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Background: Rotator cuff tendon repair in humans is a commonly performed procedure aimed at restoring the tendon-bone interface. Despite significant innovation of surgical techniques and suture anchor implants, only 60% of repairs heal successfully. One strategy to enhance repair is the use of bioactive sutures that provide the native tendon with biophysical cues for healing. We investigated the tissue response to a multifilament electrospun polydioxanone (PDO) suture in a sheep tendon injury model characterised by a natural history of failure of healing. Methodology and results: Eight skeletally mature English Mule sheep underwent repair with electrospun sutures. Monofilament sutures were used as a control. Three months after surgery, all tendon repairs healed, without systemic features of inflammation, signs of tumour or infection at necropsy. A mild local inflammatory reaction was seen. On histology the electrospun sutures were densely infiltrated with predominantly tendon fibroblast-like cells. In comparison, no cellular infiltration was observed in the control suture. Neovascularisation was observed within the electrospun suture, whilst none was seen in the control. Foreign body giant cells were rarely seen with either sutures. Conclusion: This study demonstrates that a tissue response can be induced in tendon with a multifilament electrospun suture with no safety concerns. [ABSTRACT FROM AUTHOR]

Electrospun filaments are leading to a new generation of medical yarns that have the ability to enhance tissue healing through their biophysical cues. We have recently developed a technology to fabricate continuous electrospun filaments by depositing the submicron fibres onto a thin wire. Here we investigate the influence of pyridine on the fibre deposition. We have added pyridine to polydioxanone solutions at concentrations ranging from 0 to 100 ppm, increasing the conductivity of the solutions almost linearly from 0.04 uS/cm to 7 uS/cm. Following electrospinning, this led to deposition length increasing from 1 cm to 14 cm. The samples containing pyridine easily underwent cold drawing. The strength of drawn filaments increased from 0.8 N to 1.5 N and this corresponded to a decrease in fibre diameter, with values dropping from 2.7 μm to 1 μm. Overall, these findings are useful to increase the reliability of the manufacturing process of continuous electrospun filaments and to vary their biophysical properties required for their application as medical yarns such as surgical sutures. [ABSTRACT FROM AUTHOR]

Purpose: Osteoarthritis (OA) is a common and heterogeneous arthritic disorder. Patients suffer pain and their joints are characterized by articular cartilage loss and osteophyte formation. Risk factors for OA include age and obesity with inflammation identified as a key mediator of disease pathogenesis. Interleukin-17A (IL-17) is a pro-inflammatory cytokine that has been implicated in inflammatory diseases such as rheumatoid arthritis. IL-17 can upregulate expression of inflammatory cytokines and adipocytokines. The aim of this study was to evaluate IL-17 levels in the synovial fluid of patients with end-stage knee and hip OA in relation to inflammation- and pain-related cytokines and adipocytokines in synovial fluid and serum, and clinical and radiographic disease parameters. Methods: This is a cross-sectional study of 152 patients undergoing total hip and knee arthroplasty for OA. IL-17, IL-6, leptin, adiponectin, visfatin, resistin, C-C Motif Chemokine Ligand 2 (CCL2), C-C Motif Chemokine Ligand 7 (CCL7) and nerve growth factor (NGF) protein levels were measured in synovial fluid and serum using enzyme-linked immunosorbent assay (ELISA). Baseline characteristics included age, sex, body mass index, co-morbidities, pain and function, and radiographic analyses (OA features, K&L grade, minimal joint space width). Results: 14 patients (9.2%) had detectable IL-17 in synovial fluid. These patients had significantly higher median concentrations of IL-6, leptin, resistin, CCL7 and NGF. Osteophytes, sclerosis and minimum joint space width were significantly reduced in patients with detectable IL-17 in synovial fluid. No differences were found in pain, function and comorbidities. IL-17 concentrations in synovial fluid and serum were moderately correlated (r = 0.482). Conclusion: The presence of IL-17 in the synovial fluid therefore identifies a substantial subset of primary end-stage OA patients with distinct biological and clinical features. Stratification of patients on the basis of IL-17 may identify those responsive to therapeutic targeting. [ABSTRACT FROM AUTHOR]

Objectives: To survey surgeons on their beliefs and attitudes towards the use of placebo in surgery. Methods: British orthopedic shoulder surgeons, attending a national conference in the United Kingdom, were asked to complete a self-report online questionnaire about their beliefs and attitudes towards the use of placebo related to surgical intervention. The survey included questions about ethical issues, the mechanism of placebo effects, and any concerns regarding its use. Results: 100 surgeons who participated in the survey believed that placebo surgery is ethically acceptable (96%), especially as a part of a clinical trial (46%). Respondents thought that a placebo effect in surgery is real i.e. has a scientific basis (92%), that placebo can be therapeutically beneficial (77%), and that it involves psychological mechanisms (96%). Over half of the respondents (58%) have used a surgical procedure with a significant placebo component at least once in their professional career. Their main concern about placebo use in surgery was that it might involve an element of deception. Conclusions and Implications: Surgeons generally agreed that a placebo component to surgical intervention might exist. They also supported placebo use in clinical trials and considered it ethical, providing it does not involve deception of patients. More studies are needed, particularly among other surgical specialties and with larger numbers of participants, to better understand the use of placebo in surgery. [ABSTRACT FROM AUTHOR]

Introduction: Surgeons gain expertise as they repeatedly conduct a procedure. Such learning is widely acknowledged to pose a challenge to evaluating new surgical procedures. Most surgical trials report little if any information on learning. We elicited surgeons' belief regarding learning within the context of a randomised trial which assessed two surgical procedures. Materials and Methods: Surgeons participating in the UKUFF trial were sent a postal questionnaire requesting details on current practice, prior experience and their belief regarding acquiring proficiency and the learning curve of operation time for two surgical procedures (open and arthroscopic rotator cuff repair). Results: In total 52 (58% participating surgeons returned a completed questionnaire. The median (IQR) number of procedures required to acquire proficiency were 17 (10,23) and 35 (23,50) for the open and arthroscopic repairs respectively. The distribution of surgeons' belief regarding the initial point had median (IQR) of 109 (69,128) and 145 (97,171) minutes for open and arthroscopic repair respectively. Corresponding values for the plateau point were 60 (46, 82) and 79 (58, 110). Conclusions: We have shown that information on the current practice, prior experience and beliefs on the learning process of a surgical procedure can be elicited using a short questionnaire. The approach could aid the interpretation of trial results in terms of generalisability and be used a priori in the design of a trial. [ABSTRACT FROM AUTHOR]

Mutations of UDP-N-acetyl-alpha-D-galactosamine polypeptide N-acetyl galactosaminyl transferase 3 (GALNT3) result in familial tumoural calcinosis (FTC) and the hyperostosis-hyperphosphataemia syndrome (HHS), which are autosomal recessive disorders characterised by soft-tissue calcification and hyperphosphataemia. To facilitate in vivo studies of these heritable disorders of phosphate homeostasis, we embarked on establishing a mouse model by assessing progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU), and identified a mutant mouse, TCAL, with autosomal recessive inheritance of ectopic calcification, which involved multiple tissues, and hyperphosphataemia; the phenotype was designated TCAL and the locus, Tcal. TCAL males were infertile with loss of Sertoli cells and spermatozoa, and increased testicular apoptosis. Genetic mapping localized Tcal to chromosome 2 (62.64--71.11 Mb) which contained the Galnt3. DNA sequence analysis identified a Galnt3 missense mutation (Trp589Arg) in TCAL mice. Transient transfection of wild-type and mutant Galnt3- enhanced green fluorescent protein (EGFP) constructs in COS-7 cells revealed endoplasmic reticulum retention of the Trp589Arg mutant and Western blot analysis of kidney homogenates demonstrated defective glycosylation of Galnt3 in Tcal/Tcal mice. Tcal/Tcal mice had normal plasma calcium and parathyroid hormone concentrations; decreased alkaline phosphatase activity and intact Fgf23 concentrations; and elevation of circulating 1,25-dihydroxyvitamin D. Quantitative reverse transcriptase-PCR (qRT-PCR) revealed that Tcal/Tcal mice had increased expression of Galnt3 and Fgf23 in bone, but that renal expression of Klotho, 25-hydroxyvitamin D-1α-hydroxylase (Cyp27b1), and the sodium- phosphate cotransporters type-IIa and -IIc was similar to that in wild-type mice. Thus, TCAL mice have the phenotypic features of FTC and HHS, and provide a model for these disorders of phosphate metabolism. [ABSTRACT FROM AUTHOR]

Mutations of UDP-N-acetyl-alpha-D-galactosamine polypeptide N-acetyl galactosaminyl transferase 3 (GALNT3) result in familial tumoural calcinosis (FTC) and the hyperostosis-hyperphosphataemia syndrome (HHS), which are autosomal recessive disorders characterised by soft-tissue calcification and hyperphosphataemia. To facilitate in vivo studies of these heritable disorders of phosphate homeostasis, we embarked on establishing a mouse model by assessing progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU), and identified a mutant mouse, TCAL, with autosomal recessive inheritance of ectopic calcification, which involved multiple tissues, and hyperphosphataemia; the phenotype was designated TCAL and the locus, Tcal. TCAL males were infertile with loss of Sertoli cells and spermatozoa, and increased testicular apoptosis. Genetic mapping localized Tcal to chromosome 2 (62.64-71.11 Mb) which contained the Galnt3. DNA sequence analysis identified a Galnt3 missense mutation (Trp589Arg) in TCAL mice. Transient transfection of wild-type and mutant Galnt3-enhanced green fluorescent protein (EGFP) constructs in COS-7 cells revealed endoplasmic reticulum retention of the Trp589Arg mutant and Western blot analysis of kidney homogenates demonstrated defective glycosylation of Galnt3 in Tcal/Tcal mice. Tcal/Tcal mice had normal plasma calcium and parathyroid hormone concentrations; decreased alkaline phosphatase activity and intact Fgf23 concentrations; and elevation of circulating 1,25-dihydroxyvitamin D. Quantitative reverse transcriptase-PCR (qRT-PCR) revealed that Tcal/Tcal mice had increased expression of Galnt3 and Fgf23 in bone, but that renal expression of Klotho, 25-hydroxyvitamin D-1α-hydroxylase (Cyp27b1), and the sodium-phosphate co-transporters type-IIa and -IIc was similar to that in wild-type mice. Thus, TCAL mice have the phenotypic features of FTC and HHS, and provide a model for these disorders of phosphate metabolism.