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Vibeke Andersen,1– 3 Andreas Kristian Pedersen,1 Sören Möller,4 Anders Green4 1Focused Research Unit for Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Åbenrå, Denmark; 2Institute of Regional Research (IRS-Center Sonderjylland), University of Southern Denmark, Odense, Denmark; 3Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; 4Open Patient Data Explorative Network (OPEN), Department of Clinical Research, Odense University Hospital and University of Southern Denmark, Odense, DenmarkCorrespondence: Vibeke AndersenFocused Research Unit for Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Aabenraa, Kresten Philipsens Vej 15, Åbenrå DK-6200, DenmarkEmail va@rsyd.dkBackground: Chronic inflammatory diseases (CIDs) may share aetiological factors across diseases. We used registry data to evaluate the risk of developing five common childhood CIDs dependent on the parents’ disease status.Methods: We performed a national population-based registry study by linking data from the national Danish health registers from January 1973 to March 2016 to evaluate any potential associations between parents’ disease and development of CIDs among the offspring. Results were adjusted for parental age at birth, the decade of birth, gender of the child, and type of birth. A cohort of 2,699,449 liveborn children was established for investigating the primary outcome measures: diabetes mellitus (DM), rheumatoid arthritis (RA), coeliac disease, Crohn’s disease (CD), and ulcerative colitis (UC) and all diseases combined (CID).Results: Children with one CID affected parent (Hazard ratio (HR), 95% confidence interval (95% CI)=1.75 (1.72– 1.79, p< 0.001)), one multiple CID affected parent (HR=2.23 (2.11– 2.34), p< 0.001), and both parents affected (HR=3.10 (2.98– 3.22), p< 0.001) were at higher risk than children without CID affected parents. Children with DM, RA, and COE affected parents were at increased risk of three specific diseases (DM, RA and COE), whereas children with CD and UC affected parents were at increased risk of two specific diseases (CD and UC).Conclusion: Children with CID affected parents were at increased risk of the same CID as their parents as well as other specific CIDs dependent on the parents’ CID. Future studies should address the aetiology underlying these findings to support the development of new strategies for prevention, treatment, and cure.Keywords: parents’ disease, population study, chronic inflammatory disease, inflammatory bowel diseases, rheumatoid arthritis, coeliac disease, diabetes mellitus

1 The plasma concentrations of sulphinpyrazone and four of its metabolites are reported together with the amounts excreted in urine. Eight insulin-requiring diabetics were investigated, all treated with sulphinpyrazone 600-800 mg day-1 for 2.5 years or more. 2 Blood samples were drawn before the first morning dose and 2 h later. The mean plasma concentrations were (t=0 h-t=2 h): sulphinpyrazone 7.1-16.0 microgram ml-1; sulphone 1.7-4.8 microgram ml-1; p-OH-sulphide 0.67-0.89 microgram ml-1; p-OH-sulphinpyrazone 0.10-0.16 microgram ml-1. Statistically significant correlations were found between the plasma concentrations at t=0 of the sulphide and the p-OH-sulphide and that of sulphinpyrazone. 3 In urine, a very wide range in excretion of unconjugated compounds was observed. Sulphinpyrazone were excreted in amounts corresponding to 1-30% of the daily dose. The metabolites were generally excreted to amounts corresponding to less than 1% of the daily dose; however, up to 3% was found as the sulphone. 4 Increases of the concentration of all compounds in urine were found after treatment with beta-glucuronidase indicating 0-conjugation with glucuronic acid. 5 Since both the sulphide and the sulphone were found more active as inhibitors of platelet function in vitro than their parent compound, they may together constitute the major part of the platelet inhibitory drug activity in plasma during long-term therapy with sulphinpyrazone. [ABSTRACT FROM AUTHOR]

Objectives: A randomized trial was done to compare single-chamber atrial (AAI) and dual-chamber (DDD) pacing in patients with sick sinus syndrome (SSS). Primary end points were changes in left atrial (LA) size and left ventricular (LV) size and function as measured by M-mode echocardiography.Background: In patients with SSS and normal atrioventricular conduction, it is still not clear whether the optimal pacing mode is AAI or DDD pacing.Methods: A total of 177 consecutive patients (mean age 74 +/- 9 years, 73 men) were randomized to treatment with one of three rate-adaptive (R) pacemakers: AAIR (n = 54), DDDR with a short atrioventricular delay (n = 60) (DDDR-s), or DDDR with a fixed long atrioventricular delay (n = 63) (DDDR-l). Before pacemaker implantation and at each follow-up, M-mode echocardiography was done to measure LA and LV diameters. Left ventricular fractional shortening (LVFS) was calculated. Analysis was on an intention-to-treat basis.Results: Mean follow-up was 2.9 +/- 1.1 years. In the AAIR group, no significant changes were observed in LA or LV diameters or LVFS from baseline to last follow-up. In both DDDR groups, LA diameter increased significantly (p < 0.05), and in the DDDR-s group, LVFS decreased significantly (p < 0.01). Atrial fibrillation was significantly less common in the AAIR group, 7.4% versus 23.3% in the DDDR-s group versus 17.5% in the DDDR-l group (p = 0.03, log-rank test). Mortality, thromboembolism, and congestive heart failure did not differ between groups.Conclusions: During a mean follow-up of 2.9 +/- 1.1 years, DDDR pacing causes increased LA diameter, and DDDR pacing with a short atrioventricular delay also causes decreased LVFS. No changes occur in LA or LV diameters or LVFS during AAIR pacing. Atrial fibrillation is significantly less common during AAIR pacing. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff tears (RCT) are a common musculoskeletal condition, especially in the aging population. The prevalence of rotator cuff tears varies based on factors like age, occupation, and activity level. In the general population, the prevalence of rotator cuff tears is estimated to be around 20 to 25%. Rotator cuff tears (RCT) have an impact in patients' pain level, shoulder function, sleep disturbance, and quality of life. Primary tendon surgery is in mostly cases necessary. This study aimed to examine if treatment of rotator cuff lesions with implantation of micro-fragmented adipose tissue can improve patients' reported pain and function compared to conventional surgery., Methods: The study is a prospective superiority parallel-group single-center randomized controlled trial including 30 patients between 40 and 69 years of age in Denmark. Patients will be allocated 1:1 ratio to reconstruction of the supraspinatus tendon with an injection of micro-fragmented adipose tissue into the related muscle (stem cell treatment) or the standard of care (SOC), which is conventional surgery. Patients, project assistants, physicians, and outcome adjudicators are not blinded to randomization due to practical constraints. The radiologist and the statistician performing the analysis will be blinded. The primary outcome will be the Oxford shoulder score at 12 months post-surgery., Discussion: This study will assess whether adding micro-fragmented adipose tissue therapy to conventional rotator cuff tear treatment can enhance recovery, accelerate return to daily activities, and improve functional outcomes. The research will also determine if this minimally invasive procedure could be standardized for routine patient care., Trial Registration: ClinicalTrials.gov NCT06505135. Registered on July 10, 2024., (© 2024. The Author(s).)

Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten-free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14-16 weeks in patients with CID with high versus low-to-medium gluten intake. Secondary outcomes of interest included changes in disease activity, health-related quality of life and C-reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low-to-medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14-16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium-to-low gluten group (OR = 0.96 [0.51-1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID., (© 2024 The Author(s). Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

Background: Repair of large incisional hernias is challenging, and the risks of postoperative complications have been associated with obesity, smoking, and diabetes. The present study was conducted to determine the impact of these risk factors on short and long-term outcomes following the repair with the peritoneal flap hernioplasty (PFH)., Methods: Three hundred twenty-seven patients undergoing PFH for incisional hernia repair were identified. Patient demographics and clinical data were recorded. Patients presenting signs of complications were assessed during a visit to the outpatient clinic. A multivariable regression analysis was performed to evaluate the association between BMI, smoking and diabetes, and postoperative complications., Results: The study included 157 males (48.0%) and 170 females (52.0%). Median BMI was 30.9 kg/m 2 . Diabetes was present in 13.8% of patients. 23.2% were active smokers. The recurrence rate was 2.4%. The odds ratios for postoperative complications were increased by 9% per BMI unit (P < 0.01), due predominantly to a rise in superficial wound infections (P < 0.01) and seroma production (P = 0.07). The adjusted odds ratio increased fourfold in patients with BMI > 40 kg/m 2 (P = 0.06)., Conclusion: Incisional hernia repair with the PFH technique is associated with a low risk of short and long-term complications. The risk is associated with obesity and significantly increased in patients with a BMI exceeding 40 kg/m 2 , where a fourfold increase was observed predominantly due to seroma and superficial wound infections. The recurrence rate was 2.4% and was unaltered across BMI categories. No association was established between smoking, diabetes, and the risk of all-cause complications., (© 2024. The Author(s).)

Background: Inguinal hernia repair is a frequently performed surgical procedure, with laparoscopic repair emerging as the preferred approach due to its lower complication rate and faster recovery compared to open repair. Mesh-based tension-free repair is the gold standard for both methods. In recent years, robotic hernia repair has been introduced as an alternative to laparoscopic repair, offering advantages such as decreased postoperative pain and improved ergonomics. This study aims to compare the short- and long-term outcomes, including the surgical stress response, postoperative complications, quality of life, and sexual function, between robotic-assisted transabdominal preperitoneal (rTAPP) and laparoscopic TAPP inguinal hernia repairs., Methods: This randomized controlled trial will involve 150 patients from the Surgical Department of the University Hospital of Southern Denmark, randomized to undergo either rTAPP or laparoscopic TAPP. Surgical stress will be quantified by measuring C-reactive protein (CRP) and cytokine levels. Secondary outcomes include complication rates, quality of life, sexual function, and operative times. Data analysis will adhere to the intention-to-treat principle and will be conducted once all patient data are collected, with outcomes assessed at various postoperative intervals., Discussion: This study holds significance in evaluating the potential advantages of robotic-assisted surgery in the context of inguinal hernia repairs. It is hypothesized that rTAPP will result in a lower surgical stress response and potentially lower the risk of postoperative complications compared to conventional laparoscopic TAPP. The implications of this research could influence future surgical practices and guidelines, with a focus on patient recovery and healthcare costs. The findings of this study will contribute to the ongoing discourse surrounding the utilization of robotic systems in surgery, potentially advocating for their broader implementation if the benefits are substantiated., Trial Registration: ClinicalTrials.gov NCT05839587. Retrospectively registered on 28 February 2023., (© 2024. The Author(s).)

Background: Inflammatory bowel diseases (IBDs) are associated with high healthcare utilization. This systematic review aimed to summarize what is known about the impact of sex, income, and education on the likelihood of bowel surgery, hospitalization, and use of corticosteroids and biologics among patients with IBD., Methods: We used EMBASE, MEDLINE, CINAHL, and Web of Science to perform a systematic literature search. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis for the impact of sex on the likelihood of surgery and hospitalization. In addition, we performed subgroup analyses of the effect of IBD type (Crohn's disease or ulcerative colitis) and age. Finally, meta-regression was undertaken for the year of publication., Results: In total, 67 studies were included, of which 23 studies were eligible for meta-analysis. In the main meta-analysis, male sex was associated with an increased likelihood of bowel surgery (HR 1.42 (95% CI 1.13;1.78), which was consistent with the subgroup analysis for UC only (HR 1.78, 95% CI 1.16; 2.72). Sex did not impact the likelihood of hospitalization (OR 1.05 (95% CI 0.86;1.30), although the subgroup analysis revealed an increased likelihood of hospitalization in CD patients (OR 1.42, 95% CI 1.28;1.58). In 9 of 10 studies, no significant sex-based differences in the use of biologics were reported, although in 6 of 6 studies, female patients had lower adherence to biologics. In 11 of 13 studies, no significant sex-based difference in the use of corticosteroids was reported. The evidence of the impact of income and education on healthcare utilization was sparse and pointed in different directions. The substantial heterogeneity between studies was explained, in part, by differences in IBD type and age., Conclusions: The results of this systematic review indicate that male patients with IBD are significantly more likely to have surgery than female patients with IBD but are not, overall, more likely to be hospitalized, whereas female patients appear to have statistically significantly lower adherence to biologics compared to male patients. Thus, clinicians should not underestimate the impact of sex on healthcare utilization. Evidence for income- and education-based differences remains sparse., Systematic Review Registration: PROSPERO CRD42022315788., (© 2024. The Author(s).)

Polymers are promising candidates as solid-state electrolytes due to their performance and processability, but fillers play a critical role in adjusting the polymer network structure and electrochemical, thermal, and mechanical properties. Most fillers studied so far are anisotropic, limiting the possibility of homogeneous ion transport. Here, applying metal-organic framework (MOF) glass as an isotropic functional filler, solid-state polyethylene oxide (PEO) electrolytes are prepared. Calorimetric and diffusion kinetics tests show that the MOF glass addition reduces the glass transition temperature of the polymer phase, improving the mobility of the polymer chains, and thereby facilitating lithium (Li) ion transport. By also incorporating the lithium salt and ionic liquid (IL), Li-Li symmetric cell tests of the PEO-lithium salt-MOF glass-IL electrolyte reveal low overpotential, indicating low interfacial impedance. Simulations show that the isotropic structure of the MOF glass facilitates the wettability of the IL by enhancing interfacial interactions, leading to a less confined IL structure that promotes Li-ion mobility. Finally, the obtained electrolyte is used to construct Li-lithium iron phosphate full batteries that feature high cycle stability and rate capability. This work therefore demonstrates how an isotropic functional filler can be used to enhance the electrochemical performance of solid-state polymer electrolytes., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Negativity bias is a cognitive bias that results in negative events being perceptually more salient than positive ones. For hearing care, this means that hearing aid benefits can potentially be overshadowed by adverse experiences. Research has shown that sustaining focus on positive experiences has the potential to mitigate negativity bias. The purpose of the current study was to investigate whether a positive focus (PF) intervention can improve speech-in-noise abilities for experienced hearing aid users. Thirty participants were randomly allocated to a control or PF group (N = 2 × 15). Prior to hearing aid fitting, all participants filled out the short form of the Speech, Spatial and Qualities of Hearing scale (SSQ12) based on their own hearing aids. At the first visit, they were fitted with study hearing aids, and speech-in-noise testing was performed. Both groups then wore the study hearing aids for two weeks and sent daily text messages reporting hours of hearing aid use to an experimenter. In addition, the PF group was instructed to focus on positive listening experiences and to also report them in the daily text messages. After the 2-week trial, all participants filled out the SSQ12 questionnaire based on the study hearing aids and completed the speech-in-noise testing again. Speech-in-noise performance and SSQ12 Qualities score were improved for the PF group but not for the control group. This finding indicates that the PF intervention can improve subjective and objective hearing aid benefits., Competing Interests: Declaration of Conflicting InterestsDL and AKP are employees of WS Audiology. LLAN was a master student at University of Southern Denmark at the time this study was conducted but is now employed at GN Group.

Background: Rapid and accurate detection of pathogens is needed in community-acquired pneumonia (CAP) to enable appropriate antibiotics and to slow the development of antibiotic resistance. We aimed to compare the effect of point-of-care (POC) polymerase chain reaction (PCR) detection of respiratory pathogens added to standard care with standard care only (SCO) on antibiotic prescriptions after acute hospital admission., Methods and Findings: We performed a superiority, parallel-group, open-label, multicentre, randomised controlled trial (RCT) in 3 Danish medical emergency departments (EDs) from March 2021 to February 2022. Adults acutely admitted with suspected CAP during the daytime on weekdays were included and randomly assigned (1:1) to POC-PCR (The Biofire FilmArray Pneumonia Panel plus added to standard care) or SCO (routine culture and, if requested by the attending physician, target-specific PCR) analysis of respiratory samples. We randomly assigned 294 patients with successfully collected samples (tracheal secretion 78.4% or expectorated sputum 21.6%) to POC-PCR (n = 148, 50.4%) or SCO (146, 49.6%). Patients and investigators owning the data were blinded to the allocation and test results. Outcome adjudicators and clinical staff at the ED were not blinded to allocation and test results but were together with the statistician, blinded to data management and analysis. Laboratory staff performing standard care analyses was blinded to allocation. The study coordinator was not blinded. Intention-to-treat and per protocol analysis were performed using logistic regression with Huber-White clustered standard errors for the prescription of antibiotic treatment. Loss to follow-up comprises 3 patients in the POC-PCR (2%) and none in the SCO group. Intention-to-treat analysis showed no difference in the primary outcome of prescriptions of no or narrow-spectrum antibiotics at 4 h after admission for the POC-PCR (n = 91, 62.8%) odds ratio (OR) 1.13; (95% confidence interval (CI) [0.96, 1.34] p = 0.134) and SCO (n = 87, 59.6%). Secondary outcomes showed that prescriptions were significantly more targeted at 4-h OR 5.68; (95% CI [2.49, 12.94] p < 0.001) and 48-h OR 4.20; (95% CI [1.87, 9.40] p < 0.001) and more adequate at 48-h OR 2.11; (95% CI [1.23, 3.61] p = 0.006) and on day 5 in the POC-PCR group OR 1.40; (95% CI [1.18, 1.66] p < 0.001). There was no difference between the groups in relation to intensive care unit (ICU) admissions OR 0.54; (95% CI [0.10, 2.91] p = 0.475), readmission within 30 days OR 0.90; (95% CI [0.43, 1.86] p = 0.787), length of stay (LOS) IRR 0.82; (95% CI [0.63, 1.07] p = 0.164), 30 days mortality OR 1.24; (95% CI [0.32, 4.82] p = 0.749), and in-hospital mortality OR 0.98; (95% CI [0.19, 5.06] p = 0.986)., Conclusions: In a setting with an already restrictive use of antibiotics, adding POC-PCR to the diagnostic setup did not increase the number of patients treated with narrow-spectrum or without antibiotics. POC-PCR may result in a more targeted and adequate use of antibiotics. A significant study limitation was the concurrent Coronavirus Disease 2019 (COVID-19) pandemic resulting in an unusually low transmission of respiratory virus., Trial Registration: ClinicalTrials.gov (NCT04651712)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cartuliares 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: The elderly population is expanding globally. This gives numerous challenges especially regarding hip fracture patients. In the US alone over 300.000 hip fracture patients are treated each year, and a large amount of those develop opoid addiction. Hip fractures require surgical intervention within 24 h and is associated with significant pain even at rest. Postoperative analgesic treatment need to be optimized to ensure adequate pain relief and to prevent subsequent opioid addiction. Previous studies have shown that methadone effectively decreases post-operative opioid consumption but the studies focused on younger patients undergoing elective surgery. This study focus on the use of methadone on the elderly, fragile patients undergoing acute surgery, by first determining the maximal tolerable dose.The hypothesis is the maximal tolerable doses of these hip-fracture patients lies between 0.10 mg/kg and 0.20 mg/kg. This trial aims to estimate the maximum tolerable dose of methadone when administered to elderly patients undergoing surgery for a hip fracture., Method: This project is an adaptive dose-finding trial. The continuous reassessment method will estimate the maximum tolerable dose of methadone. The primary outcome will be respiratory depression. The statistical analysis plan will be published a priori to the closure of patient recruitment and statistical analysis of database results., Conclusion: The results of this study will give valuable information about the maximally tolerated dose of methadone for postoperative pain relief for elderly patients with hip fractures and potential adverse events.This trial is registered on clinicaltrials.gov with trial registration: NCT05581901. Registered 17 October 2022, https://www.clinicaltrials.gov/ct2/show/NCT05581901?term=methadone&cond = hip&draw = 2&rank = 1., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: β -cell dysfunction and insulin resistance are the main mechanisms causing glucose intolerance in type 2 diabetes (T2D). Bariatric surgeries, i.e., sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), are procedures both known to induce weight loss, increase insulin action, and enhance β -cell function, but hepatic insulin extraction and glucose effectiveness may also play a role., Methods: To determine the contribution of these regulators on glucose tolerance after bariatric surgery, an oral glucose tolerance test (OGTT) was performed before and 2 months after surgery in 9 RYGB and 7 SG subjects. Eight healthy subjects served as metabolic controls. Plasma glucose, insulin, C-peptide, GLP-1, and GIP were measured during each OGTT. Insulin sensitivity and secretion, glucose effectiveness, and glucose rate of appearance were determined via oral minimal models., Results: RYGB and SG resulted in similar weight reductions (13%, RYGB ( p < 0.01); 14%, SG ( p < 0.05)). Two months after surgery, insulin secretion ( p < 0.05) and glucose effectiveness both improved equally in the two groups (11%, RYGB ( p < 0.01); 8%, SG ( p > 0.05)), whereas insulin sensitivity remained virtually unaltered. Bariatric surgery resulted in a comparable increase in the GLP-1 response during the OGTT, whereas GIP concentrations remained unaltered. Following surgery, oral glucose intake resulted in a comparable increase in hepatic insulin extraction, the response in both RYGB and SG patients significantly exceeding the response observed in the control subjects., Conclusions: These results demonstrate that the early improvement in glucose tolerance in obese T2D after RYGB and SG surgeries is attributable mainly to increased insulin secretion and glucose effectiveness, while insulin sensitivity seems to play only a minor role. This trial is registered with NCT02713555., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Roberto Visentin et al.)

Aims: The objectives were to describe differences in self-reported health at discharge between women diagnosed with angina or unspecific chest pain and investigate the association between self-reported health and adverse outcomes within 3 years., Methods and Results: Data from a national cohort study were used, including data from the DenHeart survey combined with 3 years of register-based follow-up. The population included two groups of women with symptoms of angina but no diagnosis of obstructive coronary artery disease at discharge (women with angina and women with unspecific chest pain). Self-reported health measured with validated instruments was combined with register-based follow-up on adverse outcomes (a composite of unplanned cardiac readmissions, revascularization, or all-cause mortality). Associations between self-reported health and time to first adverse outcomes were investigated with Cox proportional hazard models, reported as hazards ratios with 95% confidence intervals. In total, 1770 women completed the questionnaire (49%). Women with angina (n = 931) reported significantly worse self-reported health on several outcomes compared to women with unspecific chest pain (n = 839). Within the 3 years follow-up, women with angina were more often readmitted (29 vs. 23%, P = 0.011) and more underwent revascularization (10 vs. 1%, P < 0.001), whereas mortality rates were similar (4 vs. 4%, P = 0.750). Self-reported health (physical and mental) was associated with adverse outcomes between both groups (on most instruments)., Conclusion: Women with angina reported significantly worse self-reported health on most instruments compared to women with unspecific chest pain. Adverse outcomes varied between groups, with women diagnosed with angina experiencing more events., Registration: ClinicalTrials.gov (NCT01926145)., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A linear ion trap (LIT) is an affordable, robust mass spectrometer that provides fast scanning speed and high sensitivity, where its primary disadvantage is inferior mass accuracy compared to more commonly used time-of-flight or orbitrap (OT) mass analyzers. Previous efforts to utilize the LIT for low-input proteomics analysis still rely on either built-in OTs for collecting precursor data or OT-based library generation. Here, we demonstrate the potential versatility of the LIT for low-input proteomics as a stand-alone mass analyzer for all mass spectrometry (MS) measurements, including library generation. To test this approach, we first optimized LIT data acquisition methods and performed library-free searches with and without entrapment peptides to evaluate both the detection and quantification accuracy. We then generated matrix-matched calibration curves to estimate the lower limit of quantification using only 10 ng of starting material. While LIT-MS1 measurements provided poor quantitative accuracy, LIT-MS2 measurements were quantitatively accurate down to 0.5 ng on the column. Finally, we optimized a suitable strategy for spectral library generation from low-input material, which we used to analyze single-cell samples by LIT-DIA using LIT-based libraries generated from as few as 40 cells.

The article presents a follow-up study of a multi-component community-driven health promotion intervention in Denmark. The study examines the perceptions and actions of professional stakeholders 3 years after completion of a 19 months intervention period addressing healthy living, well-being and social engagement among families with young children living in three rural communities on the Danish island of Bornholm. The intervention was implemented within the framework of Project Health and Local Community, also referred to as Project SoL. Qualitative in-depth interviews were conducted with diverse professional stakeholders of the project. They represented local government, public institutions, private enterprises, civil society organizations and local mass media. The interviews addressed the extent to which the project had sustained its influence on professional stakeholders' perceptions and actions following project completion. Efforts were made to understand if persisting influences were value-based and/or manifested as concrete community-driven actions. The study showed that the project had succeeded in sustaining a positive long-term post-intervention influence among informants regarding the values and principles of the project. Despite their sustained motivation and preparedness to continue implementing coordinated community-driven actions this was severely hampered by lack of coordination after project completion. Instead, some of the stakeholders continued developing and implementing actions based on the values and principles of the project within the framework of their own professional networks. The article discusses the structural factors that are required to sustain complex community-driven interventions and the need to reconsider the nature of external support to community development from being project-based to integrated, strategic and long term., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Synovial fibroblasts (SFs) are key pathogenic drivers in rheumatoid arthritis (RA). Their in vivo activation by TNF is sufficient to orchestrate full arthritic pathogenesis in animal models, and TNF blockade proved efficacious for a high percentage of patients with RA albeit coinducing rare but serious side effects. Aiming to find new potent therapeutics, we applied the L1000CDS2 search engine, to repurpose drugs that could reverse the pathogenic expression signature of arthritogenic human TNF-transgenic (hTNFtg) SFs. We identified a neuroleptic drug, namely amisulpride, which reduced SFs' inflammatory potential while decreasing the clinical score of hTNFtg polyarthritis. Notably, we found that amisulpride function was neither through its known targets dopamine receptors D2 and D3 and serotonin receptor 7 nor through TNF-TNF receptor I binding inhibition. Through a click chemistry approach, potentially novel targets of amisulpride were identified, which were further validated to repress hTNFtg SFs' inflammatory potential ex vivo (Ascc3 and Sec62), while phosphoproteomics analysis revealed that treatment altered important fibroblast activation pathways, such as adhesion. Thus, amisulpride could prove beneficial to patients experiencing RA and the often-accompanying comorbid dysthymia, reducing SF pathogenicity along with its antidepressive activity, serving further as a "lead" compound for the development of novel therapeutics against fibroblast activation.

Background: Care home residents are frail, multi-morbid, and have an increased risk of experiencing acute hospitalisations and adverse events. This study contributes to the discussion on preventing acute admissions from care homes. We aim to describe the residents' health characteristics, survival after care home admission, contacts with the secondary health care system, patterns of admissions, and factors associated with acute hospital admissions., Method: Data on all care home residents aged 65 + years living in Southern Jutland in 2018-2019 (n = 2601) was enriched with data from highly valid Danish national health registries to obtain information on characteristics and hospitalisations. Characteristics of care home residents were assessed by sex and age group. Factors associated with acute admissions were analysed using Cox Regression., Results: Most care home residents were women (65.6%). Male residents were younger at the time of care home admission (mean 80.6 vs. 83.7 years), had a higher prevalence of morbidities, and shorter survival after care home admission. The 1-year survival was 60.8% and 72.3% for males and females, respectively. Median survival was 17.9 months and 25.9 months for males and females, respectively. The mean rate of acute hospitalisations was 0.56 per resident-year. One in four (24.4%) care home residents were discharged from the hospital within 24 h. The same proportion was readmitted within 30 days of discharge (24.6%). Admission-related mortality was 10.9% in-hospital and 13.0% 30 days post-discharge. Male sex was associated with acute hospital admissions, as was a medical history of various cardiovascular diseases, cancer, chronic obstructive pulmonary disease, and osteoporosis. In contrast, a medical history of dementia was associated with fewer acute admissions., Conclusion: This study highlights some of the major characteristics of care home residents and their acute hospitalisations and contributes to the ongoing discussion on improving or preventing acute admissions from care homes., Trial Registration: Not relevant., (© 2023. The Author(s).)

Background: Complete mesocolic excision (CME) surgery is increasingly implemented for the resection of right-sided colonic cancer, possibly resulting in improved 5-year overall and disease-free survival compared to non-CME surgery. However, it is not clear what surgical platform should be used. The aim of this study was to compare the following outcomes between robot-assisted and laparoscopic CME-surgery for right-sided colonic cancer: (i) short-term clinical outcomes, (ii) pathological specimen quality, and (iii) long-term oncological outcomes., Methods: Medline, Embase, and Cochrane Database of Systematic Reviews were searched from inception until August 2021. Pooled proportions were calculated by applying the inverse variance method. Heterogeneity was explored by I-square and supplemented by sensitivity- and meta-regression analyses. The risk of bias was evaluated by either MINORS or Cochrane's risk-of-bias tool (RoB 2)., Results: Fifty-five studies with 5.357 patients (740 robot-assisted and 4617 laparoscopic) were included in the meta-analysis. Overall postoperative morbidity was 17% [95% CI (14-20%)] in the robot-assisted group and 13% [95%CI (12-13%)] in the laparoscopic group. Robot-assisted CME was associated with a shorter hospital stay, lower intraoperative blood loss, a higher amount of harvested lymph nodes, and better 3-year oerall and disease-free survival. MINORS and RoB2 indicated a serious risk of bias across studies included., Conclusions: This review which includes predominantly non-randomized studies suggests a possible advantage of the robot-assisted CME compared with a laparoscopic technique for several short-term outcomes., (© 2022. Springer Nature Switzerland AG.)

Identification of the bacterial etiology of lower respiratory tract infections (LRTI) is crucial to ensure a narrow-spectrum, targeted antibiotic treatment. However, Gram stain and culture results are often difficult to interpret as they depend strongly on sputum sample quality. We aimed to investigate the diagnostic yield of Gram stain and culture from respiratory samples collected by tracheal suction and expiratory technique from adults admitted with suspected community-acquired LRTI (CA-LRTI). In this secondary analysis of a randomized controlled trial, 177 (62%) samples were collected by tracheal suction, and 108 (38%) by expiratory technique. We detected few pathogenic microorganisms, and regardless of sputum quality, there were no significant differences between the sample types. Common pathogens of CA-LRTI were identified by culture in 19 (7%) samples, with a significant difference between patients with or without prior antibiotic treatment ( p = 0.007). The clinical value of sputum Gram stain and culture in CA-LRTI is therefore questionable, especially in patients treated with antibiotics.

Microbiological diagnostics of good-quality sputum samples are fundamental for infection control and targeted treatment of lower respiratory tract infections (LRTI). This study aims to compare the expiratory technique and tracheal suction on the quality of sputa from adults acutely hospitalized with suspected LRTI. We performed an open-label, randomized controlled trial. Patients were randomized to sputum sampling by tracheal suction (standard care) or the expiratory technique. The primary outcome was quality of sputum evaluated by microscopy and was analysed in the intention-to-treat population. The secondary outcomes were adverse events and patients experience. In total, 280 patients were assigned to tracheal suction (n = 141, 50.4%) or the expiratory technique (n = 139, 49.6%). Sputum samples were collected from 122 (86.5%) patients with tracheal suction and 67 (48.2%) patients with expiratory technique. Good-quality sputa were obtained more often with tracheal suction than with expiratory technique (odds ratio 1.83 [95% CI 1.05 to 3.19]; p = 0.035). There was no statistical difference in adverse events (IRR 1.21 [95% CI, 0.94 to 1.66]; p = 0.136), but patient experience was better in the expiratory technique group (p < 0.0001). In conclusion, tracheal suction should be considered a routine procedure in emergency departments for patients with suspected LRTI.

Background: Biologic disease-modifying drugs have revolutionised the treatment of a number of chronic inflammatory diseases (CID). However, up to 60% of the patients do not have a sufficient response to treatment and there is a need for optimization of treatment strategies., Objective: To investigate if the treatment outcome of biological therapy is associated with the habitual dietary intake of fibre and red/processed meat in patients with a CID., Methods: In this multicentre prospective cohort study, we consecutively enrolled 233 adult patients with a diagnosis of Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis (RA), Axial Spondyloarthritis, Psoriatic Arthritis and Psoriasis, for whom biologic therapy was planned, over a 3 year period. Patients with completed baseline food frequency questionnaires were stratified into a high fibre/low red and processed meat exposed group (HFLM) and an unexposed group (low fibre/high red and processed meat intake = LFHM). The primary outcome was the proportion of patients with a clinical response to biologic therapy after 14-16 weeks of treatment., Results: Of the 193 patients included in our primary analysis, 114 (59%) had a clinical response to biologic therapy. In the HFLM group ( N = 64), 41 (64%) patients responded to treatment compared to 73 (56%) in the LFHM group ( N = 129), but the difference was not statistically significant (OR: 1.48, 0.72-3.05). For RA patients however, HFLM diet was associated with a more likely clinical response (82% vs. 35%; OR: 9.84, 1.35-71.56)., Conclusion: Habitual HFLM intake did not affect the clinical response to biological treatment across CIDs. HFLM diet in RA patients might be associated with better odds for responding to biological treatment, but this would need confirmation in a randomised trial., Trial Registration: (clinicaltrials.gov), identifier [NCT03173144]., Competing Interests: Author CH has received speaker fee from Takeda Pharma and Tillotts Pharma (unrelated to the present work). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Overgaard, Sørensen, Munk, Nexøe, Glerup, Henriksen, Guldmann, Pedersen, Saboori, Hvid, Dahlerup, Hvas, Jawhara, Andersen, Pedersen, Nielsen, Bergenheim, Brodersen, Heitmann, Halldorsson, Holmskov, Bygum, Christensen, Kjeldsen, Ellingsen and Andersen.)

Increasing numbers of patients are being referred to specialised palliative care (SPC) which, in order to be beneficial, is recommended to last more than three months. This cohort study aimed to describe time to end-of-life after initiating SPC treatment and to explore potential regional variations. We used national register data from all Danish hospital SPC teams. We included patients who started SPC treatment from 2015-2018 to explore if time to end-of-life was longer than three months. Descriptive statistics were used to summarise the data and a generalised linear model was used to assess variations among the five Danish regions. A total of 27,724 patients were included, of whom 36.7% (95% CI 36.2-37.1%) had over three months to end-of-life. In the Capital Region of Denmark, 40.1% (95% CI 39.0-41.3%) had over three months to end-of-life versus 32.5% (95% CI 30.9-34.0%) in North Denmark Region. We conclude that most patients live for a shorter period of time than the recommended three months after initiating SPC treatment. This is neither optimal for patient care, nor the healthcare system. A geographical variation between regions was shown indicating different practices, patient groups or resources. These results warrant further investigation to promote optimal SPC treatment.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease characterized by the accumulation of aggregated amyloid beta (Aβ) and hyperphosphorylated tau along with a slow decline in cognitive functions. Unlike advanced AD, the initial steps of AD pathophysiology have been poorly investigated, partially due to limited availability of animal models focused on the early, plaque-free stages of the disease. The aim of this study was to evaluate the early behavioral, anatomical and molecular alterations in wild-type rats following intracerebroventricular injections of human Aβ oligomers (AβOs). Bioactive human AD and nondemented control brain tissue extracts were characterized using ELISA and proteomics approaches. Following a bilateral infusion, rats underwent behavioral testing, including the elevated plus maze, social recognition test, Morris water maze and Y-maze within 6 weeks postinjection. An analysis of brain structure was performed with manganese-enhanced MRI. Collected brain tissues were analyzed using stereology, immunohistochemistry, ELISA and qPCR. No sensorimotor deficits affecting motor performance on different maze tasks were observed, nor was spatial memory disturbed in AD rats. In contrast, a significant impairment of social memory became evident at 21 days postinjection. This deficit was associated with a significantly decreased volume of the lateral entorhinal cortex and a tendency toward a decrease in the total brain volume. Significant increase of cleaved caspase-3-positive cells, microglial activation and proinflammatory responses accompanied by altered expression of synaptic markers were observed in the hippocampus of AD rats with immunohistochemical and qPCR approaches at 6 weeks postinjection. Our data suggest that the social memory impairment observed in AβO-injected rats might be determined by neuroinflammatory responses and synaptopathy. An infusion of native oligomeric Aβ in the rat brain represents a feasible tool to model early plaque-free events associated with AD., (© 2022. The Author(s).)

Purpose: After thyroid surgery, the overriding concern is the risk of post-thyroid bleeding (PTB). This systematic review and meta-analysis aimed to assess the safety of hemithyroidectomy in an outpatient setting compared to an inpatient setting. The objectives were to (1) find the proportion of PTB in patients scheduled for outpatient hemithyroidectomy, (2) examine if outpatient hemithyroidectomy is clinically safe compared to an inpatient setting and (3) evaluate which selection criteria are most relevant for hemithyroidectomy in an outpatient setting., Methods: A systematic review was conducted using the following databases: MEDLINE (Ovid), EMBASE (Ovid) and the Cochrane Library from inception until September 2021. We included studies reporting on PTB of patients after hemithyroidectomy in an outpatient setting. The risk of bias was assessed using the Newcastle-Ottawa tool. The results were synthesised using Bayesian meta-analysis. Certainty in evidence was assessed using the GRADE approach., Results: This review included 11 cohort studies and 9 descriptive studies reporting solely on outpatients resulting in a total of 46,866 patients. PTB was experienced by 58 of the 9025 outpatients (0.6%) and 415 of the 37,841 inpatients (1.1%). There was no difference between the PTB rate of outpatients and inpatients (RR 0.715 CrI [0.396-1.243]). The certainty of the evidence was very low due to the high risk of bias., Conclusion: The risk of PTB in an outpatient setting is very low, and outpatient hemithyroidectomy should be considered clinically safe. The most relevant selection criteria to consider in outpatient hemithyroidectomy are (1) relevant comorbidities and (2) psycho/-social factors., (© 2022. The Author(s).)

Objective: Although clinical guidelines exist, the diagnostic work-up for diagnosing inflammatory bowel disease (IBD) is complex and varies in clinical practice. This study used real-life data to characterise the current diagnostic procedures used to establish IBD diagnoses in a Danish nationwide setting., Design: Person-level data on patients diagnosed with IBD between 1 January 2014 and 30 June 2018 were linked between Danish health registers. Information on age, sex, registration of other gastrointestinal diseases, and diagnostic procedures (endoscopies, biopsies, and imaging) performed in relation to the first IBD hospital admission was analysed for the total study population and was stratified by IBD type, sex, and age., Results: The majority of the 12 871 patients with IBD included underwent endoscopy (84%), had a biopsy taken (84%), and/or underwent imaging procedures (44%). In total, 7.5% of the population (6% for Crohn's disease and 8% for ulcerative colitis) were diagnosed with IBD despite not undergoing any of these diagnostic procedures. Patients with Crohn's disease underwent more procedures than patients with ulcerative colitis (94% vs 92%, p<0.001). Children underwent slightly fewer diagnostic procedures than adults (92% vs 93%, p=0.004). Slightly more men underwent at least one procedure than women (92% vs 94%, p<0.001)., Conclusion: For 7.5% of patients with IBD, this study did not detect any registrations of the recommended diagnostic procedures for establishing an IBD diagnosis. Further research is needed to examine whether these findings are mainly explained by limitations of the register data or also indicate shortcomings of the general approach to IBD., Competing Interests: Competing interests: None declared., (© 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.)

Identifying acute myocardial infarction in patients with renal disease is notoriously difficult, due to atypical presentation and chronically elevated troponin. The aim of this study was to identify a specific troponin T/troponin I cut-off value for diagnosis of acute myocardial infarction in patients with renal impairment via meta-analysis. Two investigators screened 2590 publications from MEDLINE, Embase, PubMed, Web of Science, and the Cochrane library. Only studies that investigated alternative cut-offs according to renal impairment were included. Fifteen articles fulfilled the inclusion criteria. Six studies were combined for meta-analysis. The manufacturer's upper reference level for troponin T is 14 ng/L. Based on the meta-analyses, cut-off values for troponin in patients with renal impairment with myocardial infarction was 42 ng/L for troponin I and 48 ng/L for troponin T. For patients on dialysis the troponin T cut-off is even higher at 239 ng/L. A troponin I cut-off value for dialysis patients could not be established due to lack of data. The 15 studies analyzed showed considerable diversity in study design, study population, and the definition of myocardial infarction. Further studies are needed to define a reliable troponin cut-off value for patients with kidney disease, especially in dialysis patients, and to allow necessary subanalysis.

Background: Robot-assisted surgery is increasingly adopted in colorectal surgery. However, evidence for the implementation of robot-assisted surgery for colon cancer is sparse. This study aims to evaluate the short-term outcomes of robot-assisted colon surgery (RCS) for cancer compared to laparoscopic colon surgery (LCS)., Methods: Embase, MEDLINE, and Cochrane Library were searched between January 1, 2005 and October 2, 2020. Randomized clinical trials and observational studies were included. Non-original literature was excluded. Primary endpoints were anastomotic leakage rate, conversion to open surgery, operative time, and length of hospital stay. Secondary endpoints were surgical efficacy and postoperative morbidity. We evaluated risk of bias using RoB2 and ROBINS-I quality assessment tools. We performed a pooled analysis of primary and secondary endpoints. Heterogeneity was assessed by I 2 , and possible causes were explored by sensitivity- and meta-regression analyses. Publication bias was evaluated by Funnel plots and Eggers linear regression test. The level of evidence was assessed by GRADE., Results: Twenty studies enrolling 13,799 patients (RCS 1740 (12.6%) and LCS 12,059 (87.4%) were included in the meta-analysis that demonstrated RCS was superior regarding: anastomotic leakage (odds ratio (OR) = 0.54, 95% CI [0.32, 0.94]), conversion (OR = 0.31, 95% CI [0.23, 0.41]), overall complication rate (OR = 0.85, 95% CI [0.73, 1.00]) and time to regular diet (MD =  - 0.29, 95% CI [- 0.56, 0.02]). LCS proved to have a shortened operative time compared to RCS (MD = 42.99, 95% CI [28.37, 57.60]). Level of evidence was very low according to GRADE., Conclusion: RCS showed advantages in colonic cancer surgery regarding surgical efficacy and morbidity compared to LCS despite a predominant inclusion of non-RCT with serious risk of bias assessment and a very low level of evidence., (© 2021. The Author(s).)

Objective: Persons with multiple sclerosis (PwMS), already established as responders or non-responders to Fampridine treatment, were compared in terms of disability measures, physical and cognitive performance tests, neurophysiology, and magnetic resonance imaging (MRI) outcomes in a 1-year explorative longitudinal study. Materials and Methods: Data from a 1-year longitudinal study were analyzed. Examinations consisted of the timed 25-foot walk test (T25FW), six spot step test (SSST), nine-hole peg test (9-HPT), five times sit-to-stand test (5-STS), symbol digit modalities test (SDMT), transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) examining central motor conduction times (CMCT), peripheral motor conduction times (PMCT) and their amplitudes, electroneuronography (ENG) of the lower extremities, and brain structural MRI measures. Results: Forty-one responders and eight non-responders to Fampridine treatment were examined. There were no intergroup differences except for the PMCT, where non-responders had prolonged conduction times compared to responders to Fampridine. Six spot step test was associated with CMCT throughout the study. After 1 year, CMCT was further prolonged and cortical MEP amplitudes decreased in both groups, while PMCT and ENG did not change. Throughout the study, CMCT was associated with the expanded disability status scale (EDSS) and 12-item multiple sclerosis walking scale (MSWS-12), while SDMT was associated with number of T2-weighted lesions, lesion load, and lesion load normalized to brain volume. Conclusions: Peripheral motor conduction time is prolonged in non-responders to Fampridine when compared to responders. Transcranial magnetic stimulation-elicited MEPs and SDMT can be used as markers of disability progression and lesion activity visualized by MRI, respectively. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03401307., Competing Interests: UD has received research support, travel grants, and/or teaching honorary from Biogen Idec, Merck Serono, Novartis, Bayer Schering, and Sanofi Aventis as well as honoraria from serving on scientific advisory boards of Biogen Idec and Genzyme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mamoei, Jensen, Pedersen, Nygaard, Eskildsen, Dalgas and Stenager.)

Phytotoxins - toxins produced by plants - are contaminants with the potential to impair drinking water quality. They encompass a large group of toxic, partially persistent compounds that have been detected in seepage waters and in shallow wells used for drinking water production. If phytotoxins enter wells used for drinking water production, it is essential to know if the drinking water treatment processes will remove them from the water phase. However, it is currently unknown whether phytotoxins remain stable during traditional groundwater treatment using sand filters as the main treatment process. The objective of this study is to investigate removal potential of phytotoxins in biological sand filters and to asses if the removal potential is similar at different waterworks. Microcosms were set up with filter sand and drinking water collected at different groundwater-based waterworks. To be able to monitor phytotoxin removal ptaquiloside, caudatoside, gramine, sparteine, jacobine N-oxide, senecionine N-oxide and caffeine were applied at initial concentrations of 300 µg L -1 , which is approx. two orders of magnitude higher than currently detected in environment, but expected to cover extreme environmental conditions. Removal was monitored over a period of 14 days. Despite the high initial concentration, all filter sands removed ptaquiloside and caudatoside completely from the water phase and at waterworks where pellet softening was implemented (pH 8.4) prior to rapid sand filtration, complete removal occurred within the first 30 min. All filter sands removed gramine and sparteine, primarily by a biological process, while jacobine N-oxide, senecionine N-oxide and caffeine were recalcitrant in the filter sands. During degradation of ptaquiloside and caudatoside we observed formation and subsequent removal of degradation products pterosin B and A. Filter sands with the highest removal potential were characterised by high contents of deposited iron and manganese oxides and hence large specific surface areas. Difference between bacterial communities investigated by 16S rRNA gene analyses did not explain different removal in the filter sands. All five investigated filter sands showed similar degradation patterns regardless of water chemistry and waterworks of origin. In drinking water treatment systems biological sand filters might therefore remove phytotoxin contaminants such as ptaquiloside, caudatoside, gramine, sparteine, while for other compounds e.g. jacobine N-oxide, senecionine N-oxide further investigations involving more advanced treatment options are needed., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Robot-assisted surgery is being increasingly adopted in treating colorectal cancer, and the transition from laparoscopic surgery to robot-assisted surgery is a trend. The evidence of the benefits of robot-assisted surgery is sparse. However, findings are associated with improved patient-related outcomes and overall morbidity rates compared to laparoscopic surgery. This induction is unclear, considering both surgical modalities are characterized as minimally invasive. This study aims to evaluate the systemic and peritoneal inflammatory stress response induced by robot-assisted surgery compared with laparoscopic surgery for elective colon cancer resections in a prospective, randomized controlled clinical trial., Methods: This study is a single-centre randomized controlled superiority trial with 50 colon cancer participants. The primary endpoint is the level of systemic inflammatory response expressed as serum C-reactive protein (CRP) and interleukin 6 (IL-6) levels between postoperative days one and three. Secondary endpoints include (i) levels of systemic inflammation in serum expressed by a panel of inflammatory and pro-inflammatory cytokines measured during the first three postoperative days, (ii) postoperative surgical and medical complications (30 days) according to Clavien-Dindo classification and Comprehensive Complication Index, (iii) intraoperative blood loss, (iv) conversion rate to open surgery, (v) length of surgery, (vi) operative time, (vii) the number of harvested lymph nodes, and (viii) length of hospital stay. The exploratory endpoints are (i) levels of peritoneal inflammatory response in peritoneal fluid expressed by inflammatory and pro-inflammatory cytokines between postoperative day one and three, (ii) patient-reported health-related quality of recovery-15 (QoR-15), (iii) 30 days mortality rate, (iv) heart rate variability and (v) gene transcript (mRNA) analysis., Discussion: To our knowledge, this is the first clinical randomized controlled trial to clarify the inflammatory stress response induced by robot-assisted or laparoscopic surgery for colon cancer resections. Trial registration This trial is registered at Clinicaltrials.gov (Identifier: NCT04687384) on December, 29, 2020, Regional committee on health research ethics, Region of Southern Denmark (N75709) and Data Protection Agency, Hospital Sønderjylland, University Hospital of Southern Denmark (N20/46179)., (© 2021. The Author(s).)

Background: Targeted antimicrobial treatment is essential to avoid unnecessary use of broad-spectrum antibiotics and antimicrobial resistance. Targeted treatment relies on a precise microbiological diagnosis - in pneumonia, this poses a challenge as the usefulness of Gram stains and cultures is highly dependent on the quality of the sputum sample. This study aims to examine adverse effects and quality of sputum samples obtained by expiratory techniques (forced expiratory technique and sputum induction) compared with tracheal suction. The hypothesis is that expiratory techniques are non-inferior to tracheal suction in obtaining samples from the lower respiratory tract. This statistical analysis plan (SAP) describes the study design, method, and data analysis of the trial to increase transparency, avoid reporting bias or data-driven analysis and increase the study's reproducibility., Method: The design is a pragmatic, non-inferiority, parallel-arm randomized controlled trial including 280 patients admitted with suspected lower respiratory infection to two emergency departments. Patients are randomized to a usual care group, where sputum samples are collected by tracheal suction or to an intervention group where sputum samples are collected by forced expiratory technique and sputum induction. The statistical analysis will follow an intention-to-treat protocol. This SAP is developed and submitted before the end of recruitment, database closure, and statistical analyses., Discussion: The results of this study will provide valuable knowledge to clinical practice by comparing adverse effects and sputum sample quality associated with different sample methods., Trial Registration: Clinicaltrials.gov , NCT04595526 . Submitted on October 19, 2020., (© 2021. The Author(s).)

Background: Various tick-borne infections like borreliosis and rickettsiosis pose a health risk to humans in many parts of the world. We investigated seroprevalence of and seroconversion to Borrelia burgdorferi and Rickettsia spp. and relation to tick-bites, weather and clinical manifestations in Denmark., Methods: Blood donors were enrolled at the Hospital of Southern Jutland in June-July with follow-up November-February of 2018 and 2019. Blood samples were collected, and a questionnaire regarding tick bites, potential exposures and symptoms was completed at each visit. Samples were tested for presence of IgM and IgG antibodies directed against B. burgdorferi and Rickettsia spp. using R. helvetica and R. felis as antigens. Data were examined for correlation between tick bites, serological results, potential exposures and symptoms., Results: Two-hundred and fourteen (93 follow-ups) and 130 (38 follow-ups) blood donors were included in 2018 and 2019, respectively. The total borrelia seroconversion rate was 6.3% (CI 2.1-10.5), while the prevalence of IgM and IgG antibodies was 7.8% (CI 4.9-10.6) and 6.7% (CI 4-9.3), respectively. Seroconversion to Rickettsia spp. was detected in one participant. Tick bites and seroconversion were not significantly associated with the reported unspecific symptoms, but unspecific symptoms were common in the study population. There was no significant difference in number of tick bites or seroconversion/prevalence between seasons with highly alternating weather., Conclusions: Results suggest that weather conditions in an individual year have a limited impact. Anti-Borrelia-antibodies do not seem to persist in serum for several years. Rickettsiosis is of limited concern in Denmark.