Exercise for patients with chronic kidney disease: from cells to systems to function.

Chronic kidney disease (CKD) is among the leading causes of death and disability, affecting an estimated 800 million adults globally. The underlying pathophysiology of CKD is complex creating challenges to its management. Primary risk factors for the development and progression of CKD include diabetes mellitus, hypertension, age, obesity, diet, inflammation, and physical inactivity. The high prevalence of diabetes and hypertension in patients with CKD increases the risk for secondary consequences such as cardiovascular disease and peripheral neuropathy. Moreover, the increased prevalence of obesity and chronic levels of systemic inflammation in CKD have downstream effects on critical cellular functions regulating homeostasis. The combination of these factors results in the deterioration of health and functional capacity in those living with CKD. Exercise offers protective benefits for the maintenance of health and function with age, even in the presence of CKD. Despite accumulating data supporting the implementation of exercise for the promotion of health and function in patients with CKD, a thorough description of the responses and adaptations to exercise at the cellular, system, and whole body levels is currently lacking. Therefore, the purpose of this review is to provide an up-to-date comprehensive review of the effects of exercise training on vascular endothelial progenitor cells at the cellular level; cardiovascular, musculoskeletal, and neural factors at the system level; and physical function, frailty, and fatigability at the whole body level in patients with CKD.

Preliminary validation of muscle ultrasound in juvenile dermatomyositis (JDM).

OBJECTIVE: To compare muscle ultrasound (MUS) parameters in patients with juvenile JDM and healthy controls, and examine their association with JDM disease activity measures and MRI. METHODS: MUS of the right mid-rectus femoris was performed in 21 patients with JDM meeting probable or definite Bohan and Peter criteria and 28 demographically matched healthy control subjects. MUS parameters were quantitated by digital image processing and correlated with JDM disease activity measures and semi-quantitative thigh MRI short tau inversion recovery (STIR) and T1 scores. RESULTS: Rectus femoris MUS echogenicity was increased (median 47.8 vs 38.5, P = 0.002) in patients with JDM compared with controls. Rectus femoris MUS echogenicity correlated with Physician Global Activity (PGA), Manual Muscle Testing (MMT), and Childhood Myositis Assessment Scale (CMAS) (rs 0.4-0.54). Some MUS parameters correlated with functional quantitative measures of muscle strength: resting RF area on MUS strongly correlated with knee extension quantitative muscle testing (rs 0.76), and contracted area correlated with proximal MMT, knee extension quantitative muscle testing, and CMAS (rs 0.71-0.80). MUS echogenicity correlated with both STIR and T1 MRI (rs 0.43), and T1 MRI correlated inversely with RF contracted area (rs -0.49) on MUS. There were differences in pre- and post-exercise vascular power and colour Doppler on MUS in patients with JDM vs controls, with the percentage change of post-exercise vascular power Doppler lower in JDM compared with controls (7.1% vs 100.0%). CONCLUSIONS: These data suggest MUS may be a valuable imaging modality to assess JDM disease activity and damage.

Fatigability and the Role of Neuromuscular Impairments in Chronic Kidney Disease.

BACKGROUND: The combination of neuromuscular impairments plus psychosocial aspects of chronic kidney disease (CKD) may predispose these patients to greater risk for experiencing increased levels of fatigability. There has been extensive clinical and scientific interest in the problem of fatigue in CKD and end-stage kidney disease (ESKD) patients, whereas less attention has been directed to understanding fatigability. Accordingly, the primary purposes of this review are to (1) discuss fatigue and fatigability and their potential interactions in patients with CKD and ESKD, (2) provide evidence for increased fatigability in CKD and ESKD patients, (3) examine how commonly experienced neuromuscular impairments in CKD and ESKD patients may contribute to the severity of performance fatigability, and (4) highlight preliminary evidence on the effects of exercise as a potential clinical treatment for targeting fatigability in this population. SUMMARY: Fatigue is broadly defined as a multidimensional construct encompassing a subjective lack of physical and/or mental energy that is perceived by the individual to interfere with usual or desired activities. In contrast, fatigability is conceptualized within the context of physical activity and is quantified as the interactions between reductions in objective measures of performance (i.e., performance fatigability) and perceptual adjustments regulating activity performance (i.e., perceived fatigability). We propose herein a conceptual model to extend current understandings of fatigability by considering the interactions among fatigue, perceived fatigability, and performance fatigability. Neuromuscular impairments reported in patients with CKD and ESKD, including reductions in force capacity, skeletal muscle atrophy, mitochondrial dysfunction, abnormal skeletal muscle excitability, and neurological complications, may each contribute to the greater performance fatigability observed in these patients. KEY MESSAGES: Considering the interactions among fatigue, perceived fatigability, and performance fatigability provides a novel conceptual framework to advance the understanding of fatigability in CKD and ESKD patients. Measures of fatigability may provide valuable clinical insights into the overall health status of CKD and ESKD patients. Existing data suggest that CKD and ESKD patients are at greater risk of experiencing increased fatigability, partly due to neuromuscular impairments associated with reduced kidney function. Further investigations are warranted to determine the potential clinical role fatigability measures can play in monitoring the health of CKD and ESKD patients, and in identifying potential treatments targeting fatigability in this patient population.

Effects of virtual dance exercise on skeletal muscle architecture and function of community dwelling older women.

OBJECTIVES: The aim of this study was to analyze the effects of virtual dance exercise on skeletal muscle architecture and function in community-dwelling older women. METHODS: Forty-two moderately active older women participated in this study and chose to join either the control group (CG; n=20; 70.3 ± 5.6 years) or exercise group (EG; n=22; 69.3 ± 3.7 years). Participants in the CG maintained their lifestyle and those in the EG performed group dance exercise using Dance Central game for Xbox 360® and Kinect for 40 min, 3 times/week, for 12 weeks. The primary outcomes were: ankle plantar flexion and dorsiflexion peak torque (PT), medial gastrocnemius muscle thickness (MT), fascicle length (FL), and pennation angle (PA). The secondary outcomes were: lower limbs range of motion (ROM), calf circumference (CC), 6 m customary gait speed, and handgrip strength. Data were analyzed using an ANOVA mixed model test (p<0.05). RESULTS: EG participants improved plantar flexion PT at 60°/s (16.3%; p<0.01), MT (8.7%; p<0.01) and ankle dorsiflexion ROM (5.1%; p=0.04) when compared to baseline, and exhibited enhanced CC values compared to CG (1.7%; p=0.03). CONCLUSIONS: Virtual dance exercise can be recommended to increase muscle mass. Moreover, ankle plantar flexion strength and dorsiflexion ROM gains may contribute to improve functionality and fall avoidance in moderately active older women.

Association Between Muscle Strength and Modeling Estimates of Muscle Tissue Heterogeneity in Young and Old Adults.

OBJECTIVES: Assessing aging muscle through estimates of muscle heterogeneity may overcome some of the limitations of grayscale analyses. The objectives of this study included determining statistical model parameters that characterize muscle echogenicity and are associated with strength in younger and older participants. METHODS: Thirty-three community-dwelling participants were assigned to younger and older groups. Quantitative B-mode ultrasound scanning of the rectus femoris and isometric grip strength testing were completed. Shape or dispersion parameters from negative binomial distribution, Nakagami, gamma, and gamma mixture models were fitted to the grayscale histograms. RESULTS: The mean ages ± SDs of the younger and older groups were 24.0 ± 2.3 and 65.1 ± 6.5 years, respectively. Statistical model shape and dispersion parameters for the grayscale histograms significantly differed between the younger and older participants (P = .002-.006). Among all of the statistical models considered, the gamma mixture model showed the best fit with the grayscale histograms (χ2 goodness of fit = 62), whereas the Nakagami distribution displayed the poorest fit (χ2 goodness of fit = 2595). Grayscale values were significantly associated with peak grip strength force in younger adult participants (R2 = 0.36; P < .008). However, the negative binomial dispersion parameter k (adjusted R2 = 0.70; P < .001) and gamma shape parameter α (adjusted R2 = 0.68; P < .01) showed the highest associations with peak grip strength force in older adult participants. CONCLUSIONS: The negative binomial dispersion parameter k and the gamma shape parameter α have clinical relevance for the assessment of age-related muscle changes. Statistical models of muscle heterogeneity may characterize the association between muscle tissue composition estimates and strength better than grayscale measures in samples of community-dwelling older adults.

Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial.

OBJECTIVE: To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients. METHODS: Adults with refractory polymyositis (PM) and adults and children with refractory dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures (CSMs) for adults. Juvenile DM patients required ≥3 abnormal CSMs, with or without muscle weakness. Patients were randomized to receive either rituximab early or rituximab late, and glucocorticoid or immunosuppressive therapy was allowed at study entry. The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement (DOI) between the 2 groups. The secondary end points were the time to achieve ≥20% improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8. RESULTS: Among 200 randomized patients (76 with PM, 76 with DM, and 48 with juvenile DM), 195 showed no difference in the time to achieving the DOI between the rituximab late (n = 102) and rituximab early (n = 93) groups (P = 0.74 by log rank test), with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks, respectively. The secondary end points also did not significantly differ between the 2 treatment groups. However, 161 (83%) of the randomized patients met the DOI, and individual CSMs improved in both groups throughout the 44-week trial. CONCLUSION: Although there were no significant differences in the 2 treatment arms for the primary and secondary end points, 83% of adult and juvenile myositis patients with refractory disease met the DOI. The role of B cell-depleting therapies in myositis warrants further study, with consideration for a different trial design.

Exploring the associations between skeletal muscle echogenicity and physical function in aging adults: A systematic review with meta-analyses.

BACKGROUND: Assessment and quantification of skeletal muscle within the aging population is vital for diagnosis, treatment, and injury/disease prevention. The clinical availability of assessing muscle quality through diagnostic ultrasound presents an opportunity to be utilized as a screening tool for function-limiting diseases. However, relationships between muscle echogenicity and clinical functional assessments require authoritative analysis. Thus, we aimed to (a) synthesize the literature to assess the relationships between skeletal muscle echogenicity and physical function in older adults (≥60 years), (b) perform pooled analyses of relationships between skeletal muscle echogenicity and physical function, and (c) perform sub-analyses to determine between-muscle relationships. METHODS: CINAHL, Embase, MEDLINE, PubMed, and Web of Science databases were systematically searched to identify articles relating skeletal muscle echogenicity to physical function in older adults. Risk-of-bias assessments were conducted along with funnel plot examination. Meta-analyses with and without sub-analyses for individual muscles were performed utilizing Fisher's Z transformation for the most common measures of physical function. Fisher's Z was back-transformed to Pearson's r for interpretation. RESULTS: Fifty-one articles (n = 5095, female = ∼2759, male = ∼2301, 72.5 ± 5.8 years, mean ± SD (1 study did not provide sex descriptors)) were extracted for review, with previously unpublished data obtained from the authors of 13 studies. The rectus femoris (n = 34) and isometric knee extension strength (n = 22) were the most accessed muscle and physical qualities, respectively. The relationship between quadriceps echogenicity and knee extensor strength was moderate (n = 2924, r = -0.36 (95% confidence interval: -0.38 to -0.32), p < 0.001), with all other meta-analyses (grip strength, walking speed, sit-to-stand, timed up-and-go) resulting in slightly weaker correlations (r:  -0.34 to -0.23, all p < 0.001). Sub-analyses determined minimal differences in predictive ability between muscle groups, although combining muscles (e.g., rectus femoris + vastus lateralis) often resulted in stronger correlations with maximal strength. CONCLUSION: While correlations were modest, the affordable, portable, and noninvasive ultrasonic assessment of muscle quality was a consistent predictor of physical function in older adults. Minimal between-muscle differences suggest that echogenicity estimates of muscle quality are systemic. Therefore, practitioners may be able to scan a single muscle to estimate full-body skeletal muscle quality/composition, while researchers should consider combining multiple muscles to strengthen the model.

Blood Flow Restriction and Veterans With Multiple Sclerosis and Advanced Disability: Protocol for a Randomized Controlled Trial.

OBJECTIVE: The purpose of this study will be to determine the efficacy of low intensity lower extremity resistance training with and without blood flow restriction (BFR) on quadriceps muscle strength and thickness in veterans with advanced multiple sclerosis (MS). METHODS: This will be an assessor-blinded, 2-group (1 to 1 allocation) randomized controlled trial targeting an enrollment of 58 participants with advanced MS as defined by Patient-Determined Disease Steps scale levels 4 to 7. Both groups will complete 10 weeks of twice weekly low-load resistance training (20%-30% of 1-repetition max) targeting knee and hip extension, knee flexion, and ankle plantarflexion. The intervention group will perform all training using BFR, with limb occlusion pressures between 60% and 80% of maximal limb occlusion pressure. Primary outcomes will be quadriceps muscle strength and thickness. Secondary outcomes will include knee flexion and ankle plantarflexion strength, functional mobility, physical activity, and patient-reported measures. All outcomes will be assessed at baseline before the intervention, immediately after the intervention, and at a 2-month follow-up assessment. The change between groups postintervention and after the 2-month follow-up will be reported for all outcomes. All analyses will assume a 2-sided test of hypothesis (α = .05). IMPACT: There is very little evidence for the efficacy of exercise interventions in people with MS who have advanced mobility disability. Resistance training with BFR may be an important approach for people with advanced MS who may not tolerate more conventional, moderate-to-high intensity resistance training. The results of this study will inform clinicians regarding exercise decisions for people with advanced MS and future investigations on the role of BFR in people with MS.

Ultrasound measures of muscle morphology in people with multiple sclerosis are associated with muscle performance and functional mobility.

BACKGROUND: Neurologically-based muscle weakness is a common symptom in people with multiple sclerosis MS (MS), who may also exhibit muscle morphology changes and intrinsic muscle dysfunction. Diagnostic ultrasound (sonography) is a non-invasive, inexpensive, and clinically feasible method to measure muscle morphology. The purpose of this study was to investigate possible asymmetries in lower limb muscle morphology and performance in people with MS, and to assess the relationships of muscle morphology measures with individual patient characteristics, muscle performance, and functional mobility. METHODS: This cross-sectional study was conducted at the Washington, DC Veterans Affairs Medical Center. The study participants were 29 Veterans with MS (52% female, 79% African-American, 48.6 ± 11.2 years old, Mean Expanded Disability Status Scale: 3.6 ± 1.4) who completed seated knee extension isokinetic strength and power tests, functional assessments (Timed 25-Foot Walk - T25FW, 5-Times Sit-to-Stand - 5STS), and quantitative B-mode ultrasound image acquisition of the rectus femoris muscle to derive morphology measures (thickness and echogenicity). The limb with weaker knee extension strength was identified as the more-involved limb. Differences between the more and less-involved limb were quantified using a t-test for all muscle morphology and muscle performance measures. Relationships between muscle morphology and patient characteristics, muscle performance, and functional mobility were evaluated using bivariate and multivariate analyses. RESULTS: The rectus femoris thickness from the more-involved limb was lower (p<0.001) than that of the less-involved limb, whereas echogenicity was not different between the two limbs (p=0.147). Rectus femoris thickness of the more-involved limb was directly related to age (r=-0.63, p<0.001), muscle strength (r=0.53, p=0.003) and power (r=0.53, p=0.003), and gait speed (r=0.42, p=0.024); whereas its echogenicity was positively associated only with muscle strength (r=-0.46, p=0.013) and power (r=-0.50, p=0.006). Together rectus femoris thickness and echogenicity of the more involved limb explained 44% and 48% of the variance in muscle strength and power, respectively (p<0.001). CONCLUSION: This study supports the ability of sonography to measure muscle morphology in people with MS, identify asymmetries, and quantify associations with important clinical correlates. Compared with more invasive and costly alternatives, sonography is a clinically feasible, relatively low-cost tool that can be used to assess muscle morphology in people with MS. Further research is warranted to determine the potential clinical utility of sonographic measures of muscle morphology in evaluating changes due to disease progression or therapeutic interventions in this population.

Utilization of Mid-Thigh Magnetic Resonance Imaging to Predict Lean Body Mass and Knee Extensor Strength in Obese Adults.

Purpose: To train and test a machine learning model to automatically measure mid-thigh muscle cross-sectional area (CSA) to provide rapid estimation of appendicular lean mass (ALM) and predict knee extensor torque of obese adults. Methods: Obese adults [body mass index (BMI) = 30-40 kg/m2, age = 30-50 years] were enrolled for this study. Participants received full-body dual-energy X-ray absorptiometry (DXA), mid-thigh MRI, and completed knee extensor and flexor torque assessments via isokinetic dynamometer. Manual segmentation of mid-thigh CSA was completed for all MRI scans. A convolutional neural network (CNN) was created based on the manual segmentation to develop automated quantification of mid-thigh CSA. Relationships were established between the automated CNN values to the manual CSA segmentation, ALM via DXA, knee extensor, and flexor torque. Results: A total of 47 obese patients were enrolled in this study. Agreement between the CNN-automated measures and manual segmentation of mid-thigh CSA was high (>0.90). Automated measures of mid-thigh CSA were strongly related to the leg lean mass (r = 0.86, p < 0.001) and ALM (r = 0.87, p < 0.001). Additionally, mid-thigh CSA was strongly related to knee extensor strength (r = 0.76, p < 0.001) and moderately related to knee flexor strength (r = 0.48, p = 0.002). Conclusion: CNN-measured mid-thigh CSA was accurate compared to the manual segmented values from the mid-thigh. These values were strongly predictive of clinical measures of ALM and knee extensor torque. Mid-thigh MRI may be utilized to accurately estimate clinical measures of lean mass and function in obese adults.

Eccentric Exercise: Adaptations and Applications for Health and Performance.

The goals of this narrative review are to provide a brief overview of the muscle and tendon adaptations to eccentric resistance exercise and address the applications of this form of training to aid rehabilitative interventions and enhance sports performance. This work is centered on the author contributions to the Special Issue entitled "Eccentric Exercise: Adaptations and Applications for Health and Performance". The major themes from the contributing authors include the need to place greater attention on eccentric exercise mode selection based on training goals and individual fitness level, optimal approaches to implementing eccentric resistance exercise for therapeutic purposes, factors that affect the use of eccentric exercise across the lifespan, and general recommendations to integrate eccentric exercise in athletic training regimens. The authors propose that movement velocity and the absorption or recovery of kinetic energy are critical components of eccentric exercise programming. Regarding the therapeutic use of eccentric resistance training, patient-level factors regarding condition severity, fitness level, and stage of rehabilitation should govern the plan of care. In athletic populations, use of eccentric exercise may improve movement competency and promote improved safety and performance of sport-specific tasks. Eccentric resistance training is a viable option for youth, young adults, and older adults when the exercise prescription appropriately addresses program goals, exercise tolerability, and compliance. Despite the benefits of eccentric exercise, several key questions remain unanswered regarding its application underscoring the need for further investigation.

The Validity of the Single-Leg Heel Raise Test in People With Multiple Sclerosis: A Cross-Sectional Study.

Background: The single-leg heel raise test is a common clinical assessment; however, little is known about its validity in people with multiple sclerosis (MS). This study investigated the validity of the single-leg heel raise test in a group of people with MS and a healthy control group (CTL). Materials and Methods: Twenty-one people with MS (49 ± 12 years, Expanded Disability Status Scale 1.5-5.5) and 10 healthy controls (48 ± 12 years) performed the single-leg heel raise test, ankle plantarflexion isometric strength assessment using electromechanical dynamometry, and mobility measures (Timed 25-Foot Walk, 2-Min Walk Test, Functional Stair Test). Results: Convergent validity between the heel raise test and strength was moderate for participants with MS completing <20 heel raises (r = 0.63, p = 0.001) but weak for the entire sample (r = 0.30, p = 0.020). Compared to the average CTL group values, the heel raise test differentiated between groups on the MS groups' weaker (p < 0.001) and stronger (p = 0.003) limbs, while strength only differentiated between groups on the weaker limb (p = 0.010). Considering the weaker and strong limbs from the MS group and the CTL group average values, the mobility measures had moderate-to-strong correlations with the heel raise test on the weaker MS limb + CTL (r = 0.71-0.78) and stronger MS limb + CTL (r = 0.62-0.70), and weak-to-moderate correlations with strength on the weaker MS limb + CTL (r = 0.49-0.58, p = 0.001-0.007). Discussion: In people with MS, the single-leg heel raise test may be clinically useful as it identified impaired muscle performance and differentiated muscle performance from a healthy control group and, together with the control group, correlated with functional mobility.

Rate of Force Development Is Related to Maximal Force and Sit-to-Stand Performance in Men With Stages 3b and 4 Chronic Kidney Disease.

INTRODUCTION: The primary aims of the present study were to assess the relationships of early (0-50 ms) and late (100-200 ms) knee extensor rate of force development (RFD) with maximal voluntary force (MVF) and sit-to-stand (STS) performance in participants with chronic kidney disease (CKD) not requiring dialysis. METHODS: Thirteen men with CKD (eGFR = 35.17 ±.5 ml/min per 1.73 m2, age = 70.56 ±.4 years) and 12 non-CKD men (REF) (eGFR = 80.31 ± 4.8 ml/min per 1.73 m2, age = 70.22 ±.9 years) performed maximal voluntary isometric contractions to determine MVF and RFD of the knee extensors. RFD was measured at time intervals 0-50 ms (RFD0-50) and 100-200 ms (RFD100-200). STS was measured as the time to complete five repetitions. Measures of rectus femoris grayscale (RF GSL) and muscle thickness (RF MT) were obtained via ultrasonography in the CKD group only. Standardized mean differences (SMD) were used to examine differences between groups. Bivariate relationships were assessed by Pearson's product moment correlation. RESULTS: Knee extensor MVF adjusted for body weight (CKD=17.14 ±.1 N·kg0.67, REF=21.55 ±.3 N·kg0.67, SMD = 0.79) and STS time (CKD = 15.93 ±.4 s, REF = 12.23 ±.7 s, SMD = 1.03) were lower in the CKD group than the REF group. Absolute RFD100-200 was significantly directly related to adjusted MVF in CKD (r = 0.56, p = 0.049) and REF (r = 0.70, p = 0.012), respectively. STS time was significantly inversely related to absolute (r = -0.75, p = 0.008) and relative RFD0-50 (r = -0.65, p = 0.030) in CKD but not REF (r = 0.08, p = 0.797; r = 0.004, p = 0.991). Significant inverse relationships between RF GSL adjusted for adipose tissue thickness and absolute RFD100-200 (r =-0.59, p = 0.042) in CKD were observed. CONCLUSION: The results of the current study highlight the declines in strength and physical function that occur in older men with CKD stages 3b and 4 not requiring dialysis. Moreover, early RFD was associated with STS time in CKD while late RFD was associated MVF in both CKD and REF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03160326 and NCT02277236.

Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis.

Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expanded and antigen-driven endomysial T cells, the disease is resistant to immunotherapies. Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months. We designed a proof-of-principle study to examine if one series of Alemtuzumab infusions in sIBM patients depletes not only peripheral blood lymphocytes but also endomysial T cells and alters the natural course of the disease. Thirteen sIBM patients with established 12-month natural history data received 0.3 mg/kg/day Alemtuzumab for 4 days. The study was powered to capture > or =10% increase strength 6 months after treatment. The primary end-point was disease stabilization compared to natural history, assessed by bi-monthly Quantitative Muscle Strength Testing and Medical Research Council strength measurements. Lymphocytes and T cell subsets were monitored concurrently in the blood and the repeated muscle biopsies. Alterations in the mRNA expression of inflammatory, stressor and degeneration-associated molecules were examined in the repeated biopsies. During a 12-month observation period, the patients' total strength had declined by a mean of 14.9% based on Quantitative Muscle Strength Testing. Six months after therapy, the overall decline was only 1.9% (P < 0.002), corresponding to a 13% differential gain. Among those patients, four improved by a mean of 10% and six reported improved performance of daily activities. The benefit was more evident by the Medical Research Council scales, which demonstrated a decline in the total scores by 13.8% during the observation period but an improvement by 11.4% (P < 0.001) after 6 months, reaching the level of strength recorded 12 months earlier. Depletion of peripheral blood lymphocytes, including the naive and memory CD8+ cells, was noted 2 weeks after treatment and persisted up to 6 months. The effector CD45RA(+)CD62L(-) cells, however, started to increase 2 months after therapy and peaked by the 4th month. Repeated muscle biopsies showed reduction of CD3 lymphocytes by a mean of 50% (P < 0.008), most prominent in the improved patients, and reduced mRNA expression of stressor molecules Fas, Mip-1a and alphaB-crystallin; the mRNA of desmin, a regeneration-associated molecule, increased. This proof-of-principle study provides insights into the pathogenesis of inclusion-body myositis and concludes that in sIBM one series of Alemtuzumab infusions can slow down disease progression up to 6 months, improve the strength of some patients, and reduce endomysial inflammation and stressor molecules. These encouraging results, the first in sIBM, warrant a future study with repeated infusions

Preliminary Study of the Effects of Eccentric-Overload Resistance Exercise on Physical Function and Torque Capacity in Chronic Kidney Disease.

The purpose of this preliminary study was to describe changes in physical function and torque capacity in adults with chronic kidney disease (CKD) in response to a novel progressive eccentric-overload resistance exercise (ERE) regime. Participants included men (n = 4) diagnosed with CKD according to estimated glomerular filtration rate (eGFR) between 59 and 15 mL/kg/1.73 m2 and not requiring dialysis. Physical function was determined by the Short Physical Performance Battery (SPPB), five repetitions of a sit-to-stand (STS) task, and timed-up and go (TUG). Knee extensor strength was assessed using both isometric and isokinetic contractions and performance fatigability indexes were calculated during a 30-s maximal isometric test and a 30-contraction isokinetic test at 180°/second. None of the patients exhibited significant worsening in their health status after training. Participants demonstrated improvements in several measures of physical function and torque capacity following 24 sessions of ERE. Following training, performance fatigability remained relatively stable despite the increases in torque capacity, indicating the potential for greater fatigue resistance. These findings provide initial evidence for ERE as a potential treatment option to combat declines in physical function and neuromuscular impairments in people with CKD. Future research is required to determine optimal progression strategies for maximizing specific neuromuscular and functional outcomes when using ERE in this patient population.

The "Journal of Functional Morphology and Kinesiology" Journal Club Series: PhysioMechanics of Human Locomotion.

We are glad to introduce the Third Journal Club of Volume five, the third issue. This edition is focused on relevant studies published in the last years in the field of PhysioMechanics of Human Locomotion, chosen by our Editorial Board members and their colleagues. We hope to stimulate your curiosity in this field and to share with you the passion for the Sports Medicine and Movement Sciences seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture.

Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging.

Skeletal muscle fat infiltration (known as myosteatosis) is an ectopic fat depot that increases with aging and is recognized to negatively correlate with muscle mass, strength, and mobility and disrupt metabolism (insulin resistance, diabetes). An interdisciplinary workshop convened by the National Institute on Aging Division of Geriatrics and Clinical Gerontology on September 2018, discussed myosteatosis in the context of skeletal muscle function deficit (SMFD). Its purpose was to gain a better understanding of the roles of myosteatosis in aging muscles and metabolic disease, particularly its potential determinants and clinical consequences, and ways of properly assessing it. Special attention was given to functional status and standardization of measures of body composition (including the value of D3-creatine dilution method) and imaging approaches [including ways to better use dual-energy X-ray absorptiometry (DXA) through the shape and appearance modeling] to assess lean mass, sarcopenia, and myosteatosis. The workshop convened innovative new areas of scientific relevance to light such as the effect of circadian rhythms and clock disruption in skeletal muscle structure, function, metabolism, and potential contribution to increased myosteatosis. A muscle-bone interaction perspective compared mechanisms associated with myosteatosis and bone marrow adiposity. Potential preventive and therapeutic approaches highlighted ongoing work on physical activity, myostatin treatment, and calorie restriction. Myosteatosis' impact on cancer survivors raised new possibilities to identify its role and to engage in cross-disciplinary collaboration. A wide range of research opportunities and challenges in planning for the most appropriate study design, interpretation, and translation of findings into clinical practice were discussed and are presented here.

Patellofemoral knee pain in an adult with radiographic osteoarthritis and human immunodeficiency virus infection.

STUDY DESIGN: Resident's case problem. BACKGROUND: Kaposi's sarcoma (KS) is the most common form of cancer in patients with human immunodeficiency virus (HIV) infection. Although KS is often initially asymptomatic, this neoplasm may progress to affect multiple organ systems, including structures of the musculoskeletal system, which can produce symptoms similar to those associated with common orthopaedic conditions. This resident's case problem describes the evaluation and differential diagnosis of a 45-year-old male with HIV and KS, referred to physical therapy with an initial diagnosis of radiographic osteoarthritis (OA) and patellofemoral pain syndrome (PFPS) of the left knee. His primary complaint was knee pain during end range knee flexion. DIAGNOSIS: The history, systems review, and examination suggested a source of pain of a nonorthopaedic origin. Differential examination ruled out clinical OA, PFPS, ligament/cartilage derangement, and tendonitis. Avascular necrosis of the medial femoral condyle was also considered as a possible source of pain. Recent blood tests indicated a high viral load and low CD4 count, which might have increased susceptibility to opportunistic infections or KS tumor progression. The patient was referred back to his physician for additional follow-up. Magnetic resonance imaging (MRI) of the knees were consistent with a systemic inflammatory process such as KS. A true-cut biopsy was subsequently scheduled, which confirmed KS lesions at the left knee. DISCUSSION: Physical therapists who manage orthopaedic conditions should be aware of the disablement that may result from acquired immunodeficiency syndrome-related KS. A thorough joint-specific examination, with a broad differential diagnosis, should be employed for patients having known systemic diseases. LEVEL OF EVIDENCE: Differential diagnosis, level 4.

Acute effects of static, dynamic, and proprioceptive neuromuscular facilitation stretching on muscle power in women.

The purpose of this study was to investigate the acute effects of 3 types of stretching-static, dynamic, and proprioceptive neuromuscular facilitation (PNF)-on peak muscle power output in women. Concentric knee extension power was measured isokinetically at 60 degrees x s(-1) and 180 degrees x s(-1) in 12 healthy and recreationally active women (mean age +/- SD, 24 +/- 3.3 years). Testing occurred before and after each of 3 different stretching protocols and a control condition in which no stretching was performed. During 4 separate laboratory visits, each subject performed 5 minutes of stationary cycling at 50 W before performing the control condition, static stretching protocol, dynamic stretching protocol, or PNF protocol. Three submaximal warm-up trials preceded 3 maximal knee extensions at each testing velocity. A 2-minute rest was allowed between testing at each velocity. The results of the statistical analysis indicated that none of the stretching protocols caused a decrease in knee extension power. Dynamic stretching produced percentage increases (8.9% at 60 degrees x s(-1) and 6.3% at 180 degrees x s(-1)) in peak knee extension power at both testing velocities that were greater than changes in power after static and PNF stretching. The findings suggest that dynamic stretching may increase acute muscular power to a greater degree than static and PNF stretching. These findings may have important implications for athletes who participate in events that rely on a high level of muscular power.

Physical Therapy Considerations for Chronic Kidney Disease and Secondary Sarcopenia.

Chronic kidney disease (CKD) is a progressive condition that may negatively affect musculoskeletal health. These comorbidities may include malnutrition, osteoporosis, and decreased lean body mass. Secondary sarcopenia due to CKD may be associated with mobility limitations and elevated fall risk. Physical therapists are well-positioned among the health care team to screen for secondary sarcopenia in those with CKD and for the treatment of musculoskeletal comorbid conditions that may affect functional performance. Given the consequences of both low muscle mass and low bone mineral density, appropriate and timely physical therapy is important for fall risk assessment and intervention to minimize the susceptibility to bone fracture. While strength training has been studied less frequently than aerobic training for the management of secondary CKD conditions, evidence suggests that this patient population benefits from participation in strength training programs. However, the provision of a formal exercise prescription by a health care professional, along with formal implementation of an exercise program, may need to be more fully integrated into the standard plan of care for individuals with CKD.