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Bone marrow aspirate concentrate (BMAC) and adipose-derived stromal vascular fraction (ADSVF) are the most marketed stem cell therapies to treat a variety of conditions in the general population and elite athletes. Both tissues have been used interchangeably clinically even though their detailed composition, heterogeneity, and mechanisms of action have neither been rigorously inventoried nor compared. This lack of information has prevented investigations into ideal dosages and has facilitated anecdata and misinformation. Here, we analyzed single-cell transcriptomes, proteomes, and flow cytometry profiles from paired clinical-grade BMAC and ADSVF. This comparative transcriptional atlas challenges the prevalent notion that there is one therapeutic cell type present in both tissues. We also provide data of surface markers that may enable isolation and investigation of cell (sub)populations. Furthermore, the proteome atlas highlights intertissue and interpatient heterogeneity of injected proteins with potentially regenerative or immunomodulatory capacities. An interactive webtool is available online.

BackgroundPosterolateral rotatory instability (PLRI) results from lateral ulnar collateral ligament (LCL) deficiency. The lateral pivot shift test is used to diagnose PLRI but can be difficult to perform and is poorly tolerated. We present a new maneuver, the Posterior Radiocapitellar Subluxation Test (PRST), that we believe is easier to perform. The purpose of this study was to compare the efficacy and reproducibility of the PRST with the lateral pivot shift test.MethodsWe obtained 10 cadaveric upper extremity specimens, performed a Kocher approach on each, released the LCL origin in 5, then closed. The specimens were randomized, and 3 attending orthopedic surgeons and 1 resident blindly performed the PRST then the lateral pivot shift test after re-randomization and assessed presence or absence of PLRI. This process was repeated the following day. The data for each test were analyzed for sensitivity, specificity, and accuracy.ResultsFor the blinded testing when comparing PRST with the pivot shift test, overall accuracy was 77.5%, compared with 67.5% (P = .03), sensitivity was 75.0%, compared with 50.0% (P = .003), and specificity was 80.0%, compared with 85.0% (P = .55). Conclusions: The PRST appears to be at least as accurate as the lateral pivot shift test, with comparable intraobserver and interobserver reliability.

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes. Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair (n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae. Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that there are changing processes in the muscle at each time point. Broadly, 1-week post-repair differentially expressed genes were significantly enriched in pathways of metabolism and energetic activity, binding, and regulation. Many were also significantly enriched at 2 weeks, with the addition of NIF/NF-kappaB signaling, transcription in response to hypoxia, and mRNA stability alongside many additional pathways. There was also a shift in transcriptional activity at 4 weeks post-repair with significantly enriched pathways for lipids, hormones, apoptosis, and cytokine activity, despite an overall decrease in the number of differentially expressed genes. At 8 weeks post-repair there were no DE genes when compared to control. These transcriptional profiles were correlated with the histological findings of increased fat, degeneration, and fibrosis. Specifically, correlated gene sets were enriched for fatty acid metabolism, TGF-B-related, and other pathways. Discussion: This study identifies the timeline of transcriptional changes in muscle after RC repair, which by itself, does not induce a growth/regenerative response as desired. Instead, it is predominately related to metabolism/energetics changes at 1 week post-repair, unclear or asynchronous transcriptional diversity at 2 weeks post-repair, increased adipogenesis at 4 weeks post-repair, and a low transcriptional steady state or a dysregulated stress response at 8 weeks post-repair.

Low vertebral bone mass is a major risk factor for vertebral compression fractures. Although sarcopenia has been shown to be associated with low bone mineral density (BMD), it is not known whether trunk musculature is directly associated with lumbar BMD, and whether exercise modifies this association. Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we sought to determine the association of muscle density and fat fraction of the psoas, paraspinal, and oblique muscle groups with L3 lumbar volumetric BMD, and whether these associations were modified by exercise. We obtained L3 vBMD measurements, and fat and muscle measurements (in Hounsfield units [HU]) from abdominal computed tomography (CT) scans spanning the L2 -L4 intervertebral disc spaces. Muscle density was defined as the mean HU value for a muscle group area. Fat fraction was calculated as the mean HU value for the muscle group fat area/total muscle group area (cm2 ). Exercise data were self-reported (MET-minute/week). We utilized multivariable linear regression to evaluate these associations, stratified by gender, and adjusting for demographics, body mass index (BMI), smoking status, impaired fasting glucose, and corticosteroid and anti-resorptive medication use. Among 1923 MESA participants, mean ± standard deviation (SD) age was 62 ± 10 years, 49% were female, 40% white, 21% black, 26% Hispanic/Latino, and 13% Chinese. In fully adjusted analysis, for every 1-SD higher psoas fat fraction, there was a 3.19-SD lower L3 vBMD in men and 4.3-SD lower L3 vBMD in women (p

BackgroundLumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology.MethodsMultifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality.ResultsRelationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045).ConclusionFibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

Rotator cuff (RC) tears present a treatment challenge due to muscle atrophy and degeneration, fatty infiltration, and fibrosis. The purpose of this study was to generate a high time-resolution model of RC tear in rabbits and to characterize the progression of architectural and histological changes. Thirty-five female New Zealand White rabbits (age: 6 months) underwent left supraspinatus tenotomy. Five rabbits were used to evaluate immediate muscle architectural changes. The remaining 30 rabbits underwent right shoulder sham surgery and sacrifice at 1, 2, 4, 8, or 16 weeks. Histology was used to quantify muscle fiber cross-sectional area (CSA), muscle degeneration and regeneration, and fat localized to inter- versus intrafascicular regions. Muscle fiber CSA decreased by 26.5% compared to sham at 16 weeks (effect of treatment, p

BackgroundQuantification of the magnitude and spatial distribution of muscle blood flow changes following exercise may improve our understanding of the effectiveness of various exercise prescriptions. Intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) is a technique that quantifies molecular diffusion and microvascular blood flow, and has recently gained momentum as a method to evaluate a muscle's response to exercise. It has also been shown to predict responses to exercise-based physical therapy in individuals with low back pain. However, no study has evaluated the sensitivity of IVIM-MRI to exercise of varying intensity in humans. Here, we aimed to evaluate IVIM signal changes of the paraspinal muscles in response to moderate and high intensity lumbar extension exercise in healthy individuals.MethodsIVIM data were collected in 11 healthy volunteers before and immediately after a 3-min bout of moderate and high-intensity resisted lumbar extension. IVIM data were analyzed to determine the average perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D) in the bilateral paraspinal muscles. Changes in IVIM parameters were compared between the moderate and high intensity exercise bouts.ResultsExercise increased all IVIM parameters, regardless of intensity (p < 0.003). Moderate intensity exercise resulted in a 11.2, 19.6, and 3.5% increase in f, D* and D, respectively. High intensity exercise led to a similar increase in f (12.2%), but much greater changes in D* (48.6%) and D (7.9%).ConclusionIVIM parameter increases suggest that both the moderate and high-intensity exercise conditions elicited measurable changes in blood flow (increased f and D*) and extravascular molecular diffusion rates (increased D), and that there was a dose-dependence of exercise intensity on D* and D.

BackgroundConditions affecting skeletal muscle, such as chronic rotator cuff tears, low back pain, dystrophies, and many others, often share changes in muscle phenotype: intramuscular adipose and fibrotic tissue increase while contractile tissue is lost. The underlying changes in cell populations and cell ratios observed with these phenotypic changes complicate the interpretation of tissue-level transcriptional data. Novel single-cell transcriptomics has limited capacity to address this problem because muscle fibers are too long to be engulfed in single-cell droplets and single nuclei transcriptomics are complicated by muscle fibers' multinucleation. Therefore, the goal of this project was to evaluate the potential and challenges of a spatial transcriptomics technology to add dimensionality to transcriptional data in an attempt to better understand regional cellular activity in heterogeneous skeletal muscle tissue.MethodsThe 3' Visium spatial transcriptomics technology was applied to muscle tissue of a rabbit model of rotator cuff tear. Healthy control and tissue collected at 2 and 16 weeks after tenotomy was utilized and freshly snap frozen tissue was compared with tissue stored for over 6 years to evaluate whether this technology is retrospectively useful in previously acquired tissues. Transcriptional information was overlayed with standard hematoxylin and eosin (H&E) stains of the exact same histological sections.ResultsSequencing saturation and number of genes detected was not affected by sample storage duration. Unbiased clustering matched the underlying tissue type-based on H&E assessment. Connective-tissue-rich areas presented with lower unique molecular identifier counts are compared with muscle fibers even though tissue permeabilization was standardized across the section. A qualitative analysis of resulting datasets revealed heterogeneous fiber degeneration-regeneration after tenotomy based on (neonatal) myosin heavy chain 8 detection and associated differentially expressed gene analysis.ConclusionsThis protocol can be used in skeletal muscle to explore spatial transcriptional patterns and confidently relate them to the underlying histology, even for tissues that have been stored for up to 6 years. Using this protocol, there is potential for novel transcriptional pathway discovery in longitudinal studies since the transcriptional information is unbiased by muscle composition and cell type changes.

IntroductionThe potential of regenerative medicine to improve human health has led to the rapid expansion of stem cell clinics throughout the world with varying levels of regulation and oversight. This has led to a market ripe for stem cell tourism, with Tijuana, Mexico, as a major destination. In this study, we characterize the online marketing, intervention details, pricing of services, and assess potential safety risks through web surveillance of regenerative medicine clinics marketing services in Tijuana.MethodsWe conducted structured online search queries from March to April 2019 using 296 search terms in English and Spanish on two search engines (Google and Bing) to identify websites engaged in direct-to-consumer advertising of regenerative medicine services. We performed content analysis to characterize three categories of interest: online presence, tokens of scientific legitimacy, and intervention details.ResultsOur structured online searches resulted in 110 unique websites located in Tijuana corresponding to 76 confirmed locations. These clinics' online presence consisted of direct-to-consumer advertising mainly through a dedicated website (94.5%) or Facebook page (65.5%). The vast majority of these websites (99.1%) did not mention any affiliation to an academic institutions or other overt tokens of scientific legitimacy. Most clinics claimed autologous tissue was the source of treatments (67.3%) and generally did not specify route of administration. Additionally, of the Tijuana clinics identified, 13 claimed licensing, though only 1 matched with available licensing information.ConclusionsRegenerative medicine clinics in Tijuana have a significant online presence using direct-to-consumer advertising to attract stem-cell tourism clientele in a bustling border region between Mexico and the USA. This study adds to existing literature evidencing the unregulated nature of online stem cell offerings and provides further evidence of the need for regulatory harmonization, particularly to address stem cell services being offered online across borders.

BackgroundAdolescent idiopathic scoliosis (AIS) is a condition resulting in spinal deformity and tissue adaptation of the paraspinal muscles. Although prior studies have demonstrated asymmetries in fiber type and other energetic features of muscle on the concave side of the curve, muscle morphology, architecture, and composition have not been evaluated. Therefore, the purpose of this study was to compare differences in paraspinal muscle microarchitecture and composition between concave and convex sides of a scoliotic curve in individuals with AIS.MethodsParaspinal muscle biopsies were obtained at the apex of the scoliotic curve in 29 individuals with AIS undergoing surgical deformity correction. Histological assays were performed to quantify fiber size, evidence of muscle degeneration and regeneration, and tissue composition (proportion of muscle, collagen, and fat). Differences between contralateral muscle samples were compared using two-tailed paired Student's t tests, and relationships between clinical characteristics (age and curve severity) and muscle characteristics were investigated using Pearson correlations.ResultsMuscle fibers were significantly larger on the convex side of the curve apex (P = .001), but were lower than literature-based norms for healthy paraspinal muscle. There were no differences in amount of degeneration/regeneration (P = .490) or the proportion of muscle and collagen (P > .350) between the concave and convex sides, but high levels of collagen were observed. There was a trend toward higher fat content on the concave side (P = .074). Larger fiber size asymmetries were associated with greater age (r = .43, P = .046), and trended toward an association with greater curve severity (r = .40, P = .069).ConclusionsThis study demonstrates that although muscle fibers are larger on the convex side of the scoliotic curve in AIS, muscles on both sides are atrophic compared to non-scoliotic individuals, and demonstrate levels of collagen similar to severe degenerative spinal pathologies. These findings provide insight into biological maladaptations occurring in paraspinal muscle in the presence of AIS.

Biologically augmented surgical treatments of orthopaedic conditions are increasingly popular. Bone marrow aspirate concentrate is a key orthobiologic tissue source, and the field is moving from the standard iliac crest marrow aspiration toward local aspirations of marrow depots that are accessible during the standard-of-care procedures in an attempt to reduce morbidity, surgery time, and cost. Here, we present the aspiration of the standard iliac marrow depot, but through a novel acetabular approach during total hip arthroplasty. This procedure markedly simplifies biologic augmentation with bone marrow aspirate concentrate in this large patient cohort.

PurposeThe development of ultrashort echo time (UTE) MRI sequences has led to improved imaging of tissues with short T2 relaxation times, such as the deep layer cartilage and meniscus. UTE combined with adiabatic T1ρ preparation (UTE-Adiab-T1ρ) is an MRI measure with low sensitivity to the magic angle effect. This study aimed to investigate the sensitivity of UTE-Adiab-T1ρ to mechanical load-induced deformations in the tibiofemoral cartilage and meniscus of human cadaveric knee joints.MethodsEight knee joints from young (42 ± 12 years at death) donors were evaluated on a 3 T scanner using the UTE-Adiab-T1ρ sequence under four sequential loading conditions: load = 0 N (Load0), load = 300 N (Load1), load = 500 N (Load2), and load = 0 N (Unload). UTE-Adiab-T1ρ was measured in the meniscus (M), femoral articular cartilage (FAC), tibial articular cartilage (TAC), articular cartilage regions uncovered by meniscus (AC-UC), and articular cartilage regions covered by meniscus (AC-MC) within region of interests (ROIs) manually selected by an experienced MR scientist. The Kruskal-Wallis test, with corrected significance level for multiple comparisons, was used to examine the UTE-Adiab-T1ρ differences between different loading conditions.ResultsUTE-Adiab-T1ρ decreased in all grouped ROIs under both Load1 and Load2 conditions (-18.7% and - 16.9% for M, -18.8% and - 12.6% for FAC, -21.4% and - 10.7% for TAC, -26.2% and - 13.9% for AC-UC, and - 16.9% and - 10.7% for AC-MC). After unloading, average UTE-Adiab-T1ρ increased across all ROIs and within a lower range compared with the average UTE-Adiab-T1ρ decreases induced by the two previous loading conditions. The loading-induced differences were statistically non-significant.ConclusionsWhile UTE-Adiab-T1ρ reduction by loading is likely an indication of tissue deformation, the increase of UTE-Adiab-T1ρ within a lower range by unloading implies partial tissue restoration. This study highlights the UTE-Adiab-T1ρ technique as an imaging marker of tissue function for detecting deformation patterns under loading.

PurposeEvaluate the relationship between muscle microstructure, diffusion time (Δ), and the diffusion tensor (DT) to identify the optimal Δ where changes in muscle fiber size may be detected.MethodsThe DT was simulated in models with histology informed geometry over a range of Δ with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Δ between healthy and injured skeletal muscle models was calculated, to identify the optimal Δ at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth.ResultsAcross all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models.ConclusionThese findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Δ should be ~170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should be sampled in order to maximize diffusion contrast, particularly when the disease process is unknown.

Advancement of tissue engineering and regenerative medicine (TERM) strategies to replicate tissue structure and function has led to the need for noninvasive assessment of key outcome measures of a construct's state, biocompatibility, and function. Histology based approaches are traditionally used in pre-clinical animal experiments, but are not always feasible or practical if a TERM construct is going to be tested for human use. In order to transition these therapies from benchtop to bedside, rigorously validated imaging techniques must be utilized that are sensitive to key outcome measures that fulfill the FDA standards for TERM construct evaluation. This review discusses key outcome measures for TERM constructs and various clinical- and research-based imaging techniques that can be used to assess them. Potential applications and limitations of these techniques are discussed, as well as resources for the processing, analysis, and interpretation of biomedical images.

BackgroundDue to its unique arrangement, the deep and superficial fibers of the multifidus may have differential roles for maintaining spine stabilization and lumbar posture; the superficial multifidus is responsible for lumbar extension and the deep multifidus for intersegmental stability. In patients with chronic lumbar spine pathology, muscle activation patterns have been shown to be attenuated or delayed in the deep, but not superficial, multifidus. This has been interpreted as pain differentially influencing the deep region. However, it is unclear if degenerative changes affecting the composition and function of the multifidus differs between the superficial and deep regions, an alternative explanation for these electrophysiological changes. Therefore, the goal of this study was to investigate macrostructural and microstructural differences between the superficial and deep regions of the multifidus muscle in patients with lumbar spine pathology.MethodsIn 16 patients undergoing lumbar spinal surgery for degenerative conditions, multifidus biopsies were acquired at two distinct locations: 1) the most superficial portion of muscle adjacent to the spinous process and 2) approximately 1 cm lateral to the spinous process and deeper at the spinolaminar border of the affected vertebral level. Structural features related to muscle function were histologically compared between these superficial and deep regions, including tissue composition, fat fraction, fiber cross sectional area, fiber type, regeneration, degeneration, vascularity and inflammation.ResultsNo significant differences in fat signal fraction, muscle area, fiber cross sectional area, muscle regeneration, muscle degeneration, or vascularization were found between the superficial and deep regions of the multifidus. Total collagen content between the two regions was the same. However, the superficial region of the multifidus was found to have less loose and more dense collagen than the deep region.ConclusionsThe results of our study did not support that the deep region of the multifidus is more degenerated in patients with lumbar spine pathology, as gross degenerative changes in muscle microstructure and macrostructure were the same in the superficial and deep regions of the multifidus. In these patients, the multifidus is not protected in order to maintain mobility and structural stability of the spine.

Magnetic resonance imaging (MRI) is a diagnostic tool that can be used to noninvasively assess lumbar muscle size and fatty infiltration, important biomarkers of muscle health. Diffusion tensor imaging (DTI) is an MRI technique that is sensitive to muscle microstructural features such as fiber size (an important biomarker of muscle health), which is typically only assessed using invasive biopsy techniques. The goal of this study was to establish normative values of level-dependent lumbar muscle size, fat signal fraction, and restricted diffusion assessed by MRI in a highly active population. Forty-two active-duty Marines were imaged using a (a) high-resolution anatomical, (b) fat-water separation, and (c) DT-MRI scan. The multifidus and erector spinae muscles were compared at each level using two-way repeated measures ANOVA. Secondary analysis included Three dimensional (3D) reconstructions to qualitatively assess lumbar muscle size, fatty infiltration, and fiber orientation via tractography. The erector spinae was found to be larger than the multifidus above L5, with lower fat signal fraction above L3, and a less restricted diffusion profile than the multifidus above L4, with this pattern reversed in the lower lumbar spine. 3D reconstructions demonstrated accumulations of epimuscular fat in the anterior and posterior regions of the lumbar musculature, with minimal intramuscular fatty infiltration. Tractography images demonstrated different orientations of adjacent lumbar musculature, which cannot be visualized with standard MRI pulse sequences. The level dependent differences found in this study provide a normative baseline, for which to better understand whole muscle and microstructural changes associated with aging, low back pain, and pathology.

Study designProspective observational study-basic science (Level 1).ObjectiveThe aim of this study was to compare expression of functional groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways between paraspinal muscle biopsies from individuals with acute and chronic lumbar spine pathology.Summary of background dataLow back pain is a complex and multifactorial condition that affects a majority of the general population annually. Changes in muscle tissue composition (i.e., fatty and fibrotic infiltration) are a common feature in individuals with lumbar spine pathology associated with low back pain, which often results in functional loss. Understanding the molecular underpinnings of these degenerative changes in different phases of disease progression may improve disease prevention and treatment specificity.MethodsIntraoperative biopsies of the multifidus muscle were obtained from individuals undergoing surgery for acute (6-month duration) lumbar spine pathology. Expression of 42 genes related to myogenesis, atrophy, adipogenesis, metabolism, inflammation, and fibrosis were measured in 33 samples (eight acute, 25 chronic) using qPCR, and tissue composition of fat, muscle, and fibrosis was quantified using histology.ResultsWe found that tissue composition of the biopsies was heterogeneous, resulting in a trend toward lower RNA yields in biopsies with higher proportions of fat (r  0.635), adipogenesis (P > 0.317), myogenesis (P > 0.320), or inflammatory (P > 0.413) genes after adjusting for the proportion of muscle, fat, and connective tissue. However, in the fibrogenesis pathway, we found significant upregulation of CTGF (P = 0.046), and trends for upregulation of COL1A1 (P = 0.061), and downregulation of MMP1 and MMP9 (P = 0.061) in the chronic group.ConclusionThere is increased fibrogenic gene expression in individuals with chronic disease when compared to acute disease, without significant differences in atrophic, myogenic, adipogenic, or inflammatory pathways, suggesting increased efforts should be made to prevent or reverse fibrogenesis to improve patient function in this population.Level of evidenceN/A.

BackgroundMuscle architecture, or the arrangement of sarcomeres and fibers within muscles, defines functional capacity. There are limited data that provide an understanding of hip short external rotator muscle architecture. The purpose of this study was thus to characterize the architecture of these small hip muscles.MethodsEight muscles from 10 independent human cadaver hips were used in this study (n = 80 muscles). Architectural measurements were made on pectineus, piriformis, gemelli, obturators, quadratus femoris, and gluteus minimus. Muscle mass, fiber length, sarcomere length, and pennation angle were used to calculate the normalized muscle fiber length, which defines excursion, and physiological cross-sectional area (PCSA), which defines force-producing capacity.ResultsGluteus minimus had the largest PCSA (8.29 cm2) followed by obturator externus (4.54 cm2), whereas superior gemellus had the smallest PCSA (0.68 cm2). Fiber lengths clustered into long (pectineus - 10.38 cm and gluteus minimus - 10.30 cm), moderate (obturator internus - 8.77 cm and externus - 8.04 cm), or short (inferior gemellus - 5.64 and superior gemellus - 4.85). There were no significant differences among muscles in pennation angle which were all nearly zero. When the gemelli and obturators were considered as a single functional unit, their collective PCSA (10.00 cm2) exceeded that of gluteus minimus as a substantial force-producing group.ConclusionsThe key findings are that these muscles have relatively small individual PCSAs, short fiber lengths, and low pennation angles. The large collective PCSA and short fiber lengths of the gemelli and obturators suggest that they primarily play a stabilizing role rather than a joint rotating role.

BackgroundMuscle atrophy and fatty infiltration of the lumbar extensors is associated with LBP. Exercise-based rehabilitation targets strengthening these muscles, but few studies show consistent changes in muscle quality with standard-of-care rehabilitation. The goal of this study was to assess the effect of high-intensity resistance exercise on lumbar extensor muscle size (cross sectional area) and quality (fat fraction) in individuals with low back pain (LBP).MethodsFourteen patients with LBP were recruited from a local rehabilitation clinic. Patients underwent MRI scanning before and after a standardized 10-week high-intensity machine-based, resistance exercise program. Patient pain, disability, anxiety/depression, satisfaction, strength, and range of motion was compared pre- and post-rehabilitation using analysis of covariance (covariates: age, gender). Exercise-induced changes in MRI, and patient functional outcome measures were correlated using Pearson's correlation test.ResultsNo significant differences were found in muscle size or fatty infiltration of the lumbar extensors over the course of rehabilitation (p > 0.31). However, patients reported reduced pain (p = 0.002) and were stronger (p = 0.03) at the conclusion of the program. Improvements in muscle size and quality for both multifidus and erector spinae correlated with improvements in disability, anxiety/depression, and strength.ConclusionWhile average muscle size and fatty infiltration levels did not change with high-intensity exercise, the results suggest that a subgroup of patients who demonstrate improvements in muscle health demonstrate the largest functional improvements. Future research is needed to identify which patients are most likely to respond to this type of treatment.

Military members are required to carry heavy loads frequently during training and active duty combat. We investigated if operationally relevant axial loads affect lumbar disc kinematics in forty-one male active duty Marines with no previous clinically diagnosed pathology. Marines were imaged standing upright with and without load. From T2-weighted magnetic resonance images, IVD health and kinematic changes between loading conditions and across lumbar levels were evaluated using two-way repeated measures analysis of variance tests. IVD kinematics with loading were compared between individuals with and without signs of degeneration on imaging. Linear regression analyses were performed to determine associations between IVD position and kinematic changes with loading. Fifty-eight percent (118/205) of IVDs showed evidence of degeneration and 3% (7/205) demonstrated a disc bulge. IVD degeneration was not related to posterior annular position (p>0.205). Changes in sagittal intervertebral angle were not associated with changes in posterior annular position between baseline and loaded conditions at any lumbar level (r

Magnetization transfer (MT) magnetic resonance imaging (MRI) can be used to estimate the fraction of water and macromolecular proton pools in tissues. MT modeling paired with ultrashort echo time acquisition (UTE‐MT modeling) has been proposed to improve the evaluation of the myotendinous junction and fibrosis in muscle tissues, which the latter increases with aging. This study aimed to determine if the UTE‐MT modeling technique is sensitive to age‐related changes in the skeletal muscles of the lower leg. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. The legs of 31 healthy younger (28.1 ± 6.1 years old, BMI = 22.3 ± 3.5) and 20 older (74.7 ± 5.5 years old, BMI = 26.7 ± 5.9) female subjects were imaged using UTE sequences on a 3 T MRI scanner. MT ratio (MTR), macromolecular fraction (MMF), macromolecular T2 (T2‐MM), and water T2 (T2‐W) were calculated using UTE‐MT modeling for the anterior tibialis (ATM), posterior tibialis (PTM), soleus (SM), and combined lateral muscles. Results were compared between groups using the Wilcoxon rank sum test. Three independent observers selected regions of interest (ROIs) and processed UTE‐MRI images separately, and the intraclass correlation coefficient (ICC) was calculated for a reproducibility study. Significantly lower mean MTR and MMF values were present in the older compared with the younger group in all studied lower leg muscles. T2‐MM showed significantly lower values in the older group only for PTM and SM muscles. In contrast, T2‐W showed significantly higher values in the older group. The age‐related differences were more pronounced for MMF (−17 to −19%) and T2‐W (+20 to 47%) measurements in all muscle groups compared with other investigated MR measures. ICCs were higher than 0.93, indicating excellent consistency between the ROI selection and MRI measurements of independent readers. As demonstrated by significant differences between younger and older groups, this research emphasizes the potential of UTE‐MT MRI techniques in evaluating age‐related skeletal muscle changes. [ABSTRACT FROM AUTHOR]

OBJECTIVES:To evaluate the safety and acceptability of a novel 8-week intervention integrating exercise, exposure therapy, cognitive restructuring, and a home safety evaluation, conducted by a physical therapist, in reducing fear of falling and activity avoidance. To collect preliminary evidence of efficacy. DESIGN:Randomized pilot study comparing the intervention to time- and attention-equivalent fall prevention education. SETTING:Participants' homes. PARTICIPANTS:42 older adults with disproportionate fear of falling (high fear, low to moderate objective fall risk). MEASUREMENTS:Falls Efficacy Scale-International, modified Activity Card Sort, satisfaction, falls. RESULTS:Relative to education, the intervention reduced fear of falling (d = 1.23) and activity avoidance (d = 1.02) at 8 weeks, but effects eroded over a 6-month follow-up period. The intervention did not increase falls, and participants rated the exercise, exposure therapy, and non-specific elements as most helpful. CONCLUSIONS:An integration of exercise and exposure therapy may help older adults with disproportionate fear of falling, but modifications to the intervention or its duration may be needed to maintain participants' gains.

Background The relationship between lumbar spine posture and muscle structure is not well understood. Objectives To investigate the predictive capacity of muscle structure on lumbar spine posture in active-duty Marines. Methods Forty-three Marines were scanned in this cross-sectional study, using an upright magnetic resonance imaging scanner while standing without load and standing, sitting, and prone on elbows with body armor. Cobb, horizontal, and sacral angles were measured. Marines were then scanned while unloaded in supine using a supine magnetic resonance imaging scanner. The imaging protocol consisted of T2 intervertebral disc mapping; high-resolution, anatomical, fat-water separation, and diffusion tensor imaging to quantify disc hydration and muscle volume, fat fraction, and restricted diffusion profiles in the lumbar muscles. A stepwise multiple linear regression model was used to identify physiological measures predictive of lumbar spine posture. Results The multiple regression model demonstrated that fractional anisotropy of the erector spinae was a significant predictor of lumbar posture for 7 of 18 dependent variables measured, and explained 20% to 35% of the variance in each model. Decreased fractional anisotropy of the erector spinae predicted decreased lordosis, lumbosacral extension, and anterior pelvic tilt. Conclusion Fractional anisotropy is inversely related with muscle fiber size, which is associated with the isometric force-generating capacity of a muscle fiber. This suggests that stronger erector spinae muscles predict decreased lordosis, lumbosacral extension, and anterior pelvic tilt in a highly trained population. J Orthop Sports Phys Ther 2018;48(8):613-621. Epub 17 May 2018. doi:10.2519/jospt.2018.7865.

PurposeTo establish a series of relationships defining how muscle microstructure and diffusion tensor imaging (DTI) are related.MethodsThe relationship among key microstructural features of skeletal muscle (fiber size, fibrosis, edema, and permeability) and the diffusion tensor were systematically simulated over physiologically relevant dimensions individually, and in combination, using a numerical simulation application. Stepwise multiple regression was used to identify which microstructural features of muscle significantly predict the diffusion tensor using single-echo and multi-echo DTI pulse sequences. Simulations were also performed in models with histology-informed geometry to investigate the relationship between fiber size and the diffusion tensor in models with real muscle geometry.ResultsFiber size is the strongest predictor of λ2, λ3, mean diffusivity, and fractional anisotropy in skeletal muscle, accounting for approximately 40% of the variance in the diffusion model when calculated with single-echo DTI. This increased to approximately 70% when diffusion measures were calculated from the short T2 component of the multi-echo DTI sequence. This nonlinear relationship begins to plateau in fibers with greater than 60-μm diameter.ConclusionsAs the normal fiber size of a human muscle fiber is 40 to 60 μm, this suggests that DTI is a sensitive tool to monitor muscle atrophy, but may be limited in measurements of muscle with larger fibers. Magn Reson Med 80:317-329, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

BACKGROUND:Magnetic Resonance Imaging (MRI) is commonly used to assess the health of the lumbar spine and supporting structures. Studies have suggested that fatty infiltration of the posterior lumbar muscles is important in predicting responses to treatment for low back pain. However, methodological differences exist in defining the region of interest (ROI) of a muscle, which limits the ability to compare data between studies. The purpose of this study was to determine reliability and systematic differences within and between two commonly utilized methodologies for ROI definitions of lumbar paraspinal muscle. METHODS:T2-weighted MRIs of the mid-L4 vertebrae from 37 patients with low back pain who were scheduled for lumbar spine surgery were included from a hospital database. Fatty infiltration for these patients ranged from low to high, based on Kjaer criteria. Two methods were used to define ROI: 1) segmentation of the multifidus and erector spinae based on fascial planes including epimuscular fat, and 2) segmentation of the multifidus and erector spinae based on visible muscle boundaries, which did not include epimuscular fat. Total cross sectional area (tCSA), fat signal fraction (FSF), muscle cross sectional area, and fat cross sectional area were measured. Degree of agreement between raters for each parameter was assessed using intra-class correlation coefficients (ICC) and area fraction of overlapping voxels. RESULTS:Excellent inter-rater agreement (ICC > 0.75) was observed for all measures for both methods. There was no significant difference between area fraction overlap of ROIs between methods. Method 1 demonstrated a greater tCSA for both the erector spinae (14-15%, p

Rotator cuff (RC) muscles undergo several detrimental changes following mechanical unloading resulting from RC tendon tear. In this review, we highlight the pathological causes and consequences of mechanical alterations at the whole muscle, muscle fiber, and muscle resident cell level as they relate to RC disease progression. In brief, the altered mechanical loads associated with RC tear lead to architectural, structural, and compositional changes at the whole-muscle and muscle fiber level. At the cellular level, these changes equate to direct disruption of mechanobiological signaling, which is exacerbated by mechanically regulated biophysical and biochemical changes to the cellular and extra-cellular environment (also known as the stem cell "niche"). Together, these data have important implications for both pre-clinical models and clinical practice. In pre-clinical models, it is important to recapitulate both the atrophic and degenerative muscle loss found in humans using clinically relevant modes of injury. Clinically, understanding the mechanics and underlying biology of the muscle will impact both surgical decision-making and rehabilitation protocols, as interventions that may be good for atrophic muscle will have a detrimental effect on degenerating muscle, and vice versa. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:546-556, 2018.

Atrophy is thought to be a primary mode of muscle loss in neuromuscular injuries. The differential effects of central and peripheral injuries on atrophy and degeneration/regeneration in skeletal muscle tissue have not been well described. This study investigated skeletal muscle atrophy and degeneration/regeneration in an animal model of traumatic brain injury (TBI). Eight 8-month-old wild-type C57BL6 mice underwent either a sham craniotomy or TBI targeting the motor cortex. Atrophy (fiber area; FA) and degeneration/regeneration (centralized nuclei proportions; CN) of the soleus and tibialis anterior (TA) muscles were measured 2 months post-injury. Injured soleus FAs were smaller than sham soleus (p = 0.02) and injured TA (p

Detrimental changes in the composition and function of rotator cuff (RC) muscles are hallmarks of RC disease progression. Previous studies have demonstrated both atrophic and degenerative muscle loss in advanced RC disease. However, the relationship between gene expression and RC muscle pathology remains poorly defined, in large part due to a lack of studies correlating gene expression to tissue composition. Therefore, the purpose of this study was to determine how tissue composition relates to gene expression in muscle biopsies from patients undergoing reverse shoulder arthroplasty (RSA). Gene expression related to myogenesis, atrophy and cell death, adipogenesis and metabolism, inflammation, and fibrosis was measured in 40 RC muscle biopsies, including 31 biopsies from reverse shoulder arthroplasty (RSA) cases that had available histology data and 9 control biopsies from patients with intact RC tendons. After normalization to reference genes, linear regression was used to identify relationships between gene expression and tissue composition. Hierarchical clustering and principal component analysis (PCA) identified unique clusters, and fold-change analysis was used to determine significant differences in expression between clusters. We found that gene expression profiles were largely dependent on muscle presence, with muscle fraction being the only histological parameter that was significantly correlated to gene expression by linear regression. Similarly, samples with histologically-confirmed muscle distinctly segregated from samples without muscle. However, two sub-groups within the muscle-containing RSA biopsies suggest distinct phases of disease, with one group expressing markers of both atrophy and regeneration, and another group not significantly different from either control biopsies or biopsies lacking muscle. In conclusion, this study provides context for the interpretation of gene expression in heterogeneous and degenerating muscle, and provides further evidence for distinct stages of RC disease in humans.

Histological and cell-level changes in the lumbar musculature in individuals with chronic lumbar spine degenerative conditions are not well characterized. Although prior literature supports evidence of changes in fiber type and size, little information exists describing the tissue quality and biology of pathological features of muscle in this population. The purpose of this study was to quantify multifidus tissue composition and structure, inflammation, vascularity, and degeneration in individuals with chronic degenerative lumbar spine pathology. Human multifidus biopsies were acquired from 22 consecutive patients undergoing surgery for chronic degenerative lumbar spine pathology. Relative fractions of muscle, adipose, and extracellular matrix were quantified along with muscle fiber type and cross-sectional area (CSA) and markers of inflammation, vascularity, satellite cell density, and muscle degeneration. On average, multifidus biopsies contained 48.5% muscle, 11.7% adipose tissue, and 26.1% collagen tissue. Elevated inflammatory cell counts (48.5 ± 30.0 macrophages/mm2 ) and decreased vascularity (275.6 ± 69.4 vessels/mm2 ) were also observed compared to normative values. Satellite cell densities were on average 13 ± 9 cells per every 100 muscle fibers. Large fiber CSA (3,996.0 ± 1,909.2 µm2 ) and a predominance of type I fibers (61.8 ± 18.0%) were observed in addition to evidence of pathological degeneration-regeneration cycling (18.8 ± 9.4% centrally nucleated fibers, and 55.2 ± 24.2% of muscle regions containing degeneration). High levels of muscle degeneration, inflammation, and decreased vascularity were commonly seen in human multifidus biopsies of individuals with lumbar spine pathology in comparison to normative data. Evidence of active muscle degeneration suggests that changes in muscle tissue are more complex than simple atrophy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2700-2706, 2017.

Low back pain has a 70% higher prevalence in members of the armed forces than in the general population, possibly due to the loads and positions soldiers experience during training and combat. Although the influence of heavy load carriage on standing lumbar spine posture in this population is known, postures in other operationally relevant positions are unknown. Therefore, the purpose of this study was to characterize the effect of simulated military operational positions under relevant loading conditions on global and local lumbar spine postures in active duty male US Marines. Secondary objectives were to evaluate if intervertebral disc degeneration and low back pain affect lumbar spine postures. Magnetic resonance images were acquired on an upright scanner in the following operational positions: Natural standing with no external load, standing with body armor (11.3 kg), sitting with body armor, and prone on elbows with body armor. Custom software was used to measure global lumbar spine posture: Lumbosacral flexion, sacral slope, lordosis, local measures of intervertebral angles, and intervertebral distances. Sitting resulted in decreased lumbar lordosis at all levels of the spine except L1-L2. When subjects were prone on elbows, a significant increase in local lordosis was observed only at L5-S1 compared with all other positions. Marines with disc degeneration (77%) or history of low back pain (72%) had decreased lumbar range of motion and less lumbar extension than healthy Marines. These results indicate that a male Marine's pathology undergoes a stereotypic set of postural changes during functional tasks, which may impair performance. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2145-2153, 2017.

The ability to noninvasively assess skeletal muscle microstructure, which predicts function and disease, would be of significant clinical value. One method that holds this promise is diffusion tensor magnetic resonance imaging (DT-MRI), which is sensitive to the microscopic diffusion of water within tissues and has become ubiquitous in neuroimaging as a way of assessing neuronal structure and damage. However, its application to the assessment of changes in muscle microstructure associated with injury, pathology, or age remains poorly defined, because it is difficult to precisely control muscle microstructural features in vivo. However, recent advances in additive manufacturing technologies allow precision-engineered diffusion phantoms with histology informed skeletal muscle geometry to be manufactured. Therefore, the goal of this study was to develop skeletal muscle phantoms at relevant size scales to relate microstructural features to MRI-based diffusion measurements. A digital light projection based rapid 3D printing method was used to fabricate polyethylene glycol diacrylate based diffusion phantoms with (1) idealized muscle geometry (no geometry; fiber sizes of 30, 50, or 70 μm or fiber size of 50 μm with 40% of walls randomly deleted) or (2) histology-based geometry (normal and after 30-days of denervation) containing 20% or 50% phosphate-buffered saline (PBS). Mean absolute percent error (8%) of the printed phantoms indicated high conformity to templates when "fibers" were >50 μm. A multiple spin-echo echo planar imaging diffusion sequence, capable of acquiring diffusion weighted data at several echo times, was used in an attempt to combine relaxometry and diffusion techniques with the goal of separating intracellular and extracellular diffusion signals. When fiber size increased (30-70 μm) in the 20% PBS phantom, fractional anisotropy (FA) decreased (0.32-0.26) and mean diffusivity (MD) increased (0.44 × 10-3 mm2/s-0.70 × 10-3 mm2/s). Similarly, when fiber size increased from 30 to 70 μm in the 50% PBS diffusion phantoms, a small change in FA was observed (0.18-0.22), but MD increased from 0.86 × 10-3 mm2/s to 1.79 × 10-3 mm2/s. This study demonstrates a novel application of tissue engineering to understand complex diffusion signals in skeletal muscle. Through this work, we have also demonstrated the feasibility of 3D printing for skeletal muscle with relevant matrix geometries and physiologically relevant tissue characteristics.

Military training aims to improve load carriage performance and reduce risk of injuries. Data describing the lumbar spine (LS) postural response to load carriage throughout training are limited. We hypothesised that training would reduce the LS postural response to load. The LS posture of 27 Marines was measured from upright MR images: with and without load (22.6 kg) at the beginning, middle, and end of School of Infantry (SOI) training. Disc degeneration was graded at L5-S1. No changes in posture and disc degeneration were found throughout training. During load carriage the LS became less lordotic and the sacrum more horizontal. Marines with disc degeneration had larger sacral postural perturbations in response to load. Our findings suggest that the postural response to load is defined more by the task needs than by the physical condition of the Marine. Practitioner Summary: The effect of military training on lumbar spine posture is unknown. The lumbar posture of 27 Marines was measured from upright MR images, with and without load throughout infantry training. No changes in posture or IVD degeneration were found across training. Marines with degeneration at the L5-S1 level had larger sacral postural perturbations in response to load.

Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC muscle atrophy and fatty infiltration, with lasting damage even after surgical tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle repair in response to injury, but the inability of RC muscles to recover from chronic RCT tear indicates possible deficits in repair mechanisms. Here we investigated if muscle injury state was a crucial factor during human SMP expansion and differentiation ex vivo. SMPs were isolated from muscles in patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears. Despite using growth factors, physiological niche stiffness, and muscle-mimetic extracellular matrix (ECM) proteins, we found that SMPs isolated from human RC muscle with RCT tears proliferated slower but fused into myosin heavy chain (MHC)-positive myotubes at higher rates than SMPs from untorn RCTs. Proteomic analysis of RC muscle tissue revealed shifts in muscle composition with pathology, as muscle from massive RCT tears had increased ECM deposition compared with no tear RC muscle. Together these data imply that the remodeled niche in a torn RCT primes SMPs not for expansion but for differentiation, thus limiting longer-term self-renewal necessary for regeneration after surgical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1816-1823, 2017.

Study designRetrospective chart analysis of 199 individuals aged 18 to 80 years scheduled for lumbar spine surgery.ObjectiveThe purpose of this study was to quantify changes in muscle cross-sectional area (CSA) and fat signal fraction (FSF) with age in men and women with lumbar spine pathology and compare them to published normative data.Summary of background dataPathological changes in lumbar paraspinal muscle are often confounded by age-related decline in muscle size (CSA) and quality (fatty infiltration). Individuals with pathology have been shown to have decreased CSA and fatty infiltration of both the multifidus and erector spinae muscles, but the magnitude of these changes in the context of normal aging is unknown.MethodsIndividuals aged 18 to 80 years who were scheduled for lumbar surgery for diagnoses associated with lumbar spine pain or pathology were included. Muscle CSA and FSF of the multifidus and erector spinae were measured from preoperative T2-weighted magnetic resonance images at the L4 level. Univariate and multiple linear regression analyses were performed for each outcome using age and sex as predictor variables. Statistical comparisons of univariate regression parameters (slope and intercept) to published normative data were also performed.ResultsThere was no change in CSA with age in either sex (P > 0.05), but women had lower CSAs than men in both muscles (P  0.31).ConclusionLumbar muscle fat content, but not CSA, changes with age in individuals with pathology. In women, this increase is more profound than age-related increases in healthy individuals.Level of evidence3.

Study designRepeated measures.ObjectiveThe purpose of this study was to quantify the effect of operationally relevant loads and distributions on lumbar spine (LS) in a group of active-duty Marines.Summary of background dataLow-back pain has been associated with heavy load carriage among military personnel. Although there are data describing the LS posture in response to load, the effect of varying load characteristics on LS posture remains unknown.MethodsMagnetic resonance images of Marines (n = 12) were acquired when standing unloaded and when carrying 22, 33, and 45 kg of load distributed both 50% to 50% and 20% to 80% anteriorly and posteriorly. Images were used to measure LS and pelvic postures. Two-way repeated-measures ANOVA and posthoc tests were used to compare LS posture across load magnitudes and distributions (α = 0.05). This project was founded by the US Army Medical Research Acquisition Activity, Award No. W81XWH-13-2-0043, under Work Unit No. 1310.ResultsNo changes in LS posture were induced when load was evenly distributed. When load was carried in the 20% to 80% distribution lumbosacral flexion increased as a result of sacral anterior rotation and overall reduced lumbar lordosis. This pattern was greater as load was increased between 22 and 33 kg, but did not increase further between 33 and 45 kg. We observed that the inferior LS became uniformly less lordotic, independently of load magnitude. However, the superior LS became progressively more lordotic with increasing load magnitude CONCLUSION.: Postural adaptations were found only when load was carried with a posterior bias, suggesting that load-carriage limits based on postural changes are relevant when loads are nonuniformly distributed. Although the tendency would be to interpret that loads should be carried symmetrically to protect the spine, the relationship between postural changes and injury are not clear. Finally, the operational efficiency of carrying load in this distribution needs to be tested.Level of evidence3.

BackgroundCellular remodeling in rotator cuff muscles following a massive rotator cuff tear is poorly understood. The aim of the current study was to provide histological evidence to elucidate the mode of muscle loss in advanced human rotator cuff disease and to assess tissue-level changes in relation to findings on noninvasive imaging.MethodsRotator cuff muscle biopsy samples were taken from the scapular fossae from 23 consecutive patients undergoing reverse total shoulder arthroplasty in order to evaluate muscle composition in severe rotator cuff disease. Markers of vascularity; inflammation; fat distribution; and muscle atrophy, degeneration, and regeneration were quantified.ResultsThe samples primarily consisted of dense, organized connective tissue (48.2% ± 19.1%) and disorganized, loose connective tissue (36.9% ± 15.9%), with substantially smaller fractions of muscle (10.4% ± 22.0%) and fat (6.5% ± 11.6%). Only 25.8% of the biopsy pool contained any muscle fibers at all. Increased inflammatory cell counts (111.3 ± 81.5 macrophages/mm) and increased vascularization (66.6 ± 38.0 vessels/mm) were observed across biopsies. Muscle fiber degeneration was observed in 90.0% ± 15.6% of observable muscle fascicles, and the percentage of centrally nucleated muscle fibers was pathologically elevated (11.3% ± 6.3%). Fat accumulation was noted in both perifascicular (60.7% ± 41.4%) and intrafascicular (42.2% ± 33.6%) spaces, with evidence that lipid may replace contractile elements without altering muscle organization.ConclusionsDramatic degeneration and inflammation of the rotator cuff muscles are characteristics of the most chronic and severe rotator cuff disease states, suggesting that muscle loss is more complicated than, and distinct from, the simple atrophy found in less severe cases.Clinical relevanceIn order to address degenerative muscle loss, alternative therapeutic approaches directed at muscle regeneration must be considered if muscle function is to be restored in late-stage rotator cuff disease.

Rotator cuff (RC) tendon tears lead to negative structural and functional changes in the associated musculature. The structural features of muscle that predict function are termed "muscle architecture." Although the architectural features of "normal" rotator cuff muscles are known, they are poorly understood in the context of cuff pathology. The purpose of this study was to investigate the effects of tear and repair on RC muscle architecture. To this end thirty cadaveric shoulders were grouped into one of four categories based on tear magnitude: Intact, Full-thickness tear (FTT), Massive tear (MT), or Intervention if sutures or hardware were present, and key parameters of muscle architecture were measured. We found that muscle mass and fiber length decreased proportionally with tear size, with significant differences between all groups. Conversely, sarcomere number was reduced in both FTT and MT with no significant difference between these two groups, in large part because sarcomere length was significantly reduced in MT but not FTT. The loss of muscle mass in FTT is due, in part, to subtraction of serial sarcomeres, which may help preserve sarcomere length. This indicates that function in FTT may be impaired, but there is some remaining mechanical loading to maintain "normal" sarcomere length-tension relationships. However, the changes resulting from MT suggest more severe limitations in force-generating capacity because sarcomere length-tension relationships are no longer normal. The architectural deficits observed in MT muscles may indicate deeper deficiencies in muscle adaptability to length change, which could negatively impact RC function despite successful anatomical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2089-2095, 2016.

PurposeSimple decompression and anterior subcutaneous transposition are effective surgical interventions for cubital tunnel syndrome and yield similarly favorable outcomes. However, a substantial proportion of patients demonstrate unsatisfactory outcomes for reasons that remain unclear. We compared effects of decompression and transposition on regional ulnar nerve strain to better understand the biomechanical impacts of each strategy.MethodsPatients diagnosed with cubital tunnel syndrome and scheduled for anterior subcutaneous transposition surgery were enrolled. Simple decompression, circumferential decompression, and anterior transposition of the ulnar nerve were performed during the course of the transposition procedure. Regional ulnar nerve strain around the elbow was measured for each surgical intervention based on 4 wrist and elbow joint configurations.ResultsWith elbow extension at 180°, both circumferential decompression and anterior transposition resulted in approximately 68% higher nerve strains than simple decompression. Conversely, with elbow flexion, simple decompression resulted in higher average strains than anterior transposition. Limited regional differences in strain were observed for any surgical intervention with elbow extension. However, with elbow flexion, strains were higher in distal and central regions compared with the proximal region within all surgical groups, and proximal region strain was higher after simple decompression compared with anterior transposition.ConclusionsAs predicted by the altered anatomic course, anterior transposition results in lower ulnar nerve strains than simple decompression during elbow flexion and higher nerve strains during elbow extension. Irrespective of anatomic course, circumferential release of paraneurial tissues may also influence nerve strain. Nerve strain varies regionally and is influenced by surgery and joint configuration.Clinical relevanceOur data provide insight into how surgery resolves and redistributes traction on the ulnar nerve. These findings may help inform which surgical procedure to perform for a specific patient, guide rehabilitation protocols, and suggest regions of anatomic concern during index and revision surgery.