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The impact of demographic, lifestyle, and seminal factors on the sperm chromatin structure assay (SCSA) parameters was evaluated in a population of 277 healthy Danish men. This cohort was established within the framework of a European Concerted Action on occupational hazards to male reproductive capability in order to examine the possible reproductive effects of exposure to styrene or pesticides. The SCSA measures the susceptibility of sperm DNA to in-situ acid-induced denaturation, by multiparameter flow cytometric analysis after staining with the DNA-specific fluorescent dye acridine orange. The green versus red bivariate cytogram patterns were quite variable among donors, showing a wide heterogeneity of sperm DNA denaturability. Nevertheless, in those cases where we had the possibility to measure two semen samples from the same donor, the cytogram pattern remained stable over time (0.64 < r < 0.78). Analysis of variance demonstrated that the SCSA results can be influenced by the age of the donor (P < 0.0001), smoking habits (P < 0.05), the presence of leukocytes and immature germ forms in the ejaculate (P < 0.0001), and the duration of sexual abstinence (P < 0.0001). Furthermore, the relationship between the SCSA data and sperm concentration, morphology, and vitality was weak (-0.22 < r < -0.46). Therefore, the SCSA provides independent and complementary measurements of semen quality and is thus a useful tool for epidemiological studies, but the effects of some confounders should be accounted for in the survey design and analysis. [ABSTRACT FROM PUBLISHER]

In conventional treatment the patient with a diabetic foot ulcer travels to hospital for consultations with the experts. We conducted an organizational analysis of the cooperation taking place when telemedicine was used for treatment at home instead. In a pilot study, five patients were offered three video consultations in their home, replacing visits to the outpatient clinic. The equipment consisted of mobile videophones and an online ulcer record. The introduction of simultaneous communication between all participants solved the problem of the patient having to act as messenger between the hospital and the visiting nurse; there were other benefits as well. However, this new organization required increased efforts for coordination and may have incurred extra costs in the case of delays. Thus when designing telemedicine systems, the goal should be to facilitate the coordination and lower the barriers to real-time communication, but at the same time provide mechanisms for asynchronous communication in situations where synchronous communication is not possible. [ABSTRACT FROM AUTHOR]

The treatment of diabetic foot ulcers may not always be well organized and not all patients have access to expert evaluation. We investigated the use of telemedicine to enable a visiting nurse (in the patient's home) to coordinate the treatment with experts (at the hospital). The equipment consisted of a UMTS videophone and an Internet-based patient record. Field studies were carried out at the outpatient clinic and by following visiting nurses. A total of 15 participants were invited to five workshops and experiments held in our laboratories, at the hospital, and between hospital and patients' homes. Finally, in a pilot test, five patients were offered three teleconsultations at their homes in lieu of visits to the hospital. Preliminary results were promising: (1) both clinicians and patients found the equipment easy to use; (2) the doctor could prescribe treatment at a distance; (3) the visiting nurse had realtime contact with the hospital and treatment could begin immediately according to the doctor's orders; (4) the patient saved time in not having to travel to the hospital. [ABSTRACT FROM AUTHOR]

Background: Evolving imaging modalities, increased awareness, and prostate-specific antigen testing in men with synchronous metastatic prostate cancer (mHSPC) are expected to have prolonged survival. Here we analyze trends in survival among men diagnosed with synchronous metastatic prostate cancer in Denmark., Methods: Here, we included all men diagnosed with mHSPC (N = 12,017) in Denmark between January 1st, 1995, and December 31st, 2021. Men were followed until December 31st, 2022. Median time to death was calculated by the Kaplan Meier method and the 3-year risk of prostate cancer death per calendar year was estimated by the Aalen-Johansen estimator from time of diagnosis., Findings: Median follow-up was 9 years (IQR: 4-15), from 2015 59 % of the men with mHSPC had treatment beyond androgen depletion therapy. Median survival increased from 1.7 years (IQR: 1·3-2·0) to 3.8 years (IQR: 3·3-4·2) in men diagnosed in 1995 and 2018, respectively (p < 0·001), after which median survival was not reached. The prostate cancer-specific mortality three years after diagnosis decreased from 66 % (95 %CI: 60-72) in 1995 to 28 % (95 %CI: 25-32) in 2019 (p < 0·001). From the period 1995-1999 to 2015-2021 median overall survival increased from 1·7 years (IQR: 0·8-3·7) to 4·5 years (IQR: 2·4-not reached; p < 0·001) in men age < 65 years and from 1·5 years (IQR: 0·7-2·9) to 3·1 years (IQR: 1·6-5·7; p < 0.001) in men older than 74 years at diagnosis., Interpretation: The improved survival suggests that, among other contributing factors, implementing novel therapies has likely been efficacious outside the clinical trial setting. Still, most men diagnosed with synchronous metastatic prostate cancer will die of prostate cancer. As such the need for life-prolonging and age-tailored treatment trials remains evident., Competing Interests: Declaration of Competing Interest Hein V. Stroomberg has received travel expenses, and speaking and lecture fees from MSD Denmark, and project support from Pfizer Denmark outside of the scope of this manuscript. J. Thomas Helgstrand has received prior speaker fee from Astellas Nordic, and advisory and consultancy for Janssen, Recordati, Astellas, and Bayer outside the scope of this manuscript. Klaus Brasso has received speaker fees from Bayer Denmark outside the scope of this manuscript. Signe Benzon Larsen reports no conflicts of interest. Andreas Røder has received project support from Bayer Denmark and Pfizer Denmark, prior speaker fees from Astellas Nordic, and advisory and consultancy for Pfizer, Amgen, MSD, Sanofi, Janssen, Astra-Zeneca, Recordati, Astellas, Bayer, Orion, Ferrin, Medtronic, and Intuitive outside of the scope of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of activated sludge models (ASMs) is a common way in the field of wastewater engineering in terms of plant design, development, optimization, and testing of stand-alone treatment plants. The focus of this study was the development of a joint control system (JCS) for a municipal wastewater treatment plant (mWWTP) and an upstream industrial wastewater treatment plant (iWWTP) to create synergies for saving aeration energy. Therefore, an ASM3 + BioP model of the mWWTP was developed to test different scenarios and to find the best set-points for the novel JCS. A predictive equation for the total nitrogen load (TN) coming from the iWWTP was developed based on real-time data. The predictive TN equation together with an optimized aeration strategy, based on the modelling results, was implemented as JCS. First results of the implementation of the JCS in the real environment showed an increase in energy efficiency for TN removal., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY-NC 4.0), which permits copying, adaptation and redistribution for non-commercial purposes, provided the original work is properly cited (http://creativecommons.org/licenses/by-nc/4.0/).)

Purpose: To investigate the early implementation of combined systematic and targeted (cBx) primary biopsy in prostate cancer diagnosis and define the concordance in Gleason grading (GG) of different biopsy techniques with radical prostatectomy (RP) pathology., Methods: This population-based analysis includes data on all men in Denmark who underwent primary cBx or standalone systematic (sBx) prostate biopsy between 2012 and 2016. Biopsy results were compared to RP pathology if performed within a year. Concordance measurement was estimated using Cohen's Kappa, and the cumulative incidence of cancer-specific death was estimated at 6 years with the Aalen-Johansen estimator., Results: Concordance between biopsy and RP pathology was 0.53 (95CI: 0.43-0.63), 0.38 (95CI: 0.29-0.48), and 0.16 (95CI: 0.11-0.21) for cBx, targeted biopsy (tBx), and sBx, respectively. For standalone sBx and RP, concordance was 0.29 (95CI: 0.27-0.32). Interrelated GG concordance between tBx and sBx was 0.67 (95CI: 0.62-0.71) in cBx. The proportion of correctly assessed GG based on RP pathology was 54% in both cBx and standalone sBx. Incidence of prostate cancer-specific death was 0% regardless of biopsy technique in GG 1, and 22% (95CI: 11-32), 30% (95CI: 15-44), and 19% (95CI: 7.0-30) in GG 5 for cBx, tBx, or sBx, respectively., Conclusion: Overall, the cBx strategy demonstrates higher concordance to RP pathology than the standalone sBx. However, cBx exhibits more overgrading of the GG of RP pathology compared to sBx. Ultimately, the classic grading system does not take change in the diagnostic pathway into account, and grading should be altered accordingly to ensure appropriate treatment., (© 2024. The Author(s).)

Background: Debate regarding a nomenclature change for grade group 1 (GG 1) prostate cancer to noncancer has been revived, as this could be a powerful tool in reducing the overtreatment of indolent disease., Objective: To describe outcomes for all men diagnosed with GG 1 prostate cancer in the Danish population, with a focus on men followed conservatively., Design, Setting, and Participants: This was a population-based observational study using data from the Danish Prostate Registry., Outcome Measurements and Statistical Analysis: We measured the cumulative incidence of curative treatment, endocrine treatment, and cause-specific mortality., Results and Limitations: The cumulative incidence of endocrine therapy at 10 yr was 5.3% (95% confidence interval [CI] 4.3-6.3%) for men with initial active surveillance and 21% (95% CI 19-23%) for men with initial watchful waiting for localized GG 1. In the GG1 cohort, the prostate cancer-specific mortality rate at 15 yr was 14% (95 CI% 11-16%) for men on watchful waiting, 10% (95 CI% 6.7-14%) for men with prostate-specific antigen <10 ng/ml on watchful waiting, and 16% (95 CI% 13-19%) for men who did not receive curative-intent treatment or histological assessment. The study is limited by the historic nature of the observations over a period during which diagnostic procedures and treatments have evolved., Conclusions: GG 1 cancer can lead to disease-specific mortality in men with localized prostate cancer, and changing the nomenclature for all men may lead to undertreatment., Patient Summary: Key opinion leaders have suggested that prostate cancers of Gleason grade group 1 (GG 1) should be renamed as noncancer to reduce overtreatment. The argument is that low-grade cancer does not metastasize. However, our nationwide population-based study showed that death from prostate cancer can occur in some men diagnosed with GG 1 disease. These men should be considered in discussions on changing the name for GG 1 prostate cancer., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Recent studies indicate an important role of bacteriophages for successful fecal microbiota transplantation (FMT). However, wider clinical applications of FMT are hampered by to donor variability and concerns of infection risks by bacteria and human viruses. To overcome these challenges, mouse cecal and human fecal material were propagated in a chemostat fermentation setup supporting multiplication of bacteria, and phages, while propagation of eukaryotic viruses will be prevented in the absence of eukaryotic host cells. The results showed decrease of the median relative abundance of viral contigs of classified eukaryotic viruses below 0.01%. The corresponding virome profiles showed dilution rate dependency, a reproducibility between biological replicates, and maintained high diversity regarding both the human and mouse inocula. This proof-of-concept cultivation approach may constitute the first step of developing novel therapeutic tools with high reproducibility and with low risk of infection from the donor material to target gut-related diseases., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases., Methods: To overcome these challenges, we developed methods to broaden FVT's clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline., Results: FVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy., Conclusions: This proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches. Video Abstract., (© 2024. The Author(s).)

The protein alpha-synuclein (αSyn) plays a critical role in the pathogenesis of synucleinopathy, which includes Parkinson's disease and multiple system atrophy, and mounting evidence suggests that lipid dyshomeostasis is a critical phenotype in these neurodegenerative conditions. Previously, we identified that αSyn localizes to mitochondria-associated endoplasmic reticulum membranes (MAMs), temporary functional domains containing proteins that regulate lipid metabolism, including the de novo synthesis of phosphatidylserine. In the present study, we have analyzed the lipid composition of postmortem human samples, focusing on the substantia nigra pars compacta of Parkinson's disease and controls, as well as three less affected brain regions of Parkinson's donors. To further assess synucleinopathy-related lipidome alterations, similar analyses were performed on the striatum of multiple system atrophy cases. Our data show region-and disease-specific changes in the levels of lipid species. Specifically, our data revealed alterations in the levels of specific phosphatidylserine species in brain areas most affected in Parkinson's disease. Some of these alterations, albeit to a lesser degree, are also observed multiples system atrophy. Using induced pluripotent stem cell-derived neurons, we show that αSyn contributes to regulating phosphatidylserine metabolism at MAM domains, and that αSyn dosage parallels the perturbation in phosphatidylserine levels. Our results support the notion that αSyn pathophysiology is linked to the dysregulation of lipid homeostasis, which may contribute to the vulnerability of specific brain regions in synucleinopathy. These findings have significant therapeutic implications., Competing Interests: Competing Financial Interests SP is a member of the scientific board of Luciole Pharmaceuticals and a reviewing editor for eLife.

Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration., (© 2024. The Author(s).)

Background: A new primary cancer is a serious late effect of a pre-existing cancer diagnosis, and can be attributed to hereditary cancer syndromes, immune or hormonal factors, cancer treatment, or modifiable lifestyle or environmental factors. We investigated the absolute and relative incidence of second primary cancers in a large cohort of Danish cancer survivors. Furthermore, we examined the association between alcohol-related, smoking-related, virus-related, and hormone-related first and second primary cancers., Methods: In this retrospective cohort study, we identified a cohort of Danish adults (aged ≥40 years) diagnosed with cancer from Jan 1, 1997, to Dec 31, 2014 and alive 1 year after diagnosis. Follow-up was from date of first cancer diagnosis and lasted up to 24 years, ending on Dec 31, 2020. Cohort identification and information on second primary cancers was obtained from the Danish Cancer Registry, and comorbidity and sociodemographic information was obtained from Danish population-based registries. Overall, and for 27 cancer types, cumulative incidence functions and Cox proportional hazard regression models were used to estimate the incidence of second primary cancer and death, and hazard ratios (HRs) and 95% CIs of second primary cancer adjusted for sex, age and year of diagnosis, cohabitation status, income, and comorbidity., Findings: 457 334 Danish adults were included in our study (230 150 [50·3%] male individuals and 227 184 [49·7%] female individuals; median age at diagnosis 68·3 years, IQR 59·7-76·6; median follow-up 3·6 years, IQR 0·6-9·3). The cumulative incidence of second primary cancer increased over time from 6·3% (95% CI 6·2-6·4) 5 years after diagnosis to 10·5% (10·4-10·6) 10 years after diagnosis and to 13·5% (13·4-13·7) 15 years after diagnosis. The highest cumulative incidence of second primary cancer 10 years after diagnosis was observed in survivors of cancers in the larynx (21·8%, 20·5-23·1), oropharynx and oral cavity (19·5%, 18·7-20·3), and bladder and urinary tract (18·5%, 18·0-19·0). Survivors of cancers related to alcohol (HR 1·09, 95% CI 1·06-1·13), smoking (1·73, 1·68-1·78), diet high in red or processed meat (1·32, 1·24-1·39), or virus (1·23, 1·13-1·35) were at increased risk of developing a second cancer with the same aetiology, whereas having had a hormone-related first cancer was associated with lower risk of a second hormone-related cancer (0·77, 0·73-0·81)., Interpretation: Our results could help optimise prevention efforts targeting modifiable risk factors to reduce risk of developing a second primary cancer., Funding: Nordic Cancer Union and The Health Foundation (Helsefonden)., Competing Interests: Declaration of interests CJ received honoraria for lectures (Sanofi, Pfizer, Astellas, Janssen). TKK, EAWA, GU, SBL, PEB, JFW, MB, and SOD declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Many patients with coronary artery disease (CAD) have reduced the effect of aspirin, which may partly be explained by immature platelets. We aimed to investigate whether immature platelet markers can predict cardiovascular events in a large cohort of stable CAD patients. A total of 900 stable CAD patients were included and followed for a median of 3 years. We measured markers of immature platelets (platelet count, immature platelet count, immature platelet fraction, mean platelet volume, platelet distribution width, platelet mass, and thrombopoietin) using automated flow cytometry and studied their relation to cardiovascular events. Our primary endpoint was a composite of acute myocardial infarction (MI), ischemic stroke, and cardiovascular death. A composite of MI, ischemic stroke, stent thrombosis and all-cause mortality was analyzed as a secondary endpoint. We found no difference in immature platelet markers between CAD patients with or without cardiovascular events. Regression analysis using hazards rates showed that markers of immature platelets did not have any predictive value for endpoints (p-values >.05). Markers of immature platelets did not predict future cardiovascular events during a 3-year follow-up period in CAD patients. This suggests that immature platelets measured in a stable phase does not have a major role in predicting future cardiovascular events.

Background: Takayasu arteritis is a chronic vasculitis of unknown aetiology primarily affecting medium to large arteries, particularly the aorta and arch vessels, and is predominantly seen in younger patients. Coronary artery involvement has been reported in 10-45% of autopsy cases, but isolated coronary Takayasu arteritis is extremely rare., Case Summary: This case report describes the course of a previously healthy 22-year-old woman who suffered an acute myocardial infarction complicated by cardiogenic shock requiring temporary mechanical support subsequently urgent heart transplantation. The patient was bridged to transplant by the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The explanted heart showed evidence of Takayasu arteritis in the left coronary artery., Discussion: The case illustrates the importance of VA-ECMO treatment for cardiogenic shock, the importance of the Scandiatransplant collaboration for urgent organ allocation and the diagnostic difficulties associated with Takayasu arteritis., Competing Interests: Conflict of interest: None of the authors have any conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

In 2016, we introduced the Danish Prostate Cancer Registry (DaPCaR) which was built on the National Pathology Register from 1995 to 2011. DaPCaR was laborious to use as most data had to be manually imputed with no regular updates. In here we present a new comprehensive centralized prostate registry called the Danish Prostate Registry (DanProst), which includes all men having undergone any histological evaluation of prostate tissue merged with laboratory-, treatment-, prescription data as well as vital status. Here the data included and the methodology of DanProst are described. DanProst is built upon all men with a histological assessment of the prostate from the Danish National Registry for Pathology. The primary histology and potential prostate cancer histological diagnosis for each unique individual is extracted and translated by newly made algorithms for topography, procedure, diagnostic conclusion, and pathological staging. Further information is added from DaPCaR, the CPR Registry, the Danish Cause of Death Registry, the Danish Cancer Registry, the National Patient Registry, the Danish Register of Laboratory Results for Research, and the Danish National Prescription Registry. The translation algorithms were validated based on the comparison with DaPCaR in the period 2010-2016. DanProst includes 190,422 men. A total of 95,152 (50%) men are diagnosed with prostate cancer until 2021. Median diagnostic PSA was 11 ng/ml, most men are diagnosed by ultrasound-guided biopsy (N = 63,751; 67%), and most frequently defined primary treatment was radical prostatectomy (N = 14,778; 19%). DanProst to DaPCaR coherency was > 99%, 95%, and 94% for the primary histological procedure, primary histological conclusion, and diagnostic histological conclusion, respectively. DanProst is a continuously updated, centrally kept, validated registry with automatic integration of data from other national registries, allowing for contemporary nationwide analysis in men with histological assessment of the prostate., (© 2023. The Author(s).)

Objectives: To compare the incidence of subsequent prostate cancer diagnosis and death following an initial non-malignant systematic transrectal ultrasonography (TRUS) biopsy with that in an age- and calendar-year matched population over a 20-year period., Subjects and Methods: This population-based analysis compared a cohort of all men with initial non-malignant TRUS biopsy in Denmark between 1995 and 2016 (N = 37 231) with the Danish population matched by age and calendar year, obtained from the NORDCAN 9.1 database. Age- and calendar year-corrected standardized prostate cancer incidence (SIR) and prostate cancer-specific mortality ratios (SMRs) were calculated and heterogeneity among age groups was assessed with the Cochran's Q test., Results: The median time to censoring was 11 years, and 4434 men were followed for more than 15 years. The corrected SIR was 5.2 (95% confidence interval [CI] 5.1-5.4) and the corrected SMR was 0.74 (95% CI 0.67-0.81). Estimates differed among age groups (P < 0.001 for both), with a higher SIR and SMR among younger men., Conclusion: Men with non-malignant TRUS biopsy have a much higher incidence of prostate cancer but a risk of prostate cancer death below the population average. This underlines that the oncological risk of cancers missed in the initial TRUS biopsy is low. Accordingly, attempts to increase the sensitivity of initial biopsy are unjustified. Moreover, current follow-up after non-malignant biopsy is likely to be overaggressive, particularly in men over the age of 60 years., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: The risk of cardiovascular events in patients treated for colorectal cancer is debated due to diverging results in previous studies. Colorectal cancer and cardiovascular disease share several risk factors such as physical inactivity, obesity, and smoking. Information about confounding covariates and follow-up time are therefore essential to address the issue. This study aims to investigate the risk of new-onset cardiovascular events for patients with stage I-III colorectal cancer receiving elective surgery compared to a matched population., Material and Methods: Using a prospective cohort, we compared cardiovascular events among 876 patients treated with elective surgery for incident stage I-III colorectal cancer diagnosed between January 1st, 2001 and December 31st, 2016 to a cancer-free cohort matched by age, sex, and time since enrollment ( N = 3504). Regression analyses were adjusted for lifestyle, cardiovascular risk factors, and comorbidity. Multivariable analyses were used to identify risk factors associated with cardiovascular events in the postoperative (<90 days of elective surgery) and long-term phase (>90 days after elective surgery)., Results: After a median follow-up of 3.9 years, the hazard ratio (HR) for incident heart failure was 1.53 (95% CI 1.02-2.28) among patients operated for colorectal cancer. The postoperative risk of myocardial infarction or angina pectoris was associated with the use of lipid-lowering drugs. Long-term risks of cardiovascular events were ASA-score of III+IV and lipid-lowering drugs with HRs ranging from 2.20 to 15.8. Further, the use of antihypertensive drugs was associated with an HR of 2.09 (95% CI 1.06-4.13) for angina pectoris or acute myocardial infarction. Heart failure was associated with being overweight, diabetes, and anastomosis leakage., Conclusion: We observed an increased hazard of heart failure in patients operated on for stage I-III colorectal cancer compared to cancer-free comparisons. We identified several potential risk factors for cardiovascular events within and beyond 90 days of elective surgery.

Background: Many cancer survivors experience late effects after cancer. Comorbidity, health literacy, late effects, and help-seeking behavior may affect healthcare use and may differ among socioeconomic groups. We examined healthcare use among cancer survivors, compared with cancer-free individuals, and investigated educational differences in healthcare use among cancer survivors., Methods: A Danish cohort of 127,472 breast, prostate, lung, and colon cancer survivors from the national cancer databases, and 637,258 age- and sex-matched cancer-free individuals was established. Date of entry was 12 months after diagnosis/index date (for cancer-free individuals). Follow-up ended at death, emigration, new primary cancer, December 31st, 2018, or up to 10 years. Information about education and healthcare use, defined as the number of consultations with general practitioner (GP), private practicing specialists (PPS), hospital, and acute healthcare contacts 1-9 years after diagnosis/index date, was extracted from national registers. We used Poisson regression models to compare healthcare use between cancer survivors and cancer-free individuals, and to investigate the association between education and healthcare use among cancer survivors., Results: Cancer survivors had more GP, hospital, and acute healthcare contacts than cancer-free individuals, while the use of PPS were alike. One-to-four-year survivors with short compared to long education had more GP consultations (breast, rate ratios (RR) = 1.28, 95% CI = 1.25-1.30; prostate, RR = 1.14, 95% CI = 1.10-1.18; lung, RR = 1.18, 95% CI = 1.13-1.23; and colon cancer, RR = 1.17, 95% CI = 1.13-1.22) and acute contacts (breast, RR = 1.35, 95% CI = 1.26-1.45; prostate, RR = 1.26, 95% CI = 1.15-1.38; lung, RR = 1.24, 95% CI = 1.16-1.33; and colon cancer, RR = 1.35, 95% CI = 1.14-1.60), even after adjusting for comorbidity. One-to-four-year survivors with short compared to long education had less consultations with PPS, while no association was observed for hospital contacts., Conclusion: Cancer survivors used more healthcare than cancer-free individuals. Cancer survivors with short education had more GP and acute healthcare contacts than survivors with long education. To optimize healthcare use after cancer, we need to better understand survivors' healthcare-seeking behaviors and their specific needs, especially among survivors with short education., (© 2023. The Author(s).)

Background: Reversible P2Y12 inhibition can be obtained with cangrelor administered intravenously. More experience with cangrelor use in acute PCI with unknown bleeding risk is needed., Objectives: To describe real-world use of cangrelor including patient and procedure characteristics and patient outcomes., Methods: We performed a single-centre, retrospective, and observational study including all patients treated with cangrelor in relation to percutaneous coronary intervention at Aarhus University Hospital during the years 2016, 2017, and 2018. We recorded procedure indication and priority, the indications for cangrelor use, and patient outcomes within the first 48 hours after initiation of cangrelor treatment., Results: We treated 991 patients with cangrelor in the study period. Of these, 869 (87.7%) had an acute procedure priority. Among acute procedures, patients were mainly treated for STEMI ( n  = 723) and the remaining were treated for cardiac arrest and acute heart failure. Use of oral P2Y12 inhibitors prior to percutaneous coronary intervention was rare. Fatal bleeding events ( n  = 6) were only observed among patients undergoing acute procedures. Stent thrombosis was observed in two patients receiving acute treatment for STEMI. Thus, cangrelor can be used in relation to PCI under acute circumstances with advantages in terms of clinical management. The benefits and risks, in terms of patient outcomes, should ideally be assessed in randomized trials., Competing Interests: Steen Dalby Kristensen has received fees from Idorsia for National Coordinator work. Erik Lerkevang Grove has received speaker honoraria or consultancy fees from Alexion Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, MSD, MundiPharma, Portola Pharmaceuticals, and Lundbeck Pharma. He is an investigator in studies sponsored by AstraZeneca and has received unrestricted research grants from Boehringer Ingelheim. All other authors declare that they have no conflicts of interest., (Copyright © 2023 Troels Thim et al.)

Neurons perform input-output operations that integrate synaptic inputs with intrinsic electrical properties; these operations are generally constrained by the brevity of synaptic events. Here, we report that sustained firing of CA1 hippocampal fast-spiking parvalbumin-expressing interneurons (PV-INs) can be persistently interrupted for several hundred milliseconds following brief GABA A R-mediated inhibition in vitro and in vivo. A single presynaptic neuron could interrupt PV-IN firing, occasionally with a single action potential (AP), and reliably with AP bursts. Experiments and computational modeling reveal that the persistent interruption of firing maintains neurons in a depolarized, quiescent state through a cell-autonomous mechanism. Interrupted PV-INs are strikingly responsive to Schaffer collateral inputs. The persistent interruption of firing provides a disinhibitory circuit mechanism favoring spike generation in CA1 pyramidal cells. Overall, our results demonstrate that neuronal silencing can far outlast brief synaptic inhibition owing to the well-tuned interplay between neurotransmitter release and postsynaptic membrane dynamics, a phenomenon impacting microcircuit function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background:  New biomarkers are warranted to identify patients with coronary artery disease (CAD) at high risk of recurrent cardiovascular events. It has been reported that the expression of microRNAs (miRs) may influence the development of CAD., Objectives:  We aimed to investigate whether the expression of selected candidate miRs is a predictor of cardiovascular events in a cohort of stable CAD patients., Methods:  We performed a single-center prospective study of 749 stable CAD patients with a median follow-up of 2.8 years. We investigated the expression of nine candidate miRs and their relation to cardiovascular events in this cohort. The primary endpoint was the composite of nonfatal myocardial infarction (MI), stent thrombosis (ST), ischemic stroke, and cardiovascular death. The composite of nonfatal MI and ST was analyzed as a secondary endpoint. Furthermore, nonfatal MI, ST, ischemic stroke, and all-cause mortality were analyzed as individual endpoints., Results:  Employing receiver operating characteristic curves, it was shown that compared with traditional cardiovascular risk factors alone, combining the expression of miR-223-3p with existing traditional cardiovascular risk factors increased the predictive value of ST (area under the curve: 0.88 vs. 0.77, p  = 0.04), the primary composite endpoint (0.65 vs. 0.61, p  = 0.049), and the secondary endpoint of the composite of nonfatal MI and ST (0.68 vs. 0.62, p  = 0.04)., Conclusion:  Among patients with CAD, adding miR-223-3p expression to traditional cardiovascular risk factors may improve prediction of cardiovascular events, particularly ST. Clinical trials confirming these findings are warranted., Competing Interests: E.L.G. has received speaker honoraria or consultancy fees from Abbott, Alexion Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Lundbeck Pharma, Pfizer, MSD, Mundipharma, Organon, Portola Pharmaceuticals, and Roche. He is an investigator in studies sponsored by AstraZeneca and has received unrestricted research grants from Boehringer Ingelheim. A.-M.H. has received speaker's fees from CSL Behring, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Leo Pharma and unrestricted research support from Octapharma and CSL Behring. O.B.P., S.B.L., L.P., S.D.K., and P.H.N. have no conflicts to declare., (Thieme. All rights reserved.)

Association between alcohol intake and atrioventricular block is rare. This case describes a previously healthy 27-year-old man experiencing syncopes preceded by moderate alcohol intake. An implantable loop recorder demonstrated episodes of total atrioventricular block coinciding with an additional syncope after alcohol intake, resulting in pacemaker implantation. ( Level of Difficulty: Intermediate. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Intermetatarsal bursitis (IMB) is an inflammation of the intermetatarsal bursas. The condition causes forefoot pain with symptoms similar to those of Morton's neuroma (MN). Some studies suggest that IMB is a contributing factor to the development of MN, while others describe the condition as a differential diagnosis. Among patients with rheumatic diseases, IMB is frequent, but the scope is yet to be understood. The aim of this paper was to investigate the diagnostic considerations of IMB and its role in metatarsalgia by a systematic review approach. We identified studies about IMB by searching the electronic databases Pubmed, Embase, Cochrane Library, and Web of Science in September 2022. Of 1362 titles, 28 met the inclusion criteria. They were subdivided according to topic: anatomical studies ( n = 3), studies of patients with metatarsalgia ( n = 10), and studies of patients with rheumatic diseases ( n = 15). We conclude that IMB should be considered a cause of pain in patients with metatarsalgia and patients with rheumatic diseases. For patients presenting with spreading toes/V-sign, IMB should be a diagnostic consideration. Future diagnostic studies about MN should take care to apply a protocol that is able to differ IMB from MN, to achieve a better understanding of their respective role in forefoot pain.

Background: Prior studies of suicide risk among prostate cancer patients are conflicting. We compared the risk of suicide in prostate cancer patients to cancer-free men including adjustment for clinical stage, socioeconomic position, somatic comorbidity, and previous depression., Materials and Methods: A cohort of 37,527 men diagnosed with prostate cancer in Denmark during 1998-2011 was identified in the Danish Prostate Cancer Registry (DaPCaR) and compared with 357,384 cancer-free men matched by age at the time of diagnosis. The primary outcome was death from suicide. Data were analyzed using cumulative incidence functions and multivariable Cox regression models., Results: Among prostate cancer patients, 3813 had a previous depression, defined as filed antidepressant prescription within three years before diagnosis. In the study period, 108 prostate cancer patients were registered with suicide as the cause of death, hereof 26 with previous depression. There was no difference in the cumulative incidence of suicide between prostate cancer patients and cancer-free men. There was no effect modification of previous depression on the risk of suicide ( p  = .12). The hazard ratio (HR) for suicide varied with time since diagnosis. A sensitivity analysis showed that the risk of suicide was highest within the first year of diagnosis where prostate cancer patients had a 1.70-fold increased hazard compared with cancer-free men (95% CI, 1.11-2.59). Men with prostate cancer and previous depression had a three-fold increased hazard for suicide compared with prostate cancer patients without a history of depression (HR 2.84, 95% CI, 1.82-4.45)., Conclusion: The absolute risk of suicide is low following a prostate cancer diagnosis. Time since diagnosis and a history of depression was associated with the highest risk of suicide. Healthcare professionals should be aware of an increased risk of suicide among men with previous depression, especially in the immediate aftermath of the diagnosis.

Background: Symptoms and treatment of benign prostatic hyperplasia (BPH) or erectile dysfunction (ED) may lead to prostate cancer workup, and patterns of prescriptions before diagnosis may affect findings of pharmacoepidemiological studies. Usage of BPH and ED drugs after diagnosis may be related to prostate cancer treatment. We investigated differences in prescription rates of BPH and ED drugs among prostate cancer patients and cancer-free comparisons and between patients with localized and non-localized disease., Material and Methods: A nationwide register-based study, including all Danish men aged 50-85 years diagnosed with prostate cancer during 1998-2015 and an age-matched comparison cohort without cancer. We calculated rates of new and total prescriptions in 1-month intervals from 3 years before to 3 years after cancer diagnosis for drugs used to treat BPH and ED, overall and stratified by clinical stage., Results: We identified 54,286 men with prostate cancer and a comparison cohort of 249,645 age-matched men. The new prescription rate for BPH drugs increased for men with prostate cancer in the year before diagnosis and peaked 1 month before diagnosis with an 18-fold higher rate. Men with prostate cancer had a higher total prescription rate of BPH drugs 3 years before diagnosis, notably among men with localized disease. Before diagnosis, the new prescription rates for ED drugs were similar among men with prostate cancer and comparisons. After diagnosis, men with prostate cancer had a 7-fold higher rate of new prescriptions for ED drugs. Among men with localized disease, the total prescription rate of ED drugs increased in the months following diagnosis., Conclusion: Differences in prescription rates suggest increased prostate cancer surveillance among men receiving BPH drugs, whereas the post-diagnostic increase in ED drugs among men with localized disease is compatible with the increased risk of ED following prostate cancer treatment.

Mammalian cells autonomously activate hypoxia-inducible transcription factors (HIFs) to ensure survival in low-oxygen environments. We report here that injury-induced hypoxia is insufficient to trigger HIF1α in damaged epithelium. Instead, multimodal single-cell and spatial transcriptomics analyses and functional studies reveal that retinoic acid-related orphan receptor γt + (RORγt + ) γδ T cell-derived interleukin-17A (IL-17A) is necessary and sufficient to activate HIF1α. Protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling proximal of IL-17 receptor C (IL-17RC) activates mammalian target of rapamycin (mTOR) and consequently HIF1α. The IL-17A-HIF1α axis drives glycolysis in wound front epithelia. Epithelial-specific loss of IL-17RC, HIF1α, or blockade of glycolysis derails repair. Our findings underscore the coupling of inflammatory, metabolic, and migratory programs to expedite epithelial healing and illuminate the immune cell-derived inputs in cellular adaptation to hypoxic stress during repair.

Purpose: Magnetic resonance imaging (MRI) targeted prostate biopsy has been shown to find many high-grade prostate cancers in men with concurrent negative transrectal ultrasound (TRUS) systematic biopsy. The oncologic risk of such tumors can be explored by looking at long-term outcomes of men with negative TRUS biopsy followed without MRI. The aim was to analyze the mortality after initial and second negative TRUS biopsy., Materials and Methods: All men who underwent initial TRUS biopsies between January 1, 1995 and December 31, 2016 in Denmark were included. A total of 37,214 men had a negative initial TRUS biopsy and 6,389 underwent a re-biopsy. Risk of cause-specific mortality was analyzed with competing risks. Diagnosis of Gleason score ≥7 prostate cancer following negative biopsies was analyzed with multivariable logistic regression including time to re-biopsy, prostate specific antigen (PSA), age and digital rectal examination., Results: The 15-year prostate cancer-specific mortality was 1.9% (95% CI: 1.7-2.1). Prostate cancer-specific mortality was 1.3% (95% CI: 0.9-1.6) and 4.6% (95% CI: 3.4-5.8) for men with PSA <10 and >20 ng/ml, respectively. Of the TRUS re-biopsies 12% were Gleason score ≥7 and risk of Gleason score ≥7 increased with longer time to re-biopsy (p <0.001). Mortality after re-biopsy was similar to after initial biopsy., Conclusions: Men with negative TRUS biopsies have a very low prostate cancer-specific mortality, especially with PSA <10 ng/ml. This raises serious questions about the routine use of MRI targeting for initial prostate biopsy and suggests that MRI targeting should only be recommended for men with PSA >10 ng/ml after negative biopsy.

Background: Exposure to high doses of ionizing radiation is among the few well-established brain tumour risk factors. We used data from the Interphone study to evaluate the effects of exposure to low-dose radiation from diagnostic radiological examinations on glioma, meningioma and acoustic neuroma risk., Methods: Brain tumour cases (2644 gliomas, 2236 meningiomas, 1083 neuromas) diagnosed in 2000-02 were identified through hospitals in 13 countries, and 6068 controls (population-based controls in most centres) were included in the analysis. Participation across all centres was 64% for glioma cases, 78% for meningioma cases, 82% for acoustic neuroma cases and 53% for controls. Information on previous diagnostic radiological examinations was obtained by interviews, including the frequency, timing and indication for the examinations. Typical brain doses per type of examination were estimated based on the literature. Examinations within the 5 years before the index date were excluded from the dose estimation. Adjusted odds ratios were estimated using conditional logistic regression., Results: No materially or consistently increased odds ratios for glioma, meningioma or acoustic neuroma were found for any specific type of examination, including computed tomography of the head and cerebral angiography. The only indication of an elevated risk was an increasing trend in risk of meningioma with the number of isotope scans, but no such trends for other examinations were observed. No gradient was found in risk with estimated brain dose. Age at exposure did not substantially modify the findings. Sensitivity analyses gave results consistent with the main analysis., Conclusions: There was no consistent evidence for increased risks of brain tumours with X-ray examinations, although error from selection and recall bias cannot be completely excluded. A cautious interpretation is warranted for the observed association between isotope scans and meningioma., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Introduction: The risk of recurrent cardiovascular events in patients with coronary artery disease (CAD) is determined by multiple factors including platelet function and turnover. MicroRNAs (miRs) may regulate both platelet function and turnover. We aimed to identify candidate miRs associating with platelet function and turnover in a cohort of stable CAD patients. Furthermore, we retrieved information on binding targets of the candidate miRs to obtain a more comprehensive biological insight into miR regulation of platelet function and turnover., Methods: Based on existing literature and a pilot study, we identified nine candidate miRs. Subsequently, we investigated the expression of the candidate miRs in whole blood and their relation to platelet function and turnover in 749 CAD patients. Platelet function was analysed using impedance aggregometry, optical aggregometry and serum thromboxane B 2 measurements. Platelet turnover markers (immature platelet count, immature platelet fraction and mean platelet volume) were measured using monochromatic automated flow cytometry., Results: Expression of miR-93-5p, miR-126-3p, miR-150-5p, miR-423-3p and miR-1180-3p showed negative correlations with platelet function (p-values from <0.0001 to 0.0006, rho from -0.13 to -0.36). In addition, expression of miR-423-3p showed negative correlation with platelet turnover markers (p-values from 0.001 to 0.004, rho from -0.11 to -0.12)., Conclusions: We identified several novel miRs that may regulate platelet function and turnover, thereby contributing to the increased risk of recurrent cardiovascular events in CAD patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To investigate differences in prescription rates of commonly used drugs among prostate cancer patients and cancer-free comparisons and between patients diagnosed with localized and non-localized disease., Methods: We conducted a register-based study including all men aged 50-85 years diagnosed with prostate cancer in Denmark from 1998 to 2015 and an age-matched cancer-free comparison cohort. We calculated the number of new and total prescriptions from three years before to three years after the date of diagnosis of the case for selected drug classes divided by the number of person-months and stratified by stage at diagnosis., Results: We included 54,286 prostate cancer patients and 249,645 matched comparisons. 30,712 patients were diagnosed with localized disease and 12,884 with non-localized disease. The rates of new prescriptions increased considerably among patients within the year before the diagnosis. Hereafter the rates varied between drug classes. For most drug classes, total prescription rates for patients and comparisons increased similarly in the study period. Total prescription rates varied between men with localized and non-localized disease for all drug classes apart from statins., Conclusion: Our findings indicate that a large proportion of prostate cancer cases are likely diagnosed during medical work-up for other reasons than prostate cancer. Increased rates occur within the last year before diagnosis and future studies on the interaction between drug use and prostate cancer should at least include a one year pre-diagnostic lag-time. Post-diagnostic prescription rates demonstrated an increased use of drugs most likely associated with the consequences of the disease., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The binding of the major stress-inducible human 70-kDa heat shock protein (Hsp70) to the anionic phospholipid bis-(monoacylglycero)-phosphate (BMP) in the lysosomal membrane is crucial for its impact on cellular pathology in lysosomal storage disorders. However, the conformational features of this protein-lipid complex remain unclear. Here, we apply hydrogen-deuterium exchange mass spectrometry (HDX-MS) to describe the dynamics of the full-length Hsp70 in the cytosol and its conformational changes upon translocation into lysosomes. Using wild-type and W90F mutant proteins, we also map and discriminate the interaction of Hsp70 with BMP and other lipid components of the lysosomal membrane. We identify the N-terminal of the nucleotide binding domain (residues 87-118) as the primary orchestrator of BMP interaction. We show that the conformation of this domain is significantly reorganized in the W90F mutant, explaining its inability to stabilize lysosomal membranes. Overall, our results reveal important new molecular details of the protective effect of Hsp70 in lysosomal storage diseases, which, in turn, could guide future drug development., (© 2021. The Author(s).)

Competing Interests: Conflicts of interest The authors disclose no potential conflicts of interest.

Background: To curb future antibiotic resistance it is important to monitor and investigate current prescription patterns of antibiotics., Objectives: To examine trends in antibiotic prescription to children aged 0-6 years old and the association with socioeconomic status of municipalities in the Capital region of Denmark between 2009 and 2018., Methods: This is a register-based study combining data on antibiotic treatments from 2009 to 2018, inhabitant-data and socioeconomic municipality scores. Subjects were children aged 0-6 years, residing in the Capital Region of Denmark. The study quantifies the use of antibiotics as number of antibiotic treatments/1000 inhabitants/year (TIY), inhabitants defined as children aged 0-6. Socioeconomic status of the municipalities is evaluated by a score from 3 to 12., Results: The average TIY of the municipalities decreased from 741.2 [95%CI 689.3-793.2] in 2009 to 348.9 [329.4-368.4] in 2018. The difference between the highest and lowest prescribing municipalities was reduced from 648.3 TIY in 2009-212.5 TIY in 2018. The average increase in TIY per unit increase in socioeconomic municipality score changed from 20.05 [7.69-31.06] in 2009 to -4.58 [-16.02-5.60] in 2018, representing a decreasing association between socioeconomic municipality score and use of antibiotic in the respective municipalities., Conclusion: The trend in antibiotic prescription to children aged 0-6 years old decreased substantially in all the investigated municipalities in the 10-year study period. Local differences in prescription rates declined towards a more uniform prescription pattern across municipalities and association with socioeconomic status of the municipalities was reduced.

Objective: To compare the risk of depression after diagnostic workup for prostate cancer (PCa), regardless of the histopathologic outcome, with that of a cancer-free population., Methods: A nationwide cohort of Danish men who had a prostatic biopsy sample in 1998-2011 was identified from the Danish Prostate Cancer Registry and compared to an age-matched cohort from the background population. Men with other cancers, major psychiatric disorder, or prior use of antidepressants were excluded. The risk of depression defined as hospital contact for depression or prescription for antidepressants was determined from cumulative incidence functions and multivariate Cox regression models., Results: Of 54,766 men who underwent diagnostic workup for PCa, benign results were found for 21,418 and PCa was diagnosed in 33,347. During up to 18 years of follow-up, the adjusted hazard of depression was higher in men with PCa than in the background population, with the highest risk in the two years after diagnosis (hazard ratio (HR) 2.77, 95% CI 2.66-2.87). Comorbidity and lowest or highest income were significant risk factors for depression and the cumulative incidence was substantially higher in men with metastatic or high-risk disease. In men with benign histopathology the HR for depression was 1.22 (95% CI 1.14-1.31) in the first two years but no different from the background population after that., Conclusions: Diagnostic workup for PCa is associated with an increased risk of depression, mainly among men with a diagnosis of PCa. Clinicians should be aware of depressive symptoms in prostate cancer patients., (© 2021 John Wiley & Sons Ltd.)

Known for nearly a century but through mechanisms that remain elusive, cells retain a memory of inflammation that equips them to react quickly and broadly to diverse secondary stimuli. Using murine epidermal stem cells as a model, we elucidate how cells establish, maintain, and recall inflammatory memory. Specifically, we landscape and functionally interrogate temporal, dynamic changes to chromatin accessibility, histone modifications, and transcription factor binding that occur during inflammation, post-resolution, and in memory recall following injury. We unearth an essential, unifying role for the general stress-responsive transcription factor FOS, which partners with JUN and cooperates with stimulus-specific STAT3 to establish memory; JUN then remains with other homeostatic factors on memory domains, facilitating rapid FOS re-recruitment and gene re-activation upon diverse secondary challenges. Extending our findings, we offer a comprehensive, potentially universal mechanism behind inflammatory memory and less discriminate recall phenomena with profound implications for tissue fitness in health and disease., Competing Interests: Declaration of interests The authors declare no competing financial interests. E.F. serves as an advisory board member for Cell Stem Cell and serves on the scientific advisory boards of L’Oreal and Arsenal Biosciences., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To assess the performance of systematic TRUS-biopsies in a population-based setting to detect clinically significant PCa (csPCa) in combination with age, clinical tumor category (cT), and prostate-specific antigen (PSA) in men referred for the first biopsy., Methods: We identified all men referred for PCa work-up because of elevated PSA who underwent initial TRUS-biopsies in the nationwide Danish Prostate Cancer Registry (DaPCaR) between January 1st, 1995 and December 31st, 2016, in Denmark. Risk of histologic findings in initial TRUS-biopsies categorized as non-malignant, insignificant PCa, or significant PCa (csPCa). We defined csPCa as any biopsy containing Gleason score 3 + 4 or above as in the PRECISION trial. We assessed risk of csPCa with absolute risk, logistic regression model, and predicted risks., Results and Limitations: After exclusions, our cohort included 39,886 men. The diagnostic hit rate for csPCa was 40.8 %. Men with PSA > 20 ng/mL and ≥cT2 harbor a risk >75% for finding csPCa in the first TRUS biopsy-set. Men with cT1 tumors and PSA < 20 ng/mL have a risk of non-malignant histology of at least 58%. Limitations include the high number of exclusions based on missing information., Conclusion: The diagnostic accuracy of systematic TRUS-biopsies is high for men with palpable tumors and high PSA. Our data point to the fact that not all men need pre-biopsy MRI to find csPCa., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Body mass index (BMI) at child and adolescent ages is positively associated with adult coronary heart disease (CHD) whereas height at these ages may be inversely associated with CHD. However, potential effects of age, sex, and socioeconomic status on associations between BMI and CHD are less investigated. We conducted a systematic review and meta-analysis of BMI and height at ages 2-19 years in relation to adult CHD and examined effects of age, sex, socioeconomic status, and other factors. Twenty-two studies on BMI and five on height were included, comprising 5,538,319 individuals and 69,830 CHD events. Random effects meta-analyses were conducted. Child and adolescent BMI were positively associated with CHD (hazard ratio = 1.12; 95% confidence interval [CI] [1.01, 1.25] per standard deviation [SD]), and categorical analyses supported these findings. The associations did not significantly differ by age, sex, or by adjustment for socioeconomic status. Child and adolescent height were inversely associated with CHD (hazard ratio = 0.87; 95% CI [0.81, 0.93] per SD), and categorical analyses agreed. Insufficient studies on height precluded subgroup analyses. Heterogeneity was generally high in all analyses. We found that BMI in youth is positively associated with adult CHD regardless of sex or adjustment for socioeconomic status whereas height is inversely associated with later risk of CHD., (© 2021 World Obesity Federation.)

Objectives: To study safety and efficacy of selective endovascular trans-arterial embolization (TAE) of renal angiomyolipoma (AML) in a 10-year period at a regional tertiary referral center in Denmark., Patients and Methods: All 56 patients who underwent TAE of renal AML at Departments of Urology and Radiology, Copenhagen University Hospital - Rigshospitalet, Denmark, from 2009 to 2020 were included. Seven without preoperative and postoperative imaging were excluded, leaving 49 patients for analysis. From national electronic medical records, we retrieved patient characteristics, surgical data, and follow-up data. Tumor size at the time of embolization and during follow-up was compared using Student's paired t test. Estimated glomerular filtration rate (eGFR) pre- and post-embolization were compared using Wilcoxon rank sum test., Results: We included 49 patients of whom 4 had two tumors treated in the same TAE procedure. Median age was 50 years (interquartile range [IQR]: [29-67 years]), and the median follow-up time was 4.6 years [IQR: 3.0-6.7 years]. Post-embolization syndrome (PES) was experienced in 27 patients, and non-PES in 5 patients. Median length of hospital stay was 0 days [IQR, 0-1]. Postoperative Everolimus immunosuppressive treatment was offered to seven patients. Median tumor size was 6.0 cm [IQR: 4.6-7.9 cm] and was significantly reduced to 3.7 cm [IQR: 2.5-5.2 cm] after treatment ( p  < 0.001). Kidney function was not affected by TAE. Three deaths, not related to AML, were noted during follow-up., Conclusion: Embolization of AML was in this cohort effective to significantly reduce tumor size without serious adverse events and loss of renal function. TAE is a safe and efficacious treatment and the preferred minimally invasive treatment option of AML., Competing Interests: All authors declare no conflicts of interest., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Purpose: To estimate the risk of first-time antidepressant prescriptions as a proxy for depression or anxiety and associated risk factors in patients with prostate cancer and their female partners., Methods: We followed all men (n = 25,126) and their female cohabiting partners (n = 8785) without a history of cancer or antidepressants from the Danish Diet, Cancer and Health cohort from 1997 to 2014 or 2010, respectively. We estimated the cumulative incidence of first-time antidepressant prescriptions in men with prostate cancer compared with cancer-free men and their respective female partners, using the Danish National Prescription Registry. Sociodemographic, lifestyle-related, and clinical risk factors were assessed using Cox regression models., Results: A total of 1828 men were diagnosed with prostate cancer of whom 15% received antidepressants. The unadjusted hazard ratio of antidepressant prescription was 2.18 (95%CI, 1.92, 2.48) for men with prostate cancer and 1.27 (95%CI, 0.87, 1.85) for their partners, compared with cancer-free men and their partners, respectively. After adjusting for sociodemographic, lifestyle-related, and comorbidity factors, this risk was 2-fold to 4-fold increased among patients, but not significantly increased among partners. Significant risk factors among patients were curative and palliative treatment (vs. active surveillance and watchful waiting), nonlocalized disease, and short education., Conclusions: Men with prostate cancer have a higher risk of receiving antidepressant medication than cancer-free men. Clinical characteristics can help clinicians in identifying patients at a high risk of depression or anxiety., Implications for Cancer Survivors: Men with prostate cancer who experience symptoms of depression or anxiety should seek professional help early on. Patient education could aid in raising awareness and reducing the stigma associated with mental disorders., (© 2020. The Author(s).)

Background: Development of depression in prostate cancer patients depends on multiple disease- and patient-related factors., Objective: To investigate the risk of depression following radical prostatectomy focussing on the impact of surgery and subsequent treatment with salvage radiation or androgen deprivation therapy., Design, Setting, and Participants: A population-based cohort study of 5570 men who underwent radical prostatectomy in Denmark from 1998 to 2011 was identified in the Danish Prostate Cancer Registry., Outcome Measurements and Statistical Analysis: Data on covariates and primary outcome defined as a hospital contact for depression or a redeemed antidepressant prescription were obtained from nationwide Danish registries. The risk of depression was evaluated using cumulative incidence functions and Cox models with time since surgery as an underlying time scale. Exposure to salvage procedures was included as time-varying covariates, and analyses were adjusted for confounders., Results and Limitations: The cumulative incidence of depression was increased in men who had undergone surgery compared with cancer-free men throughout follow-up of up to 18yr, particularly among men on androgen deprivation therapy. Compared with no subsequent treatment, the risk of depression was increased with subsequent androgen deprivation therapy (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.4-2.3), salvage radiation (HR 1.3, 95% CI 1.0-1.6), and the treatments combined (HR 2.2, 95% CI 1.8-2.8) after adjustments for age, year of surgery, income, and cohabitation status. Further adjustment for comorbidity hardly changed the estimates., Conclusions: Radical prostatectomy and subsequent salvage procedures increase the risk of depression, and men with subsequent androgen deprivation therapy are mainly at risk. Clinicians should thus be aware of depressive symptoms in patients receiving treatment for postsurgical relapse., Patient Summary: In a population-based study, we found that radical prostatectomy and subsequent treatments with either radiation or endocrine manipulation significantly increased the risk of developing clinical depression., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We investigated the risk of depression in colorectal cancer (CRC) patients and associated risk factors. The 1324 patients with CRC and 6620 matched cancer-free participants from the Diet, Cancer and Health study were followed for up to 16 years for either a first hospitalization for depression or antidepressant prescription after diagnosis of CRC cancer or study entry date. Information on the outcome and covariates was retrieved from the Danish Colorectal Cancer Group database, the national health registries and questionnaires. Cumulative incidence of depression was estimated, and Cox regression models were used to evaluate the association between risk factors and depression incidence. During follow-up, 191 (14.4%) patients with CRC and 175 (2.6%) cancer-free comparison persons experienced depression. After adjustments, in the first year after cancer diagnosis, patients with CRC had a 12-fold higher hazard compared with the cancer-free population (HR, 12.01; 95% CI, 7.89-18.28). The risk decreased during follow-up but remained significantly elevated with an HR of 2.65 (95% CI, 1.61-4.36) after five years. Identified risk factors were presence of comorbidities, advanced disease stage and use of radiotherapy, while life style factors (pre-cancer or at diagnosis) and chemotherapy did not seem to contribute to the increased risk.