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Jon Gitz Holler,1 Jens Ulrik Stæhr Jensen,2– 4 Frederik Neess Engsig,5 Morten H Bestle,3,6 Birgitte Lindegaard,1,3,7 Jens Henning Rasmussen,8 Henning Bundgaard,3,9 Finn Erland Nielsen,8 Kasper Karmark Iversen,3,10 Jesper Juul Larsen,11 Barbara Juliane Holzknecht,3,12 Jonas Boel,12,13 Pradeesh Sivapalan,2,3 Theis Skovsgaard Itenov3,14 1Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark; 2Department of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Copenhagen, Denmark; 3Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 4PERSIMUNE & CHIP: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 5Department of Emergency Medicine, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; 6Department of Anesthesia and Intensive Care Medicine, Copenhagen University Hospital – North Zealand, Hilleroed, Denmark; 7Centre for Physical Activity, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 8Department of Emergency Medicine, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark; 9Department of Cardiology, The Capital Region’s Unit of Inherited Cardiac Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 10Department of Emergency Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark; 11Department of Emergency Medicine, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark; 12Department of Clinical Microbiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark; 13Copenhagen University Hospital - Capital Region Pharmacy, Copenhagen, Denmark; 14Department of Anesthesiology and Intensive Care Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkCorrespondence: Jon Gitz Holler, Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark, Tel +45-48292578, Fax +45-48293935, Email Jon.Gitz.Holler@regionh.dkAbstract: Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018– 2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥ 18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.Keywords: emergency department, infectious diseases, sepsis, shock, database, epidemiology, community acquired

The purpose of this study was to examine if fat oxidation was affected by menopausal status and to investigate if this could be related to the oxidative capacity of skeletal muscle. Forty-one healthy women were enrolled in this cross-sectional study [premenopausal (n = 19), perimenopausal (n = 8), and postmenopausal (n = 14)]. Estimated insulin sensitivity was obtained from an oral glucose tolerance test. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. Fat oxidation and energy expenditure were measured during an acute exercise bout of 45 min of ergometer biking at 50% of maximal oxygen consumption (V? O2 max). Muscle biopsies from the vastus lateralis of the quadriceps muscle were obtained before and immediately after the exercise bout. Postmenopausal women had 33% [confidence interval (CI) 95%: 12-55] lower whole body fat oxidation (P = 0.005) and 19% (CI 95%: 9-22) lower energy expenditure (P = 0.02) during exercise, as well as 4.28 kg lower lean body mass (LBM) than premenopausal women. Correction for LBM reduced differences in fat oxidation to 23% (P = 0.05), whereas differences in energy expenditure disappeared (P = 0.22). No differences between groups were found in mRNA [carnitine palmitoyltransferase I, β-hydroxyacyl-CoA dehydrogenase (β-HAD), peroxisome proliferator-activated receptor-β, citrate synthase (CS), pyruvate dehydrogenase kinase 4, peroxisome proliferator-activated receptor-β coactivator-1α (PGC-1α)], protein [phosphorylated AMPactivated protein kinase (AMPK), vascular endothelial growth factor, pyruvate dehydrogenase-1Eα, cytochrome oxidase I], or enzyme activities (β-HAD, CS) in resting skeletal muscle, except for an increased protein level of cytochrome c in the post- and perimenopausal women relative to premenopausal women. Postmenopausal women demonstrated a trend to a blunted exercise-induced increase in phosphorylation of AMPK compared with premenopausal women (P = 0.06). We conclude that reduced whole body fat oxidation after menopause is associated with reduced LBM. [ABSTRACT FROM AUTHOR]

Objective: YKL-40 is produced by macrophages, and plasma YKL-40 is elevated in patients with diseases characterized by inflammation. In the present study, YKL-40 was examined in relation to obesity, inflammation, and type 2 diabetes.Research Design and Methods: Plasma YKL-40 and adipose tissue YKL-40 mRNA levels were investigated in 199 subjects who were divided into four groups depending on the presence or absence of type 2 diabetes and obesity. In addition, plasma YKL-40 was examined in healthy subjects during a hyperglycemic clamp, in which the plasma glucose level was kept at 15 mmol/l for 3 h, and during a hyperinsulinemic-euglycemic clamp.Results: Patients with type 2 diabetes had higher plasma YKL-40 (76.7 vs. 45.1 ng/ml, P = 0.0001) but not higher expression in adipose tissue YKL-40 mRNA (1.20 vs. 0.98, P = 0.2) compared with subjects with a normal glucose tolerance. Within the groups with normal glucose tolerance and type 2 diabetes, obesity subgroups showed no difference with respect to either plasma YKL-40 or adipose tissue YKL-40 mRNA levels. Multivariate regression analysis showed that plasma YKL-40 was associated with fasting plasma glucose (beta = 0.5, P = 0.0014) and plasma interleukin (IL)-6 (beta = 0.2, P = 0.0303). Plasma YKL-40 was not related to parameters of obesity. There were no changes in plasma YKL-40 in healthy subjects during either hyperglycemic or hyperinsulinemic-euglycemic clamps.Conclusions: Plasma YKL-40 was identified as an obesity-independent marker of type 2 diabetes related to fasting plasma glucose and plasma IL-6 levels. [ABSTRACT FROM AUTHOR]

Abstract Background Standard treatment for patients with disseminated germ cell tumors is combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This treatment is highly effective, but the majority of patients experience severe adverse effects during treatment and are at risk of developing considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, and pulmonary toxicity. One neglected side effect is the significant muscular fatigue mentioned by many patients with testicular cancer both during and after treatment. Very limited information exists concerning the patho-physiological effects of antineoplastic agents on skeletal muscle. The primary aim of this study is to investigate the effects of BEP-treatment on the skeletal musculature in testicular cancer patients, and to examine whether the expected treatment-induced muscular deterioration can be attenuated or even reversed by high intensity progressive resistance training (HIPRT). Design/Methods The PROTRACT study is a randomized controlled trial in 30 testicular cancer patients undergoing three cycles of BEP chemotherapy. Participants will be randomized to either a 9-week HIPRT program (STR) initiated at the onset of treatment, or to standard care (UNT). 15 healthy matched control subjects (CON) will complete the same HIPRT program. All participants will take part in 3 assessment rounds (baseline, 9 wks, 21 wks) including muscle biopsies, maximum muscle strength tests, whole body DXA scan and blood samples. Primary outcome: mean fiber area and fiber type composition measured by histochemical analyses, satellite cells and levels of protein and mRNA expression of intracellular mediators of protein turnover. Secondary outcomes: maximum muscle strength and muscle power measured by maximum voluntary contraction and leg-extensor-power tests, body composition assessed by DXA scan, and systemic inflammation analyzed by circulating inflammatory markers, lipid and glucose metabolism in blood samples. Health related Quality of Life (QoL) will be assessed by validated questionnaires (EORTC QLQ-C30, SF-36). Discussion This study investigates the muscular effects of antineoplastic agents in testicular cancer patients, and furthermore evaluates whether HIPRT has a positive influence on side effects related to chemotherapy. A more extensive knowledge of the interaction between cytotoxic-induced physiological impairment and exercise-induced improvement is imperative for the future development of optimal rehabilitation programs for cancer patients. Trial Registration Current Controlled Trials ISRCTN32132990.

Aims: Infections have been associated with acute myocardial infarction (AMI), but differences in risk between infection types and age groups are unclear. This study aims to investigate whether infections are associated with subsequent AMI and whether the risk differs across infection sites and age groups., Methods: Nationwide registers were used to include 702596 adults hospitalized between 1987-2018 with either; pneumonia (n=344319), urinary tract infection (UTI) (n=270101), soft tissue/bone infection (n=66718), central nervous system infection (CNS) (n=17025), or endocarditis (n=4433). Patients were sex- and age-matched with two unexposed controls. Outcome was first-time AMI within ten years. A time-dependent cox proportional hazards model with cut-offs at 30 and 90 days was used for calculating adjusted hazard ratios (HR)., Results: Pneumonia, UTI, and soft tissue/bone infection were associated with increased relative rates of AMI compared to matched, unexposed controls. Highest relative rates were found within the first 0-30 days post-exposure; Pneumonia: HR 3.39 (95% CI 3.15-3.65), UTI: HR 2.44 (95% CI 2.21-2.70), Soft tissue/bone infection: HR 1.84 (95% CI 1.45-2.33). Relative rates decreased over time but remained significantly elevated throughout the follow-up period and was increased in all age groups. No association was found for CNS infection and for endocarditis only at 31-90 days, HR 2.28 (95% CI 1.20-4.33)., Conclusion: Acute infections are associated with increased relative rates of AMI across different infection sites and age groups with higher relative rates found for pneumonia. This indicates that some infections may act as a trigger for AMI with a site and/or pathogen specific risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Overweight and obesity are linked to increased hospitalization and mortality in COVID-19 patients. This study aimed to characterize induced immune responses and deep immune cell profiles stratified by BMI in hospitalized COVID-19 patients., Methods and Results: This observational multicenter cohort pilot study included 122 adult patients with PCR-confirmed COVID-19 in Denmark, stratified by BMI (normal weight, overweight, obese). Inflammation was assessed using TruCulture® and immune cell profiles by flow cytometry with a customized antibody panel (DuraClone®). Patients with obesity had a more pro-inflammatory phenotype with increased TNF-α, IL-8, IL-17, and IL-10 levels post-T cell stimulation, and altered B cell profiles. Patients with obesity showed higher concentrations of naïve, transitional, and non-isotype switched memory B cells, and plasmablasts compared to normal weight patients and healthy controls., Conclusions: Obesity in hospitalized COVID-19 patients may correlate with elevated pro-inflammatory cytokines, anti-inflammatory IL-10, and increased B cell subset activation, highlighting the need for further studies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Respiratory syncytial virus (RSV) and influenza cause significant health challenges, particularly for individuals with comorbid conditions and older adults. However, information on the clinical manifestations and outcomes of adults hospitalized with RSV in Europe remains limited., Methods: This multicenter observational cohort study of adults hospitalized with RSV or influenza A or B from March 2016 to April 2020 investigated the clinical manifestations, mortality risk factors, and association with 90-day mortality rates by logistic regression analysis after adjustment for covariates., Results: Of 988 patients hospitalized with either virus, 353 had RSV, 347 had influenza A, and 288 had influenza B infection. Patients with RSV, compared with those with influenza A or B, were more likely to have comorbid conditions (83% for RSV vs 72% for influenza A [ P = .03] and 74% for influenza B [ P = .001]) or pneumonia (41% vs 29% [ P = .03] and 24% [ P < .001], respectively). After adjustment for covariates, RSV infection was associated with an increased all-cause mortality rate within 90 days compared with influenza B (odds ratio, 2.16 [95% confidence interval, 1.20-3.87]; P = .01) but not influenza A (1.38 [.84-2.29]; P = .21). Increasing age and present pneumonia were identified as independent mortality risk factors in patients with RSV., Conclusions: Older adults hospitalized with RSV infections are at a higher risk of dying within 90 days of hospitalization than patients admitted with influenza B but at a similar risk as those admitted with influenza A, emphasizing the detrimental effects and severity of older patients being infected with RSV. Our findings underscore the need for strategic testing and vaccination approaches to mitigate the impact of RSV among older adults., Competing Interests: Potential conflicts of interest. O. R. reports a grant from the Research Foundation of Rigshospitalet and the A. P. Moller Foundation, unrelated to the current work. Z. B. H. reports grants from Independent Research Fund Denmark (grant 0134-00257B), the Lundbeck Foundation (grant R349-2020-835), and the Danish Cancer Society (grant KBVU-MS R327-A19137) and is a member of the Danish Vaccination Council. T. B. reports grants from Novo Nordisk Foundation, Lundbeck Foundation, Simonsen Foundation, GSK, Pfizer, Gilead, Kai Hansen Foundation, and Erik and Susanna Olesen's Charitable Fund and personal fees from GSK, Pfizer, Bavarian Nordic, Boehringer Ingelheim, Gilead, MSD, Pentabase ApS, Becton Dickinson, Janssen, Moderna, and Astra Zeneca, outside the submitted work. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Biomarker guided therapy could improve management of COVID-19 inpatients. Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests., Methods: COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDX and RightSign. Ease of use data was collected. Blood was also collected for centralized testing using established antibody assays (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome., Results: While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDX assay had 99.5% sensitivity and 58.1% specificity while the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDX assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes., Conclusions: Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDX test treating GenScript as the gold standard., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In patients previously hospitalised for COVID-19, a 12-week high-intensity interval training (HIIT) intervention has previously been shown to increase left ventricular mass (LVM) immediately after the intervention. In the present study, we examined the effects of the same HIIT scheme on LVM, pulmonary diffusing capacity, symptom severity and functional capacity at 12-month follow-up. In this investigator-blinded, randomised controlled trial, 12 weeks of a supervised HIIT scheme (4 × 4 min, three times a week) was compared to standard care (control) in patients recently discharged from hospital due to COVID-19. At inclusion and at 12-month follow-up, LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), while pulmonary diffusing capacity for carbon monoxide (D LCOc , secondary outcome) was examined by the single-breath method. Symptom severity and functional status were examined by the Post-COVID-19 Functional Scale (PCFS) and King's Brief Interstitial Lung Disease (KBILD) questionnaire score. Of the 28 patients assessed at baseline, 22 completed cMRI at 12-month follow-up (12.4 ± 0.6 months after inclusion). LVM was maintained in the HIIT but not the standard care group, with a mean between-group difference of 9.68 [95% CI: 1.72, 17.64] g (P = 0.0182). There was no differences in change from baseline to 12-month follow-up between groups in D LCOc % predicted (-2.45 [-11.25, 6.34]%; P = 0.578). PCFS and KBILD improved similarly in the two groups. In individuals previously hospitalised for COVID-19, a 12-week supervised HIIT scheme resulted in a preserved LVM at 12-month follow-up but did not affect pulmonary diffusing capacity or symptom severity., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Pneumonia is one of the main contributors to non-cancer mortality among patients with head and neck cancer (HNC). This study aimed to determine the vaccine uptake for pneumococcal polysaccharide and conjugate vaccines, quadrivalent influenza vaccines, and mRNA COVID-19 vaccines before and after an HNC diagnosis. Furthermore, the study investigated the timing of vaccination after a cancer diagnosis., Materials & Methods: This register based multicentre study included Danish patients ≥ 18y diagnosed with HNC between 2018 and 2021. The vaccine uptake was assessed by calculating cumulative incidence (CI), while the timing of vaccination after an HNC diagnosis was explored by calculating incidence rates of vaccination the first and second half year after a cancer diagnosis., Results: The cumulative incidence of vaccine uptake for pneumococcal vaccines was estimated to be 8 % and 16 % one year before and after an HNC diagnosis, respectively. The CIs were 36 % and 38 % for quadrivalent influenza vaccines, respectively, whereas the CIs of vaccine uptake for mRNA COVID-19 vaccines were 60 % and 89 %. The IR of mRNA COVID-19 vaccinations the first half year after HNC diagnosis were 273 per 1000 person-months of follow-up (PMFU) and 111 per 1000 PMFU the second half year, respectively (IRR: 0.38, p < 0.001). Comparing the same periods, the IR of quadrivalent influenza vaccination was 28 per 1000 PMFU and 51 per 1000 PMFU (IRR: 1.95, 0 < 0.001). The IRs of pneumococcal vaccinations were 11 per 1000 PMFU and 14 per 1000 PMFU (IRR 1.28, p = 0.21)., Conclusions: Although our study shows a significant increase in pneumococcal and COVID-19 vaccine uptake after HNC diagnosis, a gap remains in vaccine uptake before diagnosis, underscoring the need for increased awareness of vaccination options and recommendations. Our findings could serve as a reference for future recommendations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mads Frederik Eiberg reports financial support was provided by Danish Cancer Society. Zitta Barrella Harboe reports financial support was provided by Independent Research Fund Denmark. Zitta Barrella Harboe reports financial support was provided by Lundbeck Foundation. Zitta Barrella Harboe reports financial support was provided by Danish Cancer Society. Omid Rezahosseini reports financial support was provided by A.P. Møllers fonden. Omid Rezahosseini reports financial support was provided by Research Foundation of Rigshospitalet. Zitta Barrella Harboe reports a relationship with The Danish Vaccination Council that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the effect of standard care (SoC) combined with supervised in-bed cycling (Bed-Cycle) or booklet exercises (Book-Exe) versus SoC in community-acquired pneumonia (CAP)., Methods: In this randomized controlled trial, 186 patients with CAP were assigned to SoC (n = 62), Bed-Cycle (n = 61), or Book-Exe (n = 63). Primary outcome length of stay (LOS) was analyzed with analysis of covariance. Secondary outcomes, 90-day readmission, and 180-day mortality were analyzed with Cox proportional hazard regression and readmission days with negative-binominal regression., Results: LOS was -2% (95% CI: -24 to 25) and -1% (95% CI: -22 to 27) for Bed-Cycle and Book-Exe, compared with SoC. Ninety-day readmission was 35.6% for SoC, 27.6% for Bed-Cycle, and 21.3% for Book-Exe. Adjusted hazard ratio (aHR) for 90-day readmission was 0.63 (95% CI: .33-1.21) and 0.54 (95% CI: .27-1.08) for Bed-Cycle and Book-Exe compared with SoC. aHR for 90-day readmission for combined exercise was 0.59 (95% CI: .33-1.03) compared with SoC. aHR for 180-day mortality was 0.84 (95% CI: .27-2.60) and 0.82 (95% CI: .26-2.55) for Bed-Cycle and Book-Exe compared with SoC. Number of readmission days was 226 for SoC, 161 for Bed-Cycle, and 179 for Book-Exe. Incidence rate ratio for readmission days was 0.73 (95% CI: .48-1.10) and 0.77 (95% CI: .51-1.15) for Bed-Cycle and Book-Exe compared with SoC., Conclusions: Although supervised exercise training during admission with CAP did not reduce LOS or mortality, this trial suggests its potential to reduce readmission risk and number of readmission days., Clinical Trials Registration: NCT04094636., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Vaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19., Methods: A nested case-control study on adults (≥ 18 years) who received at least two doses of a mRNA-COVID-19 vaccine and were hospitalized with SARS-CoV-2 breakthrough infections and severe COVID-19 between January 7, 2021, and February 1, 2022, were eligible for inclusion. Age- and sex-matched non-vaccinated controls were identified. Immunophenotyping was performed using a custom-designed 10-color flow cytometry prefabricated freeze-dried antibody panel (DuraClone, Beckman Coulter (BC), Brea, Calif). TruCulture (Myriad RBM, Austin, USA) was used to assess induced immune response in whole blood, revealing different critical signaling pathways as a proxy for immune function. All samples were obtained within 48 hours of admission., Results: In total, 20 hospitalized patients with severe COVID-19 and a breakthrough SARS-CoV-2 infection were included, ten vaccinated and ten non-vaccinated patients. Vaccinated patients had lower concentrations of CD19 B cells (p = 0.035), naïve CD4 T cells (p = 0.015), a higher proportion of γδ1 T cells (p = 0.019), and higher unstimulated immune cell release of IL-10 (p = 0.015)., Conclusion: We observed immunological differences between vaccinated and non-vaccinated patients hospitalized due to severe COVID-19 that indicate that vaccinated patients had lower B cell concentrations, lower concentrations of CD4 naïve T cells, a skewed gamma-delta V1/V2 ratio, and an exaggerated IL-10 response at admission. These results could indicate a suboptimal immune response involved in SARS-CoV-2 breakthrough infections that cause severe COVID-19 in vaccinated adults. However, the sample size was small, and further research is needed to confirm these results., Competing Interests: CN received research funding and/or consultancy fees outside this study from Abbvie, Janssen, AstraZeneca, Takeda, Octapharma, CSL Behring, Beigene and Genmab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sejdic, Hartling, Holler, Klingen Gjærde, Lindegaard, Dungu, Gnesin, Møller, Teglgaard, Niemann, Brooks, Jørgensen, Franck, Fischer, Marquart, Harboe and Ostrowski.)

Introduction: Diabetes is associated with dysregulated immune function and impaired cytokine release, while transient acute hyperglycaemia has been shown to enhance inflammatory cytokine release in preclinical studies. Although diabetes and acute hyperglycaemia are common among patients with community-acquired pneumonia (CAP), the impact of chronic, acute, and acute-on-chronic hyperglycaemia on the host response within this population remains poorly understood. This study investigated whether chronic, acute, and acute-on- chronic hyperglycaemia are associated with distinct mediators of inflammatory, endothelial, and angiogenic host response pathways in patients with CAP., Methods: In a cross-sectional study of 555 patients with CAP, HbA1c, admission plasma (p)-glucose, and the glycaemic gap (admission p-glucose minus HbA1c- derived average p-glucose) were employed as measures of chronic, acute, and acute-on-chronic hyperglycaemia, respectively. Linear regression was used to model the associations between the hyperglycaemia measures and 47 proteins involved in inflammation, endothelial activation, and angiogenesis measured at admission. The models were adjusted for age, sex, CAP severity, pathogen, immunosuppression, comorbidity, and body mass index. Adjustments for multiple testing were performed with a false discovery rate threshold of less than 0.05., Results: The analyses showed that HbA1c levels were positively associated with IL-8, IL-15, IL-17A/F, IL-1RA, sFlt-1, and VEGF-C. Admission plasma glucose was also positively associated with these proteins and GM-CSF. The glycaemic gap was positively associated with IL-8, IL-15, IL-17A/F, IL-2, and VEGF-C., Conclusion: In conclusion, chronic, acute, and acute-on-chronic hyperglycaemia were positively associated with similar host response mediators. Furthermore, acute and acute-on-chronic hyperglycaemia had unique associations with the inflammatory pathways involving GM-CSF and IL-2, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dungu, Lundgaard, Ryrsø, Hegelund, Jensen, Kristensen, Krogh-Madsen, Faurholt-Jepsen, Ostrowski, Banasik and Lindegaard.)

Background: Adiponectin is secreted by adipocytes and is inversely associated with obesity. Given the association between low body mass index (BMI) and higher mortality risk after community-acquired pneumonia (CAP), we hypothesized that high adiponectin levels are associated with a higher risk of adverse clinical outcomes in patients with CAP., Methods: In a prospective cohort study of 502 patients hospitalized with CAP, adiponectin was measured in serum at admission. The associations between adiponectin and clinical outcomes were estimated with logistic regression analyses adjusted for age, sex, and measures of obesity (BMI, waist circumference or body fat percentage)., Results: Adiponectin was associated with higher 90-day mortality for each 1 μg/mL increase [OR 1.02, 95% CI (1.00, 1.04), p  = 0.048] independent of age and sex. Likewise, adiponectin was associated with a higher risk of 90-day readmission for each 1 μg/mL increase [OR 1.02, 95% CI (1.01, 1.04), p  = 0.007] independent of age and sex. The association between adiponectin and 90-day mortality disappeared, while the association with 90-day readmission remained after adjusting for adiposity., Conclusion: Adiponectin was positively associated with mortality and readmission. The association with mortality depended on low body fat, whereas the association with readmission risk was independent of obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dungu, Ryrsø, Hegelund, Sejdic, Jensen, Kristensen, Krogh-Madsen, Faurholt-Jepsen and Lindegaard.)

Background: The emerging use of biomarkers in research and tailored care introduces a need for information about the association between biomarkers and basic demographics and lifestyle factors revealing expectable concentrations in healthy individuals while considering general demographic differences., Methods: A selection of 47 biomarkers, including markers of inflammation and vascular stress, were measured in plasma samples from 9876 Danish Blood Donor Study participants. Using regression models, we examined the association between biomarkers and sex, age, Body Mass Index (BMI), and smoking., Results: Here we show that concentrations of inflammation and vascular stress biomarkers generally increase with higher age, BMI, and smoking. Sex-specific effects are observed for multiple biomarkers., Conclusion: This study provides comprehensive information on concentrations of 47 plasma biomarkers in healthy individuals. The study emphasizes that knowledge about biomarker concentrations in healthy individuals is critical for improved understanding of disease pathology and for tailored care and decision support tools., (© 2024. The Author(s).)

Competing Interests: Kirsten Grønbæk has received research funding and/or consultancy fees from Janssen Pharma and GSK. Carsten Utoft Niemann has received research funding and/or consultancy fees from Abbvie, AstraZeneca, Janssen, Octapharma, Beigene, Genmab, CSL Behring, Takeda, Lilly, and MSD. Anne‐Mette Lebech has received unrestricted research grant from Gilead and consultancy fees from GSK, MSD, and Pfizer.

Background: Low awareness and lack of routine testing for respiratory syncytial virus (RSV) infections among adults has led to underreporting in hospital records. This study aimed to assess the underreporting and misclassification of RSV infections among adults hospitalized with an respiratory tract infection (RTI)-coded hospitalization., Methods: This study is an observational cohort study of RSV-associated hospitalizations among Danish adults (≥18 years old) conducted, between 2015 to 2018. Data were extracted from the Danish National Patient Registry (DNPR) and the Danish Microbiology Database. We identified RSV-positive hospitalizations by linking RTI-coded hospitalizations with a positive RSV test., Results: Using hospital admission registries, we identified 440 RSV-coded hospitalizations, of whom 420 (95%) had a positive RSV test registered. By linking patients with RTI-coded hospital admissions to RSV test result, we found 570 additional episodes of RSV-positive hospitalizations without an RSV-coded diagnosis., Conclusions: Our study of national register data showed that RSV is underreported among Danish adults. The study showed that the reliability of hospitalization data to estimate the burden of RSV among adults is questionable and are sensitive to changes in practice over time, even with complete nationwide healthcare data. Healthcare data can be useful to observe seasonality but to estimate the disease burden, prospective surveillance is recommended., Competing Interests: Potential conflicts of interest. T. K. F. declared participating as a principal investigator (unpaid) in a Pfizer RSV vaccine trial on maternal vaccination, outside the submitted work. A. M. E.-C. is funded by the Independent Research Fund Denmark for her PhD project (grant number 10.46540/2096-00046B). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bacterial aerobic respiration may determine the outcome of antibiotic treatment in experimental settings, but the clinical relevance of bacterial aerobic respiration for the outcome of antibiotic treatment has not been tested. Therefore, we hypothesized that bacterial aerobic respiration is higher in sputum from patients with acute lower respiratory tract infections (aLRTI), than in sputum from patients with chronic LRTI (cLRTI), where the bacteria persist despite antibiotic treatment. The bacterial aerobic respiration was determined according to the dynamics of the oxygen (O 2 ) concentration in sputum from aLRTI patients (n = 52). This result was evaluated by comparison to previously published data from patients with cLRTI. O 2 consumption resulting in anoxic zones was more frequent in sputum with detected bacterial pathogens. The bacterial aerobic respiration in aLRTI sputum approximated 55% of the total O 2 consumption, which was significantly higher than previously published for cLRTI. The bacterial aerobic respiration in sputum was higher in aLRTI patients than previously seen in cLRTI patients, indicating the presence of bacteria with a sensitive physiology in aLRTI. These variations in bacterial physiology between aLRTI patients and cLRTI patients may contribute the huge difference in treatment success between the two patient groups., (© 2024 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

C-reactive protein (CRP) is commonly used to guide community-acquired pneumonia (CAP) treatment. A positive association between admission glucose and CRP levels has been observed in patients with CAP. The associations between prediabetes, unknown diabetes, acute-on-chronic hyperglycaemia, and CRP levels, and between admission CRP levels and insulin resistance (IR) in CAP, remain unexplored. This study investigated the associations firstly between chronic, acute, and acute-on-chronic hyperglycaemia and CRP levels, and secondly between admission CRP levels and IR in CAP. In a prospective cohort study of adults with CAP, the associations between chronic, acute, and acute-on-chronic hyperglycaemia (admission glucose minus HbA1c-derived average glucose) and CRP levels until admission day 3 were modelled with repeated-measures linear mixed models. IR was estimated with the homeostasis model assessment of IR (HOMA-IR). The association between admission CRP levels and HOMA-IR was modelled with linear regression. In 540 patients, no association between chronic, acute, or acute-on-chronic hyperglycaemia and CRP levels was found. In 266 patients, every 50 mg/L increase in admission CRP was associated with a 7% (95% CI 1-14%) higher HOMA-IR. In conclusion, our findings imply that hyperglycaemia does not influence CRP levels in patients with CAP, although admission CRP levels were positively associated with IR.

Background: Exercise training at work has the potential to improve employees' productivity, health, and well-being. However, exercise interventions for healthcare workers in hospitals may be challenged by time pressure and the ongoing workflow with patient care., Objective: The aim was to identify barriers and facilitators for participation in exercise training during work in a hospital department., Methods: Eight semi-structured interviews of 13 individuals were conducted with hospital employees from different staff groups who participated in 12 weeks of exercise twice weekly. The data analysis was a thematic approach based on the Theoretical Domains Framework and the COM-B factors in the Behavior Change Wheel., Results: Barriers and facilitators varied between different groups. Barriers included limited structure, busyness, and a discouraging culture. Facilitators included gaining a feeling of community and psychological and physical well-being. Seven contextual subthemes were vital for successful implementation of exercise in a hospital setting: sharing of knowledge and information; involvement; administration and structure; culture; individualization; purpose and objective; and incentives., Conclusions: The informants appreciated exercise training during work. Inpatient departments' informants found it difficult to participate in the intervention, whilst those with more administrative tasks found it easier. This study identified barriers and facilitators vital for a successful implementation of an exercise training intervention in a hospital department. The study explains how future interventions can improve reach, adoption, and implementation of exercise training interventions to hospital staffs.

Rationale: The ratio of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR) and platelet-to-lymphocyte (PLR) are biomarkers that have shown potential for predicting mortality in several diseases. For patients hospitalized with community-acquired pneumonia (CAP), the prognostic capabilities of these biomarkers are unknown., Objective: Investigate whether NLR, MLR or PLR were associated with 90-day mortality in CAP. Further, investigate whether the prediction rule CURB-65 could be improved by adding these biomarkers., Methods: A derivation-validation study using a Danish multicentre retrospective cohort as the derivation cohort (N = 831) and a European multicentre prospective cohort as the validation cohort (N = 2463). Associations between biomarkers and mortality were assessed using Cox proportional hazard models with adjustments for sex, CURB-65 and comorbidities. A cut-off value for biomarkers was determined using Youden's J Statistics. The performance of CURB-65 with added biomarkers was evaluated using receiver-operating characteristics., Results: In both cohorts increasing NLR and PLR were associated with 90-day mortality. In the derivation cohort, the hazard ratios for NLR and PLR were 1.016 (95% confidence interval (CI) 1.001-1.032, P = 0.038) and 1.001 (95% CI 1.000-1.001, P = 0.035), respectively. Adding these biomarkers to CURB-65 did not improve its performance., Conclusions: NLR and PLR were associated with 90-day mortality in CAP, but did not improve CURB-65., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

A large proportion of patients suffer from a persistent reduction in cardiorespiratory fitness after recovery from COVID-19, of which the effects on the heart may potentially be reversed through the effect of high-intensity interval training (HIIT). In the present study, we hypothesized that HIIT would increase left ventricular mass (LVM) and improve functional status and health-related quality of life (HRQoL) in individuals previously hospitalized for COVID-19. In this investigator-blinded, randomized controlled trial, 12 wk of supervised HIIT (4 × 4 min, three times a week) was compared with standard care (control) in individuals recently discharged from hospital due to COVID-19. LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), whereas the pulmonary diffusing capacity (D LCOc , secondary outcome) was examined by the single-breath method. Functional status and HRQoL were assessed by Post-COVID-19 functional scale (PCFS) and King's brief interstitial lung disease (KBILD) questionnaire, respectively. A total of 28 participants were included (age 57 ± 10, 9 females; HIIT: 58 ± 11, 4 females; standard care: 57 ± 9, 5 females), LVM increased in the HIIT vs. standard care group with a between-group difference of 6.8 [mean, 95%CI: 0.8; 12.8] g; P = 0.029. There were no between-group differences in D LCOc or any other lung function metric, which gradually resolved in both groups. Descriptively, PCFS suggested fewer functional limitations in the HIIT group. KBILD improved similarly in the two groups. HIIT is an efficacious exercise intervention for increasing LVM in individuals previously hospitalized for COVID-19. NEW & NOTEWORTHY In this randomized clinical trial on individuals previously hospitalized for COVID-19, a 12 wk supervised high-intensity interval training (HIIT) scheme was found to increase left ventricular mass, whereas pulmonary diffusing capacity was unaffected. The findings indicate that HIIT is an efficacious exercise intervention for targeting the heart after COVID-19.

Baseline levels of endotheliopathy are associated with worse respiratory outcomes and mortality in undifferentiated acute respiratory failure (ARF), but knowledge is lacking on the development of endotheliopathy over time in ARF. We, therefore, aimed to evaluate the prognostic significance of trajectories of endotheliopathy during the first days of ARF. We performed a secondary, exploratory analysis of a single-center prospective cohort including 459 patients requiring mechanical ventilation. Based on Days 1-3 Syndecan-1, soluble Thrombomodulin (sTM), and Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), we divided patients into subgroups using latent class mixed modeling and correlated subgroups with clinical outcomes using Cox regression. Based on Syndecan-1 and sTM, respectively, we identified two subgroups. Based on PECAM-1, we identified three subgroups. Subgroups based on Syndecan-1 and sTM were identifiable from the baseline levels, but subgroups based on PECAM-1 were not. Patients with persistently high levels of both sTM and PECAM-1 were liberated from mechanical ventilation more slowly (Group high vs. Group low, sTM: hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.50-0.88, p = .01, PECAM-1: HR: 0.59, 95% CI: 0.37-0.93, p = .02) and had higher 30-day mortality (sTM: HR: 1.90, 95% CI: 1.20-3.01, p = .01, PECAM-1: HR: 4.25, 95% CI: 1.99-9.07, p < .01). In ARF requiring mechanical ventilation, patients in subgroups with persistently high levels of sTM and PECAM-1 had lower rates of liberation from mechanical ventilation and higher 30-day mortality. However, patients with persistently high levels of sTM were identifiable based on the baseline level, and only the trajectory of PECAM-1 added information to that of the baseline level., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Introduction: The optimal duration of antibiotic therapy for community-acquired pneumonia (CAP) is unsettled. Short-course therapy has proved successful in clinical trials but is not yet implemented in everyday clinical practice. Validation of results from randomised controlled trials is crucial to evaluate existing evidence and provide clinicians with assurance of using new treatment strategies. In a pragmatic framework, we aim to assess the use of short-course antibiotic therapy guided by the onset of clinical stability in patients hospitalised with CAP., Methods and Analysis: This study is a randomised controlled trial with a non-inferiority design that will examine the efficacy of short-course antibiotic therapy in patients hospitalised with CAP. From six hospitals across Denmark, we plan to enrol 564 patients between 2019 and 2024. Within 3-5 days after initiating antibiotic therapy, participants will be randomised 1:1 to parallel treatment arms: (1) short-course antibiotic therapy of 5 days or (2) antibiotic therapy of at least 7 days. The primary outcome will be 90-day readmission-free survival and will be estimated as an absolute risk difference with a predefined non-inferiority margin of -6%. Secondary outcomes will comprise other safety measures including new antibiotics, adverse events, length of hospital stay and postdischarge outpatient visits. Both intention-to-treat and per-protocol analyses will be performed., Ethics and Dissemination: This study has been approved by the Health Research Ethics Committee of the Capital Region of Denmark (identifier number: H-19014479). Trial data will be made available in anonymous form when the trial has ended., Trial Registration Number: NCT04089787, ClinicalTrials.Gov., Competing Interests: Competing interests: TB reports grants from Novo Nordisk Foundation, Lundbeck Foundation, Simonsen Foundation, GSK, Pfizer, Gilead, Kai Hansen Foundation and Erik and Susanna Olesen’s Charitable Fund; personal fees from GSK, Pfizer, Boehringer Ingelheim, Gilead, MSD, Pentabase ApS, Becton Dickinson, Janssen and Astra Zeneca; outside the submitted work. All other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined., Methods and Analysis: Investigator-initiated multicentre, non-blinded, non-inferiority randomised controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive antibiotic treatment of 7 days or longer. Randomisation will occur in equal proportion (1:1) no later than day 5 of effective antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli ( Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.The primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital readmission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a non-inferiority margin of 10%, and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations., Ethics and Dissemination: The study is approved by the Danish Regional Committee on Health Research (H-19085920) and the Danish Medicines Agency (2019-003282-17). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal., Trial Registration Number: ClinicalTrials.Gov:NCT04291768., Competing Interests: Competing interests: TB reports grants from Novo Nordisk Foundation, Lundbeck Foundation, Simonsen Foundation, GSK, Pfizer, Gilead, Kai Hansen Foundation and Erik and Susanna Olesen’s Charitable Fund; personal fees from GSK, Pfizer, Boehringer Ingelheim, Gilead, MSD, Pentabase ApS, Becton Dickinson, Janssen and Astra Zeneca; outside the submitted work. The remaining authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated., Methods: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics., Results: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37-0.57) and 0.47 (95% confidence interval, 0.39-0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration., Conclusions: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.

Background: Chronic low-grade inflammation associated with a dysregulated adipose tissue might contribute to amplifying the inflammatory response in severe COVID-19. The aim of this study was to examine the association between levels of circulating leptin and adiponectin and the severity and mortality of COVID-19., Methods: Serum levels of leptin and adiponectin were determined at admission in 123 individuals with confirmed COVID-19 and their association with 90-day mortality and respiratory failure was analyzed by logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: The median values of circulating leptin and adiponectin were 7.2 ng/mL (IQR 3.8-13.4) and 9.0  μ g/mL (IQR 5.7-14.6), respectively. After adjustment for age, sex, body mass index, hypertension, diabetes, chronic obstructive pulmonary disease, and oxygen saturation at admission, a doubling of circulating adiponectin was associated with a 38% reduction in odds of 90-day mortality (OR 0.62, CI 0.43-0.89) and a 40% reduction in odds of respiratory failure (OR 0.60, CI 0.42-0.86). The association tended to be strongest in individuals below the median age of 72 years. Circulating leptin was not associated with outcomes., Conclusions: Circulating adiponectin at admission was inversely associated with mortality and respiratory failure in SARS-CoV-2 infection. Further studies are needed to elucidate how exactly adipokines, especially adiponectin, are linked to the progression and prognosis of COVID-19., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper. TB reports grants from Pfizer, Novo Nordisk Foundation, Simonsen Foundation, Kai foundation, Erik and Susanne Olesen's Charitable Fund, and Lundbeck Foundation, grants and personal fees from GSK and Pfizer, and personal fees from Boehringer Ingelheim, Astra Zeneca, and Janssen, outside the submitted work., (Copyright © 2023 Bettina Hindsberger et al.)

Background: Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD., Methods: An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline., Discussion: Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD., Trial Registration: ClinicalTrials.gov NCT04873856 . Registered on May 3, 2021., (© 2023. The Author(s).)

Background: Viral shedding and neutralizing antibody (NAb) dynamics among patients hospitalized with severe coronavirus disease 2019 (COVID-19) and immune correlates of protection have been key questions throughout the pandemic. We investigated the duration of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity, infectious viral shedding and NAb titers as well as the association between NAb titers and disease severity in hospitalized COVID-19 patients in Denmark 2020-2021., Materials and Methods: Prospective single-center observational cohort study of 47 hospitalized COVID-19 patients. Oropharyngeal swabs were collected at eight time points during the initial 30 days of inclusion. Serum samples were collected after a median time of 7 (IQR 5 - 10), 37 (IQR 35 - 38), 97 (IQR 95 - 100), and 187 (IQR 185 - 190) days after symptom onset. NAb titers were determined by an in-house live virus microneutralization assay. Viral culturing was performed in Vero E6 cells., Results: Patients with high disease severity had higher mean log 2 NAb titers at day 37 (1.58, 95% CI [0.34 -2.81]), 97 (2.07, 95% CI [0.53-3.62]) and 187 (2.49, 95% CI [0.20- 4.78]) after symptom onset, compared to patients with low disease severity. Peak viral load (0.072, 95% CI [- 0.627 - 0.728]), expressed as log 10 SARS-CoV-2 copies/ml, was not associated with disease severity. Virus cultivation attempts were unsuccessful in almost all (60/61) oropharyngeal samples collected shortly after hospital admission., Conclusions: We document an association between high disease severity and high mean NAb titers at days 37, 97 and 187 after symptom onset. However, peak viral load during admission was not associated with disease severity., Trial Registration: The study is registered at https://clinicaltrials.gov/ (NCT05274373)., (© 2023. The Author(s).)

Purpose: Obesity may alter the severity of infection with Coronavirus disease 2019 (COVID-19). Age may impact the association between body weight and severity of COVID-19 in patients with obesity. The aim of the study was to examine the association between obesity and severity of infection in a Danish cohort hospitalized with COVID-19 in the initial wave of the pandemic., Patients and Methods: Based on data from the nationwide, clinical database: COVID-DK, risks of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and mortality were compared among patients with and without obesity. Interaction with age was examined and we used Inverse Probability of Treatment Weighting regression for confounder adjustment., Results: Among 524 patients, 142 (27%) were admitted to the ICU, 112 (21%) required IMV, and 109 (21%) died. Compared to COVID-19 patients without obesity, patients with obesity displayed a non-significant increased risk of ICU admission (Relative Risk [RR] 1.19, 95% Confidence Interval [CI] 0.88; 1.60), IMV (RR 1.23, CI 0.86; 1.75) and mortality (RR 1.21, CI 0.84; 1.75). COVID-19 patients with obesity, <60 years had highly increased risk of ICU admission (RR 1.92, CI 1.14; 3.24) and IMV (RR 1.95, CI 1.09; 3.49)., Conclusions: In hospitalized COVID-19 patients, obesity conferred an approximately 20% increased risk for ICU admission, IMV, and death, although these relationships did not reach statistical significance. COVID-19 patients with obesity and <60 years had an almost doubled risk of ICU admission and IMV., Competing Interests: Jens Meldgaard Bruun, Sigrid Bjerge Gribsholt and Bjørn Richelsen received honoraria for lectures at Novo Nordisk Denmark A/S. Thomas Lars Benfield received grants or contracts from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Foundation, Erik and Susanna Olesen's Charitable Fund, GSK, Pfizer, Boehringer Ingelheim, Gilead Sciences, MSD, Pentabase, Roche, Novartis, Kancera AB, Janssen, and Astra Zeneca. Thomas Lars Benfield received honoraria for lectures at GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, Abbvie, and Astra Zeneca. TLB received donation of trial medication from Eli Lilly. Other authors declare no conflict of interest., (© 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Aim: To explore pituitary-gonadal hormone concentrations and assess their association with inflammation, severe respiratory failure, and mortality in hospitalized men and women with COVID-19, and compare these to hormone concentrations in hospitalized patients with bacterial community-acquired pneumonia (CAP) and influenza virus CAP and to concentrations in a reference group of healthy individuals., Methods: Serum concentrations of testosterone, estrone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and interleukin-6 (IL-6) were measured within 4 days of admission. Associations were assessed by logistic regression analysis in patients with COVID-19, and results were reported as odds ratio with 95% CI per two-fold reduction after adjustment for age, comorbidities, days to sample collection, and IL-6 concentrations., Results: In total, 278 patients with COVID-19, 21 with influenza virus CAP, and 76 with bacterial CAP were included. Testosterone concentrations were suppressed in men hospitalized with COVID-19, bacterial and influenza virus CAP, and moderately suppressed in women. Reductions in testosterone (OR: 3.43 (1.14-10.30), P = 0.028) and LH (OR: 2.51 (1.28-4.92), P = 0.008) were associated with higher odds of mehanical ventilation (MV) in men with COVID-19. In women with COVID-19, reductions in LH (OR: 3.34 (1.02-10-90), P = 0.046) and FSH (OR: 2.52 (1.01-6.27), P = 0.047) were associated with higher odds of MV., Conclusion: Low testosterone and LH concentrations were predictive of severe respiratory failure in men with COVID-19, whereas low concentrations of LH and FSH were predictive of severe respiratory failure in women with COVID-19.

Undernutrition is associated with increased mortality after hospitalization with community-acquired pneumonia (CAP), whereas obesity is associated with decreased mortality in most studies. We aimed to determine whether undernutrition and obesity are associated with increased risk of re-hospitalization and post-discharge mortality after hospitalization. This study was nested within the Surviving Pneumonia cohort, which is a prospective cohort of adults hospitalized with CAP. Patients were categorized as undernourished, well-nourished, overweight, or obese. Undernutrition was based on diagnostic criteria by the European Society for Clinical Nutrition and Metabolism. Risk of mortality was investigated using multivariate logistic regression and re-hospitalization with competing risk Cox regression where death was the competing event. Compared to well-nourished patients, undernourished patients had a higher risk of 90-day (OR 3.0, 95% CI 1.0; 21.4) mortality, but a similar 30-day and 180-day mortality risk. Obese patients had a similar re-hospitalization and mortality risk as well-nourished patients. In conclusion, among patients with CAP, undernutrition was associated with increased risk of mortality. Undernourished patients are high-risk patients, and our results indicate that in-hospital screening of undernutrition should be implemented to identify patients at mortality risk. Studies are required to investigate whether nutritional therapy after hospitalization with CAP would improve survival.

Objectives: This pilot study tested the use of an exercise offer to hospital employees during working hours and changes in work and health parameters., Methods: Employees (n = 214) from a medical department on a Danish hospital were invited to 30 minutes' exercise training twice weekly for 12 weeks. Outcomes included health- and work-related parameters., Results: Eighty employees (mean age, 44.4 [SD, 10.7] years; 81.3% women) completed the study. Intervention adherence was 36.3% (SD, 25.1%). Aerobic capacity increased from 34.6 (95% confidence interval [CI], 32.3 to 36.9) to 36.7 (95% CI, 34.1 to 39.4) mL O 2 /min per kilogram, P = 0.004. Blood pressure decreased from 120 (95% CI, 117 to 123)/79 (95% CI, 76 to 81) to 116 (95% CI, 112 to 120)/76 (95% CI, 74 to 79) mm Hg, P = 0.003. Waist circumference and musculoskeletal pain decreased. Well-being, social capital, and quality of life increased., Conclusions: Despite low training adherence, completers improved outcomes related to metabolic and self-rated health., Competing Interests: Conflict of interest: None declared., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Background: Impaired functional status is a risk factor for hospitalization in patients with community-acquired pneumonia (CAP). The aim was to determine the influence of functional status and physical activity level on severe outcomes, including length of stay, admission to the intensive care unit (ICU), readmission, and mortality in patients with CAP. Methods: A prospective cohort study among patients hospitalized with CAP. Functional status was assessed with the Barthel index and grip strength, and physical activity level was assessed using the international physical activity questionnaire. Linear regression was used to assess the association with length of stay, and logistic regression was used to assess the risk of severe outcomes. Results: Among 355 patients admitted with CAP, 18% had a low Barthel index (<80), 45% had a low grip strength, and 75% had a low physical activity level. Low Barthel index was associated with increased risk of ICU admission (OR 3.6, 95% CI 1.2−10.9), longer length of stay (27.9%, 95% CI 2.3−59.7%), readmission within 30, 90, and 180 days (OR 2.1−2.4, p < 0.05), and mortality within 90 and 180 days (OR 4.2−5.0, p < 0.05). Low grip strength was associated with increased risk of 90 days readmission (OR 1.6, 95% CI 1.0−2.6, p < 0.05) and mortality within 30, 90, and 180 days (OR 2.6−3.2, p < 0.05). Low physical activity level was associated with increased risk of readmission within 90 and 180 days (OR 1.8−2.1, p < 0.05) and mortality within 30, 90, and 180 days (OR 3.3−5.5, p < 0.05). Conclusions: Impaired functional status and low physical activity level were associated with a longer length of stay and increased risk of ICU admission, readmission, and mortality in patients hospitalized with CAP. Routine assessment of functional status and physical activity level in clinical care could enable early identification of individuals with excess risk for a poor prognosis. Trial registration: ClinicalTrials.gov, NCT03795662.

Background: Bed rest with limited physical activity is common during admission. The aim was to determine the association between daily step count and physical activity levels during and after admission with community-acquired pneumonia (CAP) and the risk of readmission and mortality., Methods: A prospective cohort study of 166 patients admitted with CAP. Step count and physical activity were assessed with accelerometers during and after admission and were categorised as sedentary, light, or moderate-vigorous physical activity. Linear regression was used to assess the association between step count and length of stay. Logistic regression was used to assess the association between step count, physical activity level, and risk of readmission and mortality., Results: Patients admitted with CAP were sedentary, light physically active, and moderate-to-vigorous physically active 96.4%, 2.6%, and 0.9% of their time, respectively, with 1356 steps/d. For every 500-step increase in daily step count on day 1, the length of stay was reduced by 6.6%. For every 500-step increase in daily step count during admission, in-hospital and 30-day mortality was reduced. Increased light and moderate-to-vigorous physical activity during admission were associated with reduced risk of in-hospital and 30-day mortality. After discharge, patients increased their daily step count to 2654 steps/d and spent more time performing light and moderate-to-vigorous physical activity. For every 500-step increase in daily step count after discharge, the risk of readmission was reduced. Higher moderate-to-vigorous physical activity after discharge was associated with a reduced risk of readmission., Conclusions: Increased physical activity during admission was associated with a reduced length of stay and risk of mortality, whereas increased physical activity after discharge was associated with a reduced risk of readmission in patients with CAP. Interventions focusing on increasing physical activity levels should be prioritised to improve the prognosis of patients admitted with CAP.

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P =0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.