This study aimed to determine if the adoption of collagenase treatment is economically viable.

Xiapex collagenase was trialled at Gloucestershire Hospitals NHS Trust in 50 patients suitable for fasciectomy, with a palpable cord and up to two affected joints. Retrospective data for contracture angle pre-injection, immediately post-manipulation and at an average 6 weeks (range 2–17) clinic follow up was collected from medical notes. At follow up the post-procedure number of days required for return to activities of daily living (ADLs) and/or work were recorded, along with overall patient satisfaction rating.

Complete data was obtained for 43 patients of average age 67 (range 45–82). At follow up 88% had ≤ 20° residual contracture. Average days return to full ADLs was 9 and work was 11. Overall satisfaction was 8.6 out of 10. Xiapex patients required an average 1 hand physiotherapy appointment post-manipulation compared to 6 for fasciectomy, saving £172.20. Total cost for one treatment course, excluding physiotherapy, was £1166 for Xiapex compared to £2801 for palmar fasciectomy and £5352 for digital fasciectomy.

The level of contracture after one Xiapex treatment course permitted return of hand function in the majority of patients whose overall treatment course required less financial and hospital resources.

Dupuytren's disease is often disabling and traditionally has been managed with various surgical methods, with recurrence rates up to 50 %. Recently clostridial collagenase injection has been licensed for use in the NHS. We prospectively analysed the results of clostridial collagenase injection in 62 patients with varying degrees of Metacarpo phalangeal (MCP) and Proximal interphalangeal (PIP) joint contractures. There were 48 males and 14 females with an average age of 66 years. The average MCPJ and PIPJ deformities were 33 and 17 degrees respectively. Following the infiltration and subsequent manipulation under local anaesthetic and night splinting for 3 months, patients were followed up at 4 weeks and 6 months. Deformities persisted in 5 patients and later required surgical correction. MCPJ deformities were more amenable for correction than PIPJ and in those with recurrence. The average residual deformity was 7 degrees. Common complications include bruising, swelling, pain not responding to routine analgesia, lymphangitis and skin break in some but none required any additional interventions. 14 patients had completed 6 month follow up and there was no recurrence. Subjective assessment through questionnaires revealed high patient satisfaction rate with early return to work within 1 week in most patients. Patients with previous operations preferred injections over operative correction. Collagenase injections are effective in deformity correction with higher satisfaction rate and low morbidity. Early results are encouraging but long term follow up is required to assess recurrence rates

Tendon-related pathologies such as tendinopathy represent a relevant clinical and socioeconomic issue. The most innovative and conservative therapeutic approaches are meant to stimulate the intrinsic healing capability of the tissue. In this study, the use of pulsed electromagnetic fields (PEMFs) was investigated in a rat model of Achilles tendinopathy as a potential therapy. Achilles tendinopathy was chemically induced in eighty-six Sprague Dawley rats by injecting collagenase Type I within the tendon fibers. Fifty-six of them were stimulated with PEMFs (8 hours/day, 1.5 ± 0.2 mT; 75 Hz), divided in different experimental groups basing on the starting-time of PEMFs exposure (after 0, 7, 15 after Collagenase injection) and its duration (7, 15 or 30 days). Thirty animals were left unstimulated (CTRL group). According to the different time points, explanted tendons were evaluated through histological and immunohistochemical analyses in term of matrix deposition, fiber re-organization, neovascularization and inflammatory reaction. The most effective PEMF stimulation was demonstrated in the 15 days of treatment. However, when PEMF were applied immediately after the collagenase injection, no significant therapeutic results were found. On the contrary, when PEMF were applied after 7 and 15 days from the collagenase injection, they promoted the deposition of extracellular matrix and tendon fiber re-organization, reducing both the inflammatory reaction and vascularization, with significant differences compared to the CTRL group (p<0.05). Therefore, these results suggest an effective activity of PEMFs stimulation that provides a satisfying restoration of the damaged tissue, although the most performing protocol of application still needs to be identified

The February 2014 Wrist & Hand Roundup. 360 . looks at: simple debridement and ulnar-sided wrist pain; needle fasciotomy or collagenase injection; joint replacement in osteoarthritic knuckles; the Mannerfelt arthrodesis; scaphoid union rates with conservative treatment; the benefits of atorvastatin for muscle re-innervation after sciatic nerve transection; and complications of trapeziectomy

Objectives. Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results. Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion. Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218–224. DOI: 10.1302/2046-3758.56.BJR-2015-0001

In December 2012 the orthopaedic Hand and wrist unit at Derriford hospital introduced the use of collagenase injections for the treatment of Dupuytrens' contracture, and currently remains the only centre to use it in the southwest peninsula. We present the short term results of our first year of use of the therapy. There was a statistically significant improvement in PEM scores by 1 and 3 months post-treatment (P: 0.0001 and 0.0016 with 95% confidence). Full correction was obtained in 81% of all MCPJ contractures included in the analysis. Success with PIPJ contractures was more limited, however there was still an average correction of 30 degrees achieved. Complications were limited to skin tears, all of which healed at subsequent follow-up, and 2 failures of therapy. We will continue to use this therapy and as experience and expertise build we hope we can improve our outcomes further

Dupuytren Disease (DD), the most common connective tissue disease in man, presents as a benign fibromatosis of the hands and fingers resulting in the formation of nodules and cords and often leading to flexion contractures in association with keloids or Peyronie disease. Surgical resection of the fibrotic nodules, and more recently intra-lesional collagenase injection are the main therapeutic options for these patients. While the exact cause of DD is still unknown, linkage and Genome Wide Association Studies (GWAS) showed molecular heterogeneity with at least 10 different susceptibility loci 6 of which are close to genes encoding proteins in the Wnt-signaling pathway. We aim to identify the molecular basis of Dupuytren Disease (DD). Twenty patients with Dupuytren disease (including 3 patients with autosomal dominant inheritance, 1 with keloids and congenital torticollis, 2 with Peronie disease), were included in this study. Chromosome Microarray Analysis (CMA), Whole Exome Sequencing (WES) of gDNA and proteomic analysis by LC-Tandem Mass Spectrometry (LC-MSMS) studies were performed. Expression and Network analysis of LCMSMS results was performed using Principal Component Analysis (PCA), ANOVA and Ingenuity Pathway Analysis (IPA). No pathogenic copy number variants (CNVs) were found in CMA (n = 3). WES showed potentially pathogenic variants in POSTN, WNT11, MMP1 and COL3A1. PCA showed three differentially expressed clusters and network-IPA identified ACTB, BAX, COL3A1, FBN1, FN1, MMP1 as potential biomarkers. Comprehensive multi-OMIC analysis of gDNA and tissue proteins in patients with DD identified several connective tissue biomarkers potentially important in the pathogenesis of DD

The collagenase of Clostridium Histolyticum enzyme infiltration is a mini-invasive treatment method for Dupuytren's disease which has emerged in recent years as an alternative to traditional surgery (selective aponeurectomy). Although both treatments are effective in the long term, a wider use of the enzyme is spreading worldwide. Indications and protocol of administration of collagenase are strictly regulated by the Italian Drug Administration Agency (AIFA). In the present study an off-label use of this medication has been experienced, in terms of wider indications and more numerous infiltration sites in the same cord (Multipoint technique) and in additional cords affecting other digits (Multicord technique). All patients suffering from Dupuytren's disease and accessing the Hand Surgery outpatient at Rizzoli Institute were considered for the study, between february 2014 and february 2016. Inclusion criteria were Dupuytren's disease and a positive tabletop test. The collagenase injection was indicated for degrees of passive extension deficit (PED) higher than AIFA regulations (MCPJoints >50° and PIPJoints >45°). These patients were compared with the same PED subgroup of surgical patients who were treated through aponeurectomy. Since the drug is dispensed in vials of 0.90 mg, but according to the protocol only 0.58 mg are to be infiltrated, the injection of the remaining 0.32 mg that would otherwise remain unused was experienced. Therefore, in patients who had only one pathological cord in the hand, the first point of the cord to be treated was inoculated with 0.58 mg, according to standards, while two additional points were selected along the fibrosis and injected with the remaining 0, 32 mg. This group was compared with patients treated with the traditional 0.58 mg only on a single cord. In patients in whom the presence of more than a single pathological cord was found, the worse lesion was injected with the usual 0.58 mg as by legislation and the second cord was infiltrated with the 0.32 mg residue and the results obtained within the second cord were compared with those achieved with the usual dose of 0.58 mg. The endpoints considered were the perioperative variations of passive extension deficit (PED) and range of motion (ROM), both expressed as degrees. Data were statistically analyzed in order to find any possible significance in the comparison of groups. Comparing the surgical patients with those treated with collagenase, for the same degrees but higher than AIFA reference, both methods showed a reduction of contracture by at least 50% at 30 days and an improvement of ROM (p>0.05), with fewer complications in those treated enzymatically (p<0.01). Infiltrating the whole dose of collagenase (0.90 mg) through the multipoint mode, has enabled an easier handling of the cord at 24 hours post-injection, a reduction in contracture of at least 50% at 30 days allowing a dowstaging of the disease and a better and faster recovery of hand function, than the classic treatment, although these results are not statistically significant (p>0.05). For degrees of contractures within AIFA indications for collagenase, the 0.32 mg dose is sufficient to cause the lysis of a cord with similar results compared to the greater AIFA-recommended dose of 0.58, in terms of all considered endpoints, with no statistically significant difference (p >0.01). This study confirms the success of treatment with collagenase compared to surgical treatment, in terms of efficacy, safety, more rapid recovery and less invasiveness. In addition, through further clinical studies, AIFA regulations can be gradually safely and effectively extended in terms of a progressive widening of indications and modalities including:. Indication to collagenase for PED higher than 50° (MCP joints) or 45° (PIP joints). Multiple injections in the same cord with the whole content of the vial (0.90 mg). Injections in multiple cords with the whole content of the vial (0.90 mg)

There has been recent interest in the treatment of Dupuytren's disease by minimally invasive techniques such as needle fasciotomy and collagenase injection, but only few studies have reported the outcomes following open fasciotomy. This study attempts to address this gap, with a retrospective analysis of a large series of patients who underwent an open fasciotomy by a single surgeon over a five-year period. The aim of the study was to determine the requirement for re-operation in the cohort and to analyse the revisionary procedures performed. Theatre coding data was used to identify a consecutive series of patients who underwent open fasciotomy over a five-year period between 2000 and 2005. Within this group medical records were obtained for those patients who underwent a secondary procedure for recurrence. All procedures were carried out by a single surgeon in a regional hand unit using an unmodified open technique. A total of 1077 patients underwent open fasciotomy for Dupuytren's disease. Of these, 865 (80.3%) were male and 212 (19.7%) were female. The mean age at initial surgery was 64.4 years (range 21.7 to 93.7 years) for males and 68.3 (range 43.6 to 89.8 years) for females. Of the 1077 patients who underwent open fasciotomy, 143 patients (13.3%) subsequently underwent a second procedure for recurrence. The medical records were available for 97 patients. The median time to re-operation in this group of patients was 42.0 months (95% CI, 8.3 to 98.0 months). The most common revision procedure being dermofasciectomy (54.2%), followed by fasciectomy (32.6%) and re-do open fasciotomy (13.2%). Mean pre-operative total extension deficit was 88 degrees (range 30–180 degrees) with intra-operative correction to a mean of 9.5 degrees (range 0–45 degrees). There is no standard definition for recurrence after Dupuytren's surgery. We have looked at the rate of revision surgery after open fasciotomy, in a relatively fixed population serviced over a 5-year period by a single hand surgeon. A low re-operation rate has been identified, with good intra-operative correction achieved by secondary surgery

Summary Statement. Increased Dkk-1 signaling is associated with OA occurrence and joint microenvironment damage. Interruption of Dkk1 action is beneficial to improve OA knees. Introduction. Osteoarthritis (OA) is a leading cause of disability and healthcare financial burden for total knee arthroplasty, rehabilitation, and disability. Inappropriate mechanical stress, immunological, or biochemical regulation reportedly disturbs homeostasis among cartilage, synovium and subchondral bone microstructure that contributes to OA pathogenesis. Control of joint-deleterious factor action is an emerging strategy to ameliorate OA-induced joint deterioration. Dickkopf-1 (Dkk-1) is a potent inhibitor for Wnt/β-catenin signaling regulation of tissue development and remodeling in physiological or pathological contexts. Dkk-1 also acts as a master deleterious factor that represses osteoblast differentiation capacity and bone repair. Associations among Dkk-1 expression, chondrocyte fate, synovial fibroblast behavior or OA incidence are merit of characterization. Patients & Methods. Cartilage, synovial tissue and fluid were harvested from informed consent OA patients underwent arthroplasty and patient with knee injuries without OA changes as controls. Primary chondrocyte cultures and synovial fibroblasts were treated with inflammatory cytokines or Dkk-1 antisense oligonucleotide or monoclonal antibodies. Knees in experimental animals were subjected to anterior cruciate ligament transection- or intra-articular collagenase injection to induce OA. Joint inflammation, integrity and subchondral bone microstructure in knees as well gait profiles were quantified using 2-deoxyglucose-probed near-infrared in vivo image, µCT, catwalk and histomorphometric analyses. Results. In clinical vignettes, patients with end-stage OA knee had higher abundances of Dkk-1 in cartilage, synovial tissue, and synovial fluid compared to control patients. Disruption of DKk-1 signaling ameliorated the promoting effects of inflammatory cytokines on the survival and cartilage matrix synthesis in primary cartilage chondrocyte cultures. Of interest, Dkk-1 neutralization attenuated the excessive angiogenic activities and matrix metalloproteinase secretion in primary synovial fibroblasts of OA knees. Dkk-1 modulation of survival or metabolic activities in chondrocytes and synovial fibroblasts were through β-catenin-dependent and -independent signaling pathways. Moreover, increased Dkk-1 expression in lesion sites and sera was associated with the incidence of femoral head osteonecrosis. Loss of Dkk-1 action alleviated bone cell apoptosis in osteonecrotic bone microenvironments. In experimental OA knee models, knockdown of Dkk-1 alleviated articular cartilage damage as evidenced by improved Mankin score in OA knees. Dkk-1 disruption also alleviated the adverse effects of OA on subchondral bone exposure and loss of trabecular bone volume and mineral acquisition in injured joints. Loss of Dkk-1 function reduced joint inflammation, vessel number, leukocyte infiltration in synovium compartment of OA joint and improved gait profiles of affected limbs. Conclusion. Dkk-1 signaling is associated with the OA knee occurrence and accelerates apoptosis, matrix degradation and angiogenic activities in chondrocytes and synovial fibroblasts of OA joint. Dkk-1 interference alleviates the promoting effects of OA on cartilage, synovial and subchondral bone remodeling. Blocking the deleterious actions of Dkk-1 in joint microenvironment will be a prospective molecular regime beneficial for retarding excessive joint deterioration in OA knees

Aims

To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytren’s disease (DD) and the value of further research from an NHS perspective.

Aims

In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.

Aims

Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process.

The June 2015 Wrist & Hand Roundup360 looks at: Collagenase and Dupuytren’s disease – a genuine alternative to surgery?; iPad PROMise?; Should we learn how to do endoscopic carpal tunnel release?; Two-week radiographs a relic of the past?; Bible? Aspirate or excise?; Patient expectations and trapeziometacarpal osteoarthritis; Splintage in the treatment of sagittal band incompetence and extensor tendon subluxation

Objectives

Injectable Bromelain Solution (IBS) is a modified investigational derivate of the medical grade bromelain-debriding pharmaceutical agent (NexoBrid) studied and approved for a rapid (four-hour single application), eschar-specific, deep burn debridement. We conducted an ex vivo study to determine the ability of IBS to dissolve-disrupt (enzymatic fasciotomy) Dupuytren’s cords.

The October 2013 Wrist & Hand Roundup³⁶⁰ looks at: Cost effectiveness of Dupuytren’s surgery; A 'new horizon' in distal radius imaging; Undisplaced means undisplaced; The mystery of the distal radial fracture continues; How thick is thick enough?: articular cartilage step off revisited; Is the midcarpal joint more important than we think?; Plates and Kirschner wires; Better early results with an IM nail?