Lower basal and postprandial muscle protein synthesis after 2 weeks single-leg immobilization in older men: No protective effect of anti-inflammatory medication.

Muscle inactivity may reduce basal and postprandial muscle protein synthesis (MPS) rates in humans. Anti-inflammatory treatment alleviates the MPS impairments in younger individuals. The present study explored the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) upon MPS during a period of inactivity in older humans. Eighteen men (age 60-80 years) were allocated to ibuprofen (1200 mg/day, Ibu) or control (Plc) groups. One lower limb was cast immobilized for 2 weeks. Postabsorptive and postprandial MPS was measured before and after the immobilization by L-[ring-13 C6 ]-phenylalanine infusion. The protein expression of select anabolic signaling molecules was investigated by western blot. Basal (0.038 ± 0.002%/h and 0.039 ± 0.005%/h, Plc and Ibu, respectively) and postprandial (0.064 ± 0.004%/h and 0.067 ± 0.010%/h, Plc and Ibu, respectively) MPS rate were higher pre-immobilization compared to basal (0.019 ± 0.005%/h and 0.020 ± 0.010%/h, Plc and Ibu, respectively) and postprandial (0.033 ± 0.005%/h and 0.037 ± 0.006%/h, Plc and Ibu, respectively) MPS rate post-immobilization (p < 0.001). NSAID treatment did not affect the suppression of MPS (p > 0.05). The anabolic signaling were in general reduced after immobilization (p < 0.05). These changes were unaffected by NSAID treatment (p > 0.05). Basal and postprandial MPS dropped markedly after 2 weeks of lower limb immobilization. NSAID treatment neither influenced the reduction in MPS nor the anabolic signaling after immobilization in healthy older individuals.

Acute loading has minor influence on human articular cartilage gene expression and glycosaminoglycan composition in late-stage knee osteoarthritis: a randomised controlled trial.

OBJECTIVE: Osteoarthritis (OA) remains clinically challenging. Regular physical exercise improves symptoms though it is unclear whether exercise influences cartilage at the molecular level. Thus, we aimed to determine the effect of acute loading on gene expression and glycosaminoglycan (GAG) content in human OA cartilage. DESIGN: Patients with primary knee OA participated in this single-blind randomised controlled trial initiated 3.5 h prior to scheduled joint replacement surgery with or without loading by performing one bout of resistance exercise (one-legged leg press). Cartilage from the medial tibia condyle was sampled centrally, under the meniscus, and from peripheral osteophytes. Samples were analysed for gene expression by real-time reverse transcriptase polymerase chain reaction, and hyaluronidase-extracted matrix was analysed for GAG composition by immuno- and dimethyl-methylene blue assays. RESULTS: Of 32 patients randomised, 31 completed the intervention: mean age 69 ± 7.5 years (SD), 58% female, BMI 29.4 ± 4.4 kg/m2. Exercise increased chondroitin sulphate extractability [95% CI: 1.01 to 2.46; P = 0.0486] but cartilage relevant gene expression was unchanged. Regionally, the submeniscal area showed higher MMP-3, MMP-13, IGF-1Ea, and CTGF, together with lower lubricin and COMP expression compared to the central condylar region. Further, osteophyte expression of MMP-1, MMP-13, IGF-1Ea, and TGF-ß3 was higher than articular cartilage and lower for aggrecan, COMP, and FGF-2. Hyaluronidase-extracted matrix from central condylar cartilage contained more GAGs but less chondroitin sulphate compared to submeniscal cartilage. CONCLUSION: Acute exercise had minor influence on cartilage GAG dynamics, indicating that osteoarthritic cartilage is not significantly affected by acute exercise. However, the regional differences suggest a chronic mechanical influence on human cartilage. GOV REGISTRATION NUMBER: NCT03410745.

The regional turnover of cartilage collagen matrix in late-stage human knee osteoarthritis.

OBJECTIVE: Cartilage collagen has very limited repair potential, though some turnover and incorporation has not been fully excluded. We aim to determine the regional turnover of human osteoarthritis cartilage. DESIGN: Patients scheduled for knee joint replacement surgery due to osteoarthritis were recruited in this prospective study of four weeks duration. Deuterium oxide (D2O) was administered orally by weekly boluses at 70% D2O, initially 150 ml followed by three boluses of 50 ml. Cartilage from the medial tibia plateau was sampled centrally, under the meniscus, and from osteophytes and treated enzymatically with hyaluronidase and trypsin. Samples were analysed for deuterium incorporation in alanine using mass spectrometry and for gene expression by real-time reverse transcriptase polymerase chain reaction. RESULTS: Twenty participants completed the study: mean (SD) age 64 ± 9.1 years, 45% female, BMI 29.5 ± 4.8 kg/m2. Enzymatically treated cartilage from central and submeniscal regions showed similar enrichments at 0.063% APE, while osteophytes showed significantly greater enrichment at 0.072% APE (95% confidence interval of difference) [0.004-0.015]). Fractional synthesis rates were similar for central 0.027%/day and submeniscal cartilage 0.022%/day but 10-fold higher in osteophytes 0.22%/day [0.098-0.363]. When compared to central cartilage, submeniscal cartilage had increased gene expression of MMP-3 and decreased lubricin expression. Untreated cartilage had higher turnover (enrichments at 0.073% APE) than enzymatically treated cartilage (0.063% APE). CONCLUSIONS: In OA, despite regional differences in gene expression, the turnover of the articular cartilage matrix across the entire joint surface is very limited, but higher turnover was observed in osteophyte cartilage.

Effects of genipin crosslinking on mechanical cell-matrix interaction in 3D engineered tendon constructs.

It is well known that cells can generate endogenous forces onto the extracellular matrix, but to what extent the mechanical properties of the matrix influences these endogenous cellular forces remains unclear. We therefore sought to quantify the influence of matrix rigidity on cell-matrix interactions by inducing cross-links using increasing concentrations of genipin (0.01-1 mM) or by blocking cross-link formation using beta-aminopropionitrile (BAPN) in engineered human tendon tissue constructs. The cell-matrix mechanics of the tendon constructs were evaluated as cell-generated tissue re-tensioning and stress-relaxation responses using a novel custom-made force monitor, which can apply and detect tensional forces in real-time in addition to mechanical failure testing. Genipin treatment had no influence on the biochemical profile (hydroxyproline, glycosaminoglycan and DNA content) of the constructs and cell viability was comparable between genipin-treated and control constructs, except at the highest genipin concentration. Endogenous re-tension after unloading was significantly decreased with increasing genipin concentrations compared to controls. Mechanical failure testing of tendon constructs showed increased (56%) peak stress at the highest genipin concentration but decreased (72%) with BAPN treatment when compared to controls. Tendon construct stiffness increased with high genipin concentrations (0.1 and 1 mM) and decreased by 70% in BAPN-treated constructs, relative to the controls. These data demonstrate that human tendon fibroblasts regulate their force exertion inversely proportional to increased cross-link capacity but did so independently of matrix stiffness. Overall, these findings support the notion of an interaction between cell force generation and cross-linking, and thus a role for this interplay in mechanical homeostasis of the tissue.

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Protective loop-ileostomy in ileal pouch-anal anastomosis for ulcerative colitis - advantages and disadvantages. A retrospective study.

AIM: The aim was to investigate the overall postoperative complication rate within 90 days following ileal pouch-anal anastomosis (IPAA), with or without a diverting stoma, together with complications 30 days after stoma closure and overall pouch failure rate. METHOD: This was a retrospective chart review including IPAA patients with or without a diverting loop-ileostomy for ulcerative colitis (1 January 1983 to 31 December 2015). Demographic data and postoperative complications were retrieved and recorded. RESULTS: A total of 434 patients were included. A diverting loop-ileostomy was performed in 348 patients (80%). Baseline data were similar in the two groups except for body mass index (BMI) and the ratio of women, which were significantly higher in the group without a protective ileostomy. Overall 90-day complication rate after IPAA [Clavien-Dindo (CD) > 2] was similar in the two groups. Clinical anastomotic leaks (CD > 2) were higher in patients without a diverting stoma (9.3% vs 1.7%) (P = 0.002). The odds ratio for leakage after adjustments (age, gender, immune-modulating medicine and BMI) was 5.0 for omitting a diverting stoma (P = 0.004). Complications (CD > 2) after loop-ileostomy closure were seen in 61 cases (14.1%). Omitting a diverting stoma at IPAA demonstrated a non-significant odds ratio of 1.04 (0.46, 2.38) (P = 0.924) for pouch failure after adjustments (age, gender, immune-modulating medicine, BMI, time from pouch formation and clinical leakage). CONCLUSION: The overall postoperative surgical and medical complication rate within 90 days after IPAA was similar in the group with and without diverting stoma. Postoperative complication rate after reversal was 14%. Omitting a diverting stoma at IPAA demonstrated an increased risk of leaks but no significant risk of long-term pouch failure.

Hoof conformation in Icelandic competition horses and its interrelationship with hoof pathologies and tölt performance.

In order to improve the four-beat-rhythm and forelimb action of the tölt in Icelandic horses (ICE), special shoeing techniques are applied particularly in the front hooves by increasing hoof length and height, or by adding weight to the distal limbs. Although regulations limit dorsal hoof wall length (LDHW) in competition ICE, their shoeing often deviates from a biomechanically optimal distal limb conformation. This study aimed to qualitatively and quantitatively describe current shoeing practices of ICE in competition. Moreover, the influence of LDHW on the occurrence of deviations from a standard hoof conformation, as well as on tölt performance was investigated. At four European competition sites, hoof dimensions of 133 randomly selected ICE were measured manually, and limb conformation and hoof balance were described. Dorsopalmar/-plantar and lateromedial radiographs of the left front and hind hooves were taken of each horse. Various parameters related to hoof dimensions and balance were measured on radiographs using the Metron-Hoof-Pro software. Flares of the dorsal hoof wall had the highest prevalence of all investigated hoof deformities. Multiple logistic regression analysis revealed that longer LDHW was associated with the occurrence of toe flares (P = 0.045), a broken hoof pastern axis (P = 0.003), and asymmetry of the quarter wall heights (P = 0.015). However, horses with a longer LDHW achieved higher scores in competition. In spite of its positive effect on tölt performance, a long LDHW is not recommendable as it may be associated with a higher prevalence of certain hoof deformities.

An anti-inflammatory phenotype in visceral adipose tissue of old lean mice, augmented by exercise.

Visceral adipose tissue is an immunogenic tissue, which turns detrimental during obesity by activation of proinflammatory macrophages. During aging, chronic inflammation increases proportional to visceral adipose tissue (VAT) mass and associates with escalating morbidity and mortality. Here, we utilize a mouse model to investigate the inflammatory status of visceral adipose tissue in lean aging mice and assess the effects of exercise training interventions. We randomized adult (11 months; n = 21) and old (23 months; n = 27) mice to resistance training (RT) or endurance training (ET), or to a sedentary control group (S). Strikingly, we observed an anti-inflammatory phenotype in the old mice, consisting of higher accumulation of M2 macrophages and IL-10 expression, compared to the adult mice. In concordance, old mice also had less VAT mass and smaller adipocytes compared to adult mice. In both age groups, exercise training enhanced the anti-inflammatory phenotype and increased PGC1-α mRNA expression. Intriguingly, the brown adipose tissue marker UCP1 was modestly higher in old mice, while remained unchanged by the intervention. In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise.

The effect of resistance exercise upon age-related systemic and local skeletal muscle inflammation.

AIM: Chronic inflammation increases with age and is correlated positively to visceral fat mass, but inversely to muscle mass. We investigated the hypothesis that resistance training would increase muscle mass and strength together with a concomitant drop in local and systemic inflammation level independent of any changes in visceral fat tissue in elderly. METHODS: 25 subjects (mean 67, range 62-70 years) were randomized to 1 year of heavy resistance training (HRT) or control (CON), and tested at 0, 4 and 12 months for physical performance, body composition (DXA), vastus lateralis muscle area (MRI) local and systemic inflammation (blood and muscle). In addition, systemic and local muscle immunological responses to acute exercise was determined before and after the training period. RESULTS: Increases in muscle mass (≈2%, p < 0.05), vastus lateralis area (≈9%. P < 0.05), isometric (≈15%) and dynamic (≈15%) muscle strength (p < 0.05) were found in the HRT group after 12 months training. HRT did not alter overall or visceral fat mass (p > 0.05). Blood C-Reactive Protein declined over time in both groups (p < 0.05), whereas muscle inflammation markers were unchanged to 1 year of HRT. Acute exercise increased plasma IL-6 and FGF-19 (p < 0.05), decreased FGF-21 (p < 0.05) and CCL-20 (p < 0.05), and increased GDNF in muscle (p < 0.001) similarly before and after 1 year in both groups. CONCLUSION: Long term resistance training increased muscle strength and improved muscle mass, but did not alter visceral fat mass and did not show any specific effect upon resting or exercise induced markers of inflammation.

Remodeling of muscle fibers approaching the human myotendinous junction.

The myotendinous junction (MTJ) is at high risk of strain injuries, due to high amounts of energy that is transferred through this structure. The risk of strain injury is significantly reduced by heavy resistance training (HRT), indicating a remodeling capacity of MTJ. We investigated the degree of remodeling of muscle fibers near the human MTJ. In 8 individuals, samples were taken from the semitendinosus and gracilis MTJ and they were stained immunohistochemically for myonuclei (DAPI), fibroblasts (TCF7L2), and satellite cells (CD56). A high portion of the muscle fibers adjacent to the MTJ contained a centrally located myonucleus (47 ± 8%, mean ± SD) and half of the muscle fibers were CD56 positive. The number of satellite cells and fibroblasts were not higher than what has previously been reported from muscle bellies. The immunohistochemical findings suggest that the rate of remodeling of muscle fibers near the MTJ is very high. The finding that there was no increased number of satellite cells and fibroblasts could be explained as a dynamic phenomenon. The effect of HRT should be evaluated in a randomized setting.

Factors associated with non-response at health-related quality of life follow-up in a septic shock trial.

BACKGROUND: Follow-up of intensive care unit (ICU) patients often includes health-related quality of life (HRQoL) surveying, but non-responders hamper the interpretation. Our aim was to assess factors for non-response to HRQoL survey in ICU patients with septic shock at follow-up in a clinical trial. METHODS: In a post hoc follow-up registry study, we assessed all the Danish survivors in the Transfusion-Requirements in Septic Shock trial patients, who were mailed the Short Form 36-item Survey (SF-36) 1-year after randomization. We used covariates from the trial database merged with covariates from nation-wide registries using the unique national identification number to explore possible factors for not responding. Five covariates were pre-specified to be included in the primary multivariate analysis: age, number of days in hospital from randomization to follow-up, level of education, cohabitation and employment status at follow-up. We compared the mortality from 1-year survival (2012-2014) till end of final follow-up (January 2016) between non-responders and responders. RESULTS: We assessed 308 survivors of whom 108 (35%) were non-responders. In the primary analysis lower age (odds ratio 1.03, 95% CI [1.01-1.05]), more admission days in hospital (1.006 [1.001-1.011]) and living alone (4.33 [2.46-7.63]) were associated with non-responding, whereas the level of education and employment status were not. Non-responders had a hazard ratio of 1.63 [0.97-2.72] for mortality from 1-year follow-up to final follow-up as compared to the responders. CONCLUSION: Being younger, spending more days in hospital and living alone were all associated with non-response at 1-year HRQoL follow-up among ICU patients with septic shock.

Pouch failures following ileal pouch-anal anastomosis for ulcerative colitis.

AIM: Ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure. METHOD: The study included 1991 patients with ulcerative colitis who underwent ileal pouch-anal anastomosis in Denmark in the period 1980-2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1 year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1-5 cases per year; low, 6-10; intermediate 11-20; high > 20), calendar year, laparoscopy and primary sclerosing cholangitis. RESULTS: Over a median 11.4 years, 295 failures occurred, corresponding to 5-, 10- and 20-year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10-1.75]. Primary non-diversion (aHR 1.63, 95% CI 1.11-2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26-4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy. CONCLUSION: In a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch-anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure.

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: A nationwide cohort study.

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC), and surveillance with ultrasound (US) and alpha-fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona-Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0-3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI95% 0.4-1.5] in 2002-2003 to 2.9/100 PY [2.4-3.4] in 2012-2013. One-year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP ≥ 20 ng mL-1 was 17%. Twenty-three (21%) patients were diagnosed with early-stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early-stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.

Skeletal muscle morphology and regulatory signalling in endurance-trained and sedentary individuals: The influence of ageing.

Muscle mass in humans is inversely associated with circulating levels of inflammatory cytokines, but the interaction between ageing and training on muscle composition and the intra-muscular signalling behind inflammation and contractile protein synthesis and degradation is unknown. We studied 15 healthy life-long endurance runners, 12 age-matched untrained controls, 10 young trained and 12 young untrained individuals. Thigh muscle composition was investigated by magnetic resonance imaging (MRI), where non-contractile intramuscular tissue (NCIT) area (fat and connective tissue) was found to be greater in older but lower in trained individuals. Subcutaneous adipose tissue was also lower in trained individuals but was not affected by age. In vastus lateralis biopsies, no influence of age or training was found on levels of endomysial collagen, determined by Sirius Red and Collagen III staining, whereas perimysial organisation tended to be more complex in older individuals. No clear difference with training was seen on intramuscular inflammatory signalling, whereas lower protein levels of NFkB subunits p105, p50 and p65 were observed with ageing. Gene expression of IL6 and TNFα was not different between groups, while IL1-receptor and TNFα-receptor1 levels were lower with age. Myostatin mRNA was lower in older and trained groups, while expression of MuRF1 was lower in trained individuals and FoxO3 expression was greater in aged groups. The association of increased muscle NCIT with age-associated muscle loss in humans is not accompanied by any major alterations in intramuscular signalling for inflammation, but rather by direct regulatory factors for protein synthesis and proteolysis in skeletal muscle.

Composition and adaptation of human myotendinous junction and neighboring muscle fibers to heavy resistance training.

The myotendinous junction (MTJ) is a common site of strain injury and yet understanding of its composition and ability to adapt to loading is poor. The main aims of this study were to determine the profile of selected collagens and macrophage density in human MTJ and adjoining muscle fibers, and to investigate whether heavy exercise loading would alter this profile. Fifteen individuals scheduled for anterior cruciate ligament repair surgery were randomized into three groups: control, acute or 4 weeks heavy resistance training. MTJ samples were collected from the semitendinosus and gracilis muscles and were sectioned and stained immunohistochemically for collagen types I, III, VI, XII, XIV, XXII, Tenascin-C and CD68. Macrophage density and distribution was evaluated and the amount of each collagen type in muscle and MTJ was graded. Collagen XXII was observed solely at the MTJ, while all other collagens were abundant at the MTJ and in muscle perimysium or endomysium. The endomysial content of collagen XIV, macrophages and Tenascin-C increased following 4 weeks of training. These findings illustrate the heterogeneity of collagen type composition of human MTJ. The increase in collagen XIV following 4 weeks of training may reflect a training-induced protection against strain injuries in this region.

In hip osteoarthritis, Nordic Walking is superior to strength training and home-based exercise for improving function.

This observer-blinded, randomized controlled trial compared the short- and long-term effects of 4 months of supervised strength training (ST) in a local fitness center, supervised Nordic Walking (NW) in a local park, and unsupervised home-based exercise (HBE, control) on functional performance in 60+-year-old persons (n = 152) with hip osteoarthritis (OA) not awaiting hip replacement. Functional performance [i.e., 30-s chair stand test (primary outcome), timed stair climbing, and 6-min walk test] and self-reported outcomes (i.e., physical function, pain, physical activity level, self-efficacy, and health-related quality of life) were measured at baseline and at 2, 4, and 12 months. Based on intention-to-treat-analyses improvements [mean (95% CI)] after intervention in number of chair stands were equal in all three groups at 4 months [ST: 0.9 (0.2-1.6), NW: 1.9 (0.8-3.0), HBE: 1.1 (0.1-2.0)] but greater in the NW group [1.4 (0.02-2.8)] than in the ST group at 12 months. Generally, improvements in functional performance were greater (P < 0.001-P < 0.03) after NW compared with HBE and ST at all follow-up time points. Furthermore, NW was superior (P < 0.01) to HBE for improving vigorous physical activity and to both ST and HBE for improving (P < 0.01) mental health. These data suggest that NW is the recommended exercise modality compared with ST and HBE.

Isometric abdominal wall muscle strength assessment in individuals with incisional hernia: a prospective reliability study.

PURPOSE: To determine the reliability of measurements obtained by the Good Strength dynamometer, determining isometric abdominal wall and back muscle strength in patients with ventral incisional hernia (VIH) and healthy volunteers with an intact abdominal wall. METHODS: Ten patients with VIH and ten healthy volunteers with an intact abdominal wall were each examined twice with a 1 week interval. Examination included the assessment of truncal flexion and extension as measured with the Good Strength dynamometer, the completion of the International Physical Activity Questionnaire (IPAQ) and the self-assessment of truncal strength on a visual analogue scale (SATS). The test-retest reliability of truncal flexion and extension was assessed by interclass correlation coefficient (ICC), and Bland and Altman graphs. Finally, correlations between truncal strength, and IPAQ and SATS were examined. RESULTS: Truncal flexion and extension showed excellent test-retest reliability for both patients with VIH (ICC 0.91 and 0.99) and healthy controls (ICC 0.97 and 0.96). Bland and Altman plots showed that no systematic bias was present for neither truncal flexion nor extension when assessing reliability. For patients with VIH, no significant correlations between objective measures of truncal strength and IPAQ or SATS were found. For healthy controls, both truncal flexion (τ 0.58, p = 0.025) and extension (τ 0.58, p = 0.025) correlated significantly with SATS, while no other significant correlation between truncal strength measures and IPAQ was found. CONCLUSIONS: The Good Strength dynamometer provided a reliable, low-cost measure of truncal flexion and extension in patients with VIH.

Skeletal muscle adaptation to immobilization and subsequent retraining in elderly men: No effect of anti-inflammatory medication.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) may enhance resistance training induced gain in skeletal muscle mass and strength, but it is unknown if NSAIDs affects muscle loss during periods of inactivity in elderly individuals. Thus, we studied the influence of NSAID treatment on human skeletal muscle during immobilization and rehabilitation resistance training (retraining). METHODS: 19 men (60-80yrs, range) were randomly assigned to ibuprofen (1200mg/d, Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2weeks and retrained for 6weeks. Moreover, whey protein isolate was ingested (2×20g/d) throughout the whole study period. Plasma inflammatory markers, quadriceps muscle mass and strength, and muscle gene expression were investigated. RESULTS: Muscle mass and strength decreased after 2weeks of immobilization (P<0.001), but returned to baseline levels after 2weeks of retraining combined with whey protein supplementation (P<0.001). Furthermore, muscle mass and strength reached beyond baseline levels after 6weeks of retraining (p<0.05), and NSAID did not significantly affect this (p>0.05). No group-differences, but differences over time, were observed for muscle gene expression of proteolytic and anabolic factors. Plasma inflammatory markers were unaffected by the study intervention and NSAID treatment. CONCLUSION: Two weeks of lower limb immobilization lead to a reduction in muscle mass and strength, but these parameters were restored already after2 weeks of retraining and whey protein supplementation. After 6weeks of retraining and whey protein supplementation, muscle mass and strength increased beyond baseline levels, and NSAID treatment did not significantly influence this in elderly.

Poor Outcomes of Complicated Pouch-Related Fistulas after Ileal Pouch-Anal Anastomosis Surgery.

BACKGROUND AND AIMS: Development of a pouch-related fistula tract is an uncommon but highly morbid complication to restorative proctocolectomy with ileal pouch-anal anastomosis. Pouch failure with permanent ileostomy is reported in 21%-30% of patients, yet the factors contributing to pouch excision remain poorly defined. The aim of this study was to determine the incidence and treatment results of complicated pouch-related fistula, as well as to evaluate factors involved in excision after pouch failure. MATERIAL AND METHODS: The study was conducted as a retrospective study. All patients with diagnosed pouch-related fistulas were registered with information related to fistula classification, treatments, and outcome. RESULTS AND CONCLUSION: The final analysis included 48 (10.7%) of the 447 total ileal pouch-anal anastomosis patients with complicated pouch-related fistulas. Pouch-vaginal fistulas, pouch-perianal fistulas, and other pouch-related fistulas were observed in 19 (63%), 29 (60%), and 10 (21%) patients, respectively, corresponding to an accumulated risk of 8%, 6%, and 2%, respectively. Time from ileal pouch-anal anastomosis surgery to fistula presentation was 24 (0.2-212) months. Overall pouch failure, defined as pouch excision or a diverting stoma, was seen in 34 (71%) patients, while pouch excision was seen in 23 (48%) of the patients. Patients who developed Crohn's disease had a significantly higher risk of pouch excision, as did patients with an early onset of the fistula after ileal pouch-anal anastomosis (P = 0.006 and P = 0.007, respectively). In conclusion, the present study demonstrated a high risk of pouch failure in patients with complicated pouch-related fistulas. Furthermore, it showed that Crohn's disease and the development of early onset fistulas are associated with pouch excision.

True risk of fetal/neonatal alloimmune thrombocytopenia in subsequent pregnancies: a prospective observational follow-up study.

OBJECTIVES: To assess neonatal platelet counts by comparing alloimmunised pregnancies from a Norwegian screening and intervention study with subsequent pregnancies from the same women. DESIGN: Prospective observational follow-up study. SETTING: A university hospital. POPULATION: HPA-1a immunised women from a large Norwegian screening study that gave birth to one or more children after the screening study ended (2004-2012). METHODS: Follow-up of maternal anti-HPA-1a antibody levels and neonatal platelet counts from the screening pregnancies were compared with subsequent pregnancies. None of the women received antenatal intravenous immunoglobulin (IVIG) treatment and neonatal platelet counts were therefore comparable. MAIN OUTCOME MEASURES: Change in neonatal platelet counts from one HPA-1a incompatible pregnancy to the next. Maternal anti-HPA-a1 antibody levels from one HPA-1a incompatible pregnancy to the next. RESULTS: Forty-five incompatible subsequent pregnancies were identified. Overall, the neonatal platelet count in the subsequent pregnancy was improved (18%), unchanged (52%), or worse (30%), compared with the corresponding screening pregnancy. There was one case of fetal intracranial haemorrhage (ICH) identified in the screening (intrauterine fetal death detected at 30 weeks of gestation) and no ICH cases recorded for the subsequent pregnancies. In cases where the platelet count was lower in the subsequent pregnancy, the maternal anti-HPA-1a antibody level was higher compared with the screening pregnancy. In comparison, the maternal antibody level was lower in subsequent pregnancies where the platelet count improved. CONCLUSIONS: In contrast to what is often stated, we found that the neonatal platelet count was increased or unchanged in the majority of subsequent pregnancies of HPA-1a-immunised women.