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Background Tourniquet use during total knee arthroplasty (TKA) improves visibility and reduces intraoperative blood loss. However, tourniquet use may also have a negative impact on early recovery of muscle strength and lower extremity function after TKA. Questions/purposes The purpose of this study was (1) to determine whether tourniquet use affects recovery of quadriceps strength (primary outcome) during the first 3 postoperative months; and (2) to examine the effects of tourniquet application on secondary outcomes: voluntary quadriceps activation, hamstring strength, unilateral limb balance as well as the effect on operative time and blood loss. Methods Twenty-eight patients (mean age 62 ± 6 years; 16 men) undergoing same-day bilateral TKA (56 lower extremities) were enrolled in a prospective, randomized study. Subjects were randomized to receive a tourniquet-assisted knee arthroplasty on one lower extremity while the contralateral limb underwent knee arthroplasty without extended tourniquet use. In the former group, the tourniquet was inflated just before the incision was made and released after cementation; in the latter group, a tourniquet was not used (10 of 28 [36%]) or inflated only during component cementation (18 of 28 [64%]). The choice of no tourniquet or use just during cementation was based on surgeon choice, because some surgeons felt a tourniquet during cementation was necessary to achieve a dry surgical field to maximize cement fixation. A median parapatellar approach and the identical posterior-stabilized TKA design were used by all four fellowship-trained knee surgeons involved. Isometric quadriceps strength, hamstring strength, voluntary quadriceps activation, and unilateral balance were assessed preoperatively, 3 weeks, and 3 months after bilateral knee arthroplasty. Other factors, including pain, range of motion, and lower extremity girth, were assessed for descriptive purposes at each of these time points as well as on the second postoperative day. Results Quadriceps strength was slightly lower in the tourniquet group compared with the no-tourniquet group (group difference = 11.27 Nm [95% confidence interval {CI}, 2.33–20.20]; p = 0.01), and these differences persisted at 3 months after surgery (group difference = 9.48 Nm [95% CI, 0.43–18.54]; p = 0.03). Hamstring strength did not differ between groups at any time point nor did measures of quadriceps voluntary activation or measures of unilateral balance ability. There was less estimated intraoperative blood loss in the tourniquet group (84 ± 26 mL) than in the no-tourniquet group (156 ± 63 mL) (group difference = −74 mL [95% CI, −100 to −49]; p < 0.001). However, there was no difference in total blood loss between the groups (group difference = −136 mL [95% CI, −318 to 45]; p = 0.13). Conclusions Patients who underwent TKA using a tourniquet had diminished quadriceps strength during the first 3 months after TKA, the clinical significance of which is unclear. Future studies may be warranted to examine the effects of tourniquet use on long-term strength and functional outcomes. Level of Evidence Level I, therapeutic study.

Background and aimsAnterior quadratus lumborum block is a truncal block, applied in close proximity to the lumbar plexus, potentially causing lower limb weakness. This trial aimed to evaluate whether a unilateral anterior quadratus lumborum block caused quadriceps muscle weakness compared with placebo.MethodsIn this randomized, non-inferiority, triple-blind trial, 20 healthy volunteers received an active unilateral anterior quadratus lumborum block with 30 mL ropivacaine 0.75% and a placebo block on the contralateral side. Primary outcome was change in maximal quadriceps muscle strength from baseline to 60 min postblock compared with placebo. Secondary outcomes were change in single-leg 6 m timed hop test, change in Timed-Up and Go test, change in mean arterial pressure from baseline to 30 min postblock and dermatomal affection.ResultsThere was no statistically significant difference in changes in maximal quadriceps muscle strength between active and placebo block; 15.88 N (95% CI −12.19 to +43.94), pnon-inf=0.003, indicating non-inferiority. Timed-Up and Go test was performed significantly faster 60 min postblock; −0.23 s (95% CI −0.38 to −0.08, p=0.005). Mean change in mean arterial pressure from baseline to 30 min postblock was 4.25 mm Hg (95% CI 0.24 to 8.26, p=0.04). Dermatome testing revealed an affection primarily of the lower abdomen (Th10-L1) with the active block.ConclusionIn this randomized controlled trial including healthy volunteers a unilateral anterior quadratus lumborum block does not cause statistical or clinical significant motor block of the quadriceps muscle compared with placebo. When administered correctly, the block can be used for procedures where early postoperative mobilization is essential.Trial registration number NCT05023343.

Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects. The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia. A total of fifty-three male subjects (72·2 (sd 4·68) years) with sarcopenia (class I or II) completed this randomised double-blind placebo-controlled study. All the participants underwent a 12-week guided resistance training programme (three sessions per week) and were supplemented with either collagen peptides (treatment group (TG)) (15 g/d) or silica as placebo (placebo group (PG)). Fat-free mass (FFM), fat mass (FM) and bone mass (BM) were measured before and after the intervention using dual-energy X-ray absorptiometry. Isokinetic quadriceps strength (IQS) of the right leg was determined and sensory motor control (SMC) was investigated by a standardised one-leg stabilisation test. Following the training programme, all the subjects showed significantly higher (P<0·01) levels for FFM, BM, IQS and SMC with significantly lower (P<0·01) levels for FM. The effect was significantly more pronounced in subjects receiving collagen peptides: FFM (TG +4·2 (sd 2·31) kg/PG +2·9 (sd 1·84) kg; P<0·05); IQS (TG +16·5 (sd 12·9) Nm/PG +7·3 (sd 13·2) Nm; P<0·05); and FM (TG –5·4 (sd 3·17) kg/PG –3·5 (sd 2·16) kg; P<0·05). Our data demonstrate that compared with placebo, collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM, muscle strength and the loss in FM.

Background The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia), and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RET). Nonetheless, the efficacy and physiological and molecular impacts of T therapy adjuvant to short‐term RET remain poorly defined. Methods Eighteen non‐hypogonadal healthy older men, 65–75 years, were assigned in a random double‐blinded fashion to receive, biweekly, either placebo (P, saline, n = 9) or T (Sustanon 250 mg, n = 9) injections over 6 week whole‐body RET (three sets of 8–10 repetitions at 80% one‐repetition maximum). Subjects underwent dual‐energy X‐ray absorptiometry, ultrasound of vastus lateralis (VL) muscle architecture, and knee extensor isometric muscle force tests; VL muscle biopsies were taken to quantify myogenic/anabolic gene expression, anabolic signalling, muscle protein synthesis (D2O), and breakdown (extrapolated). Results Testosterone adjuvant to RET augmented total fat‐free mass (P=0.007), legs fat‐free mass (P=0.02), and appendicular fat‐free mass (P=0.001) gains while decreasing total fat mass (P=0.02). Augmentations in VL muscle thickness, fascicle length, and quadriceps cross‐section area with RET occured to a greater extent in T (P < 0.05). Sum strength (P=0.0009) and maximal voluntary contract (e.g. knee extension at 70°) (P=0.002) increased significantly more in the T group. Mechanistically, both muscle protein synthesis rates (T: 2.13 ± 0.21%·day−1 vs. P: 1.34 ± 0.13%·day−1, P=0.0009) and absolute breakdown rates (T: 140.2 ± 15.8 g·day−1 vs. P: 90.2 ± 11.7 g·day−1, P=0.02) were elevated with T therapy, which led to higher net turnover and protein accretion in the T group (T: 8.3 ± 1.4 g·day−1 vs. P: 1.9 ± 1.2 g·day−1, P=0.004). Increases in ribosomal biogenesis (RNA:DNA ratio); mRNA expression relating to T metabolism (androgen receptor: 1.4‐fold; Srd5a1: 1.6‐fold; AKR1C3: 2.1‐fold; and HSD17β3: two‐fold); insulin‐like growth factor (IGF)‐1 signalling [IGF‐1Ea (3.5‐fold) and IGF‐1Ec (three‐fold)] and myogenic regulatory factors; and the activity of anabolic signalling (e.g. mTOR, AKT, and RPS6; P < 0.05) were all up‐regulated with T therapy. Only T up‐regulated mitochondrial citrate synthase activity (P=0.03) and transcription factor A (1.41 ± 0.2‐fold, P=0.0002), in addition to peroxisome proliferator‐activated receptor‐γ co‐activator 1‐α mRNA (1.19 ± 0.21‐fold, P=0.037). Conclusions Administration of T adjuvant to RET enhanced skeletal muscle mass and performance, while up‐regulating myogenic gene programming, myocellular translational efficiency and capacity, collectively resulting in higher protein turnover, and net protein accretion. T coupled with RET is an effective short‐term intervention to improve muscle mass/function in older non‐hypogonadal men.

Quadriceps muscle dysfunction is common following anterior cruciate ligament reconstruction (ACLR). Data considering the diversity of neural changes, in-concert with morphological adaptations of the quadriceps muscle, are lacking. We investigated bilateral differences in neural and morphological characteristics of the quadriceps muscle in ACLR participants (n = 11, month post-surgery: 69.4 ± 22.4) compared to controls matched by sex, age, height, weight, limb dominance, and activity level. Spinal reflex excitability was assessed using Hoffmann reflexes (H:M); corticospinal excitability was quantified via active motor thresholds (AMT) and motor-evoked potentials (MEP) using transcranial magnetic stimulation. Cortical activation was assessed using a knee flexion/extension task with functional magnetic resonance imaging (fMRI). Muscle volume was quantified using structural MRI. Muscle strength and patient-reported outcomes were also collected. 2 × 2 RM ANOVAs were used to evaluate group differences. Smaller quadriceps muscle volume (total volume, rectus femoris, vastus medialis, and intermedius) and lower strength were detected compared to contralateral and control limbs. Individuals with ACLR reported higher levels of pain and fear and lower levels of knee function compared to controls. No differences were observed for H:M. ACLR individuals demonstrated higher AMT bilaterally and smaller MEPs in the injured limb, compared to the controls. ACLR participants demonstrated greater activation in frontal lobe areas responsible for motor and pain processing compared to controls, which were associated with self-reported pain. Our results suggest that individuals with ACLR demonstrate systemic neural differences compared to controls, which are observed concurrently with smaller quadriceps muscle volume, quadriceps muscle weakness, and self-reported dysfunction.

The increase of elderly in our society requires simple tools for quantification of sarcopenia in inpatient and outpatient settings. The aim of this study was to compare parameters determined with musculoskeletal ultrasound (M-US) with muscle strength in young and elderly patients. In this prospective, randomised and observer blind study, 26 young (24.2 ± 3.7 years) and 26 old (age 67.8 ± 4.8 years) patients were included. Muscle thickness, pennation angle and echogenicity of all muscles of musculus quadriceps were measured by M-US and correlated with isometric maximum voluntary contraction force (MVC) of musculus quadriceps. Reproducibility of M-US measurements as well as simple and multiple regression models were calculated. Of all measured M-US variables the highest reproducibility was found for measurements of thickness (intraclass correlation coefficients, 85–97 %). Simple regression analysis showed a highly significant correlation of thickness measurements of all muscles of musculus quadriceps with MVC in the elderly and in the young. Multiple regression analysis revealed that thickness of musculus vastus medialis had the best correlation with MVC in the elderly. This study showed that measurement of muscle thickness, especially of musculus vastus medialis, by M-US is a reliable, bedside method for monitoring the extent of sarcopenia.

Background To evaluate the effects of stationary cycling with electromyographic (EMG) biofeedback on neuromuscular control and function in individuals with knee osteoarthritis (OA). Methods Fourteen knee OA patients were randomized into two groups: cycling with EMG biofeedback of the vastus medialis (EBF group) and cycling without biofeedback (Cycling group). Both groups underwent a six-week cycling program, 30 min per session, twice a week. Outcomes were measured at baseline and post-training. Knee pain and function were assessed using the Visual Analog Scale and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Quadriceps strength and endurance were evaluated with an isokinetic machine, and muscle activation was recorded using a wireless EMG system. A two-way mixed-model analysis of variance (ANOVA) was used to assess the differences between sides and groups. For outcomes that were not normally distributed, the non-parametric Mann-Whitney U test was performed. Results Both groups showed improvements in knee pain and function, with no significant differences between groups. Muscle strength remained largely unchanged, but the endurance was improved on the contralateral side ( p  = 0.038, η 2  = 0.312). Larger muscle activations were observed at various time points during the 30-minute cycling test in the EBF group with significant increases in muscle recruitment in the vastus medialis (p = < 0.001 ~ 0.042, η 2  = 0.482 ~ 0.996), rectus femoris ( p  = 0.003 ~ 0.040, η 2  = 0.493 ~ 0.859) and vastus lateralis ( p  = 0.002 ~ 0.036, η 2  = 0.534 ~ 0.875). Conclusions A six-week cycling program can alleviate pain and enhance knee function. EMG biofeedback of the vastus medialis significantly changed the neuromuscular control in the rectus femoris and vastus lateralis during cycling. Therefore, this study demonstrated that stationary cycling combined with electromyographic biofeedback training can enhance neuromuscular control of the quadriceps and potentially improve functional performance in patients with OA. Trial registration ClinicalTrials.gov identifier, NCT03484910 (registered at March 31st, 2018).

Fibro-adipogenic progenitors (FAPs) are typically activated in response to muscle injury, and establish functional interactions with inflammatory and muscle stem cells (MuSCs) to promote muscle repair. We found that denervation causes progressive accumulation of FAPs, without concomitant infiltration of macrophages and MuSC-mediated regeneration. Denervation-activated FAPs exhibited persistent STAT3 activation and secreted elevated levels of IL-6, which promoted muscle atrophy and fibrosis. FAPs with aberrant activation of STAT3–IL-6 signalling were also found in mouse models of spinal cord injury, spinal muscular atrophy, amyotrophic lateral sclerosis (ALS) and in muscles of ALS patients. Inactivation of STAT3–IL-6 signalling in FAPs effectively countered muscle atrophy and fibrosis in mouse models of acute denervation and ALS (SOD G93A mice). Activation of pathogenic FAPs following loss of integrity of neuromuscular junctions further illustrates the functional versatility of FAPs in response to homeostatic perturbations and suggests their potential contribution to the pathogenesis of neuromuscular diseases. Madaro et al. show that denervation induces accumulation of IL-6–STAT3-activated fibro-adipogenic progenitors without inflammation or muscle regeneration, leading to muscle atrophy and fibrosis.

Context:Low-grade inflammation is associated with obesity and the metabolic syndrome (MetS). Preclinical evidence suggests that resveratrol (RSV) has beneficial metabolic and anti-inflammatory effects that could have therapeutic implications.Objective:To investigate effects of long-term RSV treatment on inflammation and MetS.Setting and Design:A randomized, placebo-controlled, double-blind, parallel group clinical trial conducted at Aarhus University Hospital.Participants:Middle-aged community-dwelling men (N = 74) with MetS, 66 of whom completed all visits (mean ± standard error of the mean): age, 49.5 ± 0.796 years; body mass index, 33.8 ± 0.44 kg/m2; waist circumference, 115 ± 1.14 cm.Intervention:Daily oral supplementation with 1000 mg RSV (RSVhigh), 150 mg RSV, or placebo for 16 weeks.Main outcome measures:Plasma levels of high-sensitivity C-reactive protein (hs-CRP), circulating lipids, and inflammatory markers in circulation and adipose/muscle tissue biopsy specimens; glucose metabolism; and body composition including visceral fat and ectopic fat deposition.Results:RSV treatment did not lower circulating levels of hs-CRP, interleukin 6, or soluble urokinase plasminogen activator receptor in plasma, and inflammatory gene expression in adipose and muscle tissues also remained unchanged. RSV treatment had no effect on blood pressure, body composition, and lipid deposition in the liver or striated muscle. RSV treatment had no beneficial effect on glucose or lipid metabolism. RSVhigh treatment significantly increased total cholesterol (P < 0.002), low-density lipoprotein (LDL) cholesterol (P < 0.006), and fructosamine (P < 0.013) levels compared with placebo.Conclusion:RSV treatment did not improve inflammatory status, glucose homeostasis, blood pressure, or hepatic lipid content in middle-aged men with MetS. On the contrary, RSVhigh significantly increased total cholesterol, LDL cholesterol, and fructosamine levels compared with placebo.Neither high- nor low-dose resveratrol had beneficial effects on inflammation or the metabolic syndrome in middle-aged men. High-dose treatment increased lipid and fructosamine levels.

Aims/hypothesisIt has been proposed that muscle fibre type composition and perfusion are key determinants of insulin-stimulated muscle glucose uptake, and alterations in muscle fibre type composition and perfusion contribute to muscle, and consequently whole-body, insulin resistance in people with obesity. The goal of the study was to evaluate the relationships among muscle fibre type composition, perfusion and insulin-stimulated glucose uptake rates in healthy, lean people and people with obesity.MethodsWe measured insulin-stimulated whole-body glucose disposal and glucose uptake and perfusion rates in five major muscle groups (erector spinae, obliques, rectus abdominis, hamstrings, quadriceps) in 15 healthy lean people and 37 people with obesity by using the hyperinsulinaemic–euglycaemic clamp procedure in conjunction with [2H]glucose tracer infusion (to assess whole-body glucose disposal) and positron emission tomography after injections of [15O]H2O (to assess muscle perfusion) and [18F]fluorodeoxyglucose (to assess muscle glucose uptake). A biopsy from the vastus lateralis was obtained to assess fibre type composition.ResultsWe found: (1) a twofold difference in glucose uptake rates among muscles in both the lean and obese groups (rectus abdominis: 67 [51, 78] and 32 [21, 55] μmol kg−1 min−1 in the lean and obese groups, respectively; erector spinae: 134 [103, 160] and 66 [24, 129] μmol kg−1 min−1, respectively; median [IQR]) that was unrelated to perfusion or fibre type composition (assessed in the vastus only); (2) the impairment in insulin action in the obese compared with the lean group was not different among muscle groups; and (3) insulin-stimulated whole-body glucose disposal expressed per kg fat-free mass was linearly related with muscle glucose uptake rate (r2 = 0.65, p < 0.05).Conclusions/interpretationObesity-associated insulin resistance is generalised across all major muscles, and is not caused by alterations in muscle fibre type composition or perfusion. In addition, insulin-stimulated whole-body glucose disposal relative to fat-free mass provides a reliable index of muscle glucose uptake rate.