No abstract

Background: Fatty accumulation in the rotator cuff is associated with shoulder dysfunction and a risk of failure of rotator cuff repair. The aims of this study were to (1) describe cellular findings in rotator cuff muscles in patients presenting with varying degrees of rotator cuff tendon pathology by examining fat content and myofiber cross-sectional area of rotator cuff muscles and (2) correlate histologic features to magnetic resonance imaging (MRI) grades derived with the Goutallier classification.Methods: Rotator cuff muscle biopsies were performed in a consecutive series of patients undergoing arthroscopic shoulder surgery. Rotator cuffs were graded according to the Goutallier classification and labeled as either partial-thickness or fullthickness. Patients without a rotator cuff tear undergoing arthroscopic surgery served as controls. The biopsy specimens were examined using LipidTOX to visualize lipid accumulation. Laminin was used to quantify myofiber cross-sectional area.Results: Twenty-seven patients with a rotator cuff tear and 12 without a tear (controls) were included. There were 24 males (62%). The mean age was 55 years. Patients in the control cohort were younger (mean, 46 years) than those in the treatment group (mean, 60 years, p < 0.01). Within the treatment group, 12 and 15 patients were recorded as having partial and full-thickness rotator cuff tears, respectively. Lipid accumulation visualized at the cellular level was fairly-tomoderately correlated with the Goutallier classification on MRI (R s = 0.705, 95% confidence interval [CI] = 0.513, 0.829). Muscle biopsy specimens with a Goutallier grade of 21 had significantly more lipid accumulation than those with grade-0 (p < 0.01) or grade-1 (p < 0.01) fatty accumulation. Muscle biopsies at the sites of full-thickness tears showed significantly greater lipid accumulation than those associated with either partial (p < 0.01) or no (p < 0.01) tears. Partialthickness rotator cuff tears had no difference in lipid accumulation in comparison to the control group. Muscle biopsy specimens from full-thickness tears had significantly smaller myofiber cross-sectional area when compared with partialthickness tears (p = 0.02) and controls (p < 0.01).Conclusions: Cellular lipid accumulation correlates with the MRI Goutallier grade of fatty accumulation, thus verifying the Goutallier classification at the cellular level. Muscle biopsy specimens from partial-thickness tears are more similar to controls than to those from full-thickness tears, whereas full-thickness tears of all sizes showed significantly greater lipid content and smaller myofiber cross-sectional area compared with partial-thickness tears and controls.Clinical Relevance: Our research confirms the utility of using the Goutallier classification to predict rotator cuff muscle quality and shows that tendon attachment, even if partially torn, protects the muscle from fatty accumulation. Rotator cuff repairs are among the most commonly performed orthopaedic procedures in the United States 1 . Intact r...

The neural-crest derived enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal (GI) tract and controls all gut functions, including motility. Lack of ENS neurons causes various ENS disorders such as Hirschsprung Disease. One treatment option for ENS dis-orders includes the activation of resident stem cells to regenerate ENS neurons. Regeneration in the ENS has mainly been studied in mammalian species using surgical or chemically-induced injury methods. These mammalian studies showed a variety of regenerative responses with generally limited regeneration of ENS neurons, but (partial) regrowth and functional recovery of nerve fibers. Several aspects might contribute to the variety in regenerative responses, including observation time after injury, species, and gut region targeted. Zebrafish have recently emerged as a promising model system to study ENS regeneration as larvae possess the ability to generate new neurons after ablation. As the next steps in ENS regeneration research, we need a detailed under-standing of how regeneration is regulated on a cellular and molecular level both in animal models with high and low regenerative capacity. Understanding the regulatory programs necessary for robust ENS regeneration will pave the way for using neural regeneration as a therapeutic approach to treating ENS disorders.

The neural-crest-derived enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal (GI) tract and controls all gut functions, including motility. Lack of ENS neurons causes various ENS disorders such as Hirschsprung Disease. One treatment option for ENS disorders includes the activation of resident stem cells to regenerate ENS neurons. Regeneration in the ENS has mainly been studied in mammalian species using surgical or chemically induced injury methods. These mammalian studies showed a variety of regenerative responses with generally limited regeneration of ENS neurons but (partial) regrowth and functional recovery of nerve fibers. Several aspects might contribute to the variety in regenerative responses, including observation time after injury, species, and gut region targeted. Zebrafish have recently emerged as a promising model system to study ENS regeneration as larvae possess the ability to generate new neurons after ablation. As the next steps in ENS regeneration research, we need a detailed understanding of how regeneration is regulated on a cellular and molecular level in animal models with both high and low regenerative capacity. Understanding the regulatory programs necessary for robust ENS regeneration will pave the way for using neural regeneration as a therapeutic approach to treating ENS disorders.