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. Methods. We used data from the Repurposing anti-TNF for Dupuytren’s disease (RIDD) randomized controlled trial of intranodular adalimumab injections in patients with early-stage progressive DD. RIDD found that intranodular adalimumab injections reduced nodule hardness and size in patients with early-stage DD, indicating the potential to control disease progression. A within-trial cost-utility analysis compared four adalimumab injections with no further treatment against standard care alone, taking a 12-month time horizon and using prospective data on EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and resource use from the RIDD trial. We also developed a patient-level simulation model similar to a Markov model to extrapolate trial outcomes over a lifetime using data from the RIDD trial and a literature review. This also evaluated repeated courses of adalimumab each time the nodule reactivated (every three years) in patients who initially responded. Results. The within-trial economic evaluation found that adalimumab plus standard care cost £503,410 per quality-adjusted life year (QALY) gained versus standard care alone over a 12-month time horizon. The model-based extrapolation suggested that, over a lifetime, repeated courses of adalimumab could cost £14,593 (95% confidence interval £7,534 to £42,698) per QALY gained versus standard care alone. If the NHS was willing to pay £20,000/QALY gained, there is a 77% probability that adalimumab with retreatment is the best value for money. Conclusion. Repeated courses of adalimumab are likely to be a cost-effective treatment for progressive early-stage DD. The value of perfect parameter information that would eliminate all uncertainty around the parameters estimated in RIDD and the duration of quiescence was estimated to be £105 per patient or £272 million for all 2,584,411 prevalent cases in the UK. Cite this article: Bone Jt Open 2022;3(11):898–906

The purpose of this study was to profile the mRNA expression for the 23 known matrix metalloproteinases (MMPs), 4 tissue inhibitor of metalloproteinases (TIMPs) and 19 ADAMTSs (a disintegrin and metalloproteinase with thrombospontin motif) in Dupuytren's Disease and normal palmar fascia. Dupuytren's Disease (DD) is a fibroproliferative disorder affecting the palmar fascia, leading to contractures. The MMPs and ADAMTSs are related enzymes collectively responsible for turnover of the extracellular matrix. The balance between the proteolytic action of the MMPs and ADAMTSs and their inhibition by the TIMPs underpins many pathological processes. Deviation in favour of proteolysis is seen in e.g. invasive carcinomata, whereas an imbalance towards inhibition causes e.g. fibrosis. A group of patients with end-stage gastric carcinoma was treated with a broad spectrum MMP inhibitor in an attempt to reduce the rate of carcinoma advancement; a proportion developed a ‘musculoskeletal syndrome’ resembling DD. Tissue samples were obtained from patients undergoing surgery to correct contractures caused by DD and from healthy controls undergoing carpal tunnel decompression. The DD tissue was separated macroscopically into cord and nodule. Total RNA was extracted and mRNA expression analysed by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), normalised to 18S rRNA. Comparing across all genes, the DD nodule, DD cord and normal palmar fascia samples each had a distinct mRNA expression profile. Statistically significant (p<0.05) differences in mRNA expression included: higher MMP-2, -7 and ADAMTS-3 levels in both cord and nodule; higher MMP-1, -14, TIMP-1 and ADAMTS-4 and -5 in nodule alone, lower MMP-3 in nodule and cord and lower TIMP-2, -3 and -4 and ADAMTS-1 and -8 levels in nodule alone. The distinct mRNA profile of each group suggests differences in extracellular proteolytic activity which may underlie the process of fascial remodelling in DD

Background: Presently the aetiology of this common condition remains unclear. Previous research suggests that diabetes or epilepsy might increase the prevalence of the condition, but the evidence is inconsistent. Methods: Our cases were all patients diagnosed with Dupuytren’s Disease, with two controls per case individually matched by age, sex, and general practice. Information on all diagnoses of diabetes and diabetic medication, and epilepsy and anti-epileptics was extracted. All analysis was adjusted for consulting behaviour to reduce ascertainment bias. Results: There were 821 cases (1,642 controls), 588 (72%) of which were males. Mean age at diagnosis was 62 years. Prevalence = 0.2%. Diabetes was significantly associated with Dupuytren’s (OR 1.82). Insulin use was strongly associated with Dupuytren’s (OR = 4.33), as was metformin (OR = 3.67); the association was also present for sulphonlyureas (OR = 1.89). There was no association with epilepsy and Dupuytren’s (OR = 1.05). None of the treatments for epilepsy were associated with Dupuytren’s disease. Conclusion:Diabetes is a significant risk factor for Dupuytren’s Disease. There is an increased risk for treated diabetes rather than diet controlled diabetes. Epilepsy and anti-epileptic medication are not associated with Dupuytren’s Disease. Ascertainment bias may explain the association observed in previous studies

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

The matrix metalloproteinases (MMPs) and ADAMTSs (a disintegrin and metalloproteinase with thrombos-pontin motif) are related enzymes collectively responsible for turnover of the extracellular matrix. The balance between the proteolytic action of the MMPs and ADAMTSs, and their inhibition by the tissue inhibitors of metalloproteinases (TIMPs), underpins many pathological processes. Deviation in favour of proteolysis is seen in e.g. invasive carcinoma, whereas an imbalance towards inhibition causes e.g. fibrosis. Dupuytren’s Disease (DD) is a fibroproliferative disorder affecting the palmar fascia, leading to contractures. A group of patients with end-stage gastric carcinoma were treated with a broad spectrum MMP inhibitor in an attempt to reduce the rate of tumour advancement: a proportion developed a ‘musculoskeletal syndrome’ resembling DD. Several groups have looked at subsets of the metalloproteinase family in relation to DD, but to date, a study of the gene expression of all of the members has not been published. We therefore set out to profile the mRNA expression for the 23 known MMPs, 4 TIMPs & 19 ADAMTSs in DD and normal palmar fascia. Tissue samples were obtained from patients undergoing surgery to correct contractures caused by DD and from healthy controls undergoing carpal tunnel decompression. The DD tissue was separated macroscopically into cord and nodule. Total RNA was extracted and mRNA expression analysed by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), normalised to 18S rRNA. Comparing across all genes, the DD nodule, DD cord and normal palmar fascia samples each had a distinct mRNA expression profile. Statistically significant (p< 0.05) differences in mRNA expression included: higher MMP-2, -7 and ADAMTS-3 levels in both cord and nodule; higher MMP-1, -14, TIMP-1 and ADAMTS-4 and -5 in nodule alone, lower MMP-3 in nodule and cord and lower TIMP-2, -3 and -4 and ADAMTS-1 and -8 levels in nodule alone. The distinct mRNA profile of each group suggests differences in extracellular proteolytic activity which may underlie the process of fascial remodelling in DD. Further in vitro experiments are planned based on these observed differences in gene expression

Reconfiguration of elective orthopaedic surgery presents challenges and opportunities to develop outpatient pathways to reduce surgical waiting times. Dupuytren's disease (DD) is a benign progressive fibroproliferative disorder of the fascia in the hand, which can be disabling. Percutaneous-needle-fasciotomy (PNF) can be performed successfully in the outpatient clinic. The Aberdeen hand-service has over 10 years' experience running dedicated PNF clinics. NHS Grampian covers a vast area of Scotland receiving over 11749 referrals to the orthopaedic unit yearly. 250 patients undergone PNF in the outpatient department annually. 100 patients who underwent PNF in outpatients (Jan2019–Jan2020). 79M, 21F. Average age 66 years range (29–87). 95 patients were right hand dominant. DD risk factors: 6 patients were diabetic, 2 epileptic, 87 patients drank alcohol. 76 patients had a family history of DD. Disease severity, single digit 20 patients, one hand multiple digits in 15 patients, bilateral hands in 65 patients of which 5 suffered form ectopic manifestation suggestive of Dupuytren's diasthesis. Using Tubiana Total flexion deformity score pre and post fasciotomy. Type 1 total flexion deformity (TFD) between 0–45 degrees pre PNF n=60 post N= 85, Type 2 TFD 45–90 degrees pre PNF n=18 post N=9, Type 3 TFD 90–135 pre PNF n=15 post N= 5, Type 4 TFD >135 pre PNF n=1 post PNF N=1. Using Chi-square statistical test, a significant difference was found at the p<0.05 between the pre and post PNF TFD. Complication: 8 recurrence, 1 skin tear. No patients sustained digital nerve injury. Outpatients PNF clinics are a valuable resource

Introduction. Dupuytren's disease (DD) is a fibro-proliferative disorder of the palmar fascia whereby a collagen cord contracts affected joints, resulting in flexion deformity that can impair hand function. Currently, surgery is the only effective treatment option in Europe. This 2-part study, consisting of a surgeon survey and chart audit, was designed to assess current surgical practice patterns by DD severity. We report results from the surgeon survey. Methods. A total of 687 participants, including 579 orthopedic surgeons (of which 383 were hand specialists) and 108 plastic surgeons, who had been practicing for >3 and <30 years and operated on 5 DD patients between September and December 2008 were surveyed in 12 countries (UK, Germany, France, Italy, Spain, Hungary, Czech Republic, Poland, Netherlands, Sweden, Denmark, Finland). The survey included queries about procedures performed, factors involved in the decision to use a procedure, satisfaction with the procedure, use of physiotherapy, and recurrence. Results. Regardless of specialty, about 95% of surgeons performed fasciectomy in the previous 12 months. Rates for needle aponeurotomy (NA; 36%) and fasciotomy (70%) were comparable across specialties; a larger proportion of plastic surgeons (65%) used dermofasciectomy (DF) than did orthopaedic (39%) and hand surgeons (44%). Decisions to use NA/fasciotomy were driven mainly by patient comfort and quality-of-life issues (eg, aged >70 y, aesthetics, activity impairment); surgeon satisfaction was linked to shorter recovery times, reduced patient burden, few complications, and restored finger function. Decisions to use open surgeries were based mostly on DD characteristics (eg, contracture severity, speed of progression, recurrence), and surgeon satisfaction was linked to intervention efficacy and durability of the outcome. The percentage of surgeons prescribing physiotherapy and the duration of therapy increased with complexity of the first procedure: NA=86%, 5.3 weeks; fasciotomy=94%, 5.4; fasciectomy=97%, 6.7; and DF=99%, 8.7. On average, 90% of patients were enrolled in a physiotherapy program after undergoing a procedure for DD. Using survey responses, recurrence rates appeared to decrease and time to recurrence increased with procedure complexity: NA=44%, 17 months; fasciotomy=32%, 21; fasciectomy=20%, 29; and DF=20%, 34. Conclusions. To our knowledge, based on the number of participants and countries, this is the largest survey to date to collect, quantify, and describe information about the surgical management of DD in Europe. Although data from all countries were combined and results from the specialties were collapsed, it is a critical first step toward understanding DD treatment patterns. Opportunities to learn more about country- and specialty-specific practices will be presented elsewhere. This study was funded by Pfizer Inc

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.

Aims: We present a prospective study, with three-year follow-up, of the role and outcome of fasciectomy plus surgical release of structures of the PIP joint in Dupuy-tren’s contracture of the fifth ray. Methods: All patients presenting for surgery with primary Dupuytren’s contracture of the fifth ray over a six-month period were included in the study. All underwent fasciectomy followed sequentially by release of the abductor band, accessory collateral and checkrein ligaments as necessary. Deformity and range of motion in the PIPJ were measured by goniometer preoperatively, intra-operatively (post-fasciectomy and post-PIP release) and at three months and three years postoperatively. Results: Of the nineteen fingers in the study, eight (all mild deformity) achieved a full correction by fasciectomy alone. 78% correction remained at three months and 70% at three years. The remaining eleven fingers (initial mean deformity 70o flexion) obtained only a 38% correction by fasciectomy, increased to 90% with PIPJ release. Of this correction 64% was maintained at three months and 57% at three years. These figures include one recurrence of Dupuytren’s and are comparable with those of other techniques. Conclusion: We conclude that sequential PIPJ release is a useful technique for the correction of severe Dupuytren’s of the fifth ray involving that joint.

The purpose of the study was to test the hypothesis that cellular mechanisms of fibroblasts derived from primary frozen shoulder (PFS) exhibit similar activity in terms of contraction, response to cytokine transforming growth factor-beta1 (TGF beta1) and mechanical stimulation similar to that generated by fibroblasts derived from Dupuytren’s disease. Frozen shoulder has been postulated to be Dupuytren’s disease of the shoulder with an association inferred since 1936. Primary explant cultures of fibroblasts from seven patients with PFS and five control patients were obtained using standard tissue culture techniques. Fibroblasts were seeded in 3-D collagen constructs and contraction force generated over 24 hours measured using a culture force monitor (CFM) in real time. Increasing concentrations of TGF-beta1 were added to cell seeded gels and force generated measured using the CFM over 24 hours. These mechanical output data were statistically compared to data available from Dupuytren’s disease. Compared to Dupuytren’s fibroblasts, PFS fibroblasts showed a statistically reduced ability to contract a 3-D collagen gel over 24 hours (p< 0.01). In Dupuytren’s disease, fibroblasts derived from nodules and cords generate peak forces of 140 dynes and 110 dynes respectively, while PFS fibroblasts generated peak force of 8 dynes The response to TGF-beta1 stimulation, which has been shown to enhance peak force contraction in Dupuytren’s fibroblasts had no effect on PFS fibroblasts and this was statistically significant (p< 0.01). These data suggest intrinsic differences in cellular activity and mechanisms between Dupuytren’s and Primary Frozen Shoulder even though clinically they both manifest with a contracted extracellular matrix affecting function and requiring surgical intervention. This may explain increased post surgical recurrence in Dupuytren’s as compared to Primary Frozen Shoulder release

The purpose of the study was to test the hypothesis that cellular mechanisms of fibroblasts derived from primary frozen shoulder(PFS) exhibit similar activity in terms of contraction, response to cytokine (transforming growth factor-beta1) and mechanical stimulation similar to that generated by fibroblasts derived from dupuytren’s disease. PFS is a debilitating disease of unknown aetiology, characterised by fibrosis with contracture of the cora-cohumeral ligament, tissues of the rotator interval and glenohumeral ligaments, leading to restrictive shoulder movements. Frozen shoulder has been postulated to be Dupuytren’s disease of the shoulder with an association inferred since 1936. Materials and Methods: Primary explant cultures of fibroblasts from seven patients with PFS and five control patients were obtained using standard tissue culture techniques. Fibroblasts were seeded in 3-D collagen constructs and contraction force generated over 24hours measured using a culture force monitor(CFM) in real time. Increasing concentrations of TGF-beta1 were added to cell seeded gels and force generated measured using the CFM over 24hours. These mechanical output data were statistically compared to data available from Dupuytren’s disease. Results and Discussion: Compared to Dupuytren’s fibroblasts, PFS fibroblasts showed a statistically reduced ability to contract a 3-D collagen gel over 24hours (p< 0.01). In Dupuytren’s disease, fibroblasts derived from nodules and cords generate peak forces of 140dynes and 110dynes respectively, while PFS fibro-blasts generated peak force of 8dynes The response to TGF-beta1 stimulation, which has been shown to enhance peak force contraction in Dupuytren’s fibro-blasts had no effect on PFS fibroblasts and this was statistically significant (p< 0.01). Conclusion: These data suggest intrinsic differences in cellular activity and mechanisms between Dupuytren’s and Primary Frozen Shoulder even though clinically they both manifest with a contracted extracellular matrix affecting function and requiring surgical intervention. This may explain increasing post surgically recurrence in Dupuytren’s as compared to Primary Frozen Shoulder release

Objective. To assess patterns of recurrence in patients with Dupuytren's disease after surgery for proximal interphalangeal joint (PIPJ) deformity. Methods. 81 patients (94 fingers) with Duputyren's contracture of the proximal interphalangeal joint underwent surgery to have either a ‘firebreak’ skin graft (46 fingers) or a fasciectomy (48 fingers). They were reviewed after three weeks, six weeks, 6, 12, 24 and 36 months to note the range of movement and recurrence. Both groups were similar with regard to age, gender and factors considered to influence the outcome such as bilateral disease, family history, and the presence of diabetes, smoking and alcohol intake. Results. The rate of recurrent contracture of PIP joint was 12.2%. Four patterns were identified: Group 1 (Responsive group: Immediate improvement, maintained over three years), Group 2 (Improved group: Initial mild loss of position but improvement maintained), Group 3 (Stiffness group: Immediate significant worsening but maintained), and Group 4 (Recurred group: Immediate loss of position with further progressive contracture). Time since onset of Dupuytren's disease and pre-op PEM showed significant association with recurrent contracture on regression analysis (GEE, Wald chi square test, P< 0.01). Conclusion. Four distinct patterns of recurrent contracture of PIP joint were identified three years after corrective surgery for Dupuytren's disease. Pre-operative PEM and disease duration could predict recurrence

Dupuytren's disease (DD) is a fibroproliferative soft tissue disease affecting the palmar fascia of the hand causing permanent and irreversible flexion contracture. Aberrant fibrosis is likely to manifest through a combination of extrinsic, intrinsic, and environmental factors, including genetics and epigenetics. However, the role of epigenetics in soft tissue fibrosis in diseases such as DD is not well established. Therefore, we conducted a comprehensive multi-omic study investigating the epigenetic profiles that influence gene expression in DD pathology. Using control (patients undergoing carpal tunnel release) and diseased fibroblasts (patients undergoing Dupuytren's fasciectomy), we conducted ATAC-seq to assess differential chromatin accessibility between control and diseased fibroblasts. Additionally, ChIP-seq mapped common histone modifications (histone H4; H3K4me3, H3K9me3, H3K27me3, H4K16Ac, H4K20Me3) associated with fibrosis. Furthermore, we extracted RNA from control and DD tissue and performed bulk RNA-seq. ATAC-seq analysis identified 2470 accessible genomic loci significantly more accessible in diseased fibroblasts compared to control. Comparison between diseased and control cells identified numerous significantly different peaks in histone modifications (H4K20me3, H3K27me3, H3K9me3) associated with gene repression in control cells but not in diseased cells. Pathway analysis demonstrated a substantial overlap in genes being de-repressed across these histone modifications (Figure 1). Both, ATAC-seq and ChIP-seq analysis indicated pathways such as cell adhesion, differentiation, and extracellular matrix organisation were dysregulated as a result of epigenetic changes. Moreover, de novo motif enrichment analysis identified transcription factors that possibly contributed to the differential gene expression between control and diseased tissue, including HIC1, NFATC1 and TEAD2. RNA-seq analysis found that these transcription factors were upregulated in DD tissue compared to control tissue. The current epigenetic study provides insights into the aberrant fibrotic processes associated with soft tissue diseases such as DD and indicates that epigenetic-targeted therapies may be an interesting viable treatment option in future. For any figures or tables, please contact the authors directly

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

The October 2012 Wrist & Hand Roundup. 360. looks at: osteoarticular flaps to the PIPJ; prognosis after wrist arthroscopy; adipofascial flaps and post-traumatic adhesions; the torn TFCC alone; ulna-shortening osteotomy for ulnar impaction syndrome; Dupuytren’s disease; when a wrist sprain is not a sprain; and shrinking the torn intercarpal ligament

The December 2012 Wrist & Hand Roundup. 360. looks at: the imaging of scaphoid fractures; splinting to help Dupuytren’s disease; quality of life after nerve transfers; early failure of Moje thumbs; electra CMCJ arthroplasty; proximal interphalangeal joint replacement; pronator quadratus repair in distal radius fractures; and osteoporosis and wrist fractures

Introduction: Dupuytren’s contracture is a common disease in Northern Europe. Partial fasciectomy is often used to treat the whole spectrum of Dupyutren’s disease, although high recurrence rates have been reported. In our department, the majority of patients are treated by total aponeurectomy, which is defined as the complete removal of palmar tissue. It has been found out that apparently normal-looking aponeurosis can also contain an increased proportion of collagen, which may lead to recurrent disease. Consequently, the perceived advantage of total aponeurectomy over partial aponeurectomy is the potential for a lower recurrence rate as all diseased tissue is potentially removed. Against this background, we have reviewed the effectiveness of total aponeurectomy performed on 61 patients. Patients and Methods: The group of patients available for review consisted of 51 men and ten women with a mean age of 63.0 (range 42–79 years) and with a mean period of 3.45 years (range 1.03–6.39 years) between operation and review. No patient had follow-up of less than 1 year. At follow-up evaluation hands were examined for nodules, cords and retractions of the skin. The active mobility of the joints was determined with a goniometer and the Jamar hand dynamometer was used to measure grip strength in both hands. Sensitivity was examined by means of two-point-discrimination and the DASH-score was used for the analysis of rehabilitation. Patients were also asked about common risk factors for Dupuytren’s disease. Results: Post-operative complications including haematoma, seroma or necrosis were found in 13.8% of the patients. Recurrence of contracture occurred in 10.8% of the patients and 4.6% of the operated patients presented with a nerve lesion. Nerve irritation was found in 6.2% of the patients. The mean DASH-score was 3.85 (range 0–52.5). Family pre-disposition was an important risk factor for Dupuytren’s disease with 44.3% of patients having a positive family history. Conclusion: We suggest that total aponeurectomy is a promising alternative to partial fasciectomy with low risk for recurrent disease and slightly increased risk for a nerve lesion

Dupuytren’s contracture is characterised by abnormal fibroblast proliferation and extracellular matrix deposition in the palmar fascia. Fibroblast proliferation and matrix deposition in connective tissues are regulated by cytokines. A number of cytokines including transforming growth factor beta (TGFβ), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF) and epidermal growth factor (EGF) are known to have potent anabolic effects on connective tissue. The aim of this study was to investigate the role played by anabolic cytokines in the pathogenesis of Dupuytren’s disease. Twelve specimens of Dupuytren’s contracture and six control specimens of palmar fascia obtained from patients undergoing carpal tunnel release were cultured using a serumless method under standard conditions for 72 h. Levels of TGFβ-1, bFGF, PDGF and EGF in the medium were estimated using an enzyme linked immunoabsorbent assay technique. Neither Dupuytren’s tissue nor control palmar fascia produced any EGF. The mean (±S.D.)levels of bFGF, PDGF and TGFβ-1 produced by cultured palmar fascia were: 1270 ± 832, 74 ± 24, < 7, and for Dupuytren’s tissue were 722 ± 237, 139 ± 76.6, 645 ± 332, respectively. The levels of PDGF and TGFβ-1 were significantly higher in Dupuytren’s tissue. PDGF is produced in increased amounts by Dupuytren’s tissue. This may contribute to the fibroblast proliferation and increased ECM deposition observed in this condition. TGFβ-1 is not produced by normal palmar fascia but is produced in large amounts by Dupuytren’s tissue. The major physiologic role of TGFβ-1 is to stimulate formation of fibrous tissue. It plays a major role in wound healing and also in pathological conditions where fibrosis is a prominent feature. Inappropriate production of TGFβ-1 in the palmar fascia in Dupuytren’s disease may play a central role in initiating and stimulating the abnormal fibroblast proliferation and collagen synthesis seen in this condition

Aim. To determine effectiveness of Collagenase Clostridium Histolyticum (CCH) in deformity correction and hand function for patients with Dupuytren's disease. Materials & Methods. Patients with MCPJ contractures with no previous surgery to the same finger were included. Treatment consisted of one Xiapex injection to a prominent pretendinous band as an outpatient procedure. Follow up was arranged at 48 hours, 3 weeks and final follow up > 6 months. Results. 17 patients were included. Of the 21 fingers that were studied 14 were right and 7 were left sided. Average age was 69 years (56–82) and mean deformity was 37.6° (10–70). Mean follow up was 11.6 months (SD – 3.13, range 7–17). Post manipulation under correction of deformity was present in 3 fingers which improved by final follow up (mean 6.7°). Three patients had re-appearance of deformity (mean 6.7°). The remaining patients had complete correction of deformity. All deformities were significantly corrected, average correction 35.7° (p<0.05). Michigan hand questionnaire (MHQ) score improved significantly following correction of deformity (p<0.005). The subsets of MHQ – hand function, activities of daily living, aesthetics and satisfaction scores improved significantly (p<0.005). Conclusion. CCH an effective, minimally invasive option for the treatment of Dupuytren contracture