Industry Sponsorship Bias in Collagenase Clinical Trials for Dupuytren Disease: A Meta-analysis.

BACKGROUND: Collagenase clostridium histolyticum (collagenase) was introduced in 2010 creating a nonoperative treatment option for Dupuytren disease with promising results in sponsored clinical trials. A meta-analysis was performed to investigate industry sponsorship bias. METHODS: A systematic review of collagenase treatment of Dupuytren contracture was conducted. Articles containing mesh terms including "microbial collagenase" and "Dupuytren's contracture" were searched and limited to only clinical trials with similar protocols for inclusion. Meta-analysis of treatment endpoints of correction of contracture to 0-5 degrees after first and last injection was conducted comparing sponsored versus nonsponsored studies. RESULTS: Sixteen of the 29 identified articles met criteria for inclusion. Nonsponsored studies reported a significantly higher rate of meeting the primary treatment endpoint compared to sponsored studies after single injection for all joints (69.6% vs 56% P < 0.01), metacarpophalangeal joint (96% vs 64% P < 0.01), and proximal interphalangeal joint (67% vs 36% P = 0.011). The correction in contracture rates was similar between groups with studies evaluating more than one injection. CONCLUSIONS: Nonsponsored studies published higher success rates in meeting the primary endpoint of full correction after single injection than sponsored studies; however, similar results with multiple injections. This study demonstrated that sponsored studies of collagenase produced highly powered studies that may be reliably depended on for evidence-based clinical application.

Effect of nanoparticle-mediated delivery of SFRP4 siRNA for treating Dupuytren disease.

Dupuytren disease (DD) is a progressive fibrous proliferative disease. It invades the palmar aponeurosis and extends to the finger fascia, eventually leading to flexion contracture of the metacarpophalangeal or interphalangeal joint. At present, surgical resection and the local injection of collagenase are the main methods for the treatment of DD, but postoperative complications and high recurrence rates often occur. Bioinformatics analysis showed that the increased expression of SFRP4 protein was closely related to the incidence of DD. Persistent and effective inhibition of SFRP4 expression may be a promising treatment for DD. We prepared SFRP4 siRNA/nanoparticle complexes (si-SFRP4) and negative siRNA/nanoparticle complexes (NC) and applied them in vitro and in vivo. Flow cytometry analysis showed that si-SFRP4 could be successfully transfected into DD cells. MTT and EdU staining assays showed that the OD values and percentage of EdU-positive cells in the si-SFRP4 group were significantly lower than those in the NC group. Scratch tests showed that the wound healing rate of the si-SFRP4 group was lower than that of the NC group, and the difference was statistically significant. The expression of SFRP4 and α-SMA protein in the si-SFRP4 group significantly decreased in both DD cells and xenografts. Compared with the NC group, the xenograft quality of the si-SFRP4 group was significantly reduced. Masson's trichrome staining showed that the collagen and fibrous cells in the si-SFRP4 group were more uniform, slender, parallel and regular. The above experimental results suggest that the proliferation and metabolism of palmar aponeurosis cells and the quality of metacarpal fascia xenografts were both significantly decreased. We speculated that nanoparticle-mediated SFRP4 siRNA can be used as a potential new method for the treatment of DD.

Targeting Myofibroblasts as a Treatment Modality for Dupuytren Disease.

PURPOSE: Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured with platelet-rich plasma (PRP), a platelet concentration from whole blood. Reprograming myofibroblasts into adipocytes via growth factors is proposed as a powerful potential tool to target fibrosis. We aimed to assess whether the combination of ASCs and PRP reprograms DMFs into adipocytes in vitro and alters their contractile nature in vivo. METHODS: Normal human dermal fibroblasts (NHDFs) and DMFs from Dupuytren patients were isolated and cocultured with ASCs and PRP either alone or together. Adipocytes were detected by Oil Red O and perilipin staining. DMFs and NHDFs were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]) and treated with saline, PRP+ASCs, or collagenase Clostridium histolyticum (clinical comparison) 2 months later. After 2 weeks, the tissue was harvested and subjected to Masson trichrome staining, and collagen I and III and alpha-smooth muscle actin detection by immunohistochemistry. RESULTS: Myofibroblasts transform into adipocytes upon coculture with PRP+ASCs. DMFs show increased alpha-smooth muscle actin expression in vivo compared with NHDFs, which is significantly decreased after PRP+ASCs and collagenase Clostridium histolyticum treatments. DMFs induce collagen I and III expressions in rat paws compared with NHDFs, with a type III to I ratio increase. Treatment with PRP+ASC reduced the ratio, but collagenase Clostridium histolyticum did not. CONCLUSIONS: Treating DMFs with PRP+ASCs provides factors that induce myofibroblast to adipocyte transformation. This treatment reduces the contractile phenotype and fibrosis markers in vivo. Future studies should detail the mechanism of this conversion. CLINICAL RELEVANCE: The combination of PRP and ASCs to induce the differentiation of DMFs into adipocytes may serve to limit surgery to a percutaneous contracture release and biological injection, rather than a moderate or radical fasciectomy, and reduce the recurrence of Dupuytren contracture.

Focused electromagnetic high-energetic extracorporeal shockwave (ESWT) reduces pain levels in the nodular state of Dupuytren's disease-a randomized controlled trial (DupuyShock).

Dupuytren's disease is a progressive fibroproliferative disorder of the hand. In the nodular stage of Dupuytren's disease, pain might limit daily hand activities and progress to finger contractures. Focused electromagnetic high-energetic extracorporeal shockwave therapy (ESWT) may reduce pain in Dupuytren's nodules (Tubiana N). In this prospective, randomized, blinded, placebo-controlled single center trial, we enrolled 52 patients (mean age, 58.2 ± 9.2) with painful nodular Dupuytren disease Tubiana N. Randomization was done to either (group A) 3 treatments with focused electromagnetic high-energetic ESWT (2000 shots, 3 Hz, 0.35 mmJ/mm2/hand, Storz Duolith SD1, n = 27) or (group B) placebo ESWT (2000 shots, 3 Hz, 0.01 mJ/mm2/hand, n = 25) in a weekly interval. Primary outcome was the level of pain on a visual analogue scale (VAS 0-10) at 3/6/12/18 months, secondary outcomes were patient-related outcome measures (DASH score, MHQ score, URAM scale), grip strength, patient's satisfaction, and Dupuytren's disease progression over 18 months follow-up. Focused ESWT significantly improved outcomes. Pain was reduced from 3.6 ± 1.8 to 1.9 ± 1.2 at three, to 1.4 ± 0.7 at six, to 1.7 ± 1.6 after 12 months and 1.9 ± 0.8 after 18 months in the intervention group (47% reduction, p < 0.05). In the placebo group, pain on VAS increased from 2.2 ± 1.4 to 3.4 ± 1.7 at three, to 3.4 ± 1.8 at six, to 3.4 ± 1.4 at 12 and 3.1 ± 1.1 at 18 months (35% increase, p < 0.05). Quality-of-life score tended to improve in the intervention group (MHQ, 77 ± 19 to 83 ± 12; DASH, 12 ± 18 to 10 ± 9) while it deteriorated in the placebo group as Dupuytren's disease was progressing (MHQ, 79 ± 15 to 73 ± 17; DASH, 6 ± 10 to 14 ± 13). The strength of the affected hand and fingers did not change significantly in either of the groups. Patients' satisfaction was higher in the intervention group for symptom improvement (56% vs. 12%) and reduction of disease progression (59% vs. 24%). Any Dupuytren-related intervention was performed in 26% in the intervention group and in 36% in the placebo group within 18 months of follow-up (n.s.). Focused electromagnetic high-energetic ESWT can significantly reduce pain in painful nodules in Dupuytren's disease in an 18-month perspective. ( ClinicalTrials.gov Identifier: NCT01184586).

Measuring functional outcome in Dupuytren's disease: A systematic review of patient-reported outcome measures.

BACKGROUND: Functional impairments related to Dupuytren's disease (DD) can be assessed using patient-reported outcome measures (PROMs). A systematic review was published in 2013 on outcome measures for assessing treatment in individuals with DD; however, several articles have since been published on this matter. PURPOSE: To conduct a systematic review to analyze the quality and content of the evidence on the psychometric properties of PROMs used in individuals with DD. STUDY DESIGN: Systematic review. METHODS: CINAHL, EBM reviews, Embase, Medline, and Web of Science were searched to identify studies evaluating the psychometric properties of PROMs used with individuals with DD. All studies retained were appraised by two independent assessors using two validated critical appraisal tools. RESULTS: Fifteen articles on the psychometric properties of 10 PROMs were included. Construct validity and responsiveness were the most studied. Eighty percent of the studies were of good to very good methodological quality according to MacDermid's Critical appraisal checklist for psychometric articles, whereas 67% of the studies comported risks of bias according to the COSMIN checklist. Of the 10 PROMs, three were specifically developed for DD but remain mostly under-studied for their psychometric properties (≤ 2 studies for the SDSS and DIF-CHUM). The QuickDASH, MHQ, BriefMHQ, and URAM present moderate to good convergent validity. Test-retest reliability was found to be good for the MHQ, briefMHQ, URAM, SDSS, SF-36, and the multi-attribute of the HUI-3. The MHQ and BriefMHQ are highly responsive. CONCLUSION: There is a need for more psychometric studies on the PROMs used with individuals with DD. However, to date, the results included in this systematic review support that the MHQ and briefMHQ are the PROMs with the most acceptable psychometric properties.

Dupuytren Contractures: An Update of Recent Literature.

Dupuytren disease is a fibroproliferative disorder that affects the palmar fascia of the hand and results in varying degrees of nodule and cord formation. Over time, patients may develop progressive contractures, impairing their ability to type, to perform with fine instruments, or to participate in social activities such as shaking hands. Treatment options for Dupuytren contractures include needle aponeurotomy (NA), injection of collagenase Clostridium histolyticum (CCH) with manipulation of the digits, and surgical fasciectomy. Over the past decade, the use of CCH has increased. Recent studies have provided additional data regarding the pathophysiology, indications, outcomes, and costs associated with the treatment for Dupuytren contractures, and this review highlights these advances.

Content validity and responsiveness of the Patient-Specific Functional Scale in patients with Dupuytren's disease.

INTRODUCTION: Patient-reported outcome measures have become the standard tool for reflecting the patient's perspective on their treatment outcome for a wide variety of hand conditions. The Patient-Specific Functional Scale (PSFS), is an individualized questionnaire that enables patients to specify those activities with which they have difficulty in daily life. PURPOSE OF THE STUDY: This study aims to determine the content validity and responsiveness of the PSFS compared with the Michigan Hand Questionnaire (MHQ) in patients with Dupuytren's disease. STUDY DESIGN: Multicentre inception cohort. METHODS: Patients with Dupuytren's disease being treated with percutaneous needle aponeurotomy, limited fasciectomy, or skin graft were selected from a database with routine outcome measurements in usual care. To assess content validity of the PSFS, the activities specified by patients were classified into the International Classification of Function core set for hand conditions. The standardized response mean is calculated for the pre- and post-change scores of the PSFS to evaluate responsiveness. RESULTS: Three hundred and eight patients were analyzed before and three months after treatment. Content validity of the PSFS was appropriate because 95% of all items could be classified into the International Classification of Function activities and participation domain. The standardized response mean of the PSFS was 1.0 (95% confidence interval, 0.86-1.2), which was substantially larger than the standardized response mean of the MHQ score 0.58 (95% confidence interval, 0.42-0.74). DISCUSSION: The PSFS is a content-valid questionnaire which may be more responsive to change than a fixed-item instrument such as the MHQ in patients with Dupuytren's disease. CONCLUSIONS: The PSFS is a valuable tool to set therapy goals and evaluate the progress over time in patients with Dupuytren's disease.

A meta-analysis to identify novel diagnostic and therapeutic targets for Dupuytren's disease.

The aim of this study was to determine novel candidate genes for Dupuytren's disease by performing a meta-analysis. We identified 261 genes (111 up-regulated and 150 down-regulated) that were consistently expressed differentially in Dupuytren's disease across the studies. We performed functional enrichment on total sets of the identified 261 genes and confirmed that most of the genes were closely related to common processes of diseases in general. From the integrated studies of the gene-correlation network and the protein-protein interaction network, we identified three functional modules in the gene co-expression network and four hub gene clusters in the protein-protein interaction network that shared the same genes and represented similar biological functions, implying that the seven groups identified in the systematic analysis of these two networks might be involved in the pathogenesis of Dupuytren's disease. This work demonstrates potential in developing experimental and clinical strategies for understanding and treating Dupuytren's disease.

Hand therapy or not following collagenase treatment for Dupuytren's contracture? Protocol for a randomised controlled trial.

BACKGROUND: Dupuytren's contracture (DC) is a fibrotic hand condition in which one or more fingers develop progressive flexion deformities. Quality of life is diminished due to disabling limitations in performing everyday activities. For DC patients treated with collagenase, referral for subsequent hand therapy is inconsistent. It is unknown whether subsequent hand therapy is beneficial compared to no therapy. The purpose of this study is to determine whether hand therapy improves DC patients' performance of and satisfaction with performing everyday activities one year after collagenase treatment. METHODS: We will conduct a randomised controlled trial with two treatment groups (hand therapy vs. control) of DC patients who have received collagenase treatment. DC patients with contracted metacarpophalangeal joint(s) (MCPJ) (hand therapy, n = 40; control, n = 40) and those with proximal interphalangeal joint(s) (PIPJ) involvement (hand therapy, n = 40; control, n = 40) comprise two subgroups, and we will study if the treatment effect will be different between both groups (n = 160). Patients with a previous injury or treatment for DC in the treatment finger are excluded. Hand therapy includes oedema and scar management, splinting, movement exercises, and practice of everyday activities. The main outcome variable is patients' performance of and satisfaction with performing everyday activities, as assessed with the Canadian Occupational Performance Measure. Secondary outcomes are DC-specific activity problems, as assessed with the Unité Rhumatologique des Affections de la Main scale, and active/passive flexion/extension of treated joints and grip force using standard measuring tools, and self-reported pain level. Demographic and clinical variables, degree of scarring, cold hypersensitivity, number of occupational sick-leave days are collected. Self-reported global impression of change will be used to assess patient satisfaction with change in hand function. Assessments are done pre-injection and 6 weeks, 4 months, and 1 year later. Standard univariate and multivariate statistical analyses will be used to evaluate group differences. DISCUSSION: This study aims to assess whether hand therapy is beneficial for activity-related, biomechanical, and clinical outcomes in DC patients after collagenase treatment. The results will provide an objective basis for determining whether hand therapy should be conducted after collagenase treatment. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov as NCT03580213 (April 5, 2018).

The Molecular Pathogenesis of Dupuytren Disease: Review of the Literature and Suggested New Approaches to Treatment.

BACKGROUND: Ever since the classification of Dupuytren disease into the proliferative, involutional, and residual stages, extensive research has been performed to uncover the molecular underpinnings of the disease and develop better treatment modalities for patients. The aim of this article is to systematically review the basic science literature pertaining to Dupuytren disease and suggest a new approach to treatment. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted using the MEDLINE database to identify basic science literature on Dupuytren pathophysiology falling under 1 or more of the following categories: (1) Molecular alterations, (2) Structural alterations, and (3) Genetic predisposition. RESULTS: A total of 177 articles were reviewed of which 77 studies met inclusion criteria. Articles were categorized into respective sections outlined in the study methods. CONCLUSION: The pathophysiological changes involved in Dupuytren's disease can be divided into a number of molecular and structural alterations with genetic predisposition playing a contributory role. Understanding these changes can allow for the development of biologics which may disrupt and halt the disease process.

Collagenase Clostridium histolyticum for the Treatment of Distal Interphalangeal Joint Contractures in Dupuytren Disease.

PURPOSE: To explore the efficacy of injectable collagenase Clostridium histolyticum (CCH) in distal interphalangeal (DIP) joint contractures in Dupuytren disease. METHODS: A retrospective review was conducted for patients with DIP joint contractures treated with CCH. Baseline contracture and posttreatment residual contracture were recorded. The primary end point was achievement of 0° to 5° of residual contracture 30 days postmanipulation. Recurrence and adverse events are also reported. RESULTS: Twenty-one patients were treated with collagenase for DIP joint contractures and had a mean follow-up of 2.6 months. Seventeen of 21 patients reached the primary end point of less than 5° residual flexion contracture. Eleven of 21 patients experienced an adverse event, most commonly bruising and edema. No serious complications such as neurovascular injuries or tendon ruptures were recorded. Two patients had recurrence of disease. CONCLUSIONS: Injection with CCH is an option for the treatment of DIP joint contractures in Dupuytren disease. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Dupuytren's disease: limited fasciectomy, night splinting, and hand exercises-long-term results.

BACKGROUND: Dupuytren's contracture (DC) is a fibroproliferative disorder of palmar fascia that causes flexion contractures of one or more digits. There is currently no gold standard operative and postoperative protocol for reducing recurrence rates. We propose a combination of surgical intervention, night splinting, and home hand exercises as a treatment protocol. METHODS: Thirty patients were included in our study, diagnosed with DC Tubiana grade II-IV. Our treatment protocol was limited fasciectomy followed by a 24-week night splint application, combined with home hand exercises for eight weeks. The outcomes were recurrence, QuickDASH score, extension or flexion deficit, and grip strength. The mean follow-up was 4.9 years (range 2-11 years). RESULTS: Recurrence of DC occurred in two patients (7%), who had discontinued the use of the splint within two months postoperatively. All other patients had complied with the postoperative protocol. The mean QuickDASH score improved from 61.5 (SD 2.1) to 8.6 (SD 2) postoperatively (p < 0.001). Grip strength did not differ significantly in the operated hands (37.9 kg, SD 1.3) when compared to the healthy hands (40.2 kg, SD 1.3, p = 0.035). The recurrence was not significantly correlated either with the Tubiana grade (p = 0.7), or with the patients' age (p = 0.27). CONCLUSIONS: This study shows that limited fasciectomy followed by a 24-week night splint application, combined with home hand exercises for at least eight weeks, is a viable protocol which reduces the rates of recurrence of DC.

Effectiveness of Conservative, Surgical, and Postsurgical Interventions for Trigger Finger, Dupuytren Disease, and De Quervain Disease: A Systematic Review.

OBJECTIVES: To provide an evidence-based overview of the effectiveness of conservative and (post)surgical interventions for trigger finger, Dupuytren disease, and De Quervain disease. DATA SOURCES: Cochrane Library, Physiotherapy Evidence Database, PubMed, Embase, and CINAHL were searched to identify relevant systematic reviews and randomized controlled trials (RCTs). DATA SELECTION: Two reviewers independently applied the inclusion criteria to select potential studies. DATA EXTRACTION: Two reviewers independently extracted the data and assessed the methodologic quality. DATA SYNTHESIS: A best-evidence synthesis was performed to summarize the results. Two reviews (trigger finger and De Quervain disease) and 37 randomized controlled trials (RCTs) (trigger finger: n=8; Dupuytren disease: n=14, and De Quervain disease: n=15) were included. The trials reported on oral medication (Dupuytren disease), physiotherapy (De Quervain disease), injections and surgical treatment (trigger finger, Dupuytren disease, and De Quervain disease), and other conservative (De Qervain disease) and postsurgical treatment (Dupuytren disease). Moderate evidence was found for the effect of corticosteroid injection on the very short term for trigger finger, De Quervain disease, and for injections with collagenase (30d) when looking at all joints, and no evidence was found when looking at the PIP joint for Dupuytren disease. A thumb splint as additive to a corticosteroid injection seems to be effective (moderate evidence) for De Quervain disease (short term and midterm). For Dupuytren disease, use of a corticosteroid injection within a percutaneous needle aponeurotomy in the midterm and tamoxifen versus a placebo before or after a fasciectomy seems to promising (moderate evidence). We also found moderate evidence for splinting after Dupuytren surgery in the short term. CONCLUSIONS: In recent years, more and more RCTs have been conducted to study treatment of the aforementioned hand disorders. However, more high-quality RCTs are still needed to further stimulate evidence-based practice for patients with trigger finger, Dupuytren disease, and De Quervain disease.

What do we know about managing Dupuytren's disease cost-effectively?

BACKGROUND: Dupuytren's disease (DD) is a common and progressive, fibroproliferative disorder of the palmar and digital fascia of the hand. Various treatments have been recommended for advanced disease or to retard progression of early disease and to prevent deterioration of the finger contracture and quality of life. Recent studies have tried to evaluate the clinical and cost-effectiveness of therapies for DD, but there is currently no systematic assessment and appraisal of the economic evaluations. METHODS: A systematic literature review was conducted, following PRISMA guidelines, to identify studies reporting economic evaluations of interventions for managing DD. Databases searched included the Ovid MEDLINE/Embase (without time restriction), National Health Service (NHS) Economic Evaluation Database (all years) and the National Institute for Health Research (NIHR) Journals Library) Health Technology Assessment (HTA). Cost-effectiveness analyses of treating DD were identified and their quality was assessed using the CHEERS assessment tool for quality of reporting and Phillips checklist for model evaluation. RESULTS: A total of 103 studies were screened, of which 4 met the study inclusion criteria. Two studies were from the US, one from the UK and one from Canada. They all assessed the same interventions for advanced DD, namely collagenase Clostridium histolyticum injection, percutaneous needle fasciotomy and partial fasciectomy. All studies conducting a cost-utility analysis, two implemented a decision analytic model and two a Markov model approach. None of them were based on a single randomised controlled trial, but rather synthesised evidence from various sources. Studies varied in their time horizon, sources of utility estimates and perspective of analysis. The overall quality of study reporting was good based on the CHEERS checklist. The quality of the model reporting in terms of model structure, data synthesis and model consistency varied across the included studies. CONCLUSION: Cost-effectiveness analyses for patients with advanced DD are limited and have applied different approaches with respect to modelling. Future studies should improve the way they are conducted and report their findings according to established guidance for conducting economic modelling of health care technologies. TRIAL REGISTRATION: The protocol was registered ( CRD42016032989 ; date 08/01/2016) with the PROSPERO international prospective register of systematic reviews.

Dupuytren's Contracture: An Evidence Based Review.

Dupuytren's contracture, a benign condition characterized by fibrosis of the palmar and digital fascia, may be a debilitating condition that limits daily function. Several techniques exist for managing symptomatic contractures of the hand related to Dupuytren's. These techniques include the more invasive open fasciotomy or fasciectomy. More recently, less invasive techniques including administration of collagenase Clostridium histolyticum (CCH) or percutaneous needle aponeurotomy (PNA) have become part of the treatment armamentarium. A comprehensive review of the literature is performed and an algorithm for management of Dupuytren's contracture is proposed.

Factors influencing recurrence and progression of Dupuytren's disease treated by Collagenase Clostridium histolitycum.

AIM OF THE STUDY: The purpose of this study was to determine the recurrence rate, possible adverse reactions and factors influencing recurrence and progression of Dupuytren's disease (DD) treated with Collagenase from Clostridium histolyticum (CCH). METHOD: This was a prospective study of 71 patients with DD treated with CCH from 2011 to February 2013, with a minimum follow-up period of four years. Clinical, functional, patient satisfaction, drug safety and factors influencing recurrence and disease progression were evaluated. RESULTS: In all patients, the rupture of the cord was achieved after the injection, reducing joint contracture. In five patients (7%) we verified the existence of disease recurrence during the follow-up. In 11 patients (15.5%) there was a disease progression. Three patients have been surgically operated on, without added surgery difficulty; the rate of recurrence and progression was higher in grades III and IV of Tubiana, in proximal interphalangeal (PIP) punctures, and was earlier in patients younger than 60 years. DISCUSSION: No serious local complications or general complications were observed with this method. The recurrence of DD, following criteria of Felici, is mainly observed in young patients with greater severity of the disease and at the PIP level. Progression is influenced by the same factors. Patients operated on after recurrence have no added difficulty in the surgical technique, as it has also been published in other studies. CONCLUSIONS: Patients with the lowest rates of recurrence and progression were those with a single cord in the metacarpophalangeal (MCP), a grade II of Tubiana, and were older than 60 years.

Range of motion, postoperative rehabilitation and patient satisfaction in MCP and PIP joints affected by Dupuytren Tubiana stage 1-3: collagenase enzymatic fasciotomy or limited fasciectomy? A clinical study in 52 patients.

INTRODUCTION: In Switzerland, collagenase Clostridium histolyticum therapy (CCH) for Dupuytren's disease was introduced in 2011. This study analyzes possible differences between CCH and limited fasciectomy (LF) in terms of range of motion, patient satisfaction and postoperative rehabilitation. MATERIALS AND METHODS: This retrospective study included 52 patients with Dupuytren's disease stage 1-3 according to Tubiana, treated with CCH or LF between January 2012 and December 2013. Complications were analyzed for each patient. The contracture of each treated joint measured on average at the 3 months and up to 2 years follow-up was compared with the preoperative values. The Michigan Hand score was evaluated at 2 years and the patients were asked to subjectively evaluate the outcome of the treatment and whether they would repeat it if necessary. Postoperative rehabilitation was also precisely quantified. RESULTS: 11 minor complications were reported for a complication rate of 29% in the CCH group. No major complications were reported in both groups. In the CCH group, mean MCP joint contracture was, respectively, 44° ± 20°, 9° ± 2° (gain of mobility compared to the preoperative situation 35°, P < 0.001), and 10° ± 3° (gain 34°, P < 0.001), respectively, before, at the 3 months' control and at the 2-year clinical control. In the LF group, mean MCP joint contracture was, respectively, 30° ± 21°, 2° ± 0.5° (gain 28°, P < 0.001), and 1° ± 0.5° (gain 29°, P < 0.001) for the same control periods. In the CCH group, mean PIP joint contracture was, respectively, 51° ± 21°, 18° ± 3° (gain of mobility compared to the preoperative situation 33°, P < 0.001), and 32° ± 4° (gain 19°, P < 0.001), respectively, before, at the 3 months' control and at the 2-year clinical control. In the LF group, mean PIP joint contracture was, respectively, 30° ± 20°, 2° ± 0.5° (gain of mobility compared to the preoperative situation 28°, P < 0.001), and 11° ± 4° (gain 19°, P < 0.001) for the same control periods. Outcomes were compared across the LF and CCH groups: surgery performed better than collagenase for PIP joint treatment at early (P < 0.001) and 2-year follow-up (P = 0.004) controls. However, patient satisfaction was higher in the CCH group: 92% were satisfied or very satisfied of the treatment compared to 71% in the LF group. All patients would reiterate the treatment in the CCH group if necessary compared to only 71% in the LF group. Rehabilitation was highly reduced in the CCH group compared to the LF group. CONCLUSION: In this study, surgery performed better than collagenase at early and 2-year follow-up in PIP joints and similar in MCP joints. While surgery seems to achieve better results, collagenase is considered in Switzerland as an off-the-shelf therapy that provides consistent results without scars, with shorter rehabilitation time, minor hand therapy, shorter splinting time, and applicability. LEVEL OF EVIDENCE AND STUDY TYPE: Level III.

CURRENT TREATMENT OPTIONS OF DUPUYTREN´S DISEASE.

Dupuytren's disease (fibromatosis of the palmar fascia, benign neoplastic fibromatosis, Dupuytren's contracture) is a disease characterized by growth and successive contracture of single parts of the palmar aponeurosis. This condition is known and has been treated for several centuries. In the advanced stages of the disease, it leads to significant limitation of hand function, resulting in reduced quality of life of the patient. Dupuytren's disease (DD) is a life-long disease with a variable course and a heterogeneous clinical presentation. Therapy focuses on the clinical manifestations of the disease as well as on reduction of the functional limitation of the hand caused by the disease. In addition to conservative and surgical procedures, there are also some mini-invasive methods available. Treatment should be reserved for centres and experienced surgeons specialized in hand surgery.

Short-term effect of shockwave therapy, temperature controlled high energy adjustable multi-mode emission laser or stretching in Dupuytren's disease: a prospective randomized clinical trial.

Dupuytren's disease is a debilitating disease of the hand characterized by nodules on the surface of the palm with progressive loss of finger extension. The chosen forms of treatment are infiltrative and surgical. Conservative treatment could be useful but few studies have been carried out and these regarded mainly stretching exercises and thermo-therapy. To date, no study has analyzed the effects of biostimulation with shock-waves (SW) and high energy laser therapy [Temperature controlled High Energy Adjustable multi-mode emission Laser (THEAL)]. We recruited 45 patients, 32 males and 13 females (average age 63.4 years) affected by early or late stage Dupuytren's disease [33 metacarpophalangeal (MCP) joints, 12 proximal interphalangeal (PIP) joints]. We randomized the patients into three treatment groups: extracorporeal shockwave therapy (ESWT), THEAL and stretching exercises. Follow-ups were at the end of treatment (T1), after 1 month (T2), and after 3 months (T3). The three forms of treatment determined a progressive clinical-functional improvement. The pain relief was statistically significant for SW and THEAL at all follow-ups (FUs) (p

Injectable Collagenase Versus Percutaneous Needle Fasciotomy for Dupuytren Contracture in Proximal Interphalangeal Joints: A Randomized Controlled Trial.

PURPOSE: Collagenase Clostridium histolyticum (CCH) injection was introduced commercially as a treatment for Dupuytren contracture following initial phase-3 investigations in 2009 with promising results. However, the efficacy of CCH has not been prospectively investigated in a direct comparison to other active treatments of Dupuytren contracture with more than 1-year follow-up, despite a wide and increasing clinical use. METHOD: In this prospective, independent, open-label, randomized controlled trial, (Clinicaltrials.gov; NCT 01538017), percutaneous needle fasciotomy (PNF) was directly compared with CCH. Fifty patients with primary isolated proximal interphalangeal joint Dupuytren contractures were enrolled and followed for 2 years. The primary outcome was clinical improvement defined as a reduction in contracture by 50% or more relative to baseline. Secondary outcomes included change in contracture, recurrence, adverse events, complications, and Disabilities of the Arm, Shoulder, and Hand questionnaire score. RESULTS: Clinical improvement at 2 years was maintained in 7% of CCH patients (2 of 29) and 29% of PNF patients (6 of 21). Collagenase Clostridium histolyticum led to more, mainly transient, complications, in 93% of patients versus 24% of the patients treated with PNF. No other differences were observed. CONCLUSIONS: This study provides evidence that CCH is not superior to PNF in the treatment of isolated proximal interphalangeal joint Dupuytren contracture regarding clinical outcome, and it led to more complications than PNF. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.