations was calculated and reported as a percentage with estimated 95% CIs. Results: Between October 2021 and December 2022, 130 patients with clinical and BTK C481 mutation data available were enrolled (group 1, n = 53; group 2, n = 29; group 3, n = 48). The median (range) age at diagnosis was 66 y (48-85) in group 1, 66 y (37-86) in group 2, and 62 y (43-78) in group 3. The median (range) age at first therapy was 72 y (39-86) in group 2 and 65 y (44-80) in group 3. In group 1, 38 pts (72%) had Rai stage 0 disease at diagnosis compared with 8 pts (28%) in group 2 and 13 (27%) in group 3. IGHV was unmutated in 8 pts (15%) in group 1, 13 (45%) in group 2, and 33 (69%) in group 3. In group 2, 18 pts (62%) had received 1 prior line of therapy, 4 (14%) had received 2 prior lines, and 4 (14%) had received ≥3 prior lines (not including therapy received at the time of blood collection). In group 3, 17 pts (35%) had received 1 prior line of therapy, 12 (25%) had received 2, and 11 (23%) had received ≥3. BTK C481 mutations were detected in 0 patients (0%) in group 1, 0 pts (0%) in group 2, and in 10 pts (21%; 95% CI, 10-35) in group 3. Of the 10 pts with detectable BTK C481 mutations, 5 had received a BTKi as prior therapy and 5 were receiving a BTKi at the time of blood collection (Table). The median cumulative exposure to a covalent BTKi in group 3 was 27 mo (range, 1-67), with 32 pts having a cumulative exposure of ≤36 mo. BTK C481 mutations were only detected among the 16 pts with cumulative exposure to a covalent BTKi of >36 mo. Of 37 pts who were receiving BTKi therapy at the time of blood collection, 5 (14%) had a detectable BTK C481 mutation. Conclusions: In this real-world cross-sectional study, BTK C481 mutations were observed in 21% of BTKi-experienced pts with CLL/SLL, all of whom had a cumulative exposure to BTKis of >36 mo. Because two-thirds of BTKi-experienced pts had <36 mo of BTKi exposure, the prevalence of BTK C481 mutations may be higher in populations with longer BTKi exposure. Further analyses of the natural history of BTK C481 mutations will help identify patients who are at risk of covalent BTKi resistance. Recruitment for this study is ongoing.

The Danish child and parent Gait Outcomes Assessment List questionnaires were reliable and valid for cerebral palsy.

We investigated the reliability and validity of the Danish child and parent versions of the Gait Outcomes Assessment List (GOAL) questionnaires for ambulatory children with cerebral palsy (CP). Translation and cultural adaptations were performed and content validity evaluated. Participants were enrolled between 2016 and 2018 from Aarhus University Hospital, Denmark. Children and parents completed the GOAL questionnaires twice for test-retest reliability. Discriminative validity was evaluated by comparing the child and parent GOAL scores between children with Gross Motor Function Classification System (GMFCS) levels I and II. The concurrent validity of the GOAL questionnaires were investigated by comparing them with Challenge-20, which assesses motor skills in children with CP. We studied 59 children (57% boys) with CP and GMFCS I-II at a mean age of 10.6 years. Test-retest intra-class correlations were excellent for the children (0.91, 95% confidence interval (CI) 0.83-0.96) and good for the parents (0.83, 95% CI 0.67-0.91). GOAL scores decreased with increasing GMFCS (p < 0.05). Both versions correlated well. The mean children's scores were significantly (6.2/100) higher than the parents' (p < 0.001). The GOAL scores correlated positively with Challenge-20. The Danish GOAL child and parent questionnaires demonstrated good reliability and content and discriminative and concurrent validity.

A cruise-and-crash model of the cost of ruling

ABSTRACT Since the publication of Nannestad and Paldam ([1999]. “The Cost of Ruling. A Foundation Stone for Two Theories,” University of Aarhus, Denmark. Working Paper No. 1999-9. http://www.martin.paldam.dk/Papers/Gamle/Cost-of-ruling.PDF.) on the cost of ruling, their finding that incumbents lose votes in the order of 2 to 3 percentage points per term has gained the status of something like an “inductive law” of politics (Budge [2019]. Politics. A Unified Introduction to How Democracy Works. Abingdon/Oxon/New York: Routledge, 2019). We suggest that this generalization conjures up an inaccurate image, that of a gradual reduction of a ruling party’s vote over the course of an incumbency or “spell.” Our own analyses of national and state or provincial elections in Australia, Canada, Germany, and the United States demonstrate that this interpretation is not correct. Instead, while they remain in office the ruling party cruises along, averaging more or less the same share of the vote election after election, until they fail to win another term, at which point all or nearly all of the cost of ruling, like a balloon payment on a loan, comes due. Moreover, on average the magnitude of the loss is independent of the length of their stay in office. This means that a long incumbency confounds the expectations fostered by the “inductive law” because the overall loss – which we find to be reasonably constant across a wide spectrum of data sets – divided by a spell length exponentially distributed from one to many terms cannot be a constant. Nannestad and Paldam's assertion of 2.25 percentage points per term vote loss is at best a description of a mid-range value.

Implementation of a satellite-based tool for the quantification of CH4 emissions over Europe (AUMIA v1.0) – Part 1: forward modelling evaluation against near-surface and satellite data

Abstract. Methane is the second-most important greenhouse gas after carbon dioxide and accounts for around 10 % of total European Union greenhouse gas emissions. Given that the atmospheric methane budget over a region depends on its terrestrial and aquatic methane sources, inverse modelling techniques appear as powerful tools for identifying critical areas that can later be submitted to emission mitigation strategies. In this regard, an inverse modelling system of methane emissions for Europe is being implemented based on the Weather Research and Forecasting (WRF) model: the Aarhus University Methane Inversion Algorithm (AUMIA) v1.0. The forward modelling component of AUMIA consists of the WRF model coupled to a multipurpose global database of methane anthropogenic emissions. To assure transport consistency during the inversion process, the backward modelling component will be based on the WRF model coupled to a Lagrangian particle dispersion module. A description of the modelling tools, input data sets, and 1-year forward modelling evaluation from 1 April 2018 to 31 March 2019 is provided in this paper. The a posteriori methane emission estimates, including a more focused inverse modelling for Denmark, will be provided in a second paper. A good general agreement is found between the modelling results and observations based on the TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor satellite. Model–observation discrepancies for the summer peak season are in line with previous studies conducted over urban areas in central Europe, with relative differences between simulated concentrations and observational data in this study ranging from 1 % to 2 %. Domain-wide correlation coefficients and root-mean-square errors for summer months ranged from 0.4 to 0.5 and from 27 to 30 ppb, respectively. On the other hand, model–observation discrepancies for winter months show a significant overestimation of anthropogenic emissions over the study region, with relative differences ranging from 2 % to 3 %. Domain-wide correlation coefficients and root-mean-square errors in this case ranged from 0.1 to 0.4 and from 33 to 50 ppb, respectively, indicating that a more refined inverse analysis assessment will be required for this season. According to modelling results, the methane enhancement above the background concentrations came almost entirely from anthropogenic sources; however, these sources contributed with only up to 2 % to the methane total-column concentration. Contributions from natural sources (wetlands and termites) and biomass burning were not relevant during the study period. The results found in this study contribute with a new model evaluation of methane concentrations over Europe and demonstrate a huge potential for methane inverse modelling using improved TROPOMI products in large-scale applications.

Maternal pre-pregnancy BMI and reproductive health in adult sons: a study in the Danish National Birth Cohort.

Is maternal pre-pregnancy BMI associated with semen quality, testes volume, and reproductive hormone levels in sons? Maternal pre-pregnancy BMI was associated with an altered reproductive hormone profile in young adult sons, characterized by higher levels of oestradiol, LH, and free androgen index (FAI) and lower levels of sex hormone-binding globulin (SHBG) in sons born of mothers with pre-pregnancy overweight and obesity. Evidence suggests that maternal pre-pregnancy BMI may influence reproductive health later in life. Only one pilot study has investigated the association between maternal pre-pregnancy BMI and reproductive health outcomes in sons, suggesting that a high BMI was associated with impaired reproductive function in the adult sons. A population-based follow-up study of 1058 young men from the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019, was carried out. In total, 1058 adult sons (median age 19 years, 2 months), born 1998-2000 by mothers included in the DNBC, participated in FEPOS. At a clinical examination, they provided a semen and blood sample, measured their testes volume, and had height and weight measured. Maternal pre-pregnancy BMI was obtained by self-report in early pregnancy. Semen characteristics, testes volume, and reproductive hormone levels were analysed according to maternal pre-pregnancy BMI categories and as restricted cubic splines using negative binomial and ordinary least square regression models. Mediation analyses examined potential mediation by the sons' birthweight, pubertal timing, fat mass, and BMI. Additional analyses investigated the role of paternal BMI in the potential associations between maternal BMI and reproductive health outcomes. We found no consistent associations between maternal pre-pregnancy BMI and semen characteristics or testes volume. Sons of mothers with higher pre-pregnancy BMI had higher oestradiol and lower SHBG levels, both in a dose-dependent manner. Sons of mothers with pre-pregnancy obesity (≥30 kg/m2) had higher LH levels and a higher FAI than sons born by mothers with normal pre-pregnancy BMI (18.5-24.9 kg/m2). The mediation analyses suggested that the effect of maternal pre-pregnancy BMI on higher levels of oestrogen, LH, and FAI was partly mediated by the sons' birthweight, in addition to adult fat mass and BMI measured at the clinical examination, whereas most of the effect on lower levels of SHBG was primarily mediated by the sons' own fat mass and BMI. Paternal BMI was not a strong confounder of the associations in this study. This study was based in a population-based cohort with a low prevalence of overweight and obesity in both mothers and adult sons. Some men (10%) had blood for reproductive hormone assessment drawn in the evening. While several potential confounding factors were accounted for, this study's inherent risk of residual and unmeasured confounding precludes provision of causal estimates. Therefore, caution should be given when interpreting the causal effect of maternal BMI on sons' reproductive health. Given the widespread occurrence of overweight and obesity among pregnant women, it is imperative to thoroughly examine the potential consequences for reproductive hormone levels in adult sons. The potential effects of maternal pre-pregnancy obesity on sons' reproductive hormone profile may potentially be partly avoided by the prevention of overweight and obesity in the sons. The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Møller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University, Independent Research Fund Denmark (9039-00128B), and the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible. The authors declare that they have no conflict of interest. N/A.

Distal subsartorial compartment block of the saphenous nerve - A dissection study and a patient case series

Study objectiveA saphenous nerve block is an important tool for analgesia after foot and ankle surgery. The conventional midthigh approach to saphenous nerve block in the femoral triangle may impede ambulation by impairing quadriceps motor function. Primary objective: Developing a selective saphenous nerve block targeting the nerve distal to its emergence from the adductor canal in the subsartorial compartment. DesignThis study consists of A) a dissection study and B) Data from a clinical case series. SettingA) Medical University of Innsbruck, Austria (dissection of 15 cadaver sides) and.B) Aarhus University Hospital, Denmark (5 patients). InterventionsA) Five mL of methylene blue was injected into the subsartorial compartment distal to the intersection of the saphenous nerve and the tendon of the adductor magnus guided by ultrasound. B) Five patients undergoing major hindfoot and ankle surgery had a subsartorial compartment block with 10 mL of local anesthetic in addition to a popliteal sciatic nerve block. MeasurementA) The frequencies of staining the saphenous and medial vastus nerves. B) Assessment of postoperative pain by NRS score (0−10) and success rate of saphenous nerve block by presence of cutaneous anesthesia in the anteromedial lower leg, and motor impairment by ability to ambulate. Main resultsA) The saphenous nerve was stained in 15/15 cadaver sides. A terminal branch of the medial vastus nerve was stained in 2/15 cadaver sides. B) All patients were fully able to ambulate without support. No patients had any post-surgical pain from the anteromedial aspect of the ankle and foot (NRS score 0). The success rate of saphenous nerve block was 100%. ConclusionThe saphenous nerve can be targeted in the subsartorial compartment distal to the intersection of the nerve and the tendon of the adductor magnus. The subsartorial compartment block provided efficient analgesia without quadriceps motor impairment.

Toxicometabolomics as a tool for next generation environmental risk assessment.

Traditionally applied methodology in environmental risk assessment (ERA) has fallen out of step with technological advancements and regulatory requirements, challenging effectiveness and accuracy of the assessments. Extensive efforts have been focused towards a transition to a more data-driven and mechanistically-based next generation risk assessment. Metabolomics can produce detailed and comprehensive molecular insight into affected biochemical processes. Combining metabolomics with environmental toxicology can help to understand the mechanisms and/or modes of action underlying toxicity of environmental pollutants and inform adverse outcome pathways, as well as facilitate identification of biomarkers to quantify effects and/or exposure. This Technical Report describes the activities and work performed within the frame of the European Food Risk Assessment Fellowship Programme (EU-FORA), implemented at the section 'Environmental Chemistry and Toxicology' at the Department of Environmental Science at Aarhus University in Denmark with synergies to an ongoing H2020 RIA project 'EndocRine Guideline Optimisation' (ERGO). In accordance with the 'training by doing' principles of the EU-FORA, the fellowship project combined the exploration of the status of scientific discussion on methodology in ERA through literature study with hands-on training, using the metabolomics analysis pipeline established at Aarhus University. For the hands-on training, an amphibian metamorphosis assay (OECD test no.231) was used as a proof-of-concept toxicometabolomics study case. Both a targeted biomarker - and an untargeted metabolomics approach was applied.

The Most Cited Modern Articles in Refractive Surgery (2010-2020).

To provide a comprehensive analysis of the most highly cited modern articles in refractive surgery, those published between 2010 and 2020, and compare these results to a list of the most highly cited articles in refractive surgery from all timepoints. The Scopus database was searched for articles pertaining to refractive surgery using multiple search terms to identify the top 100 most cited articles in refractive surgery published between 2010 and 2020. Articles were reviewed for relevance and ranked based on total citations accrued. The 100 most cited modern articles in refractive surgery were identified. The article with the most citations by Sekundo et al has garnered nearly 600 citations to date. Almost all articles (88%) included in the top 100 had 200 or more citations. Intraocular lens (34 articles), keratorefractive lenticule extraction (ie, small incision lenticule extraction) (27 articles), and laser in situ keratomileusis (17 articles) were the predominant topics. Aarhus University in Denmark generated the most articles (5), whereas numerous articles originated from multiple countries, including the United States (16), United Kingdom (10), France (8), Spain (8), China (7), and Germany (7). This list provides a comprehensive assessment of the most cited modern articles in refractive surgery and demonstrates key focuses and trends in the field over the past decade. Intraocular lens and keratorefractive lenticule extraction were the primary topics. There was a broader representation of procedures, topics, authors, and country of origin as compared to prior work. [J Refract Surg. 2023;39(11):784-790.].

Danish Prostate Cancer Consortium Study 1 (DPCC-1) protocol: Multicentre prospective validation of the urine-based three-microRNA biomarker model uCaP

IntroductionThe primary objective of the Danish Prostate Cancer Consortium Study 1 (DPCC-1) is to provide validation for a novel urine-based microRNA biomarker, called uCaP, for a diagnosis of prostate cancer.Methods...

The testicular microvasculature in Klinefelter syndrome is immature with compromised integrity and characterized by excessive inflammatory cross-talk.

Does Klinefelter syndrome (KS) lead to a distinct gene expression pattern at single-cell level in the testes that could provide insight into the reported microvascular dysfunction in the testes? A distinct gene expression pattern within microvascular-associated cells of males with KS suggests excessive endothelial cell (EC) activation, disorganized vessel formation, and the presence of immature vessels with compromised integrity. Recent studies show that males with KS exhibit microvascular dysfunction in their testes, which affects blood flow and is associated with lower circulating levels of testosterone. A comparative cross-sectional study of males with KS (n = 6), non-obstructive azoospermia (NOA) (n = 5), cryptozoospermia (n = 3), and controls (n = 15) was carried out. We analyzed publicly available single-cell RNA sequencing data of testicular cells from males with KS, males with NOA, males with cryptozoospermia, and controls. The integration of these datasets allowed us to analyze gene expression profiles and communication patterns among the cell types within the testis and to identify capillary ECs to investigate changes at the microvascular level. Rooted in changes at the single-cell level, our study demonstrates a shift in gene expression forming the foundation for altered cellular communication, microvascular remodeling, and pro-inflammatory responses within the testes of males with KS. We identified genes that were dysregulated in capillary ECs from males with KS (Padj < 0.05). Specifically, the unique microvascular gene expression in males with KS indicated enhanced capillary EC activation and increased inflammatory cross-talk, leading to impaired vessel maturation and increased EC barrier permeability. Our study is constrained by an unbalanced design, with varying sample sizes and number of cells within each group. We acknowledge the restricted access to clinical information. In addition, our findings were deduced from changes in gene expression, which limits us to infer potential biological consequences arising from these alterations. Furthermore, the absence of a pre-pubertal age group limits the generalizability of our findings and warrants further investigation. This study offers novel insights into the testicular pathophysiology in KS and underscores the potential contribution of microvascular dysfunction to the hypogonadism and infertility observed in males with KS. While this study aims to better understand the microvascular dysfunction in KS, the precise connections to testosterone deficiency and testicular atrophy remain to be fully elucidated. A.S. was supported by the Independent Research Fund Denmark (0134-00130B). C.H.G. was supported by Novo Nordisk Foundation (NNF15OC0016474, NNF20OC0060610), 'Fonden til lægevidenskabens fremme', the Familien Hede Nielsen foundation and the Independent Research Fund Denmark (0134-00406A). E.B.J. was supported by Aarhus University and E.B.J. and C.H.G by the Independent Research Fund Denmark (2096-00165A). J.M.K. was supported by Lundbeckfonden (R307-2018-3667), Carlsberg Fonden (CF19-0687), Novo Nordisk Fonden (0073440) and Steno Diabetes Center Aarhus (SDCA). The authors declare no conflicts of interest. N/A.

Role of high‑sensitivity C‑reactive protein in patients with sarcoma.

Immunotherapy has shown promising results in lung cancer and melanomas; however, the responses have been poor in patients with sarcoma. Understanding the relationship between the immune system and sarcoma is essential to develop improved immunotherapy approaches. High-sensitivity C-reactive protein (hs-CRP) has been proposed as a prognostic marker in other cancer types; however, to the best of our knowledge, the association between hs-CRP levels and mortality in patients with sarcoma has not been investigated. The present prospective, non-randomised, non-interventional explorative study investigated the prognostic value of hs-CRP in patients with sarcoma. Patients referred to the sarcoma centre of Aarhus University Hospital (Aarhus, Denmark) were included between April 2014 and December 2020. Clinical data were obtained from the national quality sarcoma database and biomarkers other than hs-CRP were obtained from the clinical laboratory information system. The study cohort consisted primarily of patients with localised sarcoma. hs-CRP was significantly higher in patients with bone sarcoma (P=0.022) and soft tissue sarcoma (STS; P<0.001) compared with control patients. For STS, grade III tumours but not metastatic disease were associated with a higher hs-CRP level (P=0.0001). Elevated hs-CRP levels were associated with increased overall mortality [hazard ratio (HR), 1.91; 95% CI, 1.33-2.75; P=0.001]. Furthermore, elevated hs-CRP levels were also associated with decreased progression-free survival (HR, 1.64; 95% CI, 1.17-2.29; P=0.004). Furthermore, for patients with hs-CRP <8 mg/l, higher hs-CRP was associated with an increased risk of recurrent disease and reduced overall survival compared with those of patients with low hs-CRP. In conclusion, the present study demonstrated that hs-CRP was a prognostic factor for overall mortality and progression-free survival in patients with localised sarcoma at the time of diagnosis. Further studies are required to investigate the mechanism behind the association between hs-CRP and sarcoma prognosis and its potential use in clinical practice.

Diagnostic Workup, Treatment Patterns, and Clinical Outcomes in Early-Stage IB-IIIA Non-Small-Cell Lung Cancer Patients in Denmark.

Despite recent improvements in early-stage non-small-cell lung cancer (NSCLC), disease relapse remains challenging. Moreover, real-world evidence on long-term follow-up of disease-free survival (DFS) and recurrence patterns in a large, unselected cohort of early-stage NSCLC patients is lacking. This cohort study aimed to assess clinical characteristics, diagnostic workup, treatment, survival, and risk of disease relapse among early-stage NSCLC patients. Adult patients with stage IB, II, or IIIA NSCLC diagnosed and/or treated at Aarhus University Hospital in Denmark from January 2010 to December 2020 were included and followed-up until May 2021. Comprehensive clinical data were collected from electronic medical records of eligible patients and linked to Danish register data. The study population comprised 1341 early-stage NSCLC patients: 22%, 40%, and 38% were diagnosed with stage IB, II, and IIIA disease, respectively. In total, 42% of patients were tested for epidermal growth factor receptor (EGFR), of whom 10% were EGFR-mutation-positive (EGFRm+). Half of all patients received surgery, and nine percent of patients received stereotactic body radiation therapy (SBRT). Disease-free survival 5 years post-diagnosis was 49%, 42%, and 22% for stage IB, II, and stage IIIA patients, respectively. DFS improved over time both for patients treated with surgery and SBRT. However, disease relapse remained a challenge, with approximately 40% of stage IIIA having relapsed 3 years post-diagnosis. This study contributes important knowledge that puts clinical trials on new perioperative treatment modalities for early-stage NSCLC patients into perspective. Our findings cover an essential evidence gap on real-world DFS and recurrence dynamics, confirming that despite an improvement in DFS over time and across different treatment modalities, disease relapse remains a monumental challenge. Therefore, better treatment strategies are needed.

Poor usability of computer-assisted navigation for hip fracture surgery

IntroductionThe STRYKER ADAPT computer-assisted navigation system provides intraoperative feedback to the surgeon regarding implant placement of the Gamma3 nail. The usability of the ADAPT system has not been evaluated. The aim of the study was to investigate the perceived usability of the ADAPT system.Materials and methodsThis was a descriptive study with prospectively collected data. ADAPT was introduced at Aarhus University Hospital in February 2021. Prior to introduction, surgeons at the department attended a general introduction to the system. ADAPT was introduced to the surgical nurses and was on display at the surgical ward at more than one occasion, where personal introduction to the system was possible. After introduction, it was mandatory to use ADAPT when using the Gamma3 nail to treat intertrochanteric femur fractures. After each procedure, primary and an eventual supervisor answered a questionnaire, which encompassed the System Usability Scale (SUS) questionnaire. The SUS is a ten-item questionnaire regarding the perceived usability of a system. SUS scores were translated to adjectives, describing user experience on a 7-point adjective scale (worst imaginable, awful, poor, ok, good, excellent, best imaginable). User acceptability, defined as “not acceptable”, “marginal” or “acceptable”, was also used to interpret the SUS scores.ResultsADAPT was used in 50 procedures by 29 different surgeons, with varying skill-level. Median SUS-score after first-time use of ADAPT for all 29 surgeons was 43 (range: 5–60), which translated to “poor” or “not acceptable”. For surgeons who performed ≥ 3 ADAPT-assisted procedures, there were no statistically significant difference in their first to latest SUS-score (median difference: 4.3, p = 0.5). In free text comments ADAPT was positively described as helpful in placement of K-wire and providing educational opportunities for inexperienced surgeons and negatively as inconsistent, slow, time consuming, and causing excessive fluoroscopy.ConclusionsUsability and acceptability of ADAPT was rated as “poor” or “not acceptable” by the majority of operating surgeons. ADAPT has not been used at our institution based on these findings. The System Usability Scale may be used in further research exploring usability and acceptability of novel computer-assisted navigation systems for orthopaedic surgery.