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Objective To investigate the potential associations between functional capacity, muscle strength, body composition, and disease-related measures and quality of life in patients with myositis. Methods Baseline measures of functional capacity (functional index 3 (FI3), 2-minute walk test (2MWT), timed up and go (TUG) and 30-s sit-to-stand (30-STS)), muscle strength (incl. leg and handgrip strength), maximal leg extensor power, body composition (appendicular lean mass, fat percentage/mass) and disease-related measures (disease activity & damage core sets) were examined for their associations with quality of life (physical- and mental component summary scores, Short Form 36 questionnaire (SF-36)) by means of Spearman's correlation analysis. Results A total of 32 patients with myositis were included. Positive correlations between SF-36 physical component summary score (PCS) and FI3, 30-STS, TUG, 2MWT, leg extensor power, leg strength, bench press strength, and handgrip strength were observed. In contrast, fat percentage and fat mass correlated negatively with PCS. In disease-related measures, Extramuscular global assessment, health assessment questionnaire, physician global damage, and patient global damage scores were negatively associated with SF-36 PCS. No correlations to the mental component summary score of SF-36 were observed. Conclusion All measures of functional capacity were positively related to the SF-36 physical component summary score, indicating higher functional capacity positively affects quality of life in patients with myositis. Health assessment questionnaire and patient global damage scores demonstrated the strongest correlations with SF-36 physical component summary scores, further supporting these patient-reported outcomes as viable monitoring tools in patients with myositis., Objective: To investigate the potential associations between functional capacity, muscle strength, body composition, and disease-related measures and quality of life in patients with myositis. Methods: Baseline measures of functional capacity (functional index 3 (FI3), 2-minute walk test (2MWT), timed up and go (TUG) and 30-s sit-to-stand (30-STS)), muscle strength (incl. leg and handgrip strength), maximal leg extensor power, body composition (appendicular lean mass, fat percentage/mass) and disease-related measures (disease activity & damage core sets) were examined for their associations with quality of life (physical- and mental component summary scores, Short Form 36 questionnaire (SF-36)) by means of Spearman's correlation analysis. Results: A total of 32 patients with myositis were included. Positive correlations between SF-36 physical component summary score (PCS) and FI3, 30-STS, TUG, 2MWT, leg extensor power, leg strength, bench press strength, and handgrip strength were observed. In contrast, fat percentage and fat mass correlated negatively with PCS. In disease-related measures, Extramuscular global assessment, health assessment questionnaire, physician global damage, and patient global damage scores were negatively associated with SF-36 PCS. No correlations to the mental component summary score of SF-36 were observed. Conclusion: All measures of functional capacity were positively related to the SF-36 physical component summary score, indicating higher functional capacity positively affects quality of life in patients with myositis. Health assessment questionnaire and patient global damage scores demonstrated the strongest correlations with SF-36 physical component summary scores, further supporting these patient-reported outcomes as viable monitoring tools in patients with myositis.

Objective To investigate the effects of adding strength training to neuromuscular control exercises on thigh tissue composition and muscle properties in people with radiographic-symptomatic knee osteoarthritis (KOA). Methods In this exploratory secondary analysis of a randomized controlled trial, using a complete-case approach, participants performed 12 weeks of twice-weekly neuromuscular control exercise and patient education (NEMEX, n = 34) or NEMEX plus quadriceps strength training (NEMEX+ST, n = 29). Outcomes were MRI-measured inter- and intramuscular adipose tissue (InterMAT, IntraMAT), quadriceps muscle cross-sectional area (CSA), knee-extensor strength, specific strength (strength/lean CSA) and 30 s chair-stands. Between-group effects were compared using a mixed model analysis of variance. Results At 12 weeks, responses to NEMEX+ST overlapped with NEMEX for all outcomes. Both groups reduced InterMAT (NEMEX+ST=25 %, NEMEX=21 %); between-group difference: 0.8cm2 (95 % CI: -0.1, 1.7). NEMEX+ST decreased IntraMAT (2 %) and NEMEX increased IntraMAT (4 %); between-group difference 0.1 %-points (-0.3, 0.5). Both groups increased quadriceps CSA and lean CSA (CSA minus IntraMAT), improved knee-extensor strength and specific strength, and improved chair-stand performance with a trend towards greater effects in NEMEX+ST. Conclusion Adding strength training to 12 weeks of neuromuscular control exercises provided largely similar effects to neuromuscular control exercises alone in decreasing InterMAT and IntraMAT, in improving knee-extensor strength, CSA and in improving performance-based function in KOA persons, with a trend towards greater effects with additional strength training. Notably, both groups substantially reduced InterMAT and improved specific strength (an index of muscle quality). Our hypothesis-generating work warrants exploration of the roles played by InterMAT and IntraMAT in exercise effects in KOA., Objective: To investigate the effects of adding strength training to neuromuscular control exercises on thigh tissue composition and muscle properties in people with radiographic-symptomatic knee osteoarthritis (KOA). Methods: In this exploratory secondary analysis of a randomized controlled trial, using a complete-case approach, participants performed 12 weeks of twice-weekly neuromuscular control exercise and patient education (NEMEX, n = 34) or NEMEX plus quadriceps strength training (NEMEX+ST, n = 29). Outcomes were MRI-measured inter- and intramuscular adipose tissue (InterMAT, IntraMAT), quadriceps muscle cross-sectional area (CSA), knee-extensor strength, specific strength (strength/lean CSA) and 30 s chair-stands. Between-group effects were compared using a mixed model analysis of variance. Results: At 12 weeks, responses to NEMEX+ST overlapped with NEMEX for all outcomes. Both groups reduced InterMAT (NEMEX+ST=25 %, NEMEX=21 %); between-group difference: 0.8cm2 (95 % CI: -0.1, 1.7). NEMEX+ST decreased IntraMAT (2 %) and NEMEX increased IntraMAT (4 %); between-group difference 0.1 %-points (-0.3, 0.5). Both groups increased quadriceps CSA and lean CSA (CSA minus IntraMAT), improved knee-extensor strength and specific strength, and improved chair-stand performance with a trend towards greater effects in NEMEX+ST. Conclusion: Adding strength training to 12 weeks of neuromuscular control exercises provided largely similar effects to neuromuscular control exercises alone in decreasing InterMAT and IntraMAT, in improving knee-extensor strength, CSA and in improving performance-based function in KOA persons, with a trend towards greater effects with additional strength training. Notably, both groups substantially reduced InterMAT and improved specific strength (an index of muscle quality). Our hypothesis-generating work warrants exploration of the roles played by InterMAT and IntraMAT in exercise effects in KOA.

BACKGROUND: Knowledge of causes of sudden cardiac death (SCD) according to age is important in clinical decision-making and to lower the risk of SCD in family members of SCD victims.OBJECTIVE: To report overall and sex-stratified causes of SCD according to age in persons aged 1-49 years.METHODS: The study population consisted of all persons in Denmark aged 1-35 years in 2000-09 and 36-49 years in 2007-09, which equals 27.1 million person-years. Danish death certificates, discharge summaries, autopsy reports, and data from nationwide registries were used to identify all SCD cases. The SCD cases were divided into 5-year age groups.RESULTS: In the 10-year study period, there were 14,294 deaths, of which 1,362 (10%) were classified as SCD. Potentially inherited cardiac disease accounted for a large proportion (43-78%) of autopsied SCD in all age groups. A significant proportion (19-54%) of SCD was caused by sudden arrhythmic death syndrome in all age groups. Autopsy rates among both sudden unexpected death cases and SCD cases declined significantly with increasing age (74% in the youngest age group vs. 35% in the oldest).CONCLUSION: The proportion of SCD cases that were identified with a potentially inherited cardiac disease postmortem was high in all studied age groups, while autopsy rates among cases of sudden and unexpected death declined markedly with increasing age. Our findings indicate that diagnoses of inherited heart disease are likely missed in some SCD cases, along with the opportunity for treatment and prevention among surviving relatives.

Context No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AASs) usage on the myocellular properties of human skeletal muscle in previous AAS users. Objective We hypothesized that former AAS users would demonstrate smaller myonuclei domains (ie, higher myonuclei density) than matched controls. Methods A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size. Results Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101-206) and 140 (24-260) weeks in current and former AAS users, respectively (P = .482). Geometric mean (95% CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA to cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = .013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users: beta-coefficient (95% CI) −94 (−169; −18), P = .024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = .031) than controls. Conclusion Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA to cytoplasm ratio 4 years after AAS cessation suggestive of enhanced retraining capacity., CONTEXT: No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AASs) usage on the myocellular properties of human skeletal muscle in previous AAS users. OBJECTIVE: We hypothesized that former AAS users would demonstrate smaller myonuclei domains (ie, higher myonuclei density) than matched controls. METHODS: A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size. RESULTS: Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101-206) and 140 (24-260) weeks in current and former AAS users, respectively (P = .482). Geometric mean (95% CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA to cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = .013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users: beta-coefficient (95% CI) -94 (-169; -18), P = .024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = .031) than controls. CONCLUSION: Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA to cytoplasm ratio 4 years after AAS cessation suggestive of enhanced retraining capacity.

The present study examined skeletal muscle metabolism and changes in repeated sprint performance during match play for n = 20 competitive elite women outfield players. We obtained musculus vastus lateralis biopsies and blood samples before, after, and following intense periods in each half of a friendly match, along with 5 × 30-meter sprint tests and movement pattern analyses (10-Hz S5 Global Positioning System [GPS]). Muscle glycogen decreased by 39% and 42% after an intense period of the second half and after the match, respectively, compared to baseline (p < 0.05). Post-match, 80% type I fibers and 69% type II fibers were almost empty or completely empty of glycogen. Muscle lactate was higher (p < 0.05) after the intense period of the first half and post-match compared to baseline (14.3 ± 4.6 (±SEM) and 12.9 ± 5.7 vs. 6.4 ± 3.7 mmol/kg d.w.). Muscle phosphocreatine was reduced (p < 0.05) by 16% and 12%, respectively, after an intense period in the first and second half compared to baseline. Blood lactate and glucose increased during the match and peaked at 8.4 ± 2.0 and 7.9 ± 1.2 mmol/L, respectively. Mean 5 × 30 m sprint time declined by 3.2 ± 1.7 and 7.0 ± 2.1% after the first and second half, respectively, and 4.7 ± 1.6% (p < 0.05) after an intense period in the first half compared to baseline. In conclusion, match play in elite female football players resulted in marked glycogen depletion in both fiber types, which may explain fatigue at the end of a match. Repeated sprint ability was impaired after intense periods in the first half and after both halves, which may be associated with the observed muscle metabolite perturbations.

Previous evidence suggests that resistance training in combination with specific collagen peptides (CP) improves adaptive responses of the muscular apparatus. Although beneficial effects have been repeatedly demonstrated, the underlying mechanisms are not well understood. Therefore, the primary objective of the present randomized trial was to elucidate differences in gene expression pathways related to skeletal muscle signal transduction following acute high-load resistance exercise with and without CP intake. Recreationally active male participants were equally randomized to high-load leg extension exercise in combination with 15 g CP or placebo (PLA) supplementation. Muscle biopsies from the vastus lateralis muscle were obtained at baseline as well as 1, 4 and 24 h post exercise to investigate gene expression using next generation sequencing analysis. Several important anabolic pathways including PI3K-Akt and MAPK pathways were significantly upregulated at 1 and 4 h post-exercise. Significant between-group differences for both pathways were identified at the 4 h time point demonstrating a more pronounced effect after CP intake. Gene expression related to the mTOR pathway demonstrated a higher visual increase in the CP group compared to PLA by trend, but failed to achieve statistically significant group differences. The current findings revealed a significantly higher upregulation of key anabolic pathways (PI3K-Akt, MAPK) in human skeletal muscle 4 h following an acute resistance training combined with intake of 15 g of specific collagen peptides compared to placebo. Further investigations should examine potential relationships between upregulated gene expression and changes in myofibrillar protein synthesis as well as potential long-term effects on anabolic pathways on the protein level.

Sporadic inclusion body myositis (sIBM) is an idiopathic inflammatory muscle disease associated with skeletal muscle inflammation and a parallel progressive decline in muscle strength and physical function. Eventually, most sIBM patients require use of wheelchair after about 10 years of diagnosis and assistance to perform activities of daily living. This study presents data from a randomized controlled intervention trial (NCT02317094) that examined the effect of 12 weeks low-load blood-flow restricted (BFR) resistance training on maximal muscle strength, power, rate of force development (RFD), thigh lean mass (TLM), and voluntary muscle activation (VA) in sIBM patients. A time-by-group interaction in knee extensor strength was observed in the stronger leg (p ≤ 0.033) but not the weaker leg. Within-group changes were observed with BFR training (BFR) manifested by increased knee extensor strength in the strongest leg (+13.7%, p = 0.049), whereas non-exercising patients (CON) showed reduced knee extensor strength (−7.7%, p = 0.018). Maximal leg extensor power obtained for the stronger leg remained unchanged following BFR training (+9.5%, p = 0.37) while decreasing in CON (−11.1%, p = 0.05). No changes in TLM were observed. VA declined post-training (p = 0.037) in both BFR (−6.3% points) and CON (−7.5% points). The present data indicate that BFR resistance training can attenuate the rate of decline in mechanical muscle function typically experienced by sIBM patients. The preservation of muscle mass and mechanical muscle function with BFR resistance training may be considered of high clinical importance in sIBM patients to countermeasure the disease-related decline in physical function.

Objective: The primary results from the Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial have previously been reported. The objective of the current manuscript is to report long-term outcomes. Methods: The VAM-IHCA trial was a multicenter, randomized, double-blind, placebo-controlled trial conducted at ten hospitals in Denmark. Adult patients (age ≥ 18 years) were eligible for the trial if they had an in-hospital cardiac arrest and received at least one dose of epinephrine during resuscitation. The trial drugs consisted of 40 mg methylprednisolone (Solu-Medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of epinephrine. This manuscript report outcomes at 6 months and 1 year including survival, survival with favorable neurological outcome, and health-related quality of life. Results: 501 patients were included in the analysis. At 1 year, 15 patients (6.3%) in the intervention group and 22 patients (8.3%) in the placebo group were alive corresponding to a risk ratio of 0.76 (95% CI, 0.41–1.41). A favorable neurologic outcome at 1 year, based on the Cerebral Performance Category score, was observed in 14 patients (5.9%) in the intervention group and 20 patients (7.6%) in the placebo group (risk ratio, 0.78 [95% CI, 0.41–1.49]. No differences existed between groups for favorable neurological outcome and health-related quality of life at either 6 months or 1 year. Conclusions: Administration of vasopressin and methylprednisolone, compared with placebo, in patients with in-hospital cardiac arrest did not improve long-term outcomes in this trial.

Sporadic inclusion body myositis (sIBM) is characterised by skeletal muscle inflammation, progressive muscle loss and weakness, which is largely refractory to immunosuppressive treatment. Low-load blood-flow restricted (BFR) training has been shown to evoke gains in myofibre cross sectional area (mCSA) in healthy adults. This could partially be due to the activation and integration of muscle satellite cells (SC) resulting in myonuclei addition. Consequently, this study investigated the effect of 12-weeks lower limb low-load BFR resistance training in sIBM patients on SC and myonuclei content, myofibre size and capillarization. Muscle biopsies from sIBM patients randomised to 12-weeks of low-load BFR resistance training (n = 11) or non-exercising controls (CON) (n = 9) were analysed for SC and myonuclei content, myofibre size and capillarization using three-colour immunofluorescence microscopy and computerised quantification procedures. No between-group differences (time-by-group interactions) or within-groups changes were observed for resident SCs (Pax7(+)/Six1(+)), proliferating SCs (Pax7(+)/ Ki67(+)), myonuclei (Six1(+)), type 1 mCSA or capillary number (CD31(+)). However, a time-by-group interaction for type 2 mCSA was observed (p = 0.04). Satellite cell content, myonuclei number, mCSA and capillary density remained unaffected following 12-weeks low-load BFR resistance training, indicating limited myogenic capacity and satellite cell plasticity in long-term sIBM patients. (C) 2022 The Authors. Published by Elsevier B.V.

AIMS: The aim of this study was to compare short- and long-term risk of sudden cardiac death (SCD) among persons aged 18-49 years with and without chronic kidney disease (CKD).METHODS AND RESULTS: Using Danish nationwide health registries, all persons aged 18-49 years diagnosed with earlier stages of CKD or chronic kidney failure from 1 July 1995 through 2009 were identified. Non-exposed subjects matched on sex and birth-year were identified. All SCD in the Danish population aged 18-49 years in 2000-2009 have previously been identified using information from the Danish nationwide health registries, death certificates, and autopsy reports. In total, 9308 incident cases of earlier stage CKD and 1233 incident cases of chronic kidney failure were included. Among patients with earlier stage CKD, the absolute risk of SCD 1, 5, and 10 years after diagnosis was 0.14%, 0.37%, and 0.68%, respectively. Compared with age- and sex-matched subjects the corresponding relative risk (RR) was 20.3 [95% confidence interval (CI) 8.4-48.8], 7.1 (95% CI 4.2-12.0), and 6.1 (95% CI 3.8-9.7), respectively. Among patients with chronic kidney failure, the absolute 1-, 5-, and 10-year risk of SCD was 0.17%, 0.56%, and 2.07%, respectively. The corresponding RR was 12.5 (95% CI 1.4-111.6), 7.9 (95% CI 2.3-27.0), and 10.1 (95% CI 4.5-22.6).CONCLUSION: Persons with earlier stage CKD and chronic kidney failure had increased risk of SCD compared with the background population with a 6- to 20-fold increased risk of SCD. These findings underline the importance of early cardiovascular risk monitoring and assessment in persons with CKD.

In this master’s thesis, we conduct a technical analysis of the Arbitrage- Free Nelson-Siegel (AFNS) model. We display the theory, discuss the imple- mentation and fit two different constructed yield data sets. First, we replicate the original data set, used by J. H. Christensen et al. (2011) to check if the model has been implemented correctly. The estimation shows that our im- plementation using the programming language Python is accurate and results in a fairly robust replication of the original paper by J. H. Christensen et al. (2011). Thereafter, we fit the Danish yield curve in- and out-of-sample to test if it is feasible to use the affine arbitrage-free class of the Nelson-Siegel in practice. The results are mixed. In terms of fitting, the results are good. However, in terms of estimation, the optimal parameters are not only diffi- cult to estimate but also time-consuming. We suggest, to further calibrate the AFNS to enhance the estimation with the goal of ultimately be imple- mented in practice. Lastly, we have provided the programmed model in a public github repository free to download. To our knowledge, there exist no available libraries/packages in either Matlab, R or Python that can estimate this model, thus a contribution in itself.