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Line Dyreborg,1,2 Sabine Michelsen Raunbak,2 Sabrina Storgaard Sørensen,2 Dorte Melgaard,3– 5 Signe Westmark1 1Centre for Clinical Research, North Denmark Regional Hospital, Hjørring, Denmark; 2Danish Center for Health Services Research, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark; 3North Denmark Regional Hospital, Hjørring, Denmark; 4Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark; 5Mech-sense, Aalborg University Hospital, Aalborg, DenmarkCorrespondence: Signe Westmark, North Denmark Regional Hospital, Bispensgade 37, Hjørring, DK-9800, Denmark, Tel +45 2041 6541, Email s.westmark@rn.dkPurpose: This study aims to evaluate the cost-effectiveness of chin tuck against resistance (CTAR) for citizens suffering from dysphagia compared to the standard municipal treatment in Denmark.Patients and Methods: A cost-utility analysis, employing a municipal perspective, was conducted using cost data collected alongside clinical data of a randomized controlled trial evaluating the effect of CTAR training for citizens with dysphagia. The composition of the clinical randomized controlled trial, which included citizens with different diagnoses, means that participants had different disease courses. Ninety-two citizens from seven different Danish municipalities were enrolled, of whom 43 received standard care, and 49 received CTAR in addition to standard care. The effect outcome of the economic evaluation was quality-adjusted life years (QALY), estimated using the EQ-5D-5L questionnaire. Individual resource consumption of each citizen was determined based on the use of home care, home nursing care, physio- and occupational therapy, dietitian guidance, and hospital admissions. The incremental costs and QALYs between the intervention group (CTAR in addition to standard care) and standard care group were estimated using regression analysis, and sensitivity analyses were performed to investigate the robustness of the results.Results: The base case analysis showed that the intervention group was dominant compared to the standard care group, with a decrease in incremental costs of £ 542.38 and an increase in incremental QALYs of 0.0118. All sensitivity analyses demonstrated similar findings as the base case analysis, supporting the robustness of the results.Conclusion: This study found that the intervention group was the dominant alternative, hence being more effective and cost-saving, compared to the standard care group in a Danish municipality perspective with a three-month time horizon. This study adds to the scarce evidence on the cost-effectiveness of CTAR in a Danish clinical setting, but further studies should focus on estimating long-term cost-effectiveness.Keywords: cost-utility analysis, exercise, swallowing disorders, municipality, quality of life

Sabrina Storgaard Sørensen,1 Kjeld Møller Pedersen,1 Ulla Møller Weinreich,2,3 Lars Holger Ehlers,1 1Danish Center for Healthcare Improvements, Faculty of Social Sciences and Faculty of Health Sciences, Aalborg University, Aalborg East, Denmark; 2Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; 3The Clinical Institute, Aalborg University Hospital, Aalborg, Denmark Background: Case management interventions are recommended to improve quality of care and reduce costs in chronic care, but further evidence on effectiveness and cost-effectiveness is needed. The objective of this study is the reporting of the design and participant enrollment of a randomized controlled trial, conducted to evaluate the effectiveness and cost-effectiveness of a community-based case management model for patients suffering from chronic obstructive pulmonary disease (COPD). With a focus on support for self-care and care coordination, the intervention was hypothesized to result in a reduced number of COPD-related hospital admissions. Patients and methods: The design was a randomized controlled trial conducted from 2012 to 2014 with randomization and intervention at patient level. The study took place in Aalborg Municipality, a larger municipality in Denmark. A total of 150 COPD patients were randomized into two groups: the case-managed group and the usual-care group. Participant characteristics were obtained at baseline, and measures on effectiveness and costs were obtained through questionnaires and registries within a 12-month follow-up period. In the forthcoming analysis, effectiveness will be evaluated on COPD-related hospital admissions, mortality, health- related quality of life, and self-care. An economic evaluation will examine the cost-effectiveness of case management against current usual care from the perspective of the health care sector. Results: Baseline characteristics were comparable between the two groups except for the prevalence of cancer, which were borderline significantly higher in the case-managed group. This baseline difference will be adjusted for in the final analysis. A very low dropout rate for the intervention was observed, indicating that the intervention was well accepted. Conclusion: Presented in a forthcoming paper, the results of the study will provide new evidence to the future organization of case management. Keywords: personalized care, disease management, health-related quality of life, cost-effectiveness analysis

Bone scintigraphy results were compared with changes shown on orthopantomographic radiographs in a patient with facial asymmetry, before, during, and after Herbst treatment, and followed up with control of growth activity in the temporomandibular joints (TMJs) after long-term retention. The present study showed that new bone formation (modelling) was initiated asymmetrically in TMJs during treatment. The results indicate that late development of right/left asymmetry in the occlusion can be corrected and normalized using the Herbst appliance therapy, stimulating a differentiated 'catch up' growth (modelling) in the TMJ with condyles. After treatment, original growth with asymmetric activity in the TMJ was re-established. This growth activity may re-establish the asymmetry in the sagittal occlusion and the face of the patient. It is therefore recommended that the occlusion should be maintained with an appliance which stabilizes the occlusion until cessation of the primary, endochondral growth. [ABSTRACT FROM AUTHOR]

Background: Due to their vasodilatory effect, calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure (BP) seen in renal transplantation. [ABSTRACT FROM PUBLISHER]

Purpose: The Management of Post-transplant Infections in Collaborating Hospitals (MATCH) programme, initiated in 2011 and still ongoing, was created to 1) optimise the implementation of existing preventive strategies against viral infections in solid organ transplant (SOT) recipients and allogenic haematopoietic stem-cell transplant (HSCT) recipients and 2) advance research in the field of transplantation by collecting data from a multitude of sources., Participants: All SOT and HSCT recipients at Copenhagen University Hospital, Rigshospitalet, are followed in MATCH. By February 2021, a total of 1192 HSCT recipients and 2039 SOT recipients have been included. Participants are followed life long. An automated electronic data capture system retrieves prospective data from nationwide registries. Data from the years prior to transplantation are also collected., Findings to Date: Data entries before and after transplantation include the following: biochemistry: 13 995 222 and 26 127 817; microbiology, cultures: 242 023 and 410 558; other microbiological analyses: 265 007 and 566 402; and pathology: 170 884 and 200 394. There are genomic data on 2431 transplant recipients, whole blood biobank samples from 1003 transplant recipients and faeces biobank samples from 207 HSCT recipients. Clinical data collected in MATCH have contributed to 50 scientific papers published in peer-reviewed journals and have demonstrated success in reducing cytomegalovirus disease in SOT recipients. The programme has established international collaborations with the Swiss Transplant Cohort Study and the lung transplant cohort at Toronto General Hospital., Future Plans: Enrolment into MATCH is ongoing with no planned end date for enrolment or follow-up. MATCH will continue to provide high-quality data on transplant recipients and expand and strengthen international collaborations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Obesity is associated with low vitamin D and recent studies have suggested a difference in vitamin D metabolism between females and males., Objective: The aim of this study was to investigate the effects of weight loss on vitamin D status in individuals with obesity, and secondarily, whether vitamin D metabolism differs between women and men., Methods: Secondary analysis from a randomized placebo-controlled trial, designed to investigate the efficacy of 52 weeks of treatment with either liraglutide, exercise or combined, compared with placebo on weight loss maintenance after an 8-week low-calorie diet-induced weight loss in 195 individuals with obesity (BMI 32-43 kg/m2)., Results: The low-calorie diet-induced weight loss resulted in an increase in serum 25(OH)D in both women and men (12 nmol/L (95%CI 9-15) and 13 nmol/L (95%CI 8-17); p < 0.001 for both). Women who experienced a further weight loss during the 52 weeks of intervention had an increase in serum 25(OH)D compared with women regaining weight (14 nmol/L (95%CI 6-22); p = 0.001). Interestingly, women experiencing further weight loss at week 52 had a lower serum 25(OH)D at baseline compared with women regaining weight (54 nmol/L (SD 19) vs. 70 nmol/L (SD 25); p < 0.001)., Conclusion: Weight loss induced by a low-calorie diet resulted in an increase in serum 25(OH)D in both women and men. Only in women, further weight loss had an additional beneficial impact on vitamin D. Additionally, initial low serum 25(OH)D was associated with successful weight loss maintenance in women, but not men., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: In 2020, the coronavirus disease 2019 (COVID-19) pandemic caused disruptions in kidney replacement therapy (KRT) services worldwide. The aim of this study was to assess the effect of the COVID-19 pandemic in 2020 on the incidence of KRT, kidney transplantation activity, mortality and prevalence of KRT across Europe., Methods: Patients receiving KRT were included from 17 countries providing data to the European Renal Association Registry. The epidemiology of KRT in 2020 was compared with average data from the period 2017-2019. Changes occurring during the first and second waves of the pandemic were also explored., Results: The incidence of KRT was 6.2% lower in 2020 compared with 2017-2019, with the lowest point (-22.7%) during the first wave in April. The decrease varied across countries, was smaller in males (-5.2%) than in females (-8.2%) and was moderate for peritoneal dialysis (-3.7%) and haemodialysis (-5.4%) but substantial for pre-emptive kidney transplantation (-23.6%). The kidney transplantation rate decreased by 22.5%, reaching a nadir of -80.1% during the first wave, and was greatest for living donor kidney transplants (-30.5%). While in most countries the kidney transplantation rate decreased, in the Nordic/Baltic countries and Greece there was no clear decrease. In dialysis patients, mortality increased by 11.4% and was highest in those 65-74 years of age (16.1%), in those with diabetes as the primary renal disease (15.1%) and in those on haemodialysis (12.4%). In transplant recipients, the mortality was 25.8% higher, but there were no subgroups that stood out. In contrast to the rising prevalence of KRT observed over the past decades across Europe, the prevalence at the end of 2020 (N = 317 787) resembled that of 2019 (N = 317 077)., Conclusion: The COVID-19 pandemic has had a substantial impact on the incidence of KRT, kidney transplant activity, mortality of KRT and prevalence of KRT in Europe with variations across countries., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

The thermal conductivity of glasses is well-known to be significantly harder to theoretically describe compared to crystalline materials. Because of this fact, the fundamental understanding of thermal conductivity in glasses remain extremely poor when moving beyond the case of simple glasses, e.g., glassy SiO2, and into so-called "modified" oxide glasses, that is, glasses where other oxides (e.g., alkali oxides) have been added to break up the network and alter, e.g., elastic and thermal properties. This lack of knowledge is apparent despite how modified glasses comprise the far majority of known glasses. In the present work, we study an archetypical series of sodium silicate [xNa2O-(100 - x)SiO2] glasses. Analyses of modal contributions reveal how increasing Na2O content induces increasing vibrational localization with a change of vibrations to be less ordered and a related general decrease in modal contributions to thermal conductivity. We find the vibrational phases (acoustic vs optical) of sodium vibrations to be relatively disordered compared to the network-forming silicon and oxygen species, explaining how increasing Na2O content decreases thermal conductivity. Our work sheds new light on the fundamentals of glassy heat transfer as well as the interplay between thermal conduction and modal characteristics in glasses., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Aims/hypothesis: The apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV)., Methods: This was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [ΔADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI., Results: Both semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20×10 -3 mm 2 /s [95% CI -0.30, -0.10], p<0.001; empagliflozin: -0.15×10 -3 mm 2 /s [95% CI -0.26, -0.04], p=0.01). No significant change was observed in the combination-therapy group (-0.05×10 -3 mm 2 /s [95%CI -0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed ΔADC significantly from placebo, showing a decrease of -0.13×10 -3 mm 2 /s (95% CI -0.22, -0.04; p=0.01). Compared with placebo, TKV decreased by -3% (95% CI -5%, -0.3%; p=0.04), -3% (95% CI -5%, -0.4%; p=0.02) and -5% (95% CI -8%, -2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA 1c ., Conclusions/interpretation: In a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis., Trial Registration: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38., (© 2024. The Author(s).)

Background: Hearing loss (HL) is prevalent in older individuals. It is suggested that there is an association between age-related HL, walking and balance, leading to poorer function and increased risk of falls in older individuals., Research Question: Is HL associated with physical performance, gait variability, and postural sway in older adults, and will additional dizziness moderate the effect of HL on balance?, Methods: In this cross-sectional study we examined 100 older individuals (age ≥70 years, 60 % females), divided in two groups, with or without age-related HL. Physical function and balance were evaluated by the Short Physical Performance Battery (SPPB), postural sway measured on a force platform (posturography), and balance in walking (gait variability) measured with a body-worn sensor. Multiple linear regression was used to examine the relationships between the variables, with physical function and balance as outcomes and HL as a dichotomous exposure (>30 dB). For all analyses, we further tested if associations were modified by self-reported dizziness., Results: Multiple regression analysis with HL, age, sex, education, diabetes, and cardiovascular disease revealed a significant association between reduced SPPB and HL. Multiple linear regression analysis also showed that HL was associated with increased postural sway on firm surface with eyes open and closed after adjusting for age, sex, education, diabetes, and cardiovascular disease. There was significant association between HL and increased gait variability during dual task walking in all directions after adjusting for age, sex, education, diabetes, and cardiovascular disease. Further, we found that the association between HL and SPPB was significantly stronger in those with dizziness compared with those without dizziness. Dizziness also modified the association of HL with the other SPPB sub-scores but not for the other outcomes of postural sway or gait variability., Significance: In this study, age-related HL was associated with worse physical performance as measured by SPPB, postural sway, and gait variability. This relationship illustrates the importance of assessing physical performance in people with HL to prevent risk of falls and disability., Competing Interests: Declaration of Competing Interest There was no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death., Methods: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence and survival., Results: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. Immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidences, of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had 5-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death [adjusted hazard ratio 1.8 (95% confidence interval 1.6-1.9)] compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%)., Conclusion: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background and Hypothesis: Young adults starting kidney replacement therapy (KRT) during childhood and reaching their 18th birthday (i.e. adult survivors of childhood KRT) form a challenging population of interest to nephrologists treating adults, as during this period there will be a transition to adult renal centres. Nonetheless, few studies have focused on the epidemiology of KRT in this group. We aimed to provide an update on these patients' characteristics, treatment history, graft and patient survival, to report their 5-year prognosis, and expected remaining lifetime., Methods: Data on KRT patients reaching their 18th birthday in 2008-2019 were collected from 21 European countries/regions providing individual patient data to the European Renal Association (ERA) Registry. Patient characteristics and treatment trajectories were examined before and after turning 18 years. Kaplan-Meier and Cox proportional hazards regression were used for patient and graft survival analyses., Results: In total, 2944 patients were included. The proportion of adult survivors initiating KRT at a very young age (0-4 years), and undergoing pre-emptive kidney transplantation increased. Unadjusted 5-year patient survival was 96.9% (95% CI: 96.2-97.5). Dialysis patients had a higher risk of death than kidney transplant recipients (adjusted hazard ratio 5.44 (95% CI: 3.34-8.86)). Between ages 18 and 23 years, about 21% of the adult survivors lost their kidney transplant and 34% of the dialysis patients continued this treatment. Compared with the general population, life expectancy for eighteen-year-old kidney transplant and dialysis patients was 17 and 40 years shorter, respectively., Conclusion: Life expectancy of 18-year-old kidney transplant recipients was lower compared with the general population. Yet, having a functioning kidney graft at age 18 years resulted in better outcomes than being on dialysis. Nevertheless, between ages 18 and 23 years, about one-fifth of the kidney grafts failed and one-third of the patients remained on dialysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

The performance of lithium metal batteries is severely hampered by uncontrollable dendrite growth and volume change within the anode. This work addresses these obstacles by introducing a novel strategy: applying an isotropic and internal grain-boundary-free layer, specifically, a metal-organic framework (MOF) glass layer with nano-porosity onto the electrochemically plated lithium metal anode. Both ab initio and classical molecular dynamics simulations indicate that the MOF glass layer makes the lithium transport smooth and uniform via its internal monolithic and interfacial advantages. This MOF glass layer with the fast and more uniform lithium diffusion in the monolithic interior and its interface enables dendrite-free lithium plating and stripping through surface confinement effect and interfacial effect. When employed in symmetric batteries, the achieved Li metal anode can operate over 300 h at 1 mA cm -2 . The full batteries matched with LiFePO 4 exhibit high capacity (148 mAh g -1 ), excellent rate performance (61 mAh g -1 at 5 C), and outstanding cycling stability (with capacity retention of ≈90% after 1000 cycles). The full batteries matched with high-voltage LiCoO 2 also show superior performances. Therefore, the strategy of utilizing a MOF glass layer enables the development of high-performance lithium metal anodes., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio [HR] = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Susanne K. Kjær has received a research grant outside this study through her affiliating institution from Merck. Jesper H. Bonde’s institution has received research funding or consumables at reduced prices or for free to support research from BD Diagnostics, GeneFirst, SelfScreen, Qiagen, Seegene, and Roche Diagnostics. Jesper H. Bonde has received honoraria for lectures from BD Diagnostics, MSD, and Hologic Ltd. Jesper H. Bonde is an appointed member of the National Danish Cervical Screening Committee by the Danish Health Authority. Linea Landgrebe Ring, Helle Kiellberg Larsen, Merete Hædersdal, Søren Schwartz Sørensen, Kirsten Frederiksen, and Louise Thirstrup Thomsen have no conflicts of interest to disclose., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising from over-immunosuppression such as infections and cancer versus rejection stemming from under-immunosuppression. CD3 + T-lymphocyte measurements are frequently employed for treatment monitoring. However, this analysis is costly and not always accessible. The aim of this study was to investigate whether the total count of lymphocytes could replace CD3 + T-lymphocyte measurements based on data from our transplantation center combined with a review of the literature. The hypothesis was that the total lymphocyte count could serve as a diagnostic surrogate marker for CD3 + T-lymphocytes., Methods: A retrospective cohort study was conducted, including patients who underwent kidney and/or a pancreas transplantation and received ATG as induction therapy or for rejection treatment. The inclusion criterium was that the total lymphocyte count and CD3 + T-lymphocyte measurements were measured simultaneously on the same day. Additionally, PubMed and Embase were searched up to 18/10/2023 for published studies on solid organ transplantation, ATG, T-lymphocytes, lymphocyte count, and monitoring. In the retrospective cohort study, a total of 91 patients transplanted between 2016 and 2023, with 487 samples, were included., Results: Total lymphocyte counts below 0.3 x 10 9 /L had a high sensitivity (86%) as a surrogate marker of CD3 + T-lymphocytes below 0.05 x 10 9 /L, but the specificity was low (52%) for total lymphocyte counts above 0.3 x 10 9 /L as a surrogate marker for CD3 + T-lymphocytes above 0.05 x 10 9 /L. A review of the literature identified seven studies comparing total lymphocyte counts and CD3 + T-lymphocytes in ATG monitoring. These studies supported the use of a low total lymphocyte count as a surrogate marker for CD3 + T-lymphocytes and an indicator to omit ATG treatment. However, there was no consensus regarding high total lymphocyte counts as an indicator for continued treatment., Discussion: Results supports that the total lymphocyte count can be used to omit ATG treatment when below 0.3 x 10 9 /L whereas the CD3 + T-lymphocyte analysis should be reserved for higher total lymphocyte counts to avoid ATG overtreatment., 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 Rasander, Sørensen, Krohn and Bruunsgaard.)

Importance: A major concern with weight loss is concomitant bone loss. Exercise and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent weight loss strategies that may protect bone mass despite weight loss., Objective: To investigate bone health at clinically relevant sites (hip, spine, and forearm) after diet-induced weight loss followed by a 1-year intervention with exercise, liraglutide, or both combined., Design, Setting, and Participants: This study was a predefined secondary analysis of a randomized clinical trial conducted between August 2016 and November 2019 at the University of Copenhagen and Hvidovre Hospital in Denmark. Eligible participants included adults aged 18 to 65 years with obesity (body mass index of 32-43) and without diabetes. Data analysis was conducted from March to April 2023, with additional analysis in February 2024 during revision., Interventions: After an 8-week low-calorie diet (800 kcal/day), participants were randomized to 1 of 4 groups for 52 weeks: a moderate- to vigorous-intensity exercise program (exercise alone), 3.0 mg daily of the GLP-1 RA liraglutide (liraglutide alone), the combination, or placebo., Main Outcomes and Measures: The primary outcome was change in site-specific bone mineral density (BMD) at the hip, lumbar spine, and distal forearm from before the low-calorie diet to the end of treatment, measured by dual-energy x-ray absorptiometry in the intention-to-treat population., Results: In total, 195 participants (mean [SD] age, 42.84 [11.87] years; 124 female [64%] and 71 male [36%]; mean [SD] BMI, 37.00 [2.92]) were randomized, with 48 participants in the exercise group, 49 participants in the liraglutide group, 49 participants in the combination group, and 49 participants in the placebo group. The total estimated mean change in weight losses during the study was 7.03 kg (95% CI, 4.25-9.80 kg) in the placebo group, 11.19 kg (95% CI, 8.40-13.99 kg) in the exercise group, 13.74 kg (95% CI, 11.04-16.44 kg) in the liraglutide group, and 16.88 kg (95% CI, 14.23-19.54 kg) in the combination group. In the combination group, BMD was unchanged compared with the placebo group at the hip (mean change, -0.006 g/cm2; 95% CI, -0.017 to 0.004 g/cm2; P = .24) and lumbar spine (-0.010 g/cm2; 95% CI, -0.025 to 0.005 g/cm2; P = .20). Compared with the exercise group, BMD decreased for the liraglutide group at the hip (mean change, -0.013 g/cm2; 95% CI, -0.024 to -0.001 g/cm2; P = .03) and spine (mean change, -0.016 g/cm2; 95% CI, -0.032 to -0.001 g/cm2; P = .04)., Conclusions and Relevance: In this randomized clinical trial, the combination of exercise and GLP-1RA (liraglutide) was the most effective weight loss strategy while preserving bone health. Liraglutide treatment alone reduced BMD at clinically relevant sites more than exercise alone despite similar weight loss., Trial Registration: EudraCT: 2015-005585-32.

As solid organ transplant (SOT) recipients remain at risk of severe outcomes after SARS-CoV-2 infections, vaccination continues to be an important preventive measure. In SOT recipients previously vaccinated with at least three doses of BNT162b2, we investigated humoral responses to BNT162b2 booster doses. Anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G (IgG) was measured using an in-house ELISA. Linear mixed models were fitted to investigate the change in the geometric mean concentration (GMC) of anti-SARS-CoV-2 RBD IgG after vaccination in participants with intervals of more or less than six months between the last two doses of vaccine. We included 107 SOT recipients vaccinated with a BNT162b2 vaccine. In participants with an interval of more than six months between the last two vaccine doses, we found a 1.34-fold change in GMC per month (95% CI 1.25-1.44), while we found a 1.09-fold change in GMC per month (95% CI 0.89-1.34) in participants with an interval of less than six months between the last two vaccine doses, resulting in a rate ratio of 0.82 (95% CI 0.66 to 1.01, p = 0.063). In conclusion, the administration of identical COVID-19 mRNA vaccine boosters within six months to SOT recipients may result in limited humoral immunogenicity of the last dose.

Background: Several studies have been conducted with the 1.0 version of the Hospital Survey on Patient Safety Culture (HSOPSC) in Norway and globally. The 2.0 version has not been translated and tested in Norwegian hospital settings. This study aims to 1) assess the psychometrics of the Norwegian version (N-HSOPSC 2.0), and 2) assess the criterion validity of the N-HSOPSC 2.0, adding two more outcomes, namely 'pleasure of work' and 'turnover intention'., Methods: The HSOPSC 2.0 was translated using a sequential translation process. A convenience sample was used, inviting hospital staff from two hospitals (N = 1002) to participate in a cross-sectional questionnaire study. Data were analyzed using Mplus. The construct validity was tested with confirmatory factor analysis (CFA). Convergent validity was tested using Average Variance Explained (AVE), and internal consistency was tested with composite reliability (CR) and Cronbach's alpha. Criterion related validity was tested with multiple linear regression., Results: The overall statistical results using the N-HSOPSC 2.0 indicate that the model fit based on CFA was acceptable. Five of the N-HSOPSC 2.0 dimensions had AVE scores below the 0.5 criterium. The CR criterium was meet on all dimensions except Teamwork (0.61). However, Teamwork was one of the most important and significant predictors of the outcomes. Regression models explained most variance related to patient safety rating (adjusted R 2  = 0.38), followed by 'turnover intention' (adjusted R 2  = 0.22), 'pleasure at work' (adjusted R 2  = 0.14), and lastly, 'number of reported events' (adjusted R 2= 0.06)., Conclusion: The N-HSOPSC 2.0 had acceptable construct validity and internal consistency when translated to Norwegian and tested among Norwegian staff in two hospitals. Hence, the instrument is appropriate for use in Norwegian hospital settings. The ten dimensions predicted most variance related to 'overall patient safety', and less related to 'number of reported events'. In addition, the safety culture dimensions predicted 'pleasure at work' and 'turnover intention', which is not part of the original instrument., (© 2024. The Author(s).)

Background: Successful renal transplantation (RTx) relies on immunosuppression and an optimal surgical course with few surgical complications. Studies reporting the postoperative complications after RTx are heterogeneous and often lack systematic reporting of complications. This study aims to describe and identify postoperative short-term and long-term complications after RTx in a large institutional cohort and identify risk factors for a complicated surgical course., Methods: The study is a retrospective single-center cohort of 571 recipients who underwent living or deceased donor open RTx between 2014 and 2021. Data were collected on background information and perioperative and postoperative data. Complications were defined as short-term (<30 d) or long-term (>30 d) after transplantation and graded according to the Clavien-Dindo classification. Multivariable logistic regression was performed to evaluate risk factors for serious short-term complications and multivariable time-dependent Cox regression to evaluate risk factors for long-term complications., Results: A total of 351 patients received a graft from a deceased donor, and 144 of these grafts were on perfusion machine before transplantation. One or more short-term complications occurred in 345 (60%) patients. Previous RTx was associated with short-term Clavien-Dindo >2 complications in recipients (odds ratio = 2.08; 95% confidence interval [CI], 1.18-3.69; P  = 0.01). Being underweight (body mass index <18.5) in combination with increasing age increased the odds of short-term Clavien-Dindo >2 and vascular complications. Increasing blood loss per 100 mL was associated with increased odds of short-term Clavien-Dindo >2 (odds ratio = 1.11; 95% CI, 1.01-1.21; P  = 0.032). No associations were found for long-term complications after RTx. The 5-y cumulative incidence of graft loss was 12.6% (95% CI, 8.9-16.3)., Conclusions: Short-term complications are common after RTx, and risk factors for severe short-term complications include previous RTx, increasing age, and low body mass index. No risk factors were identified for severe long-term complications. Further studies should explore whether new surgical techniques can reduce surgical complications in RTx., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Preemptive kidney transplantation has better outcomes when compared to transplantation after dialysis. We aimed to examine trends in preemptive kidney transplantation between 2000 and 2019 in Europe and to provide an overview of associated policies, barriers and initiatives., Methods: Adult patients from 12 European countries who received a preemptive kidney transplant were included. The representatives of the registries providing these data were questioned on the policies, barriers and initiatives around preemptive kidney transplantation., Results: Between 2000 and 2019, 20 251 adults underwent preemptive kidney transplantation (11 169 from living donors, 8937 from deceased donors). The proportion of first kidney transplantations that were preemptive more than doubled from 7% in 2000 to 18% in 2019, reflecting a similar relative increase for living donor kidney recipients (from 21% to 43%) and deceased donor kidney recipients (from 4% to 11%). Large international differences were found. The increase in preemptive kidney transplantation was observed across all age, sex and primary renal disease groups. Countries had similar criteria for preemptive waitlisting. Barriers mentioned included donor shortage, late referral to the transplant center and long donor or recipient work-up. Suggested initiatives included raising awareness on the possibility of preemptive kidney transplantation, earlier start and shorter work-up time for recipient and living donor., Conclusions: Over the last two decades the proportion of patients receiving a first kidney transplant preemptively has more than doubled, reflecting a similar relative increase for living and deceased donor kidney recipients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Aim: Despite the increasing use of combination treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, data are limited on the effects of combination treatment on markers of cardiovascular disease. This study aimed to investigate the effect of empagliflozin, semaglutide, and their combination on vascular function., Materials and Methods: In total, 120 patients with type 2 diabetes were randomized into four groups (n = 30 in each) for 32 weeks: placebo, semaglutide, empagliflozin, and their combination. The study had two co-primary outcomes: change in arterial stiffness and kidney oxygenation. This paper reports on arterial stiffness assessed as carotid-femoral pulse wave velocity. Secondary outcomes included 24-h blood pressure (BP), 24-h central BP, urinary albumin to creatinine ratio and glycaemic control assessed by both continuous glucose monitoring and glycated haemoglobin., Results: The carotid-femoral pulse wave velocity did not change significantly in any of the groups compared with placebo. Twenty-four-hour systolic BP was reduced by 10 mmHg (95% CI 6-14), p < .001 in the combination group, significantly superior to both placebo and monotherapy (p < .05). Combination treatment increased glycaemic time in range from 72% at baseline to 91% at week 32, p < .001, without increasing time below range. The urinary albumin to creatinine ratio decreased by 36% (95% CI 4-57), p = .03 in the combination group compared with placebo., Conclusions: Empagliflozin, semaglutide, or their combination did not reduce arterial stiffness. Combination treatment showed a substantial and clinically important reduction in 24-h systolic BP compared with either treatment alone. Combination treatment increased glycaemic time in range without increasing the risk of hypoglycaemia., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes., Methods: This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m 2 ) and concomitant prediabetes (ie, glycated haemoglobin [HbA 1c ] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m 2 ) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656)., Findings: Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures., Interpretation: 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes., Funding: Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark., Competing Interests: Declaration of interests JSQ has received funding for this study from the Novo Nordisk Foundation, Innovation Foundation, and Aalborg University; for other studies from Novo Nordisk; and travel grants from American Diabetes Association, European Association for the Study of Obesity, and Trygfonden Center for Physical Activity Research. HEP is currently employed by Novo Nordisk and is co-investigator on a project partly funded by the Novo Nordisk Foundation and Innovation Fund Denmark. SP is the author of the books The Circadian Code and The Circadian Diabetes Code, which advocate for time-restricted eating. DV is currently employed by Novo Nordisk and has received research grants from Bayer, Sanofi Aventis, Novo Nordisk, and Boehringer Ingelheim and holds shares in Novo Nordisk. SST has received research grants for a study drug and lecture fees from Novo Nordisk. KKBC is currently employed by Novo Nordisk; holds shares in Novo Nordisk; and was co-investigator on this project, for which her salary was covered by a grant from the Novo Nordisk Foundation. MEN has received research grants from Bayer. NJWA has received research grants from Novo Nordisk and Mercodia and has received speaker fees and fees as a member of the advisory board from Merck, Guidepoint, and Boehringer Ingelheim. JJH has received research grants from Novo Nordisk Foundation, Arla Foods, and European Research Council; consulting fees from Alphasights, Arix Bioscience, Eli Lilly, Structure Therapeutics USA, Zealand Pharma, Alcimed, Google Ventures Management, MSD Danmark, and Novo Nordisk; and support for presentations from Eli Lilly, Zealand Pharma, Novo Nordisk, and the Mayo Clinic. MEJ holds shares in Novo Nordisk. JS holds shares in Novo Nordisk. KF is currently employed by Novo Nordisk and has received research grants from Novo Nordisk, Unilever, and AstraZeneca and holds shares in Novo Nordisk and ChemoMetec. MMJ received funding from the Danish Association for the Study of Obesity; is a co-investigator on a project funded by Novo Nordisk; and was co-investigator on this project, for which her salary was covered by grants from the Novo Nordisk Foundation and Aalborg University. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: This systematic review and meta-analysis aims to investigate the prevalence of cervical high-risk human papillomavirus (hrHPV) among kidney transplant recipients (KTRs) and, furthermore to compare it to that in immunocompetent controls., Methods: A systematic literature search was conducted in PubMed, EMBASE, and Cochrane Library databases from January 2000 to February 2023, to identify studies investigating the prevalence of cervical hrHPV in KTRs. Pooled cervical hrHPV prevalences, odds ratios (ORs) comparing KTRs to controls and corresponding confidence intervals (CIs) were estimated using random effects logistic regression models. Heterogeneity between studies was assessed through the I 2 statistic, and the significance was evaluated by the Cochrane's Q test., Results: Altogether, 16 studies covering >1200 KTRs were included. The prevalence of cervical hrHPV in KTRs was 27.7% (95% CI 21.3-35.1) with substantial interstudy heterogeneity. Stratification indicated a higher prevalence in recent years (2019-2023) and in Asia (39% (95% CI 11.2-61.4)). The prevalence of HPV16 and HPV18 in KTRs was 8.0% (95% CI 3.9-15.9) and 1.7% (95% CI 0.8-3.7), respectively. Comparing hrHPV prevalence in KTRs and controls based on six studies including >500 KTRs and 1000 controls, the OR for hrHPV was 2.0 (95% CI 1.1-3.6)., Conclusions: This meta-analysis establishes an increased cervical hrHPV prevalence in KTRs compared to controls. The increased risk may be associated with immunosuppressive therapy post-transplantation. Further research is needed to explore the potential benefits of HPV vaccination, including potential revaccination strategies in KTRs., Competing Interests: Declaration of competing interest No conflict of interest was reported by the other authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Potent incretin-based therapy shows promise for the treatment of obesity along with reduced incidence of cardiovascular events in patients with preexisting cardiovascular disease and obesity. This study assessed the efficacy and safety of the incretin-based obesity treatments, once-weekly subcutaneous semaglutide 2.4 mg and tirzepatide 10 or 15 mg, in people with obesity without diabetes. Of the 744 records identified, seven randomized controlled trials (n = 5140) were included. Five studies (n = 3288) investigated semaglutide and two studies (n = 1852) investigated tirzepatide. The treatment effect, shown as placebo-subtracted difference, on body weight was -15.0% (95% CI, -17.8 to -12.2) with -12.9% (95% CI, -14.7 to -11.1) for semaglutide and -19.2% (95% CI, -22.2 to -16.2) for tirzepatide. The treatment effect on waist circumference was -11.4 cm (95% CI, -13.7 to -9.2) with -9.7 cm (95% CI, -10.8 to -8.5) for semaglutide and -14.6 cm (95% CI, -15.8 to -13.4) for tirzepatide. The adverse events related to semaglutide and tirzepatide were primarily of mild-to-moderate severity and mostly gastrointestinal, which was more frequent during the dose-titration period and leveled off during the treatment period. This emphasizes that once-weekly subcutaneous semaglutide 2.4 mg and tirzepatide 10 or 15 mg induce large reductions in body weight and waist circumference and are generally well-tolerated., (© 2024 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT) recipients, either through natural infection or vaccination. (2) Methods: This systematic review was conducted per PRISMA guidelines. We assessed the risk of bias using the Cochrane RoB 2 and ROBINS-I and summarized the findings narratively due to the heterogeneity of the studies. (3) Results: Of the 315 screened articles, 11 were included. Tetanus immunity varied between 55% and 86%, diphtheria immunity from 23% to 75%, and pertussis immunity was between 46% and 82%. Post-vaccination immunity showed variation across the studies, with some indicating reductions and others no change, with antibody responses influenced by transplanted organs, gender, age, and immunosuppressive regimens. The single randomized study exhibited a low risk of bias, while of the ten non-randomized studies, six showed moderate and four serious risks of bias, necessitating cautious interpretation of results. (4) Conclusions: SOT recipients exhibit considerable immunity against tetanus and diphtheria at transplantation, but this immunity decreases over time. Although vaccination can enhance this immunity, the response may be suboptimal, and the increased antibody levels may not persist, underscoring the need for tailored vaccination strategies in this vulnerable population.

The glassy state of zeolitic imidazolate frameworks (ZIFs) has shown great potential for energy-related applications, including solid electrolytes. However, their thermal conductivity (κ), an essential parameter influencing thermal dissipation, remains largely unexplored. In this work, using a combination of experiments, atomistic simulations, and lattice dynamics calculations, we investigate κ and the underlying heat conduction mechanism in ZIF glasses with varying ratios of imidazolate (Im) to benzimidazolate (bIm) linkers. The substitution of bIm for Im tunes the node-linker couplings but exhibits only a minor impact on the average diffusivity of low-frequency lattice modes. On the other hand, the linker substitution induces significant volume expansion, which, in turn, suppresses the contributions from lattice vibrations to κ, leading to decreased total heat conduction. Furthermore, spatial localization of internal high-frequency linker vibrations is promoted upon substitution, reducing their mode diffusivities. This is ascribed to structural deformations of the bIm units in the glasses. Our work unveils the detailed influences of linker substitution on the dual heat conduction characteristics of ZIF glasses and guides the κ regulation of related hybrid materials in practical applications., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe., Method: The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year., Results: In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries., Conclusion: We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Water is one of the most reactive and abundant molecules on Earth, and it is thus crucial to understand its reactivity with various material families. One of the big unknown questions is how water in liquid and vapor forms impact the fast-emerging class of metal-organic frameworks (MOFs). Here, we discover that high-pressure water vapor drastically modifies the structure and hence the dynamic, thermodynamic, and mechanical properties of MOF glasses. In detail, we find that an archetypical MOF (ZIF-62) is extremely sensitive to heat treatments performed at 460 °C and water vapor pressures up to ∼110 bar. Both the melting and glass transition temperatures decrease remarkably (by >100 °C), and simultaneously, hardness and Young's modulus increase by up to 100% under very mild treatment conditions (<20 bar of hydrothermal pressure). Structural analyses suggest water to partially coordinate to Zn in the form of a hydroxide ion by replacing a bridging imidazolate-based linker. The work provides insight into the role of hot-compressed water in influencing the structure and properties of MOF glasses and opens a new route for systematically changing the thermodynamics and kinetics of MOF liquids and thus altering the thermal and mechanical properties of the resulting MOF glasses., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Kidney transplant recipients are at increased risks of cardiovascular events, but contemporary risk estimates are sparse. Using the Danish nationwide administrative databases, we quantified 1- and 5-year risks of cardiovascular disease and kidney failure among all first-time kidney transplant recipients (2005-2018) and age- and sex-matched controls (1:10 ratio)., Methods: Cumulative 1- and 5-year incidence of cardiovascular events (myocardial infarction, stroke, or heart failure), kidney failure (re-transplantation or need for dialysis >30 days post-transplant), and mortality following transplantation were calculated until maximally Dec 31, 2018., Results: A total of 2,565 kidney transplant recipients (median age 50.5 [25-75 th percentile 40.2-60.7] years, 37 % females) and 25,650 controls were included. 1-year cumulative incidence of myocardial infarction, stroke, or heart failure was 2.6 % (95 % confidence interval 1.9 %-3.2 %) among kidney transplant recipients versus 0.5 % (0.4 %-0.5 %) in controls. Cumulative 5-year risk estimates for the same endpoints were 8.3 % (7.1 %-9.5 %) for the transplant patients, and 2.6 % (2.3 %-2.8 %) among controls, respectively. For the kidney transplant cohort, cumulative mortality was 2.2 % (1.7 %-2.8 %) and 10.3 % (9.0 %-11.6 %) at 1- and 5 years, respectively, versus 0.5 % (0.4 %-0.6 %) and 3.0 % (2.7 %-3.2 %) for controls. The cumulative incidence of dialysis and re-transplantation was 6.1 % (5.2 %-7.1 %) at 1 year and 16.3 % (14.7 %-17.9 %) at 5 years, respectively., Conclusions: Despite the benefits of transplantation, kidney transplant recipients continue to have significant long-term cardiovascular disease, end-stage kidney disease, and mortality risks even with contemporary medical management. Better cardiovascular preventive strategies are warranted to improve prognosis in this segment of patients., Competing Interests: Declaration of Competing Interest Dr. Køber reports speaker's honorarium from AstraZeneca, Bayer, Boehringer, Novo and Novartis. Dr. McCausland reports consulting fees from GlaxoSmithKline, Advanced Instruments, and Zydus Therapeutics and grants from Fifth Eye, the National Institute of Diabetes and Digestive and Kidney Diseases, Satellite Healthcare, and Advanced Medical. Dr. Schou reports lecture fee from Novo Nordisk, Novartis, Bohringer Ingelheim and Astra Zeneca. Dr. Torp-Pedersen reports grants from Novo Nordisk and Bayer. Dr. Pfeffer reports research grant support from Novartis and is consultant to AstraZeneca, Boehringer Ingelheim, Eli Lilly Alliance, Corvidia, DalCor, GlaxoSmithKline, Lexicon, Novartis, Novo Nordisk, Peerbridge, and Sanofi, and has equity in DalCor. All outside the present work., (Copyright © 2023. Published by Elsevier B.V.)

Background: New obesity medications result in large weight losses. However, long-term adherence in a real-world setting is challenging, and termination of obesity medication results in weight regain towards pre-treatment body weight. Therefore, we investigated whether weight loss and improved body composition are sustained better at 1 year after termination of active treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, supervised exercise program, or both combined for 1 year., Methods: We conducted a post-treatment study in extension of a randomised, controlled trial in Copenhagen. Adults with obesity (aged 18-65 years and initial body mass index 32-43 kg/m 2 ) completed an eight-week low-calorie diet-induced weight loss of 13.1 kg (week -8 to 0) and were randomly allocated (1:1:1:1) to one-year weight loss maintenance (week 0-52) with either supervised exercise, the GLP-1 receptor agonist once-daily subcutaneous liraglutide 3.0 mg, the combination of exercise and liraglutide, or placebo. 166 Participants completed the weight loss maintenance phase. All randomised participants were invited to participate in the post-treatment study with outcome assessments one year after treatment termination, at week 104. The primary outcome of the post-treatment assessment was change in body weight from after the initial weight loss (at randomisation, week 0) to one year after treatment termination (week 104) in the intention-to-treat population. The secondary outcome was change in body-fat percentage (week 0-104). The study is registered with EudraCT, 2015-005585-32, and with ClinicalTrials.gov, NCT04122716., Findings: Between Dec 17, 2018, and Dec 17, 2020, 109 participants attended the post-treatment study. From randomisation to one year after termination of combined exercise and liraglutide treatment (week 0-104), participants had reduced body weight (-5.1 kg [95% CI -10.0; -0.2]; P = 0.040) and body-fat percentage (-2.3%-points [-4.3 to -0.3]; P = 0.026) compared with after termination of liraglutide alone. More participants who had previously received combination treatment maintained a weight loss of at least 10% of initial body weight one year after treatment termination (week -8 to 104) compared with participants who had previously received placebo (odds ratio [OR] 7.2 [2.4; 21.3]) and liraglutide (OR 4.2 [1.6; 10.8]). More participants who had previously received supervised exercise maintained a weight loss of at least 10% compared with placebo (OR 3.7 [1.2; 11.1]). During the year after termination of treatment (week 52-104), weight regain was 6.0 kg [2.1; 10.0] larger after termination of liraglutide compared with after termination of supervised exercise and 2.5 kg [-1.5 to 6.5] compared with after termination of combination treatment., Interpretation: The addition of supervised exercise to obesity pharmacotherapy seems to improve healthy weight maintenance after treatment termination compared with treatment termination of obesity pharmacotherapy alone. Body weight and body composition were maintained one year after termination of supervised exercise, in contrast to weight regain after termination of treatment with obesity pharmacotherapy alone., Funding: Helsefonden and the Novo Nordisk Foundation., Competing Interests: RMS: family member owns Novo Nordisk stocks. S.M.: Advisory boards: AstraZeneca; Boehringer Ingelheim; Eli Lilly; Merck Sharp & Dohme; Novo Nordisk; Sanofi Aventis. Lecture fees: AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi Aventis. Research Grant Recipient: Novo Nordisk, Boehringer-Ingelheim. S.S.T.: Research Grant and Lecture Fee Recipient: Novo Nordisk. J.J.H.: Advisory board: Novo Nordisk. M.B.B.: Research Grant Novo Nordisk A/S, payment made to institution. B.M.S.: Board member of Steno Diabetes Center Copenhagen. Board member of the Centre for Childhood Health, appointed by the Novo Nordisk Foundation., (© 2024 The Authors.)

Reliable methods to assess immune function after solid organ transplantation (SOT) are needed to guide dosing of immunosuppression. We hypothesized that toll-like receptor ligand-induced cytokine concentrations would decrease post-transplantation due to the use of immunosuppressive medication. Furthermore, we hypothesized that induced cytokine concentrations pre-transplantation would be higher in recipients with episodes of acute rejection post-transplantation due to underlying immunological dispositions. We aimed to investigate toll-like receptor ligand-induced cytokine concentrations by TruCulture©, a standardized immunoassay, in SOT recipients before and 3 months after SOT and explored associations with methylprednisolone-treated acute rejections. We conducted a prospective, observational cohort study including 123 participants (67 liver, 32 kidney and 24 lung transplant recipients). Whole blood was stimulated for 22 h with: (A) Lipopolysaccharide (LPS), (B) Resiquimod, (C) Polyinosinic:polycytidylic acid (Poly I:C) and (D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α and IFN-γ) were measured by Luminex. 30 participants developed methylprednisolone-treated acute rejection at a median of 9 days (IQR 5-17) post-SOT. We found that all induced cytokine concentrations decreased post-SOT except from LPS-induced and Poly I:C-induced IL-10. The induced cytokine concentration pre-transplantation did not differ in recipients with or without acute rejection. In conclusion, the induced cytokine concentrations decreased for all stimuli post-SOT, except the anti-inflammatory cytokine IL-10. Importantly, recipients developing early acute rejection did not differ in induced cytokine concentrations pre-SOT. Thus, the use of a standardized assay in SOT is feasible in a clinical setting and may provide important information on the immune function post-SOT., (© 2023 The Scandinavian Foundation for Immunology.)

Aims: To evaluate the effect of treatment with semaglutide and empagliflozin on the cortico-medullary sodium gradient (MCR; medulla/cortex ratio), urine sodium/creatinine ratio (UNACR), and estimated plasma volume (ePV) and to compare the MCR between persons with and without type 2 diabetes., Methods: Using the 23 Na magnetic resonance imaging ( 23 Na-MRI) technique, we investigated the effects of 32 weeks of treatment with semaglutide, empagliflozin or their combination on MCR in 65 participants with type 2 diabetes and high risk of cardiovascular disease. The participants were recruited from a randomized, controlled interventional trial and further characterized by UNACR and ePV. In addition, in a cross-sectional design, we compared MCR by 23 Na-MRI in 12 persons with type 2 diabetes and 17 matched controls. Data from the interventional trial were analyzed using a single, multivariate linear mixed model strategy for repeated measurements. Data from the cross-sectional study were analyzed by fitting a linear regression model adjusted for age and sex., Results: Compared to placebo, semaglutide, but not empagliflozin, significantly decreased the MCR (-9 %, 95%CI (-18, -0.06)%, p = 0.035 and -0.05 %, 95%CI(-0.15, 0.05)%, p = 0.319, respectively). The UNACR decreased in the semaglutide group(-35 %, 95 % CI(-52, -14) %, p = 0.003) but not in the empagliflozin group (7 %, 95 % CI(-21, 44)%, p = 0.657), whereas the ePV decreased in the combination group. The MCR was not different between persons with and without type 2 diabetes., Conclusion: 23 Na magnetic resonance imaging can identify drug induced changes in the MCR in persons with type 2 diabetes, and 32 weeks of semaglutide decreases the MCR in such persons. There is no difference in the MCR between persons with and without type 2 diabetes., Trial Number and Registry: EUDRACT 2019-000781-38, clinicaltrialsregister.eu., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Considerable clinical research has focused on improving graft survival and an increasing number of kidney recipients die with a functioning graft. There is a need to improve patient survival and to better understand the individualized risk of comorbidities and complications. Here, we developed a method to stratify recipients into similar subgroups based on previous comorbidities and subsequently identify complications and for a subpopulation, laboratory test values associated with survival., Methods: First, we identified significant disease patterns based on all hospital diagnoses from the Danish National Patient Registry for 5752 kidney transplant recipients from 1977 to 2018. Using hierarchical clustering, these longitudinal patterns of diseases segregate into 3 main clusters of glomerulonephritis, hypertension, and diabetes. As some recipients are diagnosed with diseases from >1 cluster, recipients are further stratified into 5 more fine-grained trajectory subgroups for which survival, stratified complication patterns as well as laboratory test values are analyzed., Results: The study replicated known associations indicating that diabetes and low levels of albumin are associated with worse survival when investigating all recipients. However, stratification of recipients by trajectory subgroup showed additional associations. For recipients with glomerulonephritis, higher levels of basophils are significantly associated with poor survival, and these patients are more often diagnosed with bacterial infections. Additional associations were also found., Conclusions: This study demonstrates that disease trajectories can confirm known comorbidities and furthermore stratify kidney transplant recipients into clinical subgroups in which we can characterize stratified risk factors. We hope to motivate future studies to stratify recipients into more fine-grained, homogenous subgroups to better discover associations relevant for the individual patient and thereby enable more personalized disease-management and improve long-term outcomes and survival., Competing Interests: S.B. has ownerships in Intomics A/S, Hoba Therapeutics Aps, Novo Nordisk A/S, Lundbeck A/S, and ALK Abello A/S and managing board memberships in Proscion A/S and Intomics A/S. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Infection with BK polyomavirus (BKPyV) is a common opportunistic infection after kidney transplantation (KT) and may affect graft function. We aimed to determine the incidence, risk factors, and clinical outcomes of BKPyV DNAemia in a prospective cohort of 601 KT recipients transplanted from 2012 to 2020. BKPyV PCR on plasma was performed at days 60, 90, 180, 270, and 360 post-KT. Any BKPyV DNAemia was defined as a single BKPyV DNA of ≥1000 copies/mL. Severe BKPyV DNAemia was defined as two consecutive BKPyV DNA of ≥10,000 copies/mL. Cumulative incidences were investigated using the Aalen-Johansen estimator, and the risk factors were investigated in Cox proportional hazard models. The incidence of any BKPyV DNAemia and severe BKPyV DNAemia was 21% (18-25) and 13% (10-16) at one year post-KT, respectively. Recipient age > 50 years (aHR, 1.72; 95% CI 1.00-2.94; p = 0.049), male sex (aHR, 1.96; 95% CI 1.17-3.29; p = 0.011), living donors (aHR, 1.65; 95% CI 1.03-2.74; p = 0.045), and >3 HLA-ABDR mismatches (aHR, 1.72; 95% CI 1.01-2.94; p = 0.046) increased the risk of severe BKPyV DNAemia. Any BKPyV DNAemia was associated with an increased risk of graft function decline (aHR, 2.26; 95% CI 1.00-5.12; p = 0.049), and severe BKPyV DNAemia was associated with an increased risk of graft loss (aHR, 3.18; 95% CI 1.06-9.58; p = 0.039). These findings highlight the importance of BKPyV monitoring post-KT.

Type 2 diabetes mellitus (T2DM) can be multifactorial where both genetics and environmental factors play a role. We aimed to investigate the use of polygenic risk scores (PRS) in the prediction of pre-transplant T2DM and post-transplant diabetes mellitus (PTDM) among solid organ transplant (SOT) patients. Using non-genetic risk scores alone; and the combination with PRS, separate logistic regression models were built and compared using receiver operator curves. Patients were assessed pre-transplant and in three post-transplant periods: 0-45, 46-365 and >365 days. A higher PRS was significantly associated with increased odds of pre-transplant T2DM. However, no improvement was observed for pre-transplant T2DM prediction when comparing PRS combined with non-genetic risk scores to using non-genetic risk scores alone. This was also true for predictions of PTDM in all three post-transplant periods. This study demonstrated that polygenic risk was only associated with the risk of T2DM among SOT recipients prior to transplant and not for PTDM. Combining PRS with a clinical model of non-genetic risk scores did not significantly improve the predictive ability, indicating its limited clinical utility in identifying patients at high risk for T2DM before transplantation, suggesting that non-genetic or different genetic factors may contribute to PTDM., 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 © 2023 dos Santos, Leung, Thorball, Ledergerber, Fellay, MacPherson, Hornum, Terrones-Campos, Rasmussen, Gustafsson, Perch, Sørensen, Ekenberg, Lundgren, Feldt‐Rasmussen and Reekie.)

Classical molecular dynamics is used to study the dynamics of alkali ions in a promising fast ion conductor glass system, i.e., Na 2 S-SiS 2 . Diffusion in such thiosilicates is found to display various salient features of alkali silicates, i.e., channel-like diffusion with typical length scales emerging as the temperature is decreased to the glassy state, and Arrhenius behavior for both Na ion diffusivity and calculated conductivity. The dynamics appears, however, to be largely heterogeneous as manifested by fast and slow Na ion motion at intermediate times, both in the high-temperature liquid and in the glassy state. In the former, a diffusion-limited regime is found due to the increased motion of the network-forming species that limits the Na ion dynamics, whereas at low temperatures, the typical dynamical heterogeneities are recovered as observed close to the glass transition.

Background/objectives: After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure., Subjects/methods: Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting., Results: On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (-1% [-13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44])., Conclusions: Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB., (© 2023. The Author(s).)

Background: Kidney transplant recipients receive maintenance immunosuppressive therapy to avoid allograft rejection resulting in increased risk of infections and infection-related morbidity and mortality. Approximately 98% of adults are infected with varicella zoster virus, which upon reactivation causes herpes zoster. The incidence of herpes zoster is higher in kidney transplant recipients than in immunocompetent individuals, and kidney transplant recipients are at increased risk of severe herpes zoster-associated disease. Vaccination with adjuvanted recombinant glycoprotein E subunit herpes zoster vaccine (RZV) prevents herpes zoster in older adults with excellent efficacy (90%), and vaccination of kidney transplant candidates is recommended in Danish and international guidelines. However, the robustness and duration of immune responses after RZV vaccination, as well as the optimal timing of vaccination in relation to transplantation remain unanswered questions. Thus, the aim of this study is to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients at different timepoints before and after transplantation., Methods: The Herpes Virus Infections in Kidney Transplant Patients (HINT) study is a prospective observational cohort study. The study will include kidney transplant candidates on the waiting list for transplantation (n = 375) and kidney transplant recipients transplanted since January 1, 2019 (n = 500) from all Danish kidney transplant centers who are offered a RZV vaccine as routine care. Participants are followed with repeated blood sampling until 12 months after inclusion. In the case of transplantation or herpes zoster disease, additional blood samples will be collected until 12 months after transplantation. The immune response will be characterized by immunophenotyping and functional characterization of varicella zoster virus-specific T cells, by detection of anti-glycoprotein E antibodies, and by measuring cytokine profiles., Discussion: The study will provide new knowledge on the immune response to RZV vaccination in kidney transplant candidates and recipients and the robustness and duration of the response, potentially enhancing preventive strategies against herpes zoster in a population at increased risk., Trial Registration: ClinicalTrials.gov (NCT05604911)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Metal-organic framework (MOF) glasses have multiple potential applications, as they combine advantages of traditional glasses with those of MOFs. The melt-quenching process used to form MOF glasses typically leads to a significant decrease in porosity, but the structural origin of this thermally induced pore collapse remains largely unknown. Here, we study the melting process of three zeolitic imidazolate frameworks (ZIFs), namely ZIF-4, ZIF-62, and ZIF-76, using ab initio molecular dynamics (MD) simulations. By analyzing the MD data using topological data analysis, we show that while the three ZIF systems exhibit similar short-range order structural changes upon heating, they exhibit significant differences in their medium-range order structure. Specifically, ZIF-76 retains more of its medium-range order structures in the liquid state compared to the other glass-forming ZIF systems, which allows it to remain more porous than ZIF-4 and ZIF-62. As such, our results may aid in understanding the structural features that govern the ability to maintain porosity in the melt-quenched glassy state.

Introduction: Herpes virus infections are a major concern after solid organ transplantation and linked to the immune function of the recipient. We aimed to determine the incidence of positive herpes virus (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1/2 (HSV-1/2), and varicella zoster virus (VZV)) PCR tests during the first year post-transplantation and assess whether a model including immune function pre-transplantation and three months post-transplantation could predict a subsequent positive herpes virus PCR., Methods: All participants were preemptively screened for CMV, and EBV IgG-negative participants were screened for EBV during the first year post-transplantation. Herpes virus PCR tests for all included herpes viruses (CMV, EBV, HSV-1/2, and VZV) were retrieved from the Danish Microbiology database containing nationwide PCR results from both hospitals and outpatient clinics. Immune function was assessed by whole blood stimulation with A) LPS, B) R848, C) Poly I:C, and D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α, and IFN-γ) were measured using Luminex., Results: We included 123 liver (54%), kidney (26%), and lung (20%) transplant recipients. The cumulative incidence of positive herpes virus PCR tests was 36.6% (95% CI: 28.1-45.1) during the first year post-transplantation. The final prediction model included recipient age, type of transplantation, CMV serostatus, and change in Poly I:C-induced IL-12p40 from pre-transplantation to three months post-transplantation. The prediction model had an AUC of 77% (95% CI: 61-92). Risk scores were extracted from the prediction model, and the participants were divided into three risk groups. Participants with a risk score <5 (28% of the cohort), 5-10 (45% of the cohort), and >10 (27% of the cohort) had a cumulative incidence of having a positive herpes virus PCR test at 5.8%, 25%, and 73%, respectively (p < 0.001)., Conclusion: In conclusion, the incidence of positive herpes virus PCR tests was high, and a risk model including immune function allowed the prediction of positive herpes virus PCR and may be used to identify recipients at higher risk., Competing Interests: OR received a grant from the Research Foundation of Rigshospitalet related to this work, and a grant from AP Møller Fonden not related to this work. MP has participated in advisory boards for Takeda, and PulmonX, served as a research consultant for AMBU, received an unlimited institutional research grant from Roche and travel grants from Boeringer-Ingelheim, received lecturing honorary from AstraZeneca, GSK, Therakos and PulmonX but declares no conflict of interest directly related to the study; FG reports consulting fees from Pfizer, Alnylam, Ionis, and Abbott and lecture fees from Novartis, not related to this work; SN received unrestricted research grants from Novo Nordisk Foundation and Independent Research Fund FSS. 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 © 2023 Møller, Sørensen, Rezahosseini, Rasmussen, Arentoft, Loft, Perch, Gustafsson, Lundgren, Scheike, Knudsen, Ostrowski, Rasmussen and Nielsen.)

Objective: The aim of this study was to perform a systematic review, meta-analysis and cost-consequence analysis of the single-use bronchoscope, Ambu aScope TM 5 Broncho, in relation to reusable flexible bronchoscopes (RFB) available within three high procedure volume university hospitals and academic institutions in the USA., Methods: The primary outcome was incremental cost and the secondary outcome was incremental cross-infection risk of use for both the single-use flexible bronchoscope (SUFB) and RFBs. Cost estimates included capital, repair, and reprocessing costs derived from a prospective observational micro-costing approach within three large university hospitals and academic institutions. All costs were valued in 2022 US dollars (USD). A meta-analysis based on literature covering cross-contamination and infection from 2010 to 2020 investigated cross-infection risk following bronchoscopy procedures with RFBs. Capital costs were discounted at 3% over 5-8 years. All parameters were evaluated using both univariate deterministic and probabilistic sensitivity analyses., Results: In high-volume hospitals, RFBs were cost minimizing compared to SUFBs. Probabilistic sensitivity analysis showed that RFBs were cost saving in 88% of iterations. Univariate analyses illustrated sensitivity of the base-case result to the procedure volume. Data from sensitivity analyses suggest that the two interventions are cost neutral at a break-even point of 756 procedures per year or 46 procedures per bronchoscope per year., Conclusion: Assuming equivalent clinical performance, single-use flexible bronchoscopes are not cost minimizing when including the costs associated with cross-infection in high-volume US university hospitals and academic institutions. Overall, the benefits of conversion from RFBs to SUFBs are dependent on the annual procedure volume of individual hospitals, expected cross-infection risk, and purchase price of the aScope 5 Broncho., (© 2023. The Author(s).)

Background: The gut derived anorexigenic hormone neurotensin (NT) is upregulated after bariatric surgery which may contribute to the sustained weight loss. In contrast, diet-induced weight loss is most often followed by weight regain. We therefore investigated whether diet-induced weight loss impacts levels of circulating NT in mice and humans and whether NT levels predicts body weight change after weight loss in humans., Methods: In vivo mice study: Obese mice were fed ad-libitum or a restricted diet (40-60 % of average food intake) for 9 days to obtain similar weight loss as observed in the human study. At termination, intestinal segments, the hypothalamus and plasma were collected for histological, real time PCR, and radioimmunoassay (RIA) analysis., Clinical Trial: Plasma samples from 42 participants with obesity, completing an 8-week low-calorie diet in a randomized controlled trial, were analyzed. Plasma NT was measured by RIA at fasting and during a meal test before and after diet-induced weight loss and after one year of intended weight maintenance., Results: In obese mice, food restriction-induced body weight loss of 14 % was associated with a 64 % reduction in fasting plasma NT (p < 0.0001). In the mouse duodenum (p = 0.07) and jejunum (p < 0.05), NT tissue concentration was decreased without tissue atrophy indicative of a physiological downregulation. In the mouse hypothalamus a downregulation of Pomc (p < 0.01) along with upregulation of Npy (p < 0.001) and Agrp (p < 0.0001) expression was found after restricted feeding in support of increased hunger after diet-induced weight loss. Therefore, we investigated the NT response in humans undergoing weight loss maintenance. In humans, similar to the mice, the low-calorie diet induced weight loss of 13 % body weight was associated with 40 % reduction in fasting plasma NT levels (p < 0.001). Meal-induced NT peak responses were greater in humans who lost additional weight during the 1 year maintenance phase compared to participants who regained weight (p < 0.05)., Conclusion: Diet-induced weight loss decreased fasting plasma NT levels in both humans and mice with obesity, and regulated hunger-associated hypothalamic gene expression in mice. Meal-induced NT responses were greater in humans who lost additional weight during the 1 year maintenance phase compared to participants who regained weight. This indicates that increased peak secretion of NT after weight loss may contribute to successful maintenance of weight loss., Clinical Trial Registration Number: NCT02094183., Competing Interests: Declaration of competing interest E.W.L. has since January 2022 been employed at Novo Nordisk A/S. B. Holst has since October 2021 been employed at the Novo Nordisk Foundation. S.M. and J.J.H. have performed consulting services for Novo Nordisk. SST have received research grants and lecture fees from Novo Nordisk. The remaining authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)