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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 115 - 115
2 Jan 2024
Akbar M Crowe L Woolcock K Cole J McInnes I Millar N
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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


Bone & Joint 360
Vol. 11, Issue 6 | Pages 26 - 30
1 Dec 2022

The December 2022 Wrist & Hand Roundup. 360. looks at: Anti-tumour necrosis factor therapy for early-stage Dupuytrens disease; Patient experiences of scaphoid waist fractures and their treatment; Postoperative complications following open a1 pulley release for a trigger finger or thumb; How certain are findings in distal radius fractures: a systematic review of randomized controlled trials; Partial wrist denervation in wrist osteoarthritis: patient-reported outcomes and objective function; Dorsal bridge plating versus bridging external fixation for management of complex distal radius fractures; How is reduction lost in distal radius fractures in females aged 50 years and older; The HAND-Q: psychometrics of a new patient-reported outcome measure for clinical and research applications


Bone & Joint Open
Vol. 3, Issue 11 | Pages 898 - 906
15 Nov 2022
Dakin H Rombach I Dritsaki M Gray A Ball C Lamb SE Nanchahal J

Aims. To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytrens disease (DD) and the value of further research from an NHS perspective. Methods. We used data from the Repurposing anti-TNF for Dupuytrens 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


Bone & Joint 360
Vol. 11, Issue 4 | Pages 21 - 25
1 Aug 2022


Bone & Joint 360
Vol. 11, Issue 3 | Pages 24 - 28
1 Jun 2022


The Bone & Joint Journal
Vol. 104-B, Issue 6 | Pages 709 - 714
1 Jun 2022
Stirling PHC Simpson CJ Ring D Duckworth AD McEachan JE

Aims

The aim of this study was to describe the introduction of a virtual pathway for the management of patients with a suspected fracture of the scaphoid, and to report patient-reported outcome measures (PROMs) and satisfaction following treatment using this service.

Methods

All adult patients who presented with a clinically suspected scaphoid fracture that was not visible on radiographs at the time of presentation during a one-year period were eligible for inclusion in the pathway. Demographic details, findings on examination, and routine four-view radiographs at the time of presentation were collected. All radiographs were reviewed virtually by a single consultant hand surgeon, with patient-initiated follow-up on request. PROMs were assessed at a minimum of one year after presentation and included the abbreviated version of the Disabilities of the Arm, Shoulder and Hand Score (QuickDASH), the EuroQol five-dimension five-level health questionnaire (EQ-5D-5L), the Net Promoter Score (NPS), and return to work.


Bone & Joint 360
Vol. 11, Issue 2 | Pages 27 - 30
1 Apr 2022


Bone & Joint 360
Vol. 11, Issue 1 | Pages 27 - 32
1 Feb 2022


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


Bone & Joint 360
Vol. 10, Issue 5 | Pages 24 - 28
1 Oct 2021


Bone & Joint 360
Vol. 10, Issue 4 | Pages 27 - 30
1 Aug 2021


Bone & Joint 360
Vol. 10, Issue 3 | Pages 16 - 20
1 Jun 2021


The Bone & Joint Journal
Vol. 103-B, Issue 5 | Pages 946 - 950
1 May 2021
Ashdown T Hayter E Morris JA Clough OT Little M Hardman J Anakwe RE

Aims. The results of surgery for Dupuytrens disease can be compromised by the potential for disease recurrence and loss of function. Selecting which patients will benefit from repeat surgery, when to operate, and what procedure to undertake requires judgement and an understanding of patient expectations and functional needs. We undertook this study to investigate patient outcomes and satisfaction following repeat limited fasciectomy for recurrent Dupuytrens disease. Methods. We prospectively identified all patients presenting with recurrence of Dupuytrens disease who were selected for surgical treatment with repeat limited fasciectomy surgery between January 2013 and February 2015. Patients were assessed preoperatively, and again at a minimum of five years postoperatively. We identified 43 patients who were carefully selected for repeat fasciectomy involving 54 fingers. Patients with severe or aggressive disease with extensive skin involvement were not included; in our practice, these patients are instead counselled and preferentially treated with dermofasciectomy. The primary outcome measured was change in the Michigan Hand Outcomes Questionnaire (MHQ) score. Secondary outcomes were change in finger range of motion, flexion contracture, Semmes-Weinstein monofilament (SWM) values, and overall satisfaction. Results. There was a significant improvement in MHQ scores, across all domains, with a mean overall score increase of 24 points (p < 0.001). The summed flexion contracture across the metacarpophalangeal joint (MCPJ) and the proximal interphalangeal joint (PIPJ) reduced from means of 72.0° (SD 15.9°) to 5.6° (SD 6.8°) (p < 0.001). A significant increase in maximal flexion was seen at the MCPJ (p < 0.001) but not the PIPJ (p = 0.550). The mean overall satisfaction score from the visual analogue scale was 8.9 (7.9 to 10.0). Complications were uncommon although five fingers showed reduced sensibility at final follow-up. Conclusion. Our study shows that repeat limited fasciectomy for selected patients presenting with recurrence of Dupuytrens disease can be an effective and safe treatment resulting in excellent patient-reported outcomes and levels of satisfaction. Cite this article: Bone Joint J 2021;103-B(5):946–950


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 704 - 710
1 Apr 2021
van den Berge BA Werker PMN Broekstra DC

Aims. With novel promising therapies potentially limiting progression of Dupuytrens disease (DD), better patient stratification is needed. We aimed to quantify DD development and progression after seven years in a population-based cohort, and to identify factors predictive of disease development or progression. Methods. All surviving participants from our previous prevalence study were invited to participate in the current prospective cohort study. Participants were examined for presence of DD and Iselin’s classification was applied. They were asked to complete comprehensive questionnaires. Disease progression was defined as advancement to a further Iselin stage or surgery. Potential predictive factors were assessed using multivariable regression analyses. Of 763 participants in our original study, 398 were available for further investigation seven years later. Results. We identified 143/398 (35.9%) participants with DD, of whom 56 (39.2%) were newly diagnosed. Overall, 20/93 (21.5%) previously affected participants had disease progression, while 6/93 (6.5%) patients showed disease regression. Disease progression occurred more often in patients who initially had advanced disease. Multivariable regression analyses revealed that both ectopic lesions and a positive family history of DD are independent predictors of disease progression. Previous hand injury predicts development of DD. Conclusion. Disease progression occurred in 21.5% of DD patients in our study. The higher the initial disease stage, the greater the proportion of participants who had disease progression at follow-up. Both ectopic lesions and a positive family history of DD predict disease progression. These patient-specific factors may be used to identify patients who might benefit from treatment that prevents progression. Cite this article: Bone Joint J 2021;103-B(4):704–710


The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1542 - 1548
2 Nov 2020
Stirling PHC Oliver WM Ling Tan H Brown IDM Oliver CW McQueen MM Molyneux SG Duckworth AD

Aims

The primary aim of this study was to describe patient satisfaction and health-related quality of life (HRQoL) following corrective osteotomy for a symptomatic malunion of the distal radius.

Methods

We retrospectively identified 122 adult patients from a single centre over an eight-year period who had undergone corrective osteotomy for a symptomatic malunion of the distal radius. The primary long-term outcome was the Patient-Rated Wrist Evaluation (PRWE) score. Secondary outcomes included the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, the EQ-5D-5L score, complications, and the Net Promoter Score (NPS). Multivariate regression analysis was used to determine factors associated with the PRWE score.


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1331 - 1340
3 Oct 2020
Attard V Li CY Self A Mann DA Borthwick LA O’Connor P Deehan DJ Kalson NS

Aims

Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties.

Methods

Well-functioning primary TKAs (n = 11), failed non-fibrotic TKAs (n = 5), and patients with a clinical diagnosis of fibrosis1 (n = 8) underwent an MRI scan with advanced metal suppression (Slice Encoding for Metal Artefact Correction, SEMAC) with gadolinium contrast. Fibrotic tissue (low intensity on T1 and T2, low-moderate post-contrast enhancement) was quantified (presence and tissue thickness) in six compartments: supra/infrapatella, medial/lateral gutters, and posterior medial/lateral.


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1354 - 1358
3 Oct 2020
Noureddine H Vejsbjerg K Harrop JE White MJ Chakravarthy J Harrison JWK

Aims

In the UK, fasciectomy for Dupuytren’s contracture is generally performed under general or regional anaesthetic, with an arm tourniquet and in a hospital setting. We have changed our practice to use local anaesthetic with adrenaline, no arm tourniquet, and perform the surgery in a community setting. We present the outcome of a consecutive series of 30 patients.

Methods

Prospective data were collected for 30 patients undergoing open fasciectomy on 36 digits (six having two digits affected), over a one-year period and under the care of two surgeons. In total, 10 ml to 20 ml volume of 1% lidocaine with 1:100,000 adrenaline was used. A standard postoperative rehabilitation regime was used. Preoperative health scores, goniometer measurements of metacarpophalangeal (MCP), proximal interphalangeal (PIP) contractures, and Unité Rheumatologique des Affections de la Main (URAM) scores were measured pre- and postoperatively at six and 12 weeks.


Bone & Joint 360
Vol. 8, Issue 6 | Pages 22 - 26
1 Dec 2019


Bone & Joint 360
Vol. 8, Issue 5 | Pages 24 - 27
1 Oct 2019


Bone & Joint 360
Vol. 8, Issue 3 | Pages 23 - 26
1 Jun 2019