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Short, intermittent episodes of disuse muscle atrophy (DMA) may have negative impact on age related muscle loss. There is evidence of variability in rate of DMA between muscles and over the duration of immobilization. As yet, this is poorly characterized. This review aims to establish and compare the time-course of DMA in immobilized human lower limb muscles in both healthy and critically ill individuals, exploring evidence for an acute phase of DMA and differential rates of atrophy between and muscle groups. MEDLINE, Embase, CINHAL and CENTRAL databases were searched from inception to April 2021 for any study of human lower limb immobilization reporting muscle volume, cross-sectional area (CSA), architecture or lean leg mass over multiple post-immobilization timepoints. Risk of bias was assessed using ROBINS-I. Where possible meta-analysis was performed using a DerSimonian and Laird random effects model with effect sizes reported as mean differences (MD) with 95% confidence intervals (95% CI) at various time-points and a narrative review when meta-analysis was not possible. Twenty-nine studies were included, 12 in healthy volunteers (total n = 140), 18 in patients on an Intensive Therapy Unit (ITU) (total n = 516) and 3 in patients with ankle fracture (total n = 39). The majority of included studies are at moderate risk of bias. Rate of quadriceps atrophy over the first 14 days was significantly greater in the ITU patients (MD -1.01 95% CI -1.32, -0.69), than healthy cohorts (MD -0.12 95% CI -0.49, 0.24) (P < 0.001). Rates of atrophy appeared to vary between muscle groups (greatest in triceps surae (-11.2% day 28), followed by quadriceps (-9.2% day 28), then hamstrings (-6.5% day 28), then foot dorsiflexors (-3.2% day 28)). Rates of atrophy appear to decrease over time in healthy quadriceps (-6.5% day 14 vs. -9.1% day 28) and triceps surae (-7.8% day 14 vs. -11.2% day 28), and ITU quadriceps (-13.2% day 7 vs. -28.2% day 14). There appears to be variability in the rate of DMA between muscle groups, and more rapid atrophy during the earliest period of immobilization, indicating different mechanisms being dominant at different timepoints. Rates of atrophy are greater amongst critically unwell patients. Overall evidence is limited, and existing data has wide variability in the measures reported. Further work is required to fully characterize the time course of DMA in both health and disease., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function when compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. Ten young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation with intramuscular electromyography (iEMG) bilaterally recorded from the vastus lateralis (VL) during knee extensor contractions normalised to maximal voluntary contraction (MVC), pre and post disuse. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in motor unit (MU) discharge and MU potential (MUP) characteristics. VL CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change in either parameter in the non-immobilised limb. Parameters of MUP size were reduced by 11% to 24% with immobilisation, while neuromuscular junction (NMJ) transmission instability remained unchanged, and MU firing rate decreased by 8% to 11% at several contraction levels. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU firing rate which may underpin the disproportionate reductions of strength relative to muscle size. KEY POINTS: Muscle mass and function decline rapidly in situations of disuse such as bed rest and limb immobilisation. The reduction in muscle function commonly exceeds that of muscle mass, which may be associated with the dysregulation of neural input to muscle. We have used intramuscular electromyography to sample individual motor unit and near fibre potentials from the vastus lateralis following 15 days of unilateral limb immobilisation. Following disuse, the disproportionate loss of muscle strength when compared to size coincided with suppressed motor unit firing rate. These motor unit adaptations were observed at multiple contraction levels and in the immobilised limb only. Our findings demonstrate neural dysregulation as a key component of functional loss following muscle disuse in humans., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: Disuse atrophy (DA) describes inactivity-induced skeletal muscle loss, through incompletely defined mechanisms. An intriguing observation is that individual muscles exhibit differing degrees of atrophy, despite exhibiting similar anatomical function/locations. We aimed to develop an innovative experimental paradigm to investigate Atrophy Resistant tibialis anterior (TA) and Atrophy Susceptible medial gastrocnemius (MG) muscles (aRaS) with a future view of uncovering central mechanisms., Method: Seven healthy young men (22 ± 1 year) underwent 15 days unilateral leg immobilisation (ULI). Participants had a single leg immobilised using a knee brace and air-boot to fix the leg (75° knee flexion) and ankle in place. Dual-energy X-ray absorptiometry (DXA), MRI and ultrasound scans of the lower leg were taken before and after the immobilisation period to determine changes in muscle mass. Techniques were developed for conchotome and microneedle TA/MG muscle biopsies following immobilisation (both limbs), and preliminary fibre typing analyses was conducted., Results: TA/MG muscles displayed comparable fibre type distribution of predominantly type I fibres (TA 67 ± 7%, MG 63 ± 5%). Following 15 days immobilisation, MG muscle volume (-2.8 ± 1.4%, p < 0.05) and muscle thickness decreased (-12.9 ± 1.6%, p < 0.01), with a positive correlation between changes in muscle volume and thickness (R 2 = 0.31, p = 0.038). Importantly, both TA muscle volume and thickness remained unchanged., Conclusion: The use of this unique "aRaS" paradigm provides an effective and convenient means by which to study the mechanistic basis of divergent DA susceptibility in humans, which may facilitate new mechanistic insights, and by extension, mitigation of skeletal muscle atrophy during human DA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bass, Hardy, Inns, Wilkinson, Piasecki, Morris, Spicer, Sale, Smith, Atherton and Phillips.)

Insulin resistance (IR) is a key feature in the development of numerous metabolic diseases. The cornerstone for treatment for IR remains diet and exercise, however these have poor rates of adherence. Beta-hydroxy-beta-methylbutyrate (HMB) is a nutraceutical with contentious effects on IR in animal models. The aim of this study was to evaluate the impact of acute HMB on IR in humans during an oral glucose tolerance test (OGTT). Young and older male volunteers underwent two 75 g OGTT with or without 3 g HMB. In young men, HMB significantly reduced the insulin area-under-the-curve (AUC), with no difference in glucose AUC, resulting in a numerical increase in the Cederholm index of insulin sensitivity. In older men, HMB had no effect on insulin or glucose responses. In conclusion, acute HMB may improve IR following a glucose load in young men; however, this does not appear to be sustained into older age., Competing Interests: The authors declare no conflicts of interest. JAR is an employee of Metabolic Technologies Inc., who supplied the free acid-HMB on a collaborative basis. Metabolic Technologies Inc., has patents pending on HMB-FA, and market HMB to nutrition companies., (© 2020 The Authors.)

Background: Pilonidal sinus disease (PNS) is not uncommon in children. Controversy remains over the best treatment and there is limited evidence. This systematic review and meta-analysis aims to establish which techniques have the best outcomes in children., Methods: MEDLINE, EMBASE and CENTRAL databases were searched. Studies reporting treatment outcomes for PNS in children were included., Results: Open healing has pooled risk of recurrence of 26% (95%CI 15-38%), risk of wound complication of 21% (9-36%) and wound healing ranged from 38-92 days. Midline primary closure has pooled risk of recurrence of 12% (8-18%), risk of wound complication of 30% (19-46%) and wound healing ranged from 8 to 32 days. Off-midline primary closure has pooled risk of recurrence of 6% (1-15%), risk of wound complication of 14% (6-25%) and wound healing was 27 days. VAC therapy has pooled risk of recurrence of 20% (0-65%) and wound healing ranged from 38 to 92 days. Minimally invasive techniques has pooled risk of recurrence of 7% (1-16%) and wound healing ranged from 21-30 days. Marsupialisation has pooled risk of recurrence of 6% (0-22%), and wound healing ranged from 6 to 41 days., Conclusion: Evidence for management of PNS in children is poor. Off-midline primary closure, minimally invasive techniques, and marsupialisation have the best outcomes., Level of Evidence Rating: IV., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pilonidal sinus disease (PSD) is a common, chronic inflammatory condition involving hair follicles within the natal cleft. It mainly affects young males and creates a significant health, social and economic burden. Traditional surgery is often radical resulting in pain, wound complications, long recovery times and poor cosmesis. The aim of our study was to evaluate fibrin glue as a primary treatment for PSD., Methods: Fibrin glue procedures for a single surgeon at our institution were identified from operative coding databases and the logbook from January 2011 to January 2016. Patients had curettage of the sinus with fibrin glue obliteration. Recurrence data was collected retrospectively., Results: One hundred and forty-six patients were identified; (115 (79%) males, mean age 30 (range 16-78 years). One hundred and forty-four (99%) were discharged the same day. Four (2.7%) were treated conservatively for wound discharge. Median operating time was 9 (range 4-28) min. There were 40 (27%) recurrences after one glue application. Median time to recurrence was 4 (range 0.25-36) months. Twenty-four (60%) of the recurrences had repeat glue treatment with 4 (16.6%) recurrences. After 2 rounds of treatment with glue alone, 126 out of 130 (96.9%) patients had healed., Conclusions: Fibrin glue application following curettage of the sinus is a quick and effective procedure for first and second line treatment of PSD.