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This book is an invaluable resource for all those seeking to enhance their proficiency in physical examination. Emphasizing its importance for thorough assessments and accurate diagnoses, it equips practitioners with comprehensive theoretical and practical knowledge. With seven sections devoted to different orthopedic structures, the book meticulously examines their underlying anatomy, pathological conditions, and diagnostic methodologies. Each author presents joint-specific tests, and detailed anatomical insights, enabling accurate assessments and identification of underlying conditions. Written and edited by members of ISAKOS, this collaboration draws upon the expertise of leading international experts. Appealing to a broad readership, it is an invaluable tool for orthopedists, sports medicine physicians, physical therapists, athletic trainers and students.

This report describes two cases of late cartilage delamination in two young adults after two different autologous cell-based techniques for cartilage restoration: 1. Matrix-assisted autologous chondrocyte implantation (MACI) and 2. Hyaluronic acid-bone marrow aspirate concentrate (HA-BMAC). Both cases demonstrate that even in patients who do not present with any ongoing symptoms after primary surgery, a cellular-based graft’s subsequent delamination can occur later. It is possible that regardless of the technique used or the time passed since the surgery, a graft failure may occur at some level, causing delamination of a previously asymptomatic cartilage restoration graft and a traumatic event with long-term follow-up. Surgeons must be alert to this injury and describe histologic findings to determine where failure occurs.

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.

Cartilage repair/regeneration procedures (e.g., microfracture, autologous chondrocyte implantation [ACI]) typically result in a satisfactory outcome in selected patients. However, the vast majority of patients with chronic symptoms and, in general, a more diseased joint, do not benefit from these surgical techniques. The aims of this work were to (1) review factors negatively influencing the joint environment; (2) review current adjuvant therapies that can be used to improve results of cartilage repair/regeneration procedures in patients with more diseased joints, (3) outline future lines of research and promising experimental approaches. Chronicity of symptoms and advancing patient age appear to be the most relevant factors negatively affecting clinical outcome of cartilage repair/regeneration. Preliminary experience with hyaluronic acid, platelet-rich plasma, and mesenchymal stem cell has been positive but there is no strong evidence supporting the use of these products and this requires further assessment with high-quality, prospective clinical trials. The use of a Tissue Therapy strategy, based on more mature engineered tissues, holds promise to tackle limitations of standard ACI procedures. Current research has highlighted the need for more targeted therapies, and (1) induction of tolerance with granulocyte colony-stimulating factor (G-CSF) or by preventing IL-6 downregulation; (2) combined IL-4 and IL-10 local release; and (3) selective activation of the prostaglandin E2 (PGE2) signaling appear to be the most promising innovative strategies. For older patients and for those with chronic symptoms, adjuvant therapies are needed in combination with microfracture and ACI.

Background: The supraspinatus is most frequently involved in rotator cuff tears, a common orthopaedic condition. However, the architecture of this muscle has been described only for the superficial, anterior, and posterior regions. Purpose: To determine the muscle architecture of the deep supraspinatus. Study Design: Descriptive laboratory study. Methods: Muscle architecture measurements were collected from 25 cadaveric supraspinatus specimens (13 intact [without tendon tears], 3 with partial-thickness tears, 9 with full-thickness tears). The muscle was divided into deep, superficial anterior, and superficial posterior regions. Pennation angle, raw and normalized fiber length, and sarcomere length and number were compared using repeated-measures analyses of variance. Results: First, mean architecture measurements were compared between regions using only the intact specimens (n = 13). The deep region had a lower mean pennation angle (3.3° ± 1.0°) compared with the posterior region (11.0° ± 3.9°; P < .0001), which in turn had a significantly higher pennation angle compared with the anterior region (7.6 ± 2.6°; P = .0005). Normalized fiber lengths in the deep region were 21.1% (P = .0052) and 34.5% (P < .0001) shorter than the posterior and anterior normalized fiber lengths, respectively. Sarcomere lengths in the deep region were longer (3.4 ± 0.2 μm) compared with the posterior (3.1 ± 0.2 μm; P = .0012) and anterior (3.2 ± 0.2 μm; P = .0390) regions. Sarcomere numbers also decreased in the deep region by 21.2% (P = .0056) and 34.2% (P < .0001) compared with the posterior and anterior regions, respectively. Conclusion: The deep supraspinatus had significantly lower pennation angles, shorter fiber lengths, and fewer but longer sarcomeres in series compared with other subregions within the muscle. These structural differences suggest a functionally unique “submuscle” within the supraspinatus. Clinical Relevance: Understanding the architecture of the supraspinatus muscle can provide insight into muscle function in health and disease. Specifically, this deep submuscle may play a different role in rotator cuff function than the rest of the muscle.

Chronic rotator cuff (RC) tears are a common and debilitating injury, characterized by dramatic expansion of adipose tissue, muscle atrophy, and limited functional recovery. The role of adipose expansion in RC pathology is unknown; however, given the identified paracrine/endocrine regulation by other adipose depots, it likely affects tissue function outside its boundaries. Therefore, we characterized the epimuscular (EM) fat depot of the human rotator cuff, defined its response to RC tears, and evaluated its influence on myogenesis in vitro. EM fat biopsies exhibited morphological and functional features of human beige fat compared with patient‐matched s.c. biopsies, which appeared whiter. The transcriptional profile of EM fat and isolated EM adipose‐derived stem cells (ASCs) shifted as a function of the tear state; EM fat from intact cuffs had significantly elevated expression of the genes associated with uncoupled respiration, and the EM fat from torn cuffs had increased expression of beige‐selective genes. EM ASC cocultures with human‐ and mouse‐derived myogenic cells exhibited increased levels of myogenesis compared with s.c. cultures. Increased fusion and decreased proliferation of myogenic cells, rather than changes to the ASCs, were found to underlie this effect. Taken together, these data suggest that EM fat in the human rotator cuff is a novel beige adipose depot influenced by cuff state with therapeutic potential for promoting myogenesis in neighboring musculature. Significance Rotator cuff tears affect millions of people in the U.S.; however, current interventions are hindered by persistent muscle degeneration. This study identifies the therapeutic potential for muscle recovery in the epimuscular fat in the rotator cuff, previously considered a negative feature of the pathology, and finds that this fat is beige, rather than white. This is important for two reasons. First, the stem cells that were isolated from this beige fat are more myogenic than those from white fat, which have been the focus of stem cell‐based therapies to date, suggesting epimuscular fat could be a better stem cell source to augment rotator cuff repair. Second, these beige stem cells promote myogenesis in neighboring cells in culture, suggesting the potential for this fat to be manipulated therapeutically to promote muscle recovery through secreted signals. The epimuscular (EM) fat depot of the human rotator cuff (RC) was characterized, its response to RC tears defined, and its influence on myogenesis in vitro evaluated. EM fat biopsies exhibited morphological and functional features of human beige fat. These data suggest that EM fat in the human RC is a novel beige adipose depot influenced by the RC state with therapeutic potential for promoting myogenesis in neighboring musculature.

in reference to Norman Webster's column (Lewis on Helping the Hungry--Feb. 3) it appears he was misinformed of the facts concerning the Committee to Name Townships in Northern Ontario.

Ligands bound to protein assemblies provide critical information for function, yet are often difficult to capture and define. Here we develop a top-down method, ‘nativeomics’, unifying ‘omics’ (lipidomics, proteomics, metabolomics) analysis with native mass spectrometry to identify ligands bound to membrane protein assemblies. By maintaining the link between proteins and ligands, we define the lipidome/metabolome in contact with membrane porins and a mitochondrial translocator to discover potential regulators of protein function. ‘Nativeomics’ enables identification of ligands bound to membrane proteins through detection of intact protein–ligand assemblies followed by dissociation and identification of individual ligands within the same mass spectrometry experiment.

Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain. In an international trial, we randomly assigned in a 1:1 ratio patients with previous myocardial infarction and clinically significant ventricular tachycardia (defined as ventricular tachycardia storm, receipt of appropriate implantable cardioverter-defibrillator [ICD] shock or antitachycardia pacing, or sustained ventricular tachycardia terminated by emergency treatment) to receive antiarrhythmic drug therapy or to undergo catheter ablation. All the patients had an ICD. Catheter ablation was performed within 14 days after randomization; sotalol or amiodarone was administered as antiarrhythmic drug therapy according to prespecified criteria. The primary end point was a composite of death from any cause during follow-up or, more than 14 days after randomization, ventricular tachycardia storm, appropriate ICD shock, or sustained ventricular tachycardia treated by medical intervention. A total of 416 patients were followed for a median of 4.3 years. A primary end-point event occurred in 103 of 203 patients (50.7%) assigned to catheter ablation and in 129 of 213 (60.6%) assigned to drug therapy (hazard ratio, 0.75; 95% confidence interval, 0.58 to 0.97; P = 0.03). Among patients in the catheter ablation group, adverse events within 30 days after the procedure included death in 2 patients (1.0%) and nonfatal adverse events in 23 patients (11.3%). Among the patients assigned to drug therapy, adverse events that were attributed to antiarrhythmic drug treatment included death from pulmonary toxic effects in 1 patient (0.5%) and nonfatal adverse events in 46 patients (21.6%). Among patients with ischemic cardiomyopathy and ventricular tachycardia, an initial strategy of catheter ablation led to a lower risk of a composite primary end-point event than antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH2 ClinicalTrials.gov number, NCT02830360.).