Publications by authors named "Torben Hansen"

726 Publications

Malnutrition, poor function and comorbidities predict mortality up to one year after hip fracture: a cohort study of 2800 patients.

Eur Geriatr Med 2021 Dec 2. Epub 2021 Dec 2.

Department of Orthopaedics, Gødstrup Hospital, University Clinic of Hand, Hip and Knee Surgery, Herning, Denmark.

Purpose: Despite extensive research, a complete understanding of factors influencing mortality risk after hip fractures is lacking. Previous research has focused on static risk factors; however, to improve outcomes, attention should be directed towards risk factors that may be optimised. The present study aimed to investigate the association of 19 risk factors with mortality among patients with hip fracture treated according to a well-defined guideline.

Methods: The study was a retrospective analysis of a large prospective patient cohort with all consecutive patients surgically treated for a hip fracture from January 2011 to December 2017 included (n = 2800). Variables were obtained from patient records and the Holstebro Hip Fracture Database comprising prospectively registered data on demographics, comorbidity, malnutrition (low Body Mass Index (BMI) or albumin) and hospital stay (including fracture and surgical data, biochemistry, mobilisation and discharge). Outcomes were 30-day and one-year mortality.

Results: Patients were predominantly female (66%); median age 81.6 years. Overall mortality was 9% at 30 days and 24% at one year. Age ≥ 75 years, male gender, nursing home residence, cognitive impairment, American Society of Anesthesiologists (ASA) score ≥ 3, BMI < 20 kg/m, albumin < 35 g/l, creatinine ≥ 100 µmol/l, a low New Mobility Score and no mobilisation were all associated with increased mortality at 30 days and one year.

Conclusion: In addition to non-modifiable risk factors, comorbidities (expressed as high ASA score and creatinine), malnutrition, and failure to achieve early post-operative mobilisation were associated with increased short and long-term mortality among patients with hip fracture: these are potentially modifiable. The effect of optimisation interventions warrants further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s41999-021-00598-xDOI Listing
December 2021

Binge drinking induces an acute burst of markers of hepatic fibrogenesis (PRO-C3).

Liver Int 2021 Nov 30. Epub 2021 Nov 30.

Department of Gastroenterology and Hepatology, Odense University Hospital, Denmark.

Background And Aims: Binge drinking is associated with increased risk of liver-disease. Morbidity and mortality of alcohol-related liver disease (ALD) is associated with collagen deposition in the hepatic extracellular matrix (ECM). However, acute effects of binge drinking on ECM turnover are unknown. We aimed to investigate the effects on hepatic ECM turnover following a binge drinking episode.

Methods: We performed a pathophysiological intervention study with 15 non-alcoholic fatty liver disease (NAFLD) patients, 15 ALD patients and 10 healthy controls. We used 40% ethanol in 9 mg/mL NaCl administered through a nasogastric tube to simulate binge drinking. Hepatic vein catheterisation allowed simultaneous hepatic- and systemic vein sampling. Markers of ECM formation and degradation were measured with competitive ELISA.

Results: The interstitial matrix formation marker PRO-C3 increased by 1.2 ng/mL (10%, P<0.001) 24 hours after binge drinking. In participants with existing liver fibrosis determined by elevated baseline PRO-C3, hepatic levels increased by 0.09 ng/mL (95% CI: 0.03; 0.15, P=0.005) while systemic PRO-C3 decreased 0.11 ng/mL (95% CI: -0.15; -0.06, P<0.001) in 3-hours. PRO-C8 increased by 30% (+0.9 ng/mL, P=0.014) in liver-diseased patients with F0-F1 but not in any other group. 24-hour changes in systemic C3M and PRO-C3 were not associated (P=0.911).

Conclusions: Binge drinking induced an acute burst of PRO-C3 in healthy individuals and patients with liver-disease. Markers of ECM degradation were not correlated to markers of ECM formation, suggestive that even a single episode of binge drinking promotes excessive hepatic fibrogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15120DOI Listing
November 2021

Neonatal Anthropometrics and Obesity Treatment Response in Children and Adolescents.

J Pediatr 2021 Nov 10. Epub 2021 Nov 10.

The Children's Obesity Clinic, accredited European Centre for Obesity Management, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Objective: To investigate the relationship between in utero growth conditions, as indicated by neonatal anthropometrics, and childhood obesity treatment response in order to examine the potential usefulness of neonatal anthropometrics as a potential childhood obesity treatment stratification tool.

Study Design: The study included 2,474 children and adolescents with obesity (mean age 11.2 years, range 5.0-18.9) treated at The Children's Obesity Clinic, Holbæk, Denmark. Treatment response was registered prospectively, and neonatal data were collected from national electronic registers.

Results: Birth weight, birth length, birth-weight-for-gestational-age, and being born large-for-gestational-age were positively associated with the degree of obesity at treatment initiation. After a mean (standard deviation) of 1.27 (0.69) years of enrollment in obesity treatment, the children exhibited a mean reduction of -0.32 (0.50) BMI SDS. No significant associations between neonatal anthropometrics and childhood obesity treatment response were detected.

Conclusion: Neonatal anthropometrics were positively associated with the degree of obesity at treatment initiation, but not with response to multidisciplinary childhood obesity treatment. individualization of obesity treatment based on neonatal anthropometry does not seem warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2021.11.014DOI Listing
November 2021

DeepFake electrocardiograms using generative adversarial networks are the beginning of the end for privacy issues in medicine.

Sci Rep 2021 Nov 9;11(1):21896. Epub 2021 Nov 9.

University of Copenhagen, 2200, Copenhagen N, Denmark.

Recent global developments underscore the prominent role big data have in modern medical science. But privacy issues constitute a prevalent problem for collecting and sharing data between researchers. However, synthetic data generated to represent real data carrying similar information and distribution may alleviate the privacy issue. In this study, we present generative adversarial networks (GANs) capable of generating realistic synthetic DeepFake 10-s 12-lead electrocardiograms (ECGs). We have developed and compared two methods, named WaveGAN* and Pulse2Pulse. We trained the GANs with 7,233 real normal ECGs to produce 121,977 DeepFake normal ECGs. By verifying the ECGs using a commercial ECG interpretation program (MUSE 12SL, GE Healthcare), we demonstrate that the Pulse2Pulse GAN was superior to the WaveGAN* to produce realistic ECGs. ECG intervals and amplitudes were similar between the DeepFake and real ECGs. Although these synthetic ECGs mimic the dataset used for creation, the ECGs are not linked to any individuals and may thus be used freely. The synthetic dataset will be available as open access for researchers at OSF.io and the DeepFake generator available at the Python Package Index (PyPI) for generating synthetic ECGs. In conclusion, we were able to generate realistic synthetic ECGs using generative adversarial neural networks on normal ECGs from two population studies, thereby addressing the relevant privacy issues in medical datasets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-01295-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578227PMC
November 2021

Are women always better able to recognize faces? The unveiling role of exposure time.

PLoS One 2021 28;16(10):e0257741. Epub 2021 Oct 28.

Department of Marketing, Copenhagen Business School, Frederiksberg, Denmark.

A longer exposure time generally improves individuals' ability to recognize faces. The current research investigates whether this effect varies between genders and whether it is influenced by the gender of the exposed faces. Based on a set of four experimental studies, we advance our knowledge of face recognition, gender, gender distribution of exposed faces, and exposure time in three main ways. First, the results reveal that women are more likely than men to suffer from a decrease in face recognition ability due to a lower exposure time. Second, the findings show that when exposure time is short (vs. long) women recognize a larger proportion of same gender faces and also recognize a larger proportion of same gender faces as compared with the proportion of same gender faces recognized by men. Third, findings reveal that when individuals are only exposed to same gender faces, women recognize more faces than men regardless whether exposure time is short, or long. In short, the findings of this research suggest that insight into the interplay between gender and exposure time length is critical to appropriately determine human beings' ability to recognize faces.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257741PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553055PMC
November 2021

Population-based pediatric reference values for serum parathyroid hormone, vitamin D, calcium, and phosphate in Danish/North-European white children and adolescents.

Clin Chim Acta 2021 Oct 22;523:483-490. Epub 2021 Oct 22.

The Children's Obesity Clinic, Accredited European Centre for Obesity Management, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Genetics, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Introduction: Parathyroid hormone (PTH) and vitamin D are essential hormones in bone metabolism, especially during pediatric growth. Vitamin D insufficiency is often asymptomatic and is prevalent in high-latitude countries.

Methods: In a Danish population-based cohort of 2211 6-18-year-olds, sex- and age-specific pediatric reference values for fasting concentrations of intact serum PTH, vitamin D (25-hydroxycholecalciferol, 25-OH-D), total calcium, and phosphate were generated in accordance with Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. The effect of season on these biomarkers of bone metabolism was evaluated.

Results: In boys, PTH concentrations increased with age, while the vitamin D and phosphate concentrations decreased (all p < .001). In girls, a peak in PTH concentrations and a nadir in vitamin D concentrations were observed in the 10-14-year-olds (both p < .001). Calcium and phosphate decreased with age for both sexes (girls: both p < .001; boys calcium: p < .05, boys phosphate: p < .001). Vitamin D was 20% lower in winter than summer for both sexes (both p < .001). Individuals with vitamin D sufficiency (25-OH-D > 50 nmol/L) exhibited a 5% lower level of PTH compared to the whole sample population (p < .001).

Conclusion: The concentrations of PTH, vitamin D, calcium, and phosphate vary during childhood and adolescence, and is dependent on sex and season. These factors should be considered when screening for and treating imbalances in bone metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2021.10.024DOI Listing
October 2021

The Soluble Urokinase-Type Plasminogen Activator Receptor as a Biomarker for Survival and Early Treatment Effect in Metastatic Colorectal Cancer.

Cancers (Basel) 2021 Oct 12;13(20). Epub 2021 Oct 12.

Danish Colorectal Cancer Center South, Department of Oncology, University Hospital of Southern Denmark, 7100 Vejle, Denmark.

The soluble urokinase-type plasminogen activator receptor (suPAR) is prognostic for overall survival (OS) in colorectal cancer (CRC). Our study explored the association between baseline suPAR and OS and progression-free survival (PFS) in metastatic CRC (mCRC). It is also the first study to explore the association between the initial change in suPAR level and OS, PFS and the first CT response evaluation. The study included 132 patients with mCRC treated with chemotherapy (FOLFIRI) with or without an EGFR-inhibitor. Blood samples were drawn before the first treatment cycle and in between the first and second treatment cycle. suPAR levels were determined using an ELISA assay. Using the Kaplan-Meyer method, we demonstrated a significantly shorter OS for patients with suPAR levels above the median (HR = 1.79, 95%CI = 1.10-2.92, = 0.01). We also showed association between plasma suPAR level, gender and performance status (PS). However, we could not show any association with PFS, and analysis on the change in suPAR level provided no significant results. The results showing association between baseline suPAR and OS are in line with previous findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13205100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534079PMC
October 2021

A Previously Undescribed Highly Prevalent Phage Identified in a Danish Enteric Virome Catalog.

mSystems 2021 Oct 19;6(5):e0038221. Epub 2021 Oct 19.

KU Leuven, Department of Microbiology, Immunology, & Transplantation, Rega Institute, Division of Clinical & Epidemiological Virology, Laboratory of Viral Metagenomics, Leuven, Belgium.

Gut viruses are important, yet often neglected, players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies has been increasing; however, we are still only scratching the surface of the immense viral diversity. In this study, 254 virus-enriched fecal metagenomes from 204 Danish subjects were used to generate the anish nteric irme atalog (DEVoC) containing 12,986 nonredundant viral scaffolds, of which the majority was previously undescribed, encoding 190,029 viral genes. The DEVoC was used to compare 91 healthy DEVoC gut viromes from children, adolescents, and adults that were used to create the DEVoC. Gut viromes of healthy Danish subjects were dominated by phages. While most phage genomes (PGs) only occurred in a single subject, indicating large virome individuality, 39 PGs were present in more than 10 healthy subjects. Among these 39 PGs, the prevalences of three PGs were associated with age. To further study the prevalence of these 39 prevalent PGs, 1,880 gut virome data sets of 27 studies from across the world were screened, revealing several age-, geography-, and disease-related prevalence patterns. Two PGs also showed a remarkably high prevalence worldwide-a crAss-like phage (20.6% prevalence), belonging to the tentative subfamily, and a previously undescribed circular temperate phage infecting Bacteroides dorei (14.4% prevalence), called LoVEphage because it encodes ots f iral lements. Due to the LoVEphage's high prevalence and novelty, public data sets in which the LoVEphage was detected were assembled, resulting in an additional 18 circular LoVEphage-like genomes (67.9 to 72.4 kb). Through generation of the DEVoC, we added numerous previously uncharacterized viral genomes and genes to the ever-increasing worldwide pool of human gut viromes. The DEVoC, the largest human gut virome catalog generated from consistently processed fecal samples, facilitated the analysis of the 91 healthy Danish gut viromes. Characterizing the biggest cohort of healthy gut viromes from children, adolescents, and adults to date confirmed the previously established high interindividual variation in human gut viromes and demonstrated that the effect of age on the gut virome composition was limited to the prevalence of specific phage (groups). The identification of a previously undescribed prevalent phage illustrates the usefulness of developing virome catalogs, and we foresee that the DEVoC will benefit future analysis of the roles of gut viruses in human health and disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSystems.00382-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525569PMC
October 2021

Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations.

PLoS One 2021 18;16(10):e0258748. Epub 2021 Oct 18.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Body mass index (BMI) is a highly heritable polygenic trait. It is also affected by various environmental and behavioral risk factors. We used a BMI polygenic risk score (PRS) to study the interplay between the genetic and environmental factors defining BMI. First, we generated a BMI PRS that explained more variance than a BMI genetic risk score (GRS), which was using only genome-wide significant BMI-associated variants (R2 = 13.1% compared to 6.1%). Second, we analyzed interactions between BMI PRS and seven environmental factors. We found a significant interaction between physical activity and BMI PRS, even when the well-known effect of the FTO region was excluded from the PRS, using a small dataset of 6,179 samples. Third, we stratified the study population into two risk groups using BMI PRS. The top 22% of the studied populations were included in a high PRS risk group. Engagement in self-reported physical activity was associated with a 1.66 kg/m2 decrease in BMI in this group, compared to a 0.84 kg/m2 decrease in BMI in the rest of the population. Our results (i) confirm that genetic background strongly affects adult BMI in the general population, (ii) show a non-linear interaction between BMI genetics and physical activity, and (iii) provide a standardized framework for future gene-environment interaction analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258748PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523041PMC
November 2021

The Impact of Patient Characteristics and Tumor Biology on the Accuracy of Preoperative Staging of Colon Cancer in Denmark. A Nationwide Cohort Study.

Cancers (Basel) 2021 Aug 30;13(17). Epub 2021 Aug 30.

Department of Regional Health Research, University of Southern Denmark, DK-7100 Vejle, Denmark.

Background: Colon cancer is a common disease in western populations. The aim of this study was to assess the impact of mismatch repair (MMR) deficiency and other patient and tumor characteristics on the accuracy of preoperative staging by comparing histopathological T- and N-categories of the resected specimen with the preoperative clinical stage in a nationwide cohort of patients treated for colon cancer by elective bowel resection with curative intent.

Methods: A register study of a cohort extracted from the Danish Colorectal Cancer Group (DCCG) database, which holds prospective data on all new cases of colon and rectum cancer in Denmark. Patients diagnosed with colon cancer and treated with an elective bowel resection with curative intent in the years 2016-2019 were analyzed.

Results: A total of 6102 patients were included ( = 3161 (52%) men and = 2941 (48%) women) with a median age of 72 years (range 23-97 years). MMR was deficient in 24% of the patients and proficient in 76%. MMR deficiency, tumor sidedness and histopathological type were significant predictors of the accuracy of preoperative staging of colon cancer in univariate and multivariate analysis. MMR status in particular showed a strong impact on the risk of overstaging.

Conclusions: MMR deficiency, but also tumor sidedness and to some degree histopathological type, impacted the accuracy of preoperative staging of colon cancer. MMR status should be taken into consideration in everyday clinical staging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13174384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431529PMC
August 2021

Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.

Nat Genet 2021 09 6;53(9):1311-1321. Epub 2021 Sep 6.

Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-021-00923-xDOI Listing
September 2021

[Endoscopic treatment of hydrocephalus].

Ugeskr Laeger 2021 08;183(35)

Endoscopic treatment of hydrocephalus provides an opportunity to reach deeply located intraventricular obstacles and, as such, it is currently the primary treatment for obstructive hydrocephalus in Denmark. This review provides an overview of conditions treatable with endoscopic neurosurgery including the surgical principles, success rate and challenges with this neurosurgical procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2021

Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer.

Cancers (Basel) 2021 Aug 22;13(16). Epub 2021 Aug 22.

Institute of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark.

Diagnosing lung cancer requires invasive procedures with high risk of complications. Methylated tumor DNA in bronchial lavage has previously shown potential as a diagnostic biomarker. We aimed to develop and validate methylated in bronchial lavage as a diagnostic biomarker of lung cancer. Participants were referred on suspicion of lung cancer. Ten mL lavage fluid was collected at bronchoscopy for analysis of methylated based on droplet digital PCR according to our previously published method. status was compared with the final diagnosis. The Discovery and Validation cohorts consisted of 101 and 95 consecutively enrolled participants, respectively. In the discovery cohort, the sensitivity and specificity were 73.1% (95% CI 60.9-83.2%) and 85.3% (95% CI 68.9-95.0%), respectively. In the validation cohort, the values were 80.0% (95% CI 66.3-90.0%) and 75.6% (95% CI 60.5-87.1%), respectively. A multiple logistic regression model including age, smoking status, and methylated status resulted in an AUC of 84.9% (95% CI 77.3-92.4%) and 85.9% (95% CI 78.4-93.4%) for the Discovery and Validation cohorts, respectively. Methylated in bronchial lavage holds potential as a supplementary tool in the diagnosis of lung cancer with a clinically relevant sensitivity and specificity. It remained significant when adjusting for age and smoking status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13164223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393370PMC
August 2021

Comprehensive lipidomics reveals phenotypic differences in hepatic lipid turnover in ALD and NAFLD during alcohol intoxication.

JHEP Rep 2021 Oct 29;3(5):100325. Epub 2021 Jun 29.

Department of Gastroenterology and Hepatology, Odense University Hospital, Odense C, Denmark.

Background & Aims: In experimental models, alcohol induces acute changes in lipid metabolism that cause hepatocyte lipoapoptosis and inflammation. Here we study human hepatic lipid turnover during controlled alcohol intoxication.

Methods: We studied 39 participants with 3 distinct hepatic phenotypes: alcohol-related liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and healthy controls. Alcohol was administrated via nasogastric tube over 30 min. Hepatic and systemic venous blood was sampled simultaneously at 3 time points: baseline, 60, and 180 min after alcohol intervention. Liver biopsies were sampled 240 min after alcohol intervention. We used ultra-high performance liquid chromatography mass spectrometry to measure levels of more than 250 lipid species from the blood and liver samples.

Results: After alcohol intervention, the levels of blood free fatty acid (FFA) and lysophosphatidylcholine (LPC) decreased, while triglyceride (TG) increased. FFA was the only lipid class to decrease in NAFLD after alcohol intervention, whereas LPC and FFA decreased and TG increased after intervention in ALD and healthy controls. Fatty acid chain uptake preference in FFAs and LPCs were oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid. Hepatic venous blood FFA and LPC levels were lower when compared with systemic venous blood levels throughout the intervention. After alcohol intoxication, liver lipidome in ALD was similar to that in NAFLD.

Conclusions: Alcohol intoxication induces rapid changes in circulating lipids including hepatic turnaround from FFA and LPC, potentially leading to lipoapoptosis and steatohepatitis. TG clearance was suppressed in NAFLD, possibly explaining why alcohol and NAFLD are synergistic risk factors for disease progression. These effects may be central to the pathogenesis of ALD.

Clinical Trials Registration: The study is registered at Clinicaltrials.gov (NCT03018990).

Lay Summary: We report that alcohol induces hepatic extraction of free unsaturated fatty acids and lysophosphatidylcholines, hepatotoxic lipids which have not been previously associated with alcohol-induced liver injury. We also found that individuals with non-alcoholic fatty liver disease have reduced lipid turnover during alcohol intoxication when compared with people with alcohol-related fatty liver disease. This may explain why alcohol is particularly more harmful in people with non-alcoholic fatty liver and why elevated BMI and alcohol have a synergistic effect on the risk of liver-related death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhepr.2021.100325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350545PMC
October 2021

The Effect of Melatonin on Incretin Hormones: Results From Experimental and Randomized Clinical Studies.

J Clin Endocrinol Metab 2021 Nov;106(12):e5109-e5123

Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.

Context: Glucose homeostasis is under circadian control through both endocrine and intracellular mechanisms, with several lines of evidence suggesting that melatonin affects glucose homeostasis.

Objective: To evaluate the acute in vivo and in situ effects of melatonin on secretion of the incretin hormones, glucagon-like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), and their impact on β-cell insulin secretion.

Design: A human randomized, double-blinded, placebo-controlled crossover study combined with a confirmatory in situ study of perfused rat intestines.

Setting: Aarhus University Hospital.

Methods: Fifteen healthy male participants were examined 2 × 2 times: an oral glucose tolerance test (OGTT) was performed on day 1 and an isoglycemic IV glucose infusion replicating the blood glucose profile of the OGTT day was performed on day 2. These pairs of study days were repeated on treatment with melatonin and placebo, respectively. For the in situ study, 6 rat intestines and 4 rat pancreases were perfused arterially with perfusion buffer ± melatonin. The intestines were concomitantly perfused with glucose through the luminal compartment.

Results: In humans, melatonin treatment resulted in reduced GIP secretion compared with placebo (ANOVA P = 0.003), an effect also observed in the perfused rat intestines (ANOVA P = 0.003), in which GLP-1 secretion also was impaired by arterial melatonin infusion (ANOVA P < 0.001). Despite a decrease in GIP levels, the in vivo glucose-stimulated insulin secretion was unaffected by melatonin (P = 0.78).

Conclusion: Melatonin reduced GIP secretion during an oral glucose challenge in healthy young men but did not affect insulin secretion. Reduced GIP secretion was confirmed in an in situ model of the rat intestine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab521DOI Listing
November 2021

Abdominal and gluteofemoral fat depots show opposing associations with postprandial lipemia.

Am J Clin Nutr 2021 10;114(4):1467-1475

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: High postprandial lipemia is associated with increased risk of cardiovascular disease, independently of fasting lipid concentrations. Abdominal and gluteofemoral fat depots handle lipoproteins differently, which could affect postprandial lipemia and contribute to the relation between abdominal fat distribution and cardiovascular disease risk.

Objectives: We aimed to study the influences of higher abdominal compared with gluteofemoral fat on postprandial lipemia after a high-fat meal in individuals with obesity.

Methods: A total of 755 adults with obesity from a randomized controlled trial in 7 European countries consumed a liquid high-fat meal. Concentrations of triglycerides (TG), glycerol, free fatty acids, and the cholesterol component of remnant-like particles (RLP), LDL, and HDL were measured postprandially for 3 h. Associations of waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) with changes in postprandial lipid concentrations, adjusted for fasting concentrations and BMI, were examined using linear regression models. To assess whether the association of WHR with postprandial lipemia could be causal, we performed instrumental variable analyses using a genetic score of 442 variants known to be associated with WHR adjusted for BMI in 2-stage least-squares regression models.

Results: WHR was associated with higher TG and RLP cholesterol concentrations, independent of fasting lipid concentrations and BMI. Instrumental variable analyses suggested that the associations of WHR with postprandial TG (β = 0.038 μmol/L*min, SE = 0.019 μmol/L*min, P = 0.044) and RLP cholesterol concentrations (β = 0.059 mmol/L, SE = 0.025 mmol/L, P = 0.020) may be causal. WC and HC showed opposite effects: higher WC was associated with higher TG and RLP cholesterol concentrations whereas higher HC was associated with lower concentrations.

Conclusions: Our results suggest that higher fat deposition abdominally versus gluteofemorally may be causally associated with elevated postprandial lipemia after a high-fat meal, independent of fasting lipid concentrations and BMI. Furthermore, higher abdominal and gluteofemoral fat depots show opposing effects on postprandial lipemia.This trial was registered at www.isrctn.com as ISRCTN25867281.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqab219DOI Listing
October 2021

Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: An IMI DIRECT Study.

Diabetes 2021 09 7;70(9):2092-2106. Epub 2021 Jul 7.

Department of Epidemiology and Data Science, Amsterdam Medical Centre, location VUMC, Amsterdam, the Netherlands.

Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants ( = 2,111) underwent a 2-h 75-g oral glucose tolerance test (OGTT) at baseline and 48 months. HbA was also measured. We classified participants as having isolated prediabetes defect (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or HbA indicative of prediabetes [IA1c]), two defects (IFG+IGT, IFG+IA1c, or IGT+IA1c), or all defects (IFG+IGT+IA1c). β-Cell function (BCF) and insulin sensitivity were assessed from OGTT. At baseline, in pooling of participants with isolated defects, they showed impairment in both BCF and insulin sensitivity compared with healthy control subjects. Pooled groups with two or three defects showed progressive further deterioration. Among groups with isolated defect, those with IGT showed lower insulin sensitivity, insulin secretion at reference glucose (ISR), and insulin secretion potentiation ( < 0.002). Conversely, those with IA1c showed higher insulin sensitivity and ISR ( < 0.0001). Among groups with two defects, we similarly found differences in both BCF and insulin sensitivity. At 48 months, we found higher type 2 diabetes incidence for progressively increasing number of prediabetes defects (odds ratio >2, < 0.008). In conclusion, the prediabetes groups showed differences in type/degree of glucometabolic impairment. Compared with the pooled group with isolated defects, those with double or triple defect showed progressive differences in diabetes incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db21-0227DOI Listing
September 2021

Re-exposure to immunotherapy in metastatic colon cancer: A case report.

Clin Case Rep 2021 Jun 24;9(6):e04349. Epub 2021 Jun 24.

Danish Colorectal Cancer Center South Vejle Hospital University Hospital of Southern Denmark Vejle Denmark.

Re-exposure to immunotherapy in metastatic colorectal cancer may be indicated in selected patients that previously benefitted from immunotherapy with tolerable irAEs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccr3.4349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223690PMC
June 2021

Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species.

Sci Rep 2021 06 24;11(1):13252. Epub 2021 Jun 24.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.

Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (P = 4.1e-03, P = 1.9e-05, respectively), waist circumference (P = 0.017, P = 1.1e-04, respectively), body fat percentage (P = 2.5e-03, P = 2.3e-06, respectively), insulin resistance (P = 0.051, P = 4.6e-4, respectively), fasting concentrations of triglycerides (P = 0.06, P = 9.2e-4, respectively) and leptin (P = 0.067, P = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of Clostridia species (P = 0.037, P = 0.013, P = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of Clostridia species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91482-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225906PMC
June 2021

Insulin resistance genetic risk score and burden of coronary artery disease in patients referred for coronary angiography.

PLoS One 2021 18;16(6):e0252855. Epub 2021 Jun 18.

Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Aims: Insulin resistance associates with development of metabolic syndrome and risk of cardiovascular disease. The link between insulin resistance and cardiovascular disease is complex and multifactorial. Confirming the genetic link between insulin resistance, type 2 diabetes, and coronary artery disease, as well as the extent of coronary artery disease, is important and may provide better risk stratification for patients at risk. We investigated whether a genetic risk score of 53 single nucleotide polymorphisms known to be associated with insulin resistance phenotypes was associated with diabetes and burden of coronary artery disease.

Methods And Results: We genotyped patients with a coronary angiography performed in the capital region of Denmark from 2010-2014 and constructed a genetic risk score of the 53 single nucleotide polymorphisms. Logistic regression using quartiles of the genetic risk score was performed to determine associations with diabetes and coronary artery disease. Associations with the extent of coronary artery disease, defined as one-, two- or three-vessel coronary artery disease, was determined by multinomial logistic regression. We identified 4,963 patients, of which 17% had diabetes and 55% had significant coronary artery disease. Of the latter, 27%, 14% and 14% had one, two or three-vessel coronary artery disease, respectively. No significant increased risk of diabetes was identified comparing the highest genetic risk score quartile with the lowest. An increased risk of coronary artery disease was found for patients with the highest genetic risk score quartile in both unadjusted and adjusted analyses, OR 1.21 (95% CI: 1.03, 1.42, p = 0.02) and 1.25 (95% CI 1.06, 1.48, p<0.01), respectively. In the adjusted multinomial logistic regression, patients in the highest genetic risk score quartile were more likely to develop three-vessel coronary artery disease compared with patients in the lowest genetic risk score quartile, OR 1.41 (95% CI: 1.10, 1.82, p<0.01).

Conclusions: Among patients referred for coronary angiography, only a strong genetic predisposition to insulin resistance was associated with risk of coronary artery disease and with a greater disease burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252855PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213191PMC
November 2021

Performance of the EarlyCDT® Lung test in detection of lung cancer and pulmonary metastases in a high-risk cohort.

Lung Cancer 2021 08 10;158:85-90. Epub 2021 Jun 10.

Institute of Regional Health Research, University of Southern Denmark, J.B. Winsløws Vej 19, 3, 5000 Odense C, Denmark; Department of Internal Medicine, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark. Electronic address:

Objectives: Early detection of lung cancer is pivotal for an optimal prognosis. CT screening is currently implemented in USA. To decrease the amount of CT scans, the application of a blood-based biomarker as part of screening criteria is desirable.

Materials And Methods: The EarlyCDT® Lung test was performed in a high-risk cohort composed 246 patients referred from their GP on suspicion of lung cancer. Blood samples were taken at first visit and patients underwent diagnostic workup on suspicion of lung cancer resulting in either a malignant diagnosis or ruled out cancer. Sensitivity and specificity of the EarlyCDT® Lung were calculated in the cohort and subgroups based on age, smoking history, sex and lung cancer stage.

Results: Overall sensitivity in the cohort was 33 % for lung cancer and 31 % for primary lung cancer and lung metastases combined. Sensitivity in age groups was 11 % (60 years or below), 31 % (61-75 years) and 55 % (>75 years). In patients with at least 10 tobacco pack years, sensitivity was 33 % while the sensitivity in patients with at least 50 tobacco pack years was 44 %. The assay sensitivity in stage I-II lung cancer patients was 21 %, while this was 40 % in stage III-IV lung cancer patients. In a subgroup of patients that met current CT screening criteria (age 55-80 years and minimum 30 tobacco pack years) the sensitivity was 37 %.

Conclusion: The rationale of screening for lung cancer is to find patients in an early and resectable stage. However, the EarlyCDT® Lung test performed best in elderly, late stage lung cancer patients with a heavy smoking history. Based on these results, the current study finds insufficient sensitivity of the EarlyCDT® Lung test to be used as part of inclusion criteria in a low-dose CT program for detection of lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2021.06.010DOI Listing
August 2021

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.

Nat Commun 2021 06 9;12(1):3505. Epub 2021 Jun 9.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23556-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190084PMC
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Do genetic risk scores for childhood adiposity operate independent of BMI of their mothers?

Int J Obes (Lond) 2021 09 28;45(9):2006-2015. Epub 2021 May 28.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Objectives: Genetic predisposition and maternal body mass index (BMI) are risk factors for childhood adiposity, defined by either BMI or overweight. We aimed to investigate whether childhood-specific genetic risk scores (GRSs) for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, or whether the associations are modified by maternal BMI.

Methods: We constructed a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS in overall 1674 genotyped children within the Danish National Birth Cohort. We applied a case-cohort (N = 1261) and exposure-based cohort (N = 912) sampling design. Using logistic regression models we estimated associations of the GRSs and child overweight at age 7 years and examined if the GRSs influence child adiposity independent of maternal BMI (per standard deviation units).

Results: In the case-cohort design analysis, maternal BMI and the child GRSs were associated with increased odds for childhood overweight [OR for maternal BMI: 2.01 (95% CI: 1.86; 2.17), OR for child BMI-GRS: 1.56 (95% CI: 1.47; 1.66), and OR for child obesity-GRS 1.46 (95% CI: 1.37; 1.54)]. Adjustment for maternal BMI did not change the results, and there were no significant interactions between the GRSs and maternal BMI. However, in the exposure-based cohort design analysis, significant interactions between the child GRSs and maternal BMI on child overweight were observed, suggesting 0.85-0.87-fold attenuation on ORs of child overweight at higher values of maternal BMI and child GRS.

Conclusion: GRSs for childhood adiposity are strongly associated with childhood adiposity even when adjusted for maternal BMI, suggesting that the child-specific GRSs and maternal BMI contribute to childhood overweight independent of each other. However, high maternal BMI may attenuate the effects of child GRSs in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41366-021-00869-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380541PMC
September 2021

Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis.

Cell 2021 Jun 27;184(13):3502-3518.e33. Epub 2021 May 27.

Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.

Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of β-adrenergic G protein-coupled receptors (GPCRs). Here, we uncover an alternate paradigm of GPCR-mediated adipose thermogenesis through the constitutively active receptor, GPR3. We show that the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gs-coupling and cAMP production without an exogenous ligand. Thus, transcriptional induction of Gpr3 represents the regulatory parallel to ligand-binding of conventional GPCRs. Consequently, increasing Gpr3 expression in thermogenic adipocytes is alone sufficient to drive energy expenditure and counteract metabolic disease in mice. Gpr3 transcription is cold-stimulated by a lipolytic signal, and dietary fat potentiates GPR3-dependent thermogenesis to amplify the response to caloric excess. Moreover, we find GPR3 to be an essential, adrenergic-independent regulator of human brown adipocytes. Taken together, our findings reveal a noncanonical mechanism of GPCR control and thermogenic activation through the lipolysis-induced expression of constitutively active GPR3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2021.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238500PMC
June 2021

Genetic markers of abdominal obesity and weight loss after gastric bypass surgery.

PLoS One 2021 28;16(5):e0252525. Epub 2021 May 28.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Weight loss after bariatric surgery varies widely between individuals, partly due to genetic differences. In addition, genetic determinants of abdominal obesity have been shown to attenuate weight loss after dietary intervention with special attention paid to the rs1358980-T risk allele in the VEGFA locus. Here we aimed to test if updated genetic risk scores (GRSs) for adiposity measures and the rs1358980-T risk allele are linked with weight loss following gastric bypass surgery.

Methods: Five hundred seventy six patients with morbid obesity underwent Roux-en-Y gastric bypass. A GRS for BMI and a GRS for waist-hip-ratio adjusted for BMI (proxy for abdominal obesity), respectively, were constructed. All patients were genotyped for the rs1358980-T risk allele. Associations between the genetic determinants and weight loss after bariatric surgery were evaluated.

Results: The GRS for BMI was not associated with weight loss (β = -2.0 kg/100 risk alleles, 95% CI -7.5 to 3.3, p = 0.45). Even though the GRS for abdominal obesity was associated with an attenuated weight loss response adjusted for age, sex and center (β = -14.6 kg/100 risk alleles, 95% CI -25.4 to -3.8, p = 0.008), it was not significantly associated with weight loss after adjustment for baseline BMI (β = -7.9 kg/100 risk alleles, 95% CI -17.5 to 1.6, p = 0.11). Similarly, the rs1358980-T risk allele was not significantly associated with weight loss (β = -0.8 kg/risk allele, 95% CI -2.2 to 0.6, p = 0.25).

Discussion: GRSs for adiposity derived from large meta-analyses and the rs1358980-T risk allele in the VEGFA locus did not predict weight loss after gastric bypass surgery. The association between a GRS for abdominal obesity and the response to bariatric surgery may be dependent on the association between the GRS and baseline BMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252525PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162622PMC
October 2021

Explaining deep neural networks for knowledge discovery in electrocardiogram analysis.

Sci Rep 2021 05 26;11(1):10949. Epub 2021 May 26.

University of Copenhagen, 2200, Copenhagen N, Denmark.

Deep learning-based tools may annotate and interpret medical data more quickly, consistently, and accurately than medical doctors. However, as medical doctors are ultimately responsible for clinical decision-making, any deep learning-based prediction should be accompanied by an explanation that a human can understand. We present an approach called electrocardiogram gradient class activation map (ECGradCAM), which is used to generate attention maps and explain the reasoning behind deep learning-based decision-making in ECG analysis. Attention maps may be used in the clinic to aid diagnosis, discover new medical knowledge, and identify novel features and characteristics of medical tests. In this paper, we showcase how ECGradCAM attention maps can unmask how a novel deep learning model measures both amplitudes and intervals in 12-lead electrocardiograms, and we show an example of how attention maps may be used to develop novel ECG features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-90285-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154909PMC
May 2021

Measurement properties of the Danish version of the Boston Carpal Tunnel Questionnaire.

JPRAS Open 2021 Sep 3;29:17-25. Epub 2021 Apr 3.

University Clinic for Hand, Hip and Knee Surgery, Department of Orthopaedics, Holstebro Regional Hospital, 7500 Holstebro, Denmark.

Background And Aims: Patient reported outcome measures are often used in medical research to evaluate symptoms and functional status in patients. The Boston Carpal Tunnel Questionnaire is specifically designed to evaluate functional status and symptom severity in patients with Carpal Tunnel Syndrome. The aim of this study was to validate and examine the measurement properties of the Functional Status Scale and Symptom Severity Scale from the Danish translated Boston Carpal Tunnel Questionnaire.

Material And Methods: We analyzed 88 prospectively enrolled patients in the validity and responsiveness group and 31 prospectively enrolled patients in the reliability group. Patients in the validity and responsiveness group answered the Quick Disabilities of the Arm, Shoulder and Hand Questionnaire and the Danish translated Boston Carpal Tunnel Questionnaire preoperatively and after surgery. Patients in the responsiveness group answered the same questionnaire two times prior to surgery.

Results: Responsiveness of the two subscales were high (Effect Size 0.99/1.76; Standardized Response Mean 0.86/1.50). Correlation to the Danish validated QuickDASH was high (rho 0.75/0.89). Test-retest reliability was high (ICC 0.94/0.90) and the internal consistency was high (Cronbach's alpha 0.93/0.92).

Conclusion: Our study shows satisfactory results of both subscales of the Danish translated Boston Carpal Tunnel Questionnaire. This makes it highly useful when conducting research on patients with Carpal Tunnel Syndrome.

Trial Registration: The Danish Data Protection Agency: jr. nr. 2007-58-0010.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpra.2021.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099587PMC
September 2021

Poor adherence to guidelines in treatment of fragile and cognitively impaired patients with hip fracture: a descriptive study of 2,804 patients.

Acta Orthop 2021 Oct 12;92(5):544-550. Epub 2021 May 12.

University Clinic of Hand, Hip and Knee Surgery, Department of Orthopaedics, Regional Hospital West Jutland.

Background and purpose - Following a hip fracture, most patients will encounter poorer functional outcomes and an increased risk of death. Treatment-monitoring of hip fracture patients is in many countries done by national audits. However, they do not allow for a deeper understanding of treatment limitations. We performed a local evaluation study to investigate adherence to 7 best-practice indicators, and to investigate patient groups at risk of suboptimal treatment.Patients and methods - 2,804 patients were surgically treated for a hip fracture from 2011 to 2017 at our institution. Data regarding admission, hospital stay, and discharge was prospectively collected, and adherence to the 7 best practice indicators (nerve block, surgical delay, antibiotics, implant choice, thromboprophylaxis, mobilization, and blood transfusions) was analyzed. Patient groups with lower adherence were identified.Results - 34% of patients received all 7 best practice indicators after considering contraindications; in particular, nerve blocks and thromboprophylaxis displayed low adherence at 61% and 91% respectively. Nursing home residents and patients with cognitive impairment, multiple comorbidities, or low functional levels were at risk of having a lower adherence.Interpretation - The most dependent patients with cognitive impairment, comorbidities, or low functional levels had lower guideline adherence. This large patient subgroup needs a higher treatment focus and more resources. Our findings are likely similar to those in other national and international institutions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17453674.2021.1925430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519558PMC
October 2021

Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health.

Gut 2021 Nov 11;70(11):2105-2114. Epub 2021 May 11.

Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK

Objective: Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health.

Design: In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes.

Results: In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the 2 enterotype compared with Ruminococcaceae or enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion.

Conclusion: Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2020-323314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515120PMC
November 2021
-->