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Proficiency in basic lung ultrasound is highly recommended for clinicians in general and internal medicine. This article will review and provide guidance for novice users on how to use lung ultrasound in clinical practice, through a pathology-oriented approach. The authors recommend a 12-zone protocol and describe how to perform and apply it in clinical practice while examining patients with clinical suspicion for the following diseases: pleural effusion, heart failure, pneumonia (bacterial and viral), interstitial lung disease, and pneumothorax., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This scoping review was conducted to provide an overview of the evidence of point-of-care lung ultrasound (LUS) in emergency medicine. By emphasizing clinical topics, time trends, study designs, and the scope of the primary outcomes, a map is provided for physicians and researchers to guide their future initiatives., Research Question: Which study designs and primary outcomes are reported in published studies of LUS in emergency medicine?, Study Design and Methods: We performed a systematic search in the PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library databases for LUS studies published prior to May 13, 2023. Study characteristics were synthesized quantitatively. The primary outcomes in all papers were categorized into the hierarchical Fryback and Thornbury levels., Results: A total of 4,076 papers were screened and, following selection and handsearching, 406 papers were included. The number of publications doubled from January 2020 to May 2023 (204 to 406 papers). The study designs were primarily observational (n = 375 [92%]), followed by randomized (n = 18 [4%]) and case series (n = 13 [3%]). The primary outcome measure concerned diagnostic accuracy in 319 papers (79%), diagnostic thinking in 32 (8%), therapeutic changes in 4 (1%), and patient outcomes in 14 (3%). No increase in the proportions of randomized controlled trials or the scope of primary outcome measures was observed with time. A freely available interactive database was created to enable readers to search for any given interest (https://public.tableau.com/app/profile/blinded/viz/LUSinEM_240216/INFO)., Interpretation: Observational diagnostic studies have been produced in abundance, leaving a paucity of research exploring clinical utility. Notably, research exploring whether LUS causes changes to clinical decisions is imperative prior to any further research being made into patient benefits., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: S. H. O. reports a relationship with Danish Society for Ultrasound in General Practice that includes travel reimbursement, and a relationship with USabcd that includes speaking and lecture fees. M. D. A. reports relationships with the Danish Society for Ultrasound in General Practice and the Danish Emergency Medical Conference 10 (DEMC10) that include travel reimbursement. J. W. reports a relationship with DEMC10 that includes travel reimbursement. I. W. Y. M. reports a relationship with Research Chair, the John A. Buchanan Chair in General Internal Medicine, University of Calgary that includes funding grants, relationships with the 3rd Vice President of the American Institute of Ultrasound in Medicine and with the Governor, Alberta Chapter, American College of Physicians that include board membership, and relationships with American College of Physicians, the American Institute of Ultrasound in Medicine, Cornell University, University of Alberta, Sonography Canada, the Canadian Society of Internal Medicine, the Canadian Thoracic Society, American Society of Regional Anesthesia and Pain Medicine, the International Pediatric Nephrology Association, and the Canadian Rheumatology Ultrasound Society that include: speaking and lecture fees. None declared (A. H. C., H. K., B. L., R. A., M. H. L., A. H. K., M. B. C., C. F., L. T., A. R., R. L., J. D.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Point-of-care ultrasound (POCUS) helps emergency department (ED) physicians make prompt and appropriate decisions, but the optimal diagnostic integration and potential clinical benefits remain unclear. We describe the protocol and statistical analysis plan for a randomized controlled trial. The objective is to determine the effect of a POCUS-driven diagnostic pathway in adult dyspneic ED patients on the proportion of patients having a hospital stay of less than 24 hours when compared to the standard diagnostic pathway., Patients and Methods: This is a multicenter, randomized, investigator-initiated, open-labeled, pragmatic, controlled trial. Adult ED patients with chief complaint dyspnea are eligible. Patients are randomized (1:1) to the POCUS-driven diagnostic pathway or standard diagnostic pathway, with 337 patients in each group. The primary outcome is the proportion of patients having a hospital stay (from ED arrival to hospital discharge) of less than 24 hours. Key secondary outcomes include hospital length-of-stay, 72-hour revisits, and 30-day hospital-free days., Conclusion: Sparse evidence exists for any clinical benefit from a POCUS-integrated diagnostic pathway. The results from this trial will help clarify the promising signals for POCUS to influence patient care among ED patients with dyspnea., Competing Interests: Dr. Christian B Laursen reports the following financial relationships: Royalties as author/editor from Munksgaard (Publisher); fees for giving presentations at educational events organized by AstraZeneca, Chiesi Pharma, and GSK. These financial relationships do not influence the design, conduct, or reporting of the research findings in this manuscript. The authors report no other conflicts of interest in this work., (© 2024 Ovesen et al.)

Objective: Childhood spinal tumors often present with musculoskeletal symptoms, potentially causing a misdiagnosis and delays in diagnosis and treatment. This study aims to identify, characterize, and compare children with spinal tumors who had prior musculoskeletal misdiagnoses to those without, analyzing clinical presentation, diagnostic interval, and outcome., Study Design: This retrospective cohort study evaluated all children aged 0-14 years diagnosed with a spinal tumor in Denmark from 1996 to 2018. The cohort was identified through the Danish Childhood Cancer Registry, and the registry data were supplemented with data from medical records. The survival was compared using the Kaplan-Meier method., Results: Among 58 patients, 57% (33/58) received musculoskeletal misdiagnoses before the spinal tumor diagnosis. Misdiagnoses were mostly nonspecific (64%, 21/33), involving pain and accidental lesions, while 36% (12/33) were rheumatologic diagnoses. The patients with prior misdiagnosis had less aggressive tumors, fewer neurological/general symptoms, and 5.5 months median diagnostic interval versus 3 months for those without a misdiagnosis. Those with prior misdiagnoses tended to have a higher 5-year survival of 83% (95% confidence interval [CI]: 63%-92%) compared to 66% (95% CI: 44%-82%) for those without (p = .15)., Conclusion: Less aggressive spinal tumors may manifest as gradual skeletal abnormalities and musculoskeletal symptoms without neurological/general symptoms, leading to misdiagnoses and delays., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Objectives: The incidence of cervical cancer among patients with postcoital bleeding (PCB) was the primary objective of this study. Furthermore, the proportion of cervical intraepithelial neoplasia requiring treatment and the correlation between PCB and the presence of high-risk human papillomavirus (HPV) was determined. Lastly, the study aimed to identify risk factors among the referred women., Methods: A retrospective cohort study was conducted at a university hospital in Denmark between January 1, 2017 and December 31, 2019. Women referred with PCB were identified with the ICD diagnosis codes "DN930 Postcoital and contact bleeding" and "DN930B Contact bleeding." Demographic and paraclinical data were extracted from the journals and the supportive systems: Patoweb and the Danish Microbiology Database., Results: A total of 789 women were included in this study, with only 0.25% ( n = 2) diagnosed with cervical cancer and 2.5% ( n = 20) diagnosed with cervical intraepithelial neoplasia II-III and adenocarcinoma in situ. Human papillomavirus testing was only conducted in a minority of cases, and a low incidence of high-risk human papilloma virus was detected in the 22 cases, n = 5., Conclusions: A very low incidence of cervical cancer and high-grade cervical intraepithelial neoplasia reported among women referred with PCB. Prognostic factors as body mass index, smoking, and HPV vaccination status may predict the risk of cervical cancer. Selection criteria like primary testing for hrHPV and cytology as cotests before referral to colposcopy may reduce the number of unnecessary colposcopies., Competing Interests: There are no publishable conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASCCP.)

Background: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. PsA disease involves flares, which are associated with increased joint inflammation and tissue remodeling. There is a need for identifying biomarkers related to PsA disease activity and flares to improve the management of PsA patients and decrease flares. The tissue turnover imbalance that occurs during the inflammatory and fibro-proliferative processes during flares leads to an increased degradation and/or reorganization of the extracellular matrix (ECM), where increased proteolysis plays a key role. Hence, protease-mediated fragments of inflammatory and tissue-remodeling components could be used as markers reflecting flares in PsA patients., Methods: A broad panel of protease-mediated biomarkers reflecting inflammation and tissue remodeling was measured in serum and synovial fluid (SF) obtained from PsA patients experiencing flares (acutely swollen joint[s], PsA-flare). In serum, biomarker levels assessed in PsA-flare patients were compared to controls and in early-diagnosed PsA patients not experiencing flares (referred to as PsA without flare). Furthermore, the biomarker levels assessed in SF from PsA-flare patients were compared to the levels in SF of osteoarthritis (OA) patients., Results: In serum, levels of the PRO-C3 and C3M, reflecting formation and degradation of the interstitial matrix, were found significantly elevated in PsA-flare compared to controls and PsA without flare. The remodeling marker of the basement membrane, PRO-C4, was significantly elevated in PsA-flare compared to PsA without flare. The inflammation and immune cell activity related markers, CRPM, VICM, and CPa9-HNE were significantly elevated in PsA-flare patients compared to controls and PsA without flare. In addition, VICM (AUC = 0.71), CPa9-HNE (AUC = 0.89), CRPM (AUC = 0.76), and PRO-C3 (AUC = 0.86) showed good discriminatory performance for separating PsA-flare from PsA without flare. In SF, the macrophage activity marker, VICM, was significantly elevated whereas the type II collagen formation marker, PRO-C2, was significantly reduced in the PsA-flare compared to OA. The combination of five serum markers reflecting type III and IV collagen degradation (C3M and C4M, respectively), type III and VI collagen formation (PRO-C3 and PRO-C6, respectively), and neutrophil activity (CPa9-HNE) showed an excellent discriminatory performance (AUC = 0.98) for separating PsA-flare from PsA without flares., Conclusions: The serum biomarker panel of C3M, C4M, PRO-C3, PRO-C6, and CPa9-HNE reflecting synovitis, enthesitis, and neutrophil activity may serve as novel tool for quantitatively monitoring flares in PsA patients., (© 2024. The Author(s).)

Purpose: Family-based treatment (FBT) has contributed significantly to the treatment of anorexia nervosa (AN) in young people (YP). However, parents are concerned that FBT and the active role of parents in the task of refeeding may have a negative impact on family relations. The aim of the review is to assess whether families engaged in FBT for AN are more or less impacted in their family wellbeing and caregiver burden, compared to families with a YP diagnosed with AN, who are not undergoing treatment with FBT., Method: Computerized searches across six databases complemented by a manual search resulted in 30 papers being included in the scoping review., Results: The review identified 19 longitudinal studies on change in family wellbeing in families in FBT-like treatments, and 11 longitudinal studies on change in family wellbeing in treatment where parents are not in charge of refeeding. Only three randomized controlled studies directly compare FBT to treatment without parent-led refeeding., Conclusion: The available research suggests no difference between intervention types regarding impact on family wellbeing. Approximately half of the studies find improvements in family wellbeing in both treatment with and without parent-led refeeding, while the same proportion find neither improvement nor deterioration. As parents play a pivotal role in FBT, there is a need for good quality studies to elucidate the impact of FBT on family wellbeing. Level of evidence Level V: Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees., (© 2024. The Author(s).)

Background: Biomarkers associated with disease severity and comorbid metabolic syndrome (MetS) in patients with hidradenitis suppurativa (HS) are lacking., Objective: To identify biomarkers associated with disease severity and comorbid MetS in patients with HS., Methods: Data on hospital outpatients with HS were obtained through clinical examination and interviews. Indicators of systemic inflammation; C-reactive protein (CRP), erythrocyte sedimentation-rate (ESR), neutrophil/lymphocyte-ratio (NLR), platelet/lymphocyte-ratio (PLR), monocyte/lymphocyte-ratio (MLR), platelet/neutrophil-ratio (PNR), pan-immune-inflammation-value (PIV), and systemic-immune-inflammatory-index (SII), were calculated from blood samples., Results: Seven hundred patients were included; of those 444 (63.4%) and 256 (36.6%) were female and male, respectively, with a median age of 38.3 years (IQR = 27.9-51.0). Increasing CRP, ESR, NLR, PIV, and SII ( P  < .001) were significantly associated with increasing Hurley-stage and international hidradenitis suppurativa severity score system 4 (IHS4)-score in adjusted analysis. A doubling in CRP (OR 1.59 (1.36-1.85), P  < .001), ESR (OR 1.39 (1.17-1.66), P  < .001) and PIV (OR 1.41 (1.12-1.77) P  = .002) was associated with MetS in adjusted analysis. ESR was the best estimator for severe IHS4-score (AUC = 0.72 (0.66-0.77), P  < .001) and Hurley III (AUC = 0.79 (0.73-0.85), P  < .001) whereas CRP was best for MetS (AUC = 0.67 (0.62-0.72), P  < .001)., Limitations: Patients in a hospital setting tend to have more severe disease., Conclusion: Biomarkers like CRP, ESR, and PIV measuring systemic inflammation were associated with disease severity and comorbid MetS in patients with HS., Competing Interests: None disclosed., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Objective: To explore the potential of a panel of ECM remodelling markers as endotyping tools for axial spondyloarthritis (axSpA) by separating patients into subtypes and investigate how they differ among each other in disease activity scores and response to treatment with adalimumab., Methods: In three axSpA studies, a panel of 14 blood-based ECM biomarkers related to formation of collagen (PRO-C2, PRO-C3, PRO-C6), degradation of collagen by metalloproteinases (C1M, C2M, T2CM, C3M, C4M, C6M, C10C), matrix metalloproteinase (MMP)-degraded prolargin (PROM), MMP-degraded and citrullinated vimentin (VICM), basement membrane turnover (PRO-C4) and neutrophil activity (CPa9-HNE) were assessed to enable patient clustering (endotyping). MASH (n=41) was a cross-sectional study, while Adalimumab in Axial Spondyloarthritis study (ASIM,n=45) and Danish Multicenter Study of Adalimumab in Spondyloarthritis (DANISH, n=49) were randomised, double-blind placebo-controlled trials of adalimumab versus placebo every other week for 6 or 12 weeks, respectively, followed by active treatment. Biomarker data were log-transformed, standardised by mean centering and scaled by the SD prior to principal component analysis and K-means clustering., Results: Based on all three studies, we identified two orthogonal dimensions reflecting: (1) inflammation and neutrophil activity (driven by C1M and CPa9-HNE) and (2) collagen turnover (driven by PRO-C2). Three endotypes were identified: high inflammation endotype (Endotype1), low inflammation endotype (Endotype 2) and high collagen turnover endotype (Endotype3). Endotype1 showed higher disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS)) at baseline compared with Endotype2 and Endotype3 and higher percentage of patients responding to adalimumab based on ASDAS clinical improvement at week 24. Endotype3 showed higher percentage of patients with 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index response at week 24 compared with Endotype2., Conclusion: These endotypes differ in their tissue remodelling profile and may in the future have utility for patient stratification and treatment tailoring., Competing Interests: Competing interests: MØ: research grants from AbbVie, BMS, Merck, Novartis and UCB, and speaker and/or consultancy fees from AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. SJP: speaker’s bureau MSD, Pfizer, AbbVie, UCB, Novartis. Consulting fees and/or honoraria: AbbVie, UCB, Novartis. Grant/research support: AbbVie, MSD and Novartis. HP: none. Frederik Christiansen: Employed at Nordic Bioscience A/S. SHN: employed and shareholder of Nordic Bioscience A/S. PF: none. A-CB-J: employed and shareholder of Nordic Bioscience A/S. MK Shareholder of: employed and shareholder of Nordic Bioscience A/S. SS: None. IJS: none. AGL: speaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, and UCB. Research grant from Novartis. ORM: none., (© 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.)

Introduction: T-helper 17 (Th17) cells produce IL-17A playing a critical role in activating the pathogenic chain leading to joint tissue inflammation and destruction. Elevated levels of Th17 cells and IL-17A have been detected in skin lesions, blood, and synovial fluid from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Moreover, IL-17A inhibitors suppress disease activity in psoriasis, PsA and AS, supporting the evidence of IL-17A contributing to the disease pathogenesis. Although, IL-17A inhibitors are widely approved, it remains unclear how the inhibitory effect of IL-17A alters the extracellular matrix (ECM) of the joint in a Th17-conditioned inflammatory milieu. Therefore, the aim of this study was to establish a cartilage model cultured with conditioned medium from Th17 cells and inhibitors to explore the effect of IL-17A inhibition on joint tissue remodeling., Methods: Naïve CD4 + T cells from healthy human buffy coat were differentiated into Th17 cells, followed by Th17 cell activation to secrete Th17-related cytokines and molecules into media. The activated Th17 cells were isolated from the conditioned media (CM) and analyzed using flow cytometry to verify Th17 cell differentiation. The CM were assessed with ELISA to quantify the concentrations of cytokines secreted into the media by the Th17 cells. Healthy bovine cartilage explants were cultured with the Th17-CM and treated with IL-17A and TNFα inhibitors for 21 days. In harvested supernatant from the cartilage cultures, MMP- and ADAMTS-mediated biomarker fragments of type II collagen, aggrecan, and fibronectin were measured by ELISA to investigate the ECM remodeling within the cartilage tissue., Results: Th17-CM stimulated a catabolic response in the cartilage. Markers of type II collagen and aggrecan degradation were upregulated, while anabolic marker of type II collagen formation remained on similar levels as the untreated explants. The addition of IL-17A inhibitor to Th17-CM decreased the elevated type II collagen and aggrecan degradation, however, degenerative levels were still elevated compared to untreated group. The addition of TNFα inhibitor completely reduced both type II collagen and aggrecan degradation compared to untreated explants. Moreover, the TNFα inhibitor treatment did not alter the type II collagen formation compared to untreated group., Conclusion: This study suggests that inhibition of IL-17A in Th17-conditioned cartilage tissue only partially reduced the MMP-mediated type II collagen degradation and ADAMTS-mediated aggrecan degradation, while the TNFα inhibitor treatment fully reduced both MMP- and ADAMTS-mediated ECM degradation. This exploratory study where ECM biomarkers are combined with Th17-conditioned ex vivo model may hold great potential as output for describing joint disease mechanisms and predicting structural effects of treatment on joint tissue., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Solveig Skovlund Groen reports financial support was provided by Den Danske Forskningsfond. Anne-Christine Bay-Jensen, Signe Holm Nielsen, Christian S. Thudium reports a relationship with Nordic Bioscience that includes: employment and equity or stocks. 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., (© 2024 The Authors.)

Introduction: Approximately 7,000 tonsillectomies are performed annually in Denmark on a benign basis. The cold steel surgical technique is the gold standard. The risk of post tonsillectomy bleeding (PTH) in a centre in Jutland is 7.9%. A new impedance-dependent tissue sealer (IDTS) device has been developed, with preliminary results showing a reduction in operation time, perioperative bleeding and post-operative risk of bleeding of 4.5%., Methods: A randomised, controlled, double-blinded multicentre trial of cold steel tonsillectomy versus IDTS will be performed on 1,250 patients. The main endpoint is PTH, perioperative bleeding, operation time and post-operative pain. The secondary outcomes are days until return to work, food intake, activity and quality of life. Included in the study are patients with indication for surgery weighing ≥ 16 kg, and excluded are patients with malignancy, bleeding disorders and unwillingness to participate in the study., Conclusions: To our knowledge, the present study is the largest randomised controlled trial in ENT surgery in the Nordic countries. The study will potentially provide evidence on PTH regarding two tonsillectomy methods., Funding: The authors have no potential conflicts of interest to declare. The study is supplied with instruments from Medtronic needed for the surgical procedures. Furthermore, a minor part of the funding of the entire project is provided by the aforementioned company. The funding providers have no role in design or conduct of the study., Clinicaltrials: gov with the identification number NCT05270109., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: Diabetic cardiovascular autonomic neuropathy (CAN) and distal symmetrical polyneuropathy (DSPN) are severe diabetic complications. Collagen type VI (COL6) and III (COL3) have been associated with nerve function. We investigated if markers of COL6 formation (PRO-C6) and COL3 degradation (C3M) were associated with neuropathy in people with type 1 diabetes (T1D)., Methods: In a cross-sectional study including 300 people with T1D, serum and urine PRO-C6 and C3M were obtained. CAN was assessed by cardiovascular reflex tests: heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuver (VM). Two or three pathological CARTs constituted CAN. DSPN was assessed by biothesiometry. Symmetrical vibration sensation threshold above 25 V constituted DSPN., Results: Participants were (mean (SD)) 55.7 (9.3) years, 51% were males, diabetes duration was 40.0 (8.9) years, HbA 1c was 63 (11 mmol/mol, (median (IQR)) serum PRO-C6 was 7.8 (6.2;11.0) ng/ml and C3M 8.3 (7.1;10.0) ng/ml. CAN and DSPN were diagnosed in 34% and 43% of participants, respectively. In models adjusted for relevant confounders a doubling of serum PRO-C6, was significantly associated with odds ratio > 2 for CAN and > 1 for DSPN, respectively. Significance was retained after additional adjustments for eGFR only for CAN. Higher serum C3M was associated with presence of CAN, but not after adjustment for eGFR. C3M was not associated with DSPN. Urine PRO-C6 analyses indicated similar associations., Conclusions: Results show previously undescribed associations between markers of collagen turnover and risk of CAN and to a lesser degree DSPN in T1D., (© 2023. The Author(s).)

Background: Diabetic kidney disease is a major cause of morbidity and mortality. Dysregulated turnover of collagen type III is associated with development of kidney fibrosis. We investigated whether a degradation product of collagen type III (C3M) was a risk marker for progression of chronic kidney disease (CKD), occurrence of cardiovascular disease (CVD), and mortality during follow up in people with type 2 diabetes (T2D) and microalbuminuria. Moreover, we investigated whether C3M was correlated with markers of inflammation and endothelial dysfunction at baseline., Methods: C3M was measured in serum (sC3M) and urine (uC3M) in 200 participants with T2D and microalbuminuria included in an observational, prospective study at Steno Diabetes Center Copenhagen in Denmark from 2007-2008. Baseline measurements included 12 markers of inflammation and endothelial dysfunction. The endpoints were CVD, mortality, and CKD progression (>30% decline in eGFR)., Results: Mean (SD) age was 59 (9) years, eGFR 90 (17) ml/min/1.73m2 and median (IQR) urine albumin excretion rate 102 (39-229) mg/24-h. At baseline all markers for inflammation were positively correlated with sC3M (p≤0.034). Some, but not all, markers for endothelial dysfunction were correlated with C3M. Median follow-up ranged from 4.9 to 6.3 years. Higher sC3M was associated with CKD progression (with mortality as competing risk) with a hazard ratio (per doubling) of 2.98 (95% CI: 1.41-6.26; p = 0.004) adjusted for traditional risk factors. uC3M was not associated with CKD progression. Neither sC3M or uC3M were associated with risk of CVD or mortality., Conclusions: Higher sC3M was a risk factor for chronic kidney disease progression and was correlated with markers of inflammation., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DGKR, SHN, FG, and MAK are employees of Nordic Bioscience. Nordic Bioscience is a privately owned, small- to medium-sized enterprise, partly focused on the development of biomarkers. None of the authors received fees, bonuses, or other benefits for the work regarding this article. DGKR, SHN, FG, and MAK holds stocks in Nordic Bioscience. The funder provided support in the form of salaries for DGKR and SHN but did not play any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Outside this work, BJvS is employed by Novo Nordisk, and PR has received institutional grants from Bayer, Novo Nordisk and AstraZeneca and has acted as consultant for Novo Nordisk, Bayer, Astellas, Boehringer Ingelheim, AstraZeneca, Gilead, Merk, Mundipharma, and Sanofi (honoraria to institution). MFM has received lecture fees from Novartis, Sanofi, Boehringer Ingelheim and Baxter. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Poulsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Follow-up programs for gynecological cancer patients are currently under revision. There is limited evidence that traditional follow-up and clinical examinations improve survival in an early-stage gynecological setting. Further, traditional follow-up programs fail to accommodate the patient's need for psychosocial and sexual supportive care and to actively involve patients and their relatives in the follow-up process. Individualized programs may replace traditional routine follow-up with fixed intervals and length. Focusing on alarm-symptoms and self-reporting may ensure detection of recurrence while allowing a continuous attention to the patient's well-being and return to daily life. In this study, a nurse-led, individualized, and need-based intervention with a specific focus on patient empowerment is tested against a standard physician-led model primarily focusing on the detection of recurrence., Methods: The study is designed as a clinical, randomized trial conducted in one of four national onco-gynecological centers in Denmark. Patients with early-stage cervical or endometrial cancer are eligible for inclusion. The intervention group undergoes individualized, nurse-led follow-up supporting patient empowerment including repeated use of electronic patient-reported outcome measures (ePROMs) before each contact as a dialogue support tool. The follow-up contacts are mainly conducted by telephone. All project nurses attended a special training program before project start and are all well-educated and dedicated onco-gynecological nurses. The control group receives standard, physician-led, follow-up without use of ePROMs or specific focus on empowerment. The effect of the intervention is evaluated by questionnaires completed by patients at baseline (3 months after surgery) and 12, 18, and 36 months after surgery. Outcomes include empowerment using the Skill and technique subscale of the HEI-Q questionnaire as the primary outcome while fear of cancer recurrence and health-related quality of life as well as the remaining subscales of the HEI-Q represent secondary outcomes. Data is collected by use of the REDCap technology, which also provides a customized visual support function for the dialogue tool., Discussion: This study will provide new information about follow-up in early-stage gynecological cancer settings and thereby contribute to improvement of future follow-up programs. Importantly, the study will provide knowledge about the impact of specific focus on patient empowerment in follow-up programs and, further, how to facilitate empowerment among patients., Trial Registration: The study is registered at clinicaltrials.gov: ID no. NCT03838861. Registered on 6 February 2019. Protocol version 2, issue date 21 November 2022., (© 2023. The Author(s).)

Objective: Chronic inflammatory arthritis is a hallmark of axial spondyloarthritis (axSpA), where coexistence of Crohn disease (CD) is prominent. We investigated the association between biomarkers of collagen degradation in healthy controls (HCs) and in patients with axSpA, CD, and CD and axSpA overlap (CD-axSpA), with the aim to investigate the ability of the biomarkers to identify patients with CD-axSpA., Methods: Patients with axSpA who fulfilled Assessment of Spondyloarthritis international Society criteria (n = 13), had biopsy-proven CD (n = 14), had CD-axSpA (n = 10), and HCs (n = 11) undergoing standard-of-care colonoscopies were included in the study. The collagen biomarkers measuring type III, IV, VI and X collagen (C3M, C4M, C6M, and C10C, respectively) were measured in plasma samples from all subject groups. Statistical analysis was performed using an ANCOVA adjusted for age, an area under the receiver-operating characteristic (AUROC) curve analysis, and Spearman correlation., Results: C4M was significantly higher in patients with CD-axSpA overlap compared to axSpA, CD, and HCs (all P < 0.001). In an AUROC analysis, C4M showed a complete separation between the patients with CD-axSpA overlap compared to HC, axSpA and CD with an area under the curve (AUC) = 1.00 ( P < 0.001). No differences were found between the patient groups for C3M, C6M, and C10C. No correlations were found between the collagen biomarkers and C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Simple Clinical Colitis Activity Index, or Harvey-Bradshaw Index scores., Conclusion: Degradation of type IV collagen quantified by C4M showed a complete separation of patients with CD-axSpA overlap, compared to axSpA, CD, and HCs, and indicates excessive collagen degradation and epithelial turnover. This biomarker could potentially be used to identify patients affected by both manifestations and to guide treatment decisions., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: To investigate correlations between biomarkers of bone remodelling and extracellular matrix turnover with baseline disease activity and treatment response in patients with early rheumatoid arthritis (RA)., Methods: A ssessing V ery E arly R heumatoid arthritis T reatment-2 (AVERT-2; NCT02504268) included disease-modifying antirheumatic drug-naive, anti-citrullinated protein antibody (ACPA)-positive patients randomised to weekly subcutaneous abatacept+methotrexate (MTX) or abatacept placebo+MTX for 56 weeks. This post hoc exploratory subanalysis assessed the association between baseline disease activity and eight biomarkers (Spearman's correlation coefficient), and whether baseline biomarkers (continuous or categorical variables) could predict treatment response at weeks 24 and 52 (logistic regression)., Results: Patient characteristics were similar between overall (n=752) and biomarker subgroup (n=535) populations and across treatments. At baseline, neoepitopes of matrix metalloproteinase-mediated degradation products of types III and IV collagen and of C reactive protein (CRP) showed the greatest correlations with disease activity; cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) showed weak correlation. Only CTX-I predicted treatment response; baseline CTX-I levels were significantly associated with achieving Simplified Disease Activity Index remission and Disease Activity Score in 28 joints (DAS28 (CRP)) <2.6 (weeks 24 and 52), and American College of Rheumatology 70 response (week 52), in patients treated with abatacept+MTX but not abatacept placebo+MTX. CTX-I predicted significant differential response between arms for DAS28 (CRP) <2.6 (week 24). Treatment differences were greater for abatacept+MTX in patients with medium/high versus low baseline CTX-I., Conclusion: In MTX-naive, ACPA-positive patients with early RA, baseline CTX-I predicted treatment response to abatacept+MTX but not abatacept placebo+MTX., Competing Interests: Competing interests: CW, YH, SEC and JL are employees of and shareholders in Bristol Myers Squibb. PS is an employee of Bristol Myers Squibb and shareholder in Bristol Myers Squibb and Celgene Corporation; has received support for meetings/travel from Bristol Myers Squibb; and has patent applications with Bristol Myers Squibb. RW was an employee of Bristol Myers Squibb at the time of analysis and has stock options in Bristol Myers Squibb. SHN has received grant/research support from Innovation Fund Denmark and owns stock in Nordic Bioscience. A-CB-J is an employee of and has stock or stock options in Nordic Bioscience. PE has received grant/research support from Bristol Myers Squibb, Lilly, Novartis and Samsung; has received consulting fees from Boehringer Ingelheim, Bristol Myers Squibb, Lilly and Novartis; has received honoraria from Bristol Myers Squibb, Celltrion, GlaxoSmithKline, Lilly, Novartis and Samsung; and received support for meetings/travel from Novartis. YT has received grant/research support from AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Corrona, Daiichi-Sankyo, Eisai and Takeda; and has received honoraria from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Mitsubishi-Tanabe and Pfizer. VPB has received grant/research support from NIH/fNIH (Accelerated Medicines Program; funds to institution; grants 1UH2AR067691-01 and GRANT11652401) and Cedar Hill; has received consulting fees from Amgen, Bristol Myers Squibb, Genzyme, Gilead, Janssen, Sanofi and UCB; has participated on a Data Safety Monitoring Board for KAI; and acted as Project Advisor for Pfizer. Additionally, VPB’s spouse is an employee of and has ownership interest in Brainstorm Therapeutics. COB has received grant/research support from Bristol Myers Squibb; has received royalties from Up to Date; has received consulting fees from AbbVie, Bristol Myers Squibb, Janssen, Pfizer, Regeneron and Sanofi; has participated on a Data Safety Monitoring Board for Moderna; and is on the Executive Committee for OMERACT (unpaid). TWJH/the Department of Rheumatology LUMC has received research support/lecture fees/consultancy fees from Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen and Pfizer. RF has received consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Cambrian, GlaxoSmithKline, Novartis, Pfizer, Teijin and Vyne; has received honoraria from AbbVie and Pfizer; and has participated on Data Safety Monitoring Boards for AbbVie, GlaxoSmithKline and Pfizer., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In this study we aimed to assess if a focused lung ultrasound examination predicts the need for mechanical ventilation, admission to an intensive care unit, high-flow oxygen treatment, death from COVID-19 within 30 days and 30-day all-cause mortality in patients with clinical suspicion of COVID-19 or PCR-verified SARS-CoV-2 infection., Methods: A multicentre prospective cohort trial was performed. Film clips from focused lung ultrasound examinations were recorded and rated by blinded observers using different scoring systems. A prediction model was built and used to test relationship between lung ultrasound scores and clinical outcomes. Diagnostic performance of scoring systems was analysed., Results: A total of 3889 film clips of 398 patients were analysed. Patients who had any of the outcomes of interest had a significantly higher ultrasound score than those who did not. Multivariable logistic regression analyses showed that lung ultrasound predicts mechanical ventilation (relative risk 2.44, 95% CI 1.32-5.52), admission to intensive care (relative risk 2.55, 95% CI 1.41-54.59) and high-flow oxygen treatment (relative risk 1.95, 95% CI 1.5-2.53) but not survival when adjusting for sex, age and relevant comorbidity. There was no diagnostic difference in area under the receiver operating characteristic curve between a scoring system using only anterolateral thorax zones and a scoring system that also included dorsal zones., Conclusion: Focused lung ultrasound in patients with clinical suspicion of COVID-19 predicts respiratory failure requiring mechanical ventilation, admission to intensive care units and the need for high-flow oxygen treatment. Thus, focused lung ultrasound may be used to risk stratify patients with COVID-19 symptoms., Competing Interests: Conflict of interest: None of the authors have any conflicts of interest to report., (Copyright ©The authors 2022.)

Objective: Autism is more prevalent among persons with Restrictive type eating disorders (R-ED) compared to the general population and is associated with poorer outcomes across treatment modalities. Knowledge is sparse with regard to whether poorer outcomes are also associated with Family-based treatment (FBT), which is recommended as the first choice of treatment for young persons (YPs) with R-ED. This case series compares outcome between groups with and without autism in a large consecutive series of YPs with R-ED treated with FBT., Method: In an earlier described consecutive series of 157 YPs with R-ED treated with FBT, we compared the outcomes of the subgroup with (N = 16) and without (N = 141) comorbid autism. Primary ICD-10 diagnoses were typical (50.0) or atypical anorexia nervosa (AN) (F50.1), the latter implying a condition as typical AN but with a failure to meet one of the diagnostic criteria. Autism diagnoses were clinically assigned. The outcomes were receiving intensified care, weight normalisation and overall successful treatment., Results: 10.2% (N = 16) of the sample had autism. 2.5% (N = 4) had autism diagnosed prior to the Eating Disorder (ED), and an additional 7.7% (N = 12) were diagnosed with autism during ED treatment. Significantly more YPs with autism (50%, N = 8) compared with YPs without autism (16%, N = 23) received intensified care (day programme or inpatient treatment) during their treatment. No significant difference between groups regarding neither weight normalisation nor successful ending of the treatment were found., Conclusion: This small sample of YPs with autism suggests that comparable proportions of YPs with and without autism may restore normal weight and end the treatment successfully within 12 months. However, more YPs with comorbid autism needed more intensive treatment, indicating that outpatient treatment delivery may not be sufficient to bring about desired change in this patient group. Findings need confirmation in a larger sample with a systematic screening for autism., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Introduction: Guselkumab, a novel interleukin-23p19 subunit monoclonal antibody, has been shown to effectively improve the diverse manifestations of active psoriatic arthritis (PsA) in two phase 3 trials (DISCOVER-1, DISCOVER-2). Serum concentrations of extracellular matrix (ECM) biomarkers at baseline and following treatment with guselkumab were evaluated in patients with active PsA, and the relationship of these biomarkers with baseline PsA characteristics and clinical response to guselkumab treatment was explored., Methods: Serum samples were collected at weeks 0, 4, 24, and 52 from a selected subset (N = 260) of the 739 biologic-naïve patients with PsA treated with guselkumab 100 mg every 4 or 8 weeks or placebo in DISCOVER-2. Demographically matched healthy controls (N = 76) were used for comparison. The samples were analyzed for ECM biomarkers associated with collagen degradation (C1M, C2M, C3M, C4M, C6M, C10C) and collagen formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4, PRO-C6)., Results: Baseline concentrations of collagen degradation biomarkers C1M, C3M, C4M, and C6M and collagen formation biomarkers PRO-C3 and PRO-C6 were significantly higher (i.e., ≥ 1.25-fold and false discovery rate adjusted p < 0.05) in PsA patients than in healthy controls. Serum C1M, C3M, C4M, and C6M levels declined from baseline in guselkumab-treated patients in both dosing regimens. In addition, guselkumab-treated ACR20 responders (≥ 20% improvement in American College of Rhematology response criteria) had significantly lower C1M levels than ACR20 nonresponders., Conclusion: These data demonstrate that serum collagen biomarkers are elevated in patients with PsA compared with healthy controls and that treatment with guselkumab decreases levels of C1M, C3M, C4M, and C6M. Importantly, C1M serves as a biomarker that associates with improvement of joint signs and symptoms., Trial Registration: ClinicalTrials.gov identifier: NCT03158285., (© 2022. The Author(s).)

Background and Aims: Extracellular matrix (ECM) remodeling is one of the key components in the formation of vulnerable atherosclerotic plaques and cardiovascular events. We recently showed that the full-length ECM-proteoglycan osteoglycin was associated with plaque vulnerability and future cardiovascular events. In the present study, we aimed to investigate the association of cleaved osteoglycin with plaque phenotype., Methods: Two-hundred human carotid plaques were analyzed by immunohistochemistry. Cleaved osteoglycin and active caspase-3 were assessed by ELISA. ECM components (collagen, elastin and glycosaminoglycans) were assessed by colorimetric assays in plaque tissue homogenates. Matrix metalloproteinases (MMPs) were assessed using Milliplex. MMP-cleavage of osteoglycin and its effect on apoptosis were studied in vitro. Cardiovascular events were recorded during follow-up using national registries., Results: Plaque levels of cleaved osteoglycin were significantly higher in asymptomatic plaques and correlated to α-actin plaque area, collagen, elastin and inversely to lipids, active. caspase-3 and a histological vulnerability index. Cleaved osteoglycin correlated to several MMPs, especially MMP-12, which was also shown to cleave osteoglycin in vitro. In vitro cleavage of osteoglycin was also associated with less smooth muscle cell apoptosis. Patients with high plaque levels of cleaved osteoglycin had a significantly lower risk to suffer from future cardiovascular events., Conclusions: The current study shows that cleaved osteoglycin is associated with a stable plaque phenotype and lower risk for future cardiovascular events. Potentially due to reduced cell apoptosis and ability to retain LDL. These results indicate that targeting the cleavage of osteoglycin may be a potential therapeutic strategy to stabilize plaques., (Copyright © 2022. Published by Elsevier B.V.)

Preference testing is a valuable source of information that can be provided by both healthcare professionals (HCPs) and patients (users). It can be used to improve the design and development of medical devices by feeding into device usability and, ultimately, risk management. Furthermore, it can aid with selecting the most appropriate clinical endpoints to be used in the clinical evaluation of a device and increase patient engagement by incorporating patient-relevant outcomes. Preference testing is widely conducted in the food industry but is not widespread in the medical field due to limited guidelines and a lack of regulatory framework. As such, manufacturers may be unaware of the benefits of preference testing and fail to take full advantage of it, or conversely, may use inappropriate methodology and/or analyses and consequently fail to collect meaningful data. In this position paper, we aim to highlight the benefits and uses of preference testing, along with potential methods that could be used for preference testing of medical devices. A key step towards the wider implementation of preference testing in medical devices is for the publication of international standards and guidelines for the collection, assessment, and implementation of preference data into the life cycle of a medical device., Competing Interests: Dr Amie Smirthwaite reports on working for a medical devices consultancy. The authors report no other conflicts of interest in this work., (© 2022 Lewis et al.)

Background: Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly identify patients with axSpA from other subjects with buttock or low back pain attributable to other reasons. We aimed to investigate circulating biomarkers of ECM/inflammation (MMP-degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), and X (C10C, COL10NC) collagens, CRPM, PROM and VICM) and ECM formation of type II (PRO-C2), III (PRO-C3), IV (PRO-C4), and VI (PRO-C6) collagens as potential biomarkers to identify patients with axSpA., Methods: We measured biomarkers from a cross-sectional study with 204 participants by enzyme-linked immunosorbent assay (ELISA). The study included axSpA patients (N = 41), women with postpartum buttock/pelvic pain (N = 46), disc herniation (N = 25), and a group of healthy subjects (including women without postpartum pelvic pain (N = 14), subjects with various types of physical strain (cleaning staff (N = 26) long-distance runners (N = 23)), and healthy men (N = 29)). Differences between the groups were calculated by ANCOVA and AUC, while Spearman's correlations were performed with ECM biomarkers and clinical scores., Results: Patients with axSpA expressed significantly higher levels of C1M, C4M, and VICM (p < 0.05-p < 0.0001) compared to all the non-axSpA control groups. Further, C6M and PRO-C4 were significantly higher in patients with axSpA (both p < 0.0001) compared to women with postpartum pelvic pain and healthy subjects, whereas PRO-C3 was significantly lower compared to healthy subjects (p = 0.01). The best ECM common biomarker to differentiate between axSpA and the non-axSpA control groups was PRO-C4 (AUC ≥ 0.75; specificity ≥ 0.79, sensitivity = 0.65). Mild correlations were observed between collagen turnover and inflammation biomarkers and CRP and MRI (ρ ≥ 0.3; p < 0.05-p < 0.001)., Conclusions: Biomarkers of type I, IV, and VI collagen and biomarkers of inflammation showed an altered turnover in patients with axSpA compared with the non-axSpA control groups. Such biomarkers may be useful in combination with MRI or independently to separate patients with axSpA from other back pain conditions., (© 2022. The Author(s).)

The pathogenesis of psoriatic arthritis (PsA) involves inflammation and bone and soft tissue turnover. Dietary fatty acids have previously been associated with pro-inflammatory effects induced by saturated fatty acids (SFA) and anti-inflammatory effects achieved by at least some polyunsaturated fatty acids (PUFA). The aim of the study was to investigate the correlations between the content of fatty acids in granulocytes and clinical and biochemical markers of PsA. A total of 140 patients with PsA were included. Skin and joint disease activity were assessed. Fatty acid composition in granulocytes was determined by gas chromatography. Competitive enzyme-linked immunosorbent assays were used to assess bone and soft tissue turnover. The content of SFA, n-6 PUFA or n-3 PUFA in granulocytes was not associated with disease activity. Marine n-3 PUFA was significantly positively correlated with collagen degradation. In contrast, n-6 PUFA was significantly positively correlated with collagen formation and negatively correlated with collagen degradation. However, the correlations were all weak. No association was found between the content of fatty acids in granulocytes and disease activity in this population of patients with PsA. The correlation between fatty acids and biomarkers of bone and soft tissue turnover needs further investigation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: To improve the outcomes of dyspnoeic patients, it is potentially important to determine the influence of uncertain diagnostic aetiology and to characterise this patient group. A change in diagnosis from emergency department (ED) contact to hospital discharge (i.e., a discordant diagnosis) served as a surrogate measure for an uncertain diagnostic aetiology. This study investigated the association between a change in diagnosis from ED contact to hospital discharge and length of stay (LOS), readmission and mortality in patients whose chief complaint was dyspnoea. The study also characterises the group of patients found to have a discordant diagnosis., Methods: This cohort study was based on data from all ED contacts at Aarhus University Hospital from 1 July 2016 to 30 June 2017. Patients triaged with dyspnoea and subsequently admitted to an inpatient unit were included., Results: Concordant contacts had an average LOS of 3.63 days, whereas discordant contacts had an average LOS of 4.65 days; the adjusted relative difference was 1.28 (95% CI: 1.10-1.48). Readmission, whether at seven or 30 days, was not significantly different between the groups. The 30-day mortality was 5% in the concordant and 10% in the discordant group, with an adjusted OR of 2.32 (95% CI: 1.08-4.96)., Conclusions: We found an association between a change in diagnosis and longer LOS, and between a change in diagnosis and 30-day mortality. The effort made to achieve diagnostic certainty in the ED may have an impact lasting throughout the entire hospital stay., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Emergency department (ED) patients present with complaints and not diagnoses. Characterization and risk stratification based on chief complaint can therefore help clinicians improve ED workflow and clinical outcome. In this study we investigated the 30-day mortality and readmission among ED patients based on chief complaint., Methods: In this cohort study we retrieved routinely collected data from electronic medical records and the Danish Civil Registration System of all ED contacts from July 1, 2016 through June 30, 2017. All patients triaged with one chief complaint using the Danish Emergency Process Triage system were included. Patients with minor injuries were excluded. The chief complaint assigned by the triaging nurse was used as exposure, and 30-day mortality and 30-day readmission were the primary outcomes. Logistic regression was used to determine crude and adjusted ORs with reference to the remaining study population., Results: A total of 41 470 patients were eligible. After exclusion of minor injuries and patients not triaged, 19 325 patients were included. The 30-day mortality and 30-day readmission differed significantly among the chief complaints. The highest 30-day mortality was observed among patients presenting with altered level of conscousness (ALOC) (8.4%, OR=2.0, 95% CI 1.3 to 3.1) and dyspnea (8.0%, OR=2.1, 95% CI 1.6 to 2.6). 30-day readmission was highest among patients presenting with fever/infection (11.7%, OR=1.9, 95% CI 1.4 to 2.4) and dyspnea (11.2%, OR=1.7, 95% CI 1.4 to 2.0)., Discussion: Chief complaint is associated with 30-day mortality and readmission in a mixed ED population. ALOC and dyspnea had the highest mortality; fever/infection and dyspnea had the highest readmission rate. This knowledge may assist in improving and optimizing symptom-based initial diagnostic workup and treatment, and ultimately improve workflow and clinical outcome., Level of Evidence: Level III., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Family-based treatment (FBT) has demonstrated efficacy for anorexia nervosa (AN) in youth in randomized, controlled trials. It is important to assess if it shows a similar effectiveness when implemented in standard care., Aim: To evaluate outcomes of FBT for restrictive-type eating disorders, delivered as standard care in a public mental health service. Outcomes are remission, frequency of hospital admissions and day-patient treatment, and frequency of other adaptations within 12 months from commencement of treatment. Second, to compare the collaborative clinical decisions of successful treatment in standard care made by family therapist at the end of treatment, with more objective definitions of recovery., Methods: The design is a prospective, uncontrolled study of a consecutive series of patients with restrictive-type eating disorders, treated with FBT in a specialty unit at the Child and Adolescent Mental Health Centre in the Capital Region of Denmark., Results: FBT was successfully completed within 12 months by 57% of participants, and 47% completed with 20 sessions or fewer. Weight restoration was achieved by 75% within 12 months, and 46% achieved both normalisation of body weight and behavioural symptoms of AN within 12 months. A total of 20% needed intensified treatment. All aspects of remission were often not present simultaneously, and the collaborative clinical decisions of successful treatment only partly aligned with other parameters of remission., Conclusion: FBT showed good results when implemented as standard care, and it can be adapted to the specifics of local service organisation without compromising effectiveness., (© 2021. The Author(s).)

Angina and no obstructive coronary artery disease (CAD) have an unfavorable prognosis, possibly due to diffuse myocardial fibrosis (DMF). In DMF the proteoglycans biglycan and versican are actively remodeled by matrix metalloproteinase. We investigated biglycan and versican in females with angina and possible DMF assessed by cardiac magnetic resonance (CMR). Seventy-one females with angina and no obstructive CAD were included. Asymptomatic females served as controls. Versican and biglycan were measured and CMR was performed measuring extracellular volume. Biglycan and versican levels were higher in symptomatic females compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p < 0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p < 0.001) and moderately correlated to extracellular volume (r 2 = 0.38, p<0.001 and r 2 = 0.26, p = 0.015). Turnover of biglycan and versican was increased in angina females compared with controls and associated with extracellular volume, supporting a link between angina with no obstructive CAD and fibrotic remodeling., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background & Aims: Acute-on-chronic liver failure (ACLF) is characterised by organ failure(s), high short-term mortality, and, pathophysiologically, deranged inflammatory responses. The extracellular matrix (ECM) is critically involved in regulating the inflammatory response. This study aimed to determine alterations in biomarkers of ECM turnover in ACLF and their association with inflammation, organ failures, and mortality., Methods: We studied 283 patients with cirrhosis admitted for acute decompensation (AD) with or without ACLF, 64 patients with stable cirrhosis, and 30 healthy controls. A validation cohort (25 ACLF, 9 healthy controls) was included. Plasma PRO-C3, PRO-C4, PRO-C5, PRO-C6, and PRO-C8 ( i.e. collagen type III-VI and VIII formation ) and C4M and C6M ( i.e. collagen type IV and VI degradation ) were measured. Immunohistochemistry of PRO-C6 was performed on liver biopsies (AD [n = 7], ACLF [n = 5]). A competing-risk regression analysis was performed to explore the prognostic value of biomarkers of ECM turnover with 28- and 90-day mortality., Results: PRO-C3 and PRO-C6 were increased in ACLF compared to AD ( p  = 0.089 and p <0.001, respectively), whereas collagen degradation markers C4M and C6M were similar. Both PRO-C3 and PRO-C6 were strongly associated with liver function and inflammatory markers. Only PRO-C6 was associated with extrahepatic organ failures and 28- and 90-day mortality (hazard ratio [HR; on log-scale] 6.168, 95% CI 2.366-16.080, p <0.001, and 3.495, 95% CI 1.509-8.093, p  = 0.003, respectively). These findings were consistent in the validation cohort. High PRO-C6 expression was observed in liver biopsies of patients with ACLF., Conclusions: This study shows, for the first time, evidence of severe net interstitial collagen deposition in ACLF and makes the novel observation of the association between PRO-C6 and (extrahepatic) organ failures and mortality. Further studies are needed to define the pathogenic significance of these observations., Lay Summary: This study describes a disrupted turnover of collagen type III and VI in Acute-on-chronic liver failure (ACLF). Plasma biomarkers of these collagens (PRO-C3 and PRO-C6) are associated with the severity of liver dysfunction and inflammation. PRO-C6, also known as the hormone endotrophin, has also been found to be associated with multi-organ failure and prognosis in acute decompensation and ACLF., Competing Interests: AJCK has none to declare. SG has none to declare. EA has none to declare. ID is a full-time employee at Takeda Pharmaceuticals International Co. IL is a full-time employee at Nordic Bioscience. AH has none to declare. SHN is a full-time employee at Nordic Bioscience. MJN is a full-time employee at Nordic Bioscience. HG received an investigator-initiated research grant from Intercept and research grants from AbbVie, ADS AIPHIA Development Services AG (Switzerland), ARLA Food for Health, and the NOVO Nordisk Foundation. HG is on an advisory board at Ipsen. ÀA has none to declare. DY is a full-time employee at Takeda Pharmaceuticals International Co. JM is a co-founder of Yaqrit Ltd. RPM has research collaboration with Yaqrit Ltd., of which he is a co-founder. He also has research collaborations with UCL spin-out Hepyx Ltd. and with Cyberliver Limited. He also has provided a consultancy role to Inventiva Pharmaceuticals. SM has none to declare. FA has none to declare. RM has none to declare. VA is a member of the Yaqrit Scientific Advisory Board. In 2016–2020, PA was on the Biovie Advisory Board and filed a patent application; in 2014–2020, he was invited as a speaker by and received a travel grant from CSL Behring; and in 2018–2019, he was on the Advisory Board at Ferring. DJL is a full-time employee and stockholder at Nordic Bioscience. WT is a full-time employee at Takeda Pharmaceuticals International Co. MAK is a full-time employee and stockholder at Nordic Bioscience. RJ has research collaborations with Yaqrit and Takeda. RJ is the inventor of OPA, which has been patented by the University College London and licensed to Mallinckrodt Pharma. He is also a founder of Yaqrit Ltd., a spinout company from the University College London. He has also co-founded Hepyx Ltd. and Cyberliver Ltd. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Author(s).)

Objectives: There is an unmet medical need for biomarkers in OA which can be applied in clinical drug development trials. The present study describes the development of a specific and robust assay measuring type II collagen degradation (T2CM) and discusses its potential as a noninvasive translational biomarker., Methods: A type II collagen specific neoepitope (T2CM) was identified by mass spectrometry and monoclonal antibodies were raised towards the epitope, employed in a chemiluminescence immunoassay. T2CM was assessed in bovine cartilage explants with or without MMP-13 inhibitor, and explant supernatants were analyzed by Western blot. T2CM was measured in plasma samples from one study (n ​= ​48 patients) where OA patients were referred to total knee replacement (TKR). Additionally, T2CM was quantified in serum from OA patients receiving salmon calcitonin treatment (sCT) (n ​= ​50) compared to placebo (n ​= ​57)., Results: The T2CM assay was technically robust (13/4 ​% inter/intra-variation) and specific for the type II collagen fragment cleaved by MMP-1 and -13. The MMP-13 inhibitor reduced the T2CM release from bovine cartilage explants receiving catabolic treatment. These results were confirmed by Western blot. In human end-stage OA patients (scheduled for TKR), the T2CM levels were elevated compared to moderate OA ( p<0.004 ). The OA patients receiving sCT had lower levels of T2CM compared to placebo group after 1, 6, and 24 months of treatment (p ​= ​0.0285, p ​= ​0.0484, p ​= ​0.0035)., Conclusions: To our knowledge, T2CM is the first technically robust serological biomarker assay which has shown biological relevance in ex vivo models and OA cohorts. This suggests that T2CM may have potential as a translational biomarker for cartilage degradation., Competing Interests: The study was supported by The Danish Council for Technology and Innovation and The Danish National Advanced Technology Foundation. Morten A. Karsdal, Anne-Christine Bay-Jensen, Christian S. Thudium and Signe Holm Nielsen, Joseph Blair, and Line Mærsk are employees of Nordic Bioscience. Morten A. Karsdal holds stock in Nordic Bioscience. Sven Lindemann and Daniela Werkmann are employees of Merck. Solveig Skovlund Groen, Simon Francis Thomsen, Dovile Sinkeviciute, Patrik Önnerfjord, and Lars Arendt-Nielsen have no competing interest., (© 2021 The Author(s).)

Objective: To assess the relationship between self-management skills and adherence to follow-up guidelines among gynecological cancer survivors in the Netherlands, Norway, and Denmark, and to assess the relationship between adherence to follow-up programs and use of additional healthcare services., Methods: For this international, multicenter, cross-sectional study, we recruited gynecological cancer survivors 1-5 years after completion of treatment. Information on follow-up visits, use of healthcare resources, self-management (measured by the Health Education Impact Questionnaire), clinical characteristics, and demographics were obtained by validated questionnaires. Participants were categorized as adherent if they attended the number of follow-up visits recommended by national guidelines, non-adherent if they had fewer visits than recommended, or over-users if they had more visits than recommended., Results: Of 4455 invited survivors, 2428 (55%) returned the questionnaires, and 911 survivors were included in the analyses. Survivors with high self-management most frequently adhered to recommended follow-up. Non-adherent survivors showed lower self-management in the health-directed activity domain (OR 1.54, 95% CI 1.03 to 2.32) than adherent survivors. No other associations between self-management and follow-up adherence were revealed. Non-adherent survivors tended to have endometrial cancer, surgical treatment only, be older, and be Danish residents. Over-users reported more follow-up visits and also used additional healthcare services more frequently than adherent survivors., Conclusion: Low self-management appears to reduce the likelihood of adherence to national guidelines for gynecological cancer follow-up. Focusing on patient education for survivors at risk of low self-management to ensure adherence to recommended follow-up may improve personalization of follow-up., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Exercise at home and improvement in the ability to undertake daily tasks are highly valued by older people after hospitalisation. New telerehabilitation (TR) technologies make it possible to supervise and communicate with exercising participants through videoconferencing equipment. This technology has been shown to be both feasible and effective in Danish chronic obstructive pulmonary disease patients in terms of basic mobility, safety, social interactions and patient perception. This study sought to examine whether it was feasible to carry out TR through home exercises in groups., Methods: Both medical and hip-fracture home-dwelling patients aged 65 years and older admitted to the Emergency Department (ED) and Department of Geriatrics for acute reasons were asked to participate in the study just before their discharge. The inclusion criteria were normal cognitive function, being dependent on a walking aid and computer users before hospitalisation., Results: At discharge, 333 patients were consecutively screened for participation. Of those, 300 patients were excluded. Thirty-three patients met the inclusion criteria. They had a mean age of 82.3 years (± 7.8) and 76% were women. Nine patients agreed to participate, but seven withdrew. The most frequent explanation was exhaustion in the continuation of hospitalisation., Conclusion: It was not possible to conduct a videoconference TR study in a geriatric population, as many were excluded and those who were eligible withdrew after inclusion. During the COVID-19 pandemic, TR may be an important tool for isolated older persons to hinder functional decline. Aspects such as recruitment procedures and IT solutions designed for older people must be considered., (© 2021. European Geriatric Medicine Society.)

Aims: Patient-reported outcome measures (PROMs) may predict poor clinical outcome in patients with heart failure (HF). It remains unclear whether PROMs are associated with subsequent adherence to HF medication. We aimed to determine whether health-related quality of life, anxiety, and depression were associated with long-term medication adherence in these patients., Methods and Results: A national cohort study of Danish patients with HF with 3-year follow-up (n = 1464). PROMs included the EuroQol five-dimensional, five-level questionnaire (EQ-5D-5L), the HeartQoL and the Hospital Anxiety and Depression Scale (HADS). Patient-reported outcomes (PRO) data were linked to demographic and clinical data at baseline, and data on all redeemed prescriptions for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor neprilysin inhibitors (ACEI/ARB/ARNI), β-blockers, and mineralocorticoid receptor antagonists during follow-up. Medication non-adherence was defined as <80% of proportion of days covered. In adjusted regression analyses, lower health-related quality of life (EQ-5D and HeartQoL) and symptoms of depression (HADS-D) at discharge were associated with non-adherence. After 3 years of follow-up, lower health-related quality of life (EQ-5D) was associated with non-adherence for ACEI/ARB/ARNI [adjusted OR 2.78, 95% confidence interval (CI): 1.19-6.49], β-blockers (adjusted OR 2.35, 95% CI: 1.04-5.29), whereas HADS-D was associated with non-adherence for ACEI/ARB/ARNI (adjusted OR 1.07, 95% CI: 1.03-1.11) and β-blockers (adjusted OR 1.06, 95% CI: 1.02-1.10)., Conclusion: Lower health-related quality of life and symptoms of depression were associated with non-adherence across HF medications at 1 and 3 years of follow-up. Person-centred care using PROMs may carry a potential for identifying patients at increased risk of future medication non-adherence., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: An in-depth understanding of the prognostic value of patient-reported outcomes (PRO) is essential to facilitate person-centred care in heart failure (HF). This study aimed to clarify the prognostic role of subjective mental and physical health status in patients with HF., Methods and Results: Patients with HF were identified from the DenHeart Survey (n = 1499) and PRO data were obtained at hospital discharge, including the EuroQol five-dimensional questionnaire (EQ-5D), the HeartQoL, and the Hospital Anxiety and Depression Scale (HADS). Clinical baseline data were obtained from medical records and linked to nationwide registries with patient-level data on sociodemographics and healthcare contacts. Outcomes were all-cause and cardiovascular (CV) mortality, CV events, and HF hospitalization with 1- and 3-year follow-up. Analysing the PRO data on a continuous scale, a worse score in the following were associated with risk of all-cause and CV mortality after 1 year: the HeartQoL (adjusted hazard ratios (HRs) 1.91, 95% confidence interval (CI) 1.42-2.57 and 2.17, 95% CI 1.50-3.15, respectively), the EQ-5D (adjusted HRs 1.26, 95% CI 1.15-1.38 and 1.27, 95% CI 1.13-1.42, respectively), the HADS depression subscale (adjusted HRs 1.12, 95% CI 1.07-1.17 and 1.11, 95% CI 1.05-1.17, respectively), and the HADS anxiety subscale (adjusted HRs 1.08, 95% CI 1.03-1.13 and 1.09, 95% CI 1.04-1.15, respectively). Three-year results were overall in concordance with the 1-year results. A similar pattern was also observed for non-fatal outcomes., Conclusion: Health-related quality of life and symptoms of anxiety and depression at discharge were associated with all-cause and CV mortality at 1- and 3-year follow-up., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Spondyloarthritis (SpA) is an umbrella term describing a family of chronic inflammatory rheumatic diseases. These diseases are characterised by inflammation of the axial skeleton, peripheral joints, and entheseal insertion sites throughout the body which can lead to structural joint damage including formation of axial syndesmophytes and peripheral osteophytes. Genetic evidence, preclinical and clinical studies indicate a clear role of interleukin (IL)- 23 and IL-17 as mediators in SpA pathogenesis. Targeting the IL-23/-17 pathways seems an efficient strategy for treatment of SpA patients, and despite the remaining challenges the pathway holds great promise for further advances and improved therapeutic opportunities. Much research is focusing on serological markers and imaging strategies to correctly diagnose patients in the early stages of SpA. Biomarkers may facilitate personalised medicine tailored to each patient's specific disease to optimise treatment efficacy and to monitor therapeutic response. This narrative review focuses on the IL-17 pathway in SpA-related diseases with emphasis on its role in pathogenesis, current approved IL-17 inhibitors, and the need for biomarkers reflecting core disease pathways for early diagnosis and measurement of disease activity, prognosis, and response to therapy., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The use of simulation-based team training has increased over the past decades. Simulation-based team training within emergency medicine and critical care contexts is best known for its use by trauma teams and teams involved in cardiac arrest. In the domain of emergency medicine, simulation-based team training is also used for other typical time-critical clinical presentations. We aimed to review the existing literature and current state of evidence pertaining to non-technical skills obtained via simulation-based team training in emergency medicine and critical care contexts, excluding trauma and cardiac arrest contexts., Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Before the initiation of the study, the protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database. We conducted a systematic literature search of 10 years of publications, up to December 17, 2019, in the following databases: PubMed/MEDLINE, EMBASE, Cochrane Library, and CINAHL. Two authors independently reviewed all the studies and extracted data., Results: Of the 456 studies screened, 29 trials were subjected to full-text review, and 13 studies were included in the final review. None of the studies was randomized controlled trials, and no studies compared simulation training to different modalities of training. Studies were heterogeneous; they applied simulation-training concepts of different durations and intensities and used different outcome measures for non-technical skills. Two studies reached Kirkpatrick level 3. Out of the remaining 11 studies, nine reached Kirkpatrick level 2, and two reached Kirkpatrick level 1., Conclusions: The literature on simulation-based team training in emergency medicine is heterogeneous and sparse, but somewhat supports the hypothesis that simulation-based team training is beneficial to teams' knowledge and attitudes toward non-technical skills (Kirkpatrick level 2). Randomized trials are called for to clarify the effect of simulation compared to other modalities of team training. Future research should focus on the transfer of skills and investigate improvements in patient outcomes (Kirkpatrick level 4).

Aim: Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer types with a high amount of fibrosis activity, namely for outcome in hepatocellular carcinoma (HCC) cirrhotic patients., Patients & Methods: Plasma C6M, PRO-C6 and alphafeto-protein (AFP) were assessed in 309 patients with mixed etiologies (hepatitis C, hepatitis B, alcohol and nonalcoholic fatty liver) diagnosed as cirrhotics, cirrhotics with HCC, noncirrhotics and healthy controls. Progression-free survival and overall survival (OS) data were collected up to 6120 days after diagnosis. The ability of each marker to predict survival was investigated., Results & Conclusion: The level of endotrophin assessed by PRO-C6 was able to separate healthy controls, noncirrhotics and cirrhotics from HCC (p < 0.05-0.0001). Both endotrophin and C6M provided value in the prediction of OS in cirrhotic patients with HCC. In the multivariate analysis for identifying HCC, in patients with high endotrophin (highest quartile) and that were positive for AFP (≥20 IU/ml), the hazard ratio for predicting OS was increased from 3.7 (p = 0.0006) to 14.4 (p = 0.0001) when comparing with AFP positive as a stand-alone marker. In conclusion, plasma levels for markers of Type VI collagen remodeling were associated with survival in cirrhotic patients with HCC. A combination of AFP with endotrophin improved the prognostic value compared with AFP alone for predicting OS in cirrhotic patients with HCC., Competing Interests: Financial & competing interests disclosure This work was funded by the Danish Innovation Foundation and Danish Research Foundation. J George is supported by grants from the NSW Cancer Council (APP1145008; APP1070076 to CL and LQ), the RW Storr Bequest to the Sydney Medical Foundation, University of Sydney and National Health and Medical Research Council of Australia (NHMRC) Program Grant (APP1053206, APP1149976) and Project grants (APP1107178 and APP1108422). D Schuppan receives project related support by the EU Horizon 2020 under grant agreement no. 634413 (EPoS, European Project on Steatohepatitis) and 777377 (LITMUS, Liver Investigation on Marker Utility in Steatohepatitis), and by the German Research Foundation collaborative research project grants DFG CRC 1066/B3 and CRC 1292/08. MA Karsdal, SH Nielsen, MJ Nielsen, AL Reese-Petersen and DJ Leeming are full-time employees of Nordic Bioscience. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Nordic Bioscience.)

In Denmark, the annual incidence of paranasal malignancies is approximately 60, often presenting with symptoms from growth into neighbouring structures. This case report is of a primary neuroendocrine paranasal tumour with distant metastases in an 81-year-old woman. Following a tooth extraction, the patient developed left side proptosis. A CT-scan showed a tumour of left ethmoidal sinus with local spreading to orbita, skull base, and contralateral ethmoid, and following scans visualised lymph node infiltration and multiple metastases. Paranasal malignancies can present with symptoms from teeth in upper jaw.

Osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, all have one clear common denominator; an altered turnover of bone. However, this may be more complex than a simple change in bone matrix and mineral turnover. While these diseases share a common tissue axis, their manifestations in the area of pathology are highly diverse, ranging from sclerosis to erosion of bone in different regions. The management of these diseases will benefit from a deeper understanding of the local versus systemic effects, the relation to the equilibrium of the bone balance (i.e., bone formation versus bone resorption), and the physiological and pathophysiological phenotypes of the cells involved (e.g., osteoblasts, osteoclasts, osteocytes and chondrocytes). For example, the process of endochondral bone formation in chondrocytes occurs exists during skeletal development and healthy conditions, but also in pathological conditions. This review focuses on the complex molecular and cellular taxonomy of bone in the context of rheumatological diseases that alter bone matrix composition and maintenance, giving rise to different bone turnover phenotypes, and how biomarkers (biochemical markers) can be applied to potentially describe specific bone phenotypic tissue profiles.

Background and Aims: A vulnerable plaque is an atherosclerotic plaque that is rupture-prone with a higher risk to cause cardiovascular symptoms such as myocardial infarction or stroke. Mimecan or osteoglycin is a small leucine-rich proteoglycan, important for collagen fibrillogenesis, that has been implicated in atherosclerotic disease, yet the role of mimecan in human atherosclerotic disease remains unknown., Methods: 196 human atherosclerotic carotid plaques were immunostained for mimecan. Smooth muscle cells, macrophages and intraplaque haemorrhage were also measured with immunohistochemistry. Neutral lipids were stained with Oil Red O and calcium deposits were quantified. Plaque homogenate levels of MCP-1, IL-6 and MIP-1β were measured using a Proximity Extension Assay and MMP-9 levels were measured using Mesoscale. Glycosaminoglycans, collagen and elastin were assessed by colorimetric assays and TGF-β1, β2 and β3 were measured using a multiplex assay. Mimecan gene expression in THP-1 derived macrophages was quantified by qPCR and protein expression in vitro was visualized with immunofluorescence. Cardiovascular events were registered using medical charts and national registers during follow-up., Results: Mimecan correlated positively with plaque area of lipids, macrophages, intraplaque haemorrhage and inversely with smooth muscle cell staining. Mimecan also correlated positively with plaque levels of MMP-9 and MCP-1. Mimecan was upregulated in THP-1 derived macrophages upon stimulation with MCP-1. Patients with high levels of mimecan (above median) had higher risk for cardiovascular death., Conclusions: This study indicates that mimecan is associated with a vulnerable plaque phenotype, possibly regulated by plaque inflammation. In line, plaque levels of mimecan independently predict future cardiovascular death., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Hemithyroidectomy for benign thyroid disease has traditionally been considered an inpatient procedure due to concerns about post-operative complications, in particular the risk of post-thyroidectomy bleeding (PTB). Hemithyroidectomy in an outpatient setting has not yet been evaluated in a Danish context. This study aimed to evaluate outpatient compared to inpatient hemithyroidectomy in selected patients (no suspicion of malignancy, lesser-than 100 ml lobe, American Society of Anesthesiologists class I or II and no anticoagulation therapy) to investigate the safety of the procedure., Methods: This cohort study was conducted between June 2014 and June 2019 in a Danish regional hospital and included all hemithyroidectomy patients. Data were obtained retrospectively from medical records. The primary outcome was PTB, and secondary outcomes included nerve injury, infection, perioperative drain placement, reintervention and unplanned hospital contacts., Results: Hemithyroidectomy was performed in 229 patients. For 137 patients, the procedure was planned in an outpatient setting; and among these, 124 patients (91%) were completed as planned. None of the patients in either the outpatient or inpatient setting experienced PTB. In the outpatient group, 1.5% had permanent nerve injury of the recurrent nerve and 0.7% had a superficial wound infection which was treated with oral antibiotics., Conclusions: Hemithyroidectomy for benign thyroid disease is safe to perform in an outpatient setting for a selected patient group., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

In this nation-wide cohort study we report the first long-term results of the association between having a atrial septal defects (ASD) on psychiatric disorders and use of psychotropic agents. Through population-based registries we included Danish individuals born before 1994 who received an ASD diagnosis between 1959and 2013. We used Cox proportional hazards regression and Fine and Grey competing risk regression to estimate the risk of receiving a psychiatric diagnosis and use of psychotropic medicine compared with a gender and age matched background population cohort. In 2,277 patients with a median follow-up from ASD diagnosis of 23.4 years (range 0.2 to 59.3 years) we found ASD patients to have a higher risk of psychiatric disorders (adjusted hazard ratio [HR]: 3.9; 95% confidence interval [CI] 3.4 to 4.5) compared with the comparison cohort and a cumulative incidence of using psychotropic agents 30 years after the ASD diagnosis of 47.4% (95% CI: 40.3 to 55.1) in the ASD patients and 25.5%, (95% CI: 23.5 to 27.8) in the comparison cohort. Diagnosis of the ASD before the age of 15 years (adjusted HR: 3.4; 95% confidence interval: 2.0 to 4.0) and surgical correction of the defect (HR: 1.5 (95% CI: 1.2 to 1.8), p <0.0001) had a higher risk than those with an ASD diagnosis after the age of 15 years and those with transcatheter closure of the defect. In conclusion, ASD patients had increased long-term risk of psychiatric disorder and use of psychotropic agents compared with a gender and age matched general population controls., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mentalization is a developmental achievement defined as the capacity to understand behavior in terms of mental states. This study investigated mentalization in psychoanalytic psychotherapy (PPT) and cognitive behavior therapy (CBT) through a secondary data analysis of findings from a randomized controlled trial for bulimia nervosa. It was hypothesized that mentalization would predict alliance and outcome in both treatments, whereas increase in mentalization was only expected after PPT. Furthermore, it was investigated whether change in mentalization predicted symptom change. A total of 70 participants with bulimia nervosa were randomized to PPT or CBT. Participants were assessed at 3 time points with the Eating Disorder Examination and the Adult Attachment Interview (rated for reflective functioning [RF]). Therapy sessions were rated with the Vanderbilt Therapeutic Alliance Scale. Higher intake RF significantly predicted better alliance, whereas no association was observed between RF and outcome. A significant interaction between time, therapy type, and RF found RF improving more in PPT than in CBT. There was a significant association between RF change and symptom change in the PPT group. The study suggests a relation between RF and psychotherapy process, whereas the relation between RF and outcome is more complex. Furthermore, PPT seems to enhance mentalization, which seems related to symptomatic improvement, suggesting that mentalization might serve as a specific mechanism of change in PPT. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

In recent years, production of biosynthesized human milk oligosaccharides (HMOs) has become scalable to industrial standards. As a result, infant formula fortified with 2'-fucosyllactose (2'-FL), the most abundant HMO in human breast milk, is now commercially available. 2'-FL and 3-fucosyllactose (3-FL), another abundant HMO, are thought to be beneficial for infant health and development. Products containing HMOs are projected to expand in the future, showing the need for robust, easily applicable analytical methods for the quantitative assessment of HMOs in different food applications. We present here a validated high-performance liquid chromatography method for the quantification of 2'-FL and 3-FL in whole milk, infant formula, and cereal bars. The sample preparation was simple dispersion and extraction of the sample. The samples were analyzed by hydrophilic interaction liquid chromatography with refractive index detection and a runtime of 19 min. The method had a high degree of linearity (R 2 > 0.9995) in the range 0.2 to 12 mg/mL. The recovery for 2'-FL was 88% to 105% and for 3-FL 94% to 112%. The limit of detection (LOD) for whole milk was 0.1 mg/mL for 2'-FL and 0.2 mg/mL for 3-FL. In infant formula and cereal bars, the LOD was 0.6 mg/g for both 2'-FL and 3-FL. To show the practical application of this method, it was successfully utilized in stability studies of 2'-FL and 3-FL in whole milk, UHT milk, and yoghurt. The method provides a means of simultaneous and robust quantification of 2'-FL and 3-FL in various food matrices with high accuracy and high reproducibility. PRACTICAL APPLICATION: 2'-Fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) are two of the most abundant human milk oligosaccharides (HMOs) present in human breast milk. We present a fast HPLC method for the robust quantification of these two compounds in infant formula, whole milk, UHT milk, cereal bars, and yoghurt. This method can easily be set up by food producers and researchers to analyze the dosage of 2'-FL and 3-FL in their product or perform shelf life studies in different food applications., (© 2020 The Authors. Journal of Food Science published by Wiley Periodicals, Inc. on behalf of Institute of Food Technologists.)

Renal fibrosis is a hallmark of chronic kidney disease (CKD) caused by an imbalance between formation and degradation of extracellular matrix proteins. We investigated the collagen turnover profile of 81 non-dialysis CKD stage 2-5 patients by measuring peptides reflecting formation and degradation of collagen type (COL) I, III, IV, and VI. Based on the collagen turnover profile, we identified four clusters of patients. Cluster 1 contained one patient with prostate cancer, who had a distinct collagen turnover. The other clusters generally had severe (Cluster 2), moderate (Cluster 4), or mild CKD (Cluster 3). Cluster 4 patients were characterized by higher levels of COL III, COL IV, and COL VI (all p < 0.001) degradation fragments in plasma, while patients in Clusters 2 and 4 had higher levels of COL VI formation (p < 0.05). COL IV fragments in plasma were lower in Cluster 2 (p < 0.01). Urinary COL III fragments decreased from Cluster 3 to 4, and from Cluster 4 to 2 (both p < 0.001). We show that patients with similar kidney function have a different collagen remodeling profile, suggesting that different phenotypes exist with different disease activity and potentially disease progression. Biomarkers of collagen remodeling could provide additional information to traditional markers of renal function.

Small clusters of spherical colloids that mimic real molecules, so-called colloidal molecules, hold great promise as building blocks in bottom-up routes to new materials. However, their typical hard sphere nature has hampered their assembly into ordered structures, largely due to a lack of control in the interparticle interactions. To provide easy external control of the interactions, the present work focuses on the preparation of colloidal molecules from temperature-responsive microgel particles that undergo a transition from a soft repulsive to a short-range attractive state as their characteristic volume phase transition temperature (VPTT) is crossed. Preparation of the colloidal molecules starts with the use of a droplet-based microfluidics device to form highly uniform water-in-oil (W/O) emulsion droplets containing, on average and with a narrow distribution, four microgels per droplet. Evaporation of the water then leads to the formation of colloidal molecule-like clusters, which can be harvested following cross-linking and phase transfer. We use a mixture of two types of microgels, one based on poly( N -isopropylacrylamide) (PNIPAM) and the other on poly( N -isopropylmethacrylamide) (PNIPMAM), to prepare bicomponent colloidal molecules, and show that the difference in VPTT between the two allows for induction of attractive interparticle interactions between the PNIPAM interaction sites at temperatures in between the two VPTTs, analogous to the interactions among patchy biomacromolecules such as many proteins.

The self-assembly of small colloidal clusters, so-called colloidal molecules, into crystalline materials has proven extremely challenging, the outcome often being glassy, amorphous states where positions and orientations are locked. In this paper, a new type of colloidal molecule is therefore prepared, assembled from poly(N-isopropylacrylamide) (PNIPAM)-based microgels that due to their well documented softness and temperature-response allow for greater defect tolerance compared to hard spheres and for convenient in situ tuning of size, volume fraction and inter-particle interactions with temperature. The microgels (B) are assembled by electrostatic adsorption onto oppositely charged, smaller-sized microgels (A), where the relative size of the two determines the valency (n) of the resulting core-satellite ABn-type colloidal molecules. Following assembly, a microfluidic deterministic lateral displacement (DLD) device is used to effectively isolate AB4-type colloidal molecules of tetrahedral geometry that possess a repulsive-to-attractive transition on crossing the microgels' volume phase transition temperature (VPTT). These soft, temperature-responsive colloidal molecules constitute highly promising building blocks for the preparation of new materials with emergent properties, and their optical wavelength-size makes them especially interesting for optical applications.