Amadio, Peter C.

Abstract The carpal tunnel contains the digital flexor tendons and the median nerve, which are embedded in a unique network of fibrovascular interconnected subsynovial connective tissue (SSCT). Fibrous hypertrophy of the SSCT and subsequent adaptations in mechanical response are found in patients with carpal tunnel syndrome (CTS), but not much is known about the development of the SSCT. This observational study describes the morphological development of SSCT using histology and ultramicroscopy in an animal model at four time points between late‐term fetuses through adulthood. A transition is seen between 3 days and 6 weeks post‐partum from a dense solid SSCT matrix to a complex multilayered structure connected with collagenous fibrils. These preliminary data show a developmental pattern that matches an adaptive response of the SSCT to loading and motion. Understanding the anatomical development aids in recognizing the pathophysiology of CTS and supports research on new therapeutic approaches.

ObjectivesCorticosteroid injections can provide (temporary) relief in patients with mild to moderate carpal tunnel syndrome (CTS). Hydrodissection as part of an injection has been associated with positive clinical outcomes but data for CTS so far has been scarce. This study is designed to assess patient tolerance and secondarily provide pilot data on the added effect of hydrodissection.MethodsTwenty CTS patients were randomized to an ultrasound‐guided betamethasone injection with hydrodissection (5 mL) or without (2 mL). Patient tolerance was assessed directly after intervention and patient‐reported outcome after 4 and 24 weeks. Intra‐group data were compared using Wilcoxon Signed Rank and inter‐group with Wilcoxon rank‐sum tests.ResultsTolerance and pain scores did not differ between the two groups. Symptom scores decreased in both groups, but to a lesser extent in the hydrodissection group with a mean difference of −0.8 versus −1.5 in the control group at 4 weeks (P = .02). At 6 months, this difference was no longer present (P = .81). No statistically significant differences were found between the hydrodissection and control groups in the function or pain scores at follow‐up at either time point.ConclusionAfter injection, both symptomatic and functional scores improved, but the hydrodissected group did not show additional improvement. Data presented can be used to support larger studies to assess the value of hydrodissection in CTS management.

AbstractBackgroundShear wave elastography (SWE) shows promise in peripheral neuropathy evaluation but has potential limitations due to tissue size and heterogeneity. We tested SWE sensitivity to elasticity change and the effect of probe position in a median nerve cadaver model.MethodsTen specimens were used to measure median nerve elasticity under increasing loads using SWE and indentation. Measurements were compared using repeated‐measures analysis of variance.ResultsIndentation and SWE‐based longitudinal nerve elasticity increased with tensile loading (P< .01), showing a similar relationship. Acquisition in a transverse plane showed lower values compared with longitudinal measurements, mostly under higher loads (P= .03), as did postdissection elasticity (P= .02). Elasticity did not change when measured proximal to the carpal tunnel.ConclusionsLongitudinal SWE is sensitive to changes in median nerve elasticity. Measuring elasticity of peripheral nerves noninvasively could elucidate intra‐neural pathology related to compression neuropathies, and proof to be of added value as a diagnostic or prognostic tool.

AbstractFlexor tendon injuries and tendinopathy are very common but remain challenging in clinical treatment. Exosomes‐based cell‐free therapy appears to be a promising strategy for tendon healing, while limited studies have evaluated its impacts on tenocyte biology. The objective of this study was to characterize a novel purified exosome product (PEP) derived from plasma, as well as to explore its cellular effects on canine tenocyte biology. The transmission electron microscope revealed that exosomes of PEP present cup‐shaped structures with the diameters ranged from 80 to 141 nm, and the NanoSight report presented that their size mainly concentrated around 100 nm. The enzyme‐linked immunosorbent assay kits analysis showed that PEP was positive for CD63 and AChE expression, and the cellular uptake of exosomes internalized into tenocyte cytoplasm was observed. The cell growth assays displayed that tenocyte proliferation ability was enhanced by PEP solution in a dose‐dependent manner. Tenogenic phenotype was preserved as is evident by that tendon‐related genes expression (SCX, COL1A, COL3A1, TNMD, DCN, and MKX) were expressed insistently in a high level, while tenocytes were treated with 5% PEP solution. Furthermore, migration capability was maintained and total collagen deposition was increased. More interesting, dexamethasone‐induced cellular apoptosis was attenuated during the incubation of tenocytes with a 5% PEP solution. These findings will provide the basic understandings about the PEP, and support the potential use of this biological strategy for tendon healing.

Background: In hand surgery, and specifically carpal tunnel syndrome, it is currently unknown whether experiences with health care influence surgical outcome. To investigate whether there is an association between patient-reported experience measures and symptom relief, data were gathered using a cohort of patients undergoing surgical treatment for carpal tunnel syndrome. Methods: Patient-reported experience measures and patient-reported outcome measures were registered in a national database of 16 hand surgery practices. The experience measure data were gathered at 3 months after surgery and included six subscales on different health care delivery aspects (e.g., provided information, communication, facility, operative care). The outcome measure data were acquired before and 3 months after surgery with the Boston Carpal Tunnel Assessment Questionnaire. The association was tested using linear regression analyses. Results: A total of 1607 patients were included in the analysis. The experience measure scores were good to excellent, with a median value between 8.0 and 8.5 on a 10-point scale. Regression analyses showed a significant (p < 0.001) association with the Boston Carpal Tunnel Assessment Questionnaire for all individual patient-reported experience measure subscales. The greatest effects were found in physician communication and treatment information. Patient-reported experience measures accounted for more than 5 percent of the explained variance, with patient characteristics explaining an approximately additional 3 percent. Conclusions: In this large data set of carpal tunnel syndrome patients who underwent surgical release, a significant impact of health care experiences on self-reported clinical outcome was found. This is relevant information, not only for directing care providers in improving health care experiences as a quality-of–health care measure but now also potentially to achieve better clinical outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Objectives Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery. Methods A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs). Results Failed-repair stump tissue showed cellular accumulation of crumpled and disoriented collagen fibres. Compared with normal tendon, stump tissue had significantly higher gene expression of collagens I and III, matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF). The stump TDSCs presented both mesenchymal stem and haematopoietic cell markers with significantly increased expression of CD34, CD44, and CD90 markers. Stump TDSCs exhibited similar migration but a lower proliferation rate, as well as similar osteogenic differentiation but a lower chondrogenic/adipogenic differentiation capability, compared with normal TDSCs. Stump TDSCs also showed increasing levels of SRY-box 2 (Sox2), octamer-binding transcription factor 4 (Oct4), tenomodulin (TNMD), and scleraxis (Scx) protein and gene expression. Conclusion We found that a failed repair stump had increased cellularity that preserved both mesenchymal and haematopoietic stem cell characteristics, with higher collagen synthesis, MMP, and growth factor gene expression. This study provides evidence that tendon stump tissue has regenerative potential. Cite this article: C-C. Lu, T. Zhang, R. L. Reisdorf, P. C. Amadio, K-N. An, S. L. Moran, A. Gingery, C. Zhao. Biological analysis of flexor tendon repair-failure stump tissue: A potential recycling of tissue for tendon regeneration. Bone Joint Res 2019;8:232–245. DOI: 10.1302/2046-3758.86.BJR-2018-0239.R1.

ABSTRACTFlexor tendon injury is often associated with suboptimal outcomes and results in substantial digit dysfunction. Stem cells have been isolated from several experimental animals for the growing interest and needs of utilizing cell‐based therapies. Recently, turkey has been developed as a new large animal model for flexor tendon research. In the present study, we reported the isolation and characterization of bone marrow‐derived mesenchymal stem cells (BMSCs) from 8‐ to 12‐month‐old heritage‐breed turkeys. The isolated cells demonstrated fibroblast‐like morphology, clonogenic capacity, and high proliferation rate. These cells were positive for surface antigens CD90, CD105, and CD44, but were negative for CD45. The multipotency of turkey BMSCs was determined by differentiating cells into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. There was upregulated gene expression of tenogenic markers, including mohawk, tenomodulin, and EGR1 as well as increased collagen synthesis in BMP12 induced cells. The successful isolation and verification of bone marrow‐derived MSCs from turkey would provide opportunities of studying cell‐based therapies and developing new treatments for tendon injuries using this novel preclinical large animal model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1419–1428, 2019.