Patient-specific Instrumentation Versus Standard Surgical Instruments in Primary Reverse Total Shoulder Arthroplasty: A Retrospective Comparative Clinical Study.

Aims: Patient-specific instrumentation (PSI) in primary shoulder arthroplasty has been studied; results supported the positive impact of the PSI on the glenoid positioning. Nevertheless, no clinical outcomes have been reported. We compare the clinical outcomes of primary reverse total shoulder arthroplasty using PSI versus the standard methods. Methods: Fifty-three patients with full records and a minimum of 24-months follow-up were reviewed, 35 patients received primary standard RSTA, and 18 patients received primary PSI RSTA. All patients were operated on in a single center. The median follow-up was 46 months (53 months in the standard group vs 39 months in the PSI group). Results: There was an overall significant post-operative improvement in the whole cohort (P< 0.05). The standard group had more deformed glenoids (B2, B3, C&D) and significantly low preoperative constant score and forward flexion (P=0.02 & 0.034). Compared to the PSI group (all were A1, A2, B1 &one type D), there were no statistically significant differences in any clinical outcome postoperatively. PSI neither prolonged the waiting time to surgery (P=0.693) nor the intraoperative time (P=0.962). Radiologically, PSI secured a higher percentage of optimum baseplate position and screw anchorage; however, no statistical correlation was found. Conclusion: In this series, both groups achieved comparable good outcomes. PSI did not achieve significantly better clinical outcomes than Standard after primary RSTA. Yet comparison has some limitations. PSI did not negatively impact the waiting time or the surgical time.

Histopathological dataset and demographic details of synovial tissues from patients with end-stage osteoarthritis, soft tissue and traumatic injuries of the knee.

Degradation of articular cartilage is the defining feature of end-stage osteoarthritis (OA) with osteophytes, subchondral sclerosis, malalignment and joint space narrowing being additional indicators of advanced disease. Obesity, older age and female gender are OA risk factors. Differing degrees of synovitis are observed in OA, soft tissue and traumatic injuries of the knee. The synovium is also subject to systemic, enhanced lipids and inflammatory mediators characteristic of obesity. Synovial cellular composition changes specific to OA and associated with its handling of cartilage debris are unclear. Triangulation of data from three knee pathologies was used to highlight findings pertaining to OA compared to non-OA. OA patient data was compared to non-OA from knee ligament and tibial frature patients at surgery. Knee pathology, gender and BMI informed patient identification. Once consented, patient inclusion and characterisation utilised data from clinical assessments, blood tests, function scores, and radiological imaging, scores and intraoperative assessment. Intra-operative synovial tissues from the same site and processed identically underpins in-depth analyses and comparisons of histopathological images from these different knee pathologies. This supports the identification of distinct changes in the cellular composition of the knee synovium characteristic of OA. This data underpins a better understanding of OA pathogenesis and disease progression vital for the design of targeted therapeutics. The tissue and cell data include detailed results from the semi-quantitative synovitis score established by Krenn and observational data for morphological features such as cartilage debris inclusion, inflammatory cells aggregate and infiltration. This histopathological data is presented in the context of detailed clinical and functional information. This data and the holistic study design can be used as a foundation for the multifactorial collection and analysis of clinical data from OA patients, OA severity measures, tissue immuno-histology and synovial inflammation analysis to underpin the details and comparisons needed in further studies into OA and its treatment globally.

Naturally-derived endoplasmic reticulum stress inhibitors for osteoarthritis?

Osteoarthritis (OA) is a chronic degenerative disease that affects the whole synovial joint. OA causes severe pain and disability that significantly affects the livelihood of an individual and incurs a huge socioeconomic burden. Current management strategies are limited to supporting functional improvement with physiotherapy and pain reduction as there are no drugs available that can reverse the progression of OA with only joint replacement surgery for late stage OA. OA is associated with advancing age and obesity, both of which compromise the functions of key endoplasmic reticulum (ER) molecular chaperones leading to improper protein folding and ER stress. Failure to restore protein homeostasis leads to increased cellular stress and eventually apoptotic cell death. Cartilage is avascular and is dependent on its constituent cells, chondrocytes, for extracellular matrix maintenance. Chondrocytes have limited proliferative capacity and their apoptosis eventually leads to extracellular matrix loss and cartilage degeneration. Recent studies on attenuating ER stress and chondrocytes apoptosis offer a credible strategy for reducing OA progression. The established roles of ER stress responses in OA have paved the way for targeted drug discovery studies aiming to mitigate ER stress and OA progression. In this review, in vitro, pre-clinical and clinical evidence of naturally-derived ER stress inhibitors for OA, the prospect and challenges in bringing these compounds to clinics are discussed.

Development of a novel in vitro insulin resistance model in primary human tenocytes for diabetic tendinopathy research.

BACKGROUND: Type 2 diabetes mellitus (T2DM) had been reported to be associated with tendinopathy. However, the underlying mechanisms of diabetic tendinopathy still remain largely to be discovered. The purpose of this study was to develop insulin resistance (IR) model on primary human tenocytes (hTeno) culture with tumour necrosis factor-alpha (TNF-α) treatment to study tenocytes homeostasis as an implication for diabetic tendinopathy. METHODS: hTenowere isolated from human hamstring tendon. Presence of insulin receptor beta (INSR-ß) on normal tendon tissues and the hTeno monolayer culture were analyzed by immunofluorescence staining. The presence of Glucose Transporter Type 1 (GLUT1) and Glucose Transporter Type 4 (GLUT4) on the hTeno monolayer culture were also analyzed by immunofluorescence staining. Primary hTeno were treated with 0.008, 0.08, 0.8 and 8.0 µM of TNF-α, with and without insulin supplement. Outcome measures include 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) assay to determine the glucose uptake activity; colourimetric total collagen assay to quantify the total collagen expression levels; COL-I ELISA assay to measure the COL-I expression levels and real-time qPCR to analyze the mRNA gene expressions levels of Scleraxis (SCX), Mohawk (MKX), type I collagen (COL1A1), type III collagen (COL3A1), matrix metalloproteinases (MMP)-9 and MMP-13 in hTeno when treated with TNF-α. Apoptosis assay for hTeno induced with TNF-α was conducted using Annexin-V FITC flow cytometry analysis. RESULTS: Immunofluorescence imaging showed the presence of INSR-ß on the hTeno in the human Achilles tendon tissues and in the hTeno in monolayer culture. GLUT1 and GLUT4 were both positively expressed in the hTeno. TNF-α significantly reduced the insulin-mediated 2-NBDG uptake in all the tested concentrations, especially at 0.008 µM. Total collagen expression levels and COL-I expression levels in hTeno were also significantly reduced in hTeno treated with 0.008 µM of TNF-α. The SCX, MKX and COL1A1 mRNA expression levels were significantly downregulated in all TNF-α treated hTeno, whereas the COL3A1, MMP-9 and MMP-13 were significantly upregulated in the TNF-α treated cells. TNF-α progressively increased the apoptotic cells at 48 and 72 h. CONCLUSION: At 0.008 µM of TNF-α, an IR condition was induced in hTeno, supported with the significant reduction in glucose uptake, as well as significantly reduced total collagen, specifically COL-I expression levels, downregulation of candidate tenogenic markers genes (SCX and MKX), and upregulation of ECM catabolic genes (MMP-9 and MMP-13). Development of novel IR model in hTeno provides an insight on how tendon homeostasis could be affected and can be used as a tool for further discovering the effects on downstream molecular pathways, as the implication for diabetic tendinopathy.

Matrix metalloproteinase expression is related to angiogenesis and histologic grade in spindle cell soft tissue neoplasms of the extremities.

We defined the immunocytochemical expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in benign soft tissue neoplasms, fibromatoses, and sarcomas, together with the activity of gelatinase MMPs and TIMPs measured by zymography and reverse zymography in a subset of cases. The most strongly expressed MMP in all tumors was MMP-1, with weaker expression of MMP-10, MMP-11, and MMP-14 in most tumors. Nuclear expression of MMP-1, MMP-8, and MMP-13 was an unusual feature. TIMP-2 was expressed in all tumors, with stronger expression in fibromatoses than in sarcomas. Fibromatoses and high-grade sarcomas showed greater MMP-1 expression than other groups, and endothelial MMP-2 expression was more extensive in sarcomas. Differences in MMP and TIMP expression might be linked to the biologic behavior of soft tissue neoplasms. The activation of endothelial MMP-2 linked to widespread MMP-14 expression provides a mechanism for sarcomas to modulate their matrix and facilitate angiogenesis.