Tommy Lindau

Dupuytren Contracture Recurrence Following Treatment with Collagenase Clostridium Histolyticum (CORDLESS Study): 3-Year Data

PURPOSE To evaluate long-term efficacy and safety of collagenase clostridium histolyticum (CCH) after the third year of a 5-year nontreatment follow-up study, Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study. METHODS This study enrolled Dupuytren contracture patients from 5 previous clinical studies. Beginning 2 years after their first CCH injection, we re-evaluated patients annually for joint contracture and safety. Recurrence in a previously successfully treated joint (success = 0° to 5° contracture after CCH administration) was defined as 20° or greater worsening in contracture in the presence of a palpable cord or medical/surgical intervention to correct new or worsening contracture. We assessed partially corrected joints (joints reduced 20° or more from baseline contracture but not to 0° to 5°) for nondurable response, also defined as 20° or greater worsening of contracture or medical/surgical intervention. RESULTS Of 1,080 CCH-treated joints (648 metacarpophalangeal [MCP]; 432 proximal interphalangeal [PIP]; n = 643 patients), 623 (451 MCP, 172 PIP) had achieved 0° to 5° contracture in the original study. Of these joints, 35% (217 of 623) recurred (MCP 27%; PIP 56%). Of these recurrences, an intervention was performed in 7%. Of the 1,080 CCH-treated joints, 301 were partially corrected in the original study. Of these, 50% (150 of 301; MCP: 38% [57 of 152]; PIP: 62% [93 of 149]) had nondurable response. We identified no new long-term or serious adverse events attributed to CCH during follow-up. Anti-clostridial type I collagenase and/or anti-clostridial type II collagenase antibodies were reported for 96% or more of patients who received 2 or more CCH injections and 82% who received 1 injection. CONCLUSIONS The recurrence rate, which is comparable to other standard treatments, and the absence of long-term adverse events 3 years after initial treatment indicate that CCH is an effective and safe treatment for Dupuytren contracture. Most successfully treated joints had a contracture well below the threshold for surgical intervention 3 years after treatment. Recurrence rates among successfully treated joints were lower than nondurable response rates among partially corrected joints. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

Dupuytren Contracture Recurrence Following Treatment With Collagenase Clostridium Histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]): 5-Year Data

PURPOSE Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study was a 5-year noninterventional follow-up study to determine long-term efficacy and safety of collagenase clostridium histolyticum (CCH) treatment for Dupuytren contracture. METHODS Patients from previous CCH clinical studies were eligible. Enrolled patients were evaluated annually for contracture and safety at 2, 3, 4, and 5 years after their first injection (0.58 mg) of CCH. In successfully treated joints (≤ 5° contracture following CCH treatment), recurrence was defined as 20° or greater worsening (relative to day 30 after the last injection) with a palpable cord or any medical/surgical intervention to correct new/worsening contracture. A post hoc analysis was also conducted using a less stringent threshold (≥ 30° worsening) for comparison with criteria historically used to assess surgical treatment. RESULTS Of 950 eligible patients, 644 enrolled (1,081 treated joints). At year 5, 47% (291 of 623) of successfully treated joints had recurrence (≥ 20° worsening)-39% (178 of 451) of metacarpophalangeal and 66% (113 of 172) of proximal interphalangeal joints. At year 5, 32% (198 of 623) of successfully treated joints had 30° or greater worsening (metacarpophalangeal 26% [119 of 451] and proximal interphalangeal 46% [79 of 172] joints). Of 105 secondary interventions performed in the successfully treated joints, 47% (49 of 105) received fasciectomy, 30% (32 of 105) received additional CCH, and 23% (24 of 105) received other interventions. One mild adverse event was attributed to CCH treatment (skin atrophy [decreased ring finger circumference from thinning of Dupuytren tissue]). Antibodies to clostridial type I and/or II collagenase were found in 93% of patients, but over the 5 years of follow-up, this did not correspond to any reported clinical adverse events. CONCLUSIONS Five years after successful CCH treatment, the overall recurrence rate of 47% was comparable with published recurrence rates after surgical treatments, with one reported long-term treatment-related adverse event. Collagenase clostridium histolyticum injection proved to be an effective and safe treatment for Dupuytren contracture. For those receiving treatment during follow-up, both CCH and fasciectomy were elected options. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic II.

The Natural Course of Traumatic Triangular Fibrocartilage Complex Tears in Distal Radial Fractures: A 13–15 Year Follow-up of Arthroscopically Diagnosed but Untreated Injuries

PURPOSE To evaluate the long-term results of a prospective, longitudinal case series of untreated, traumatic triangular fibrocartilage complex (TFCC) tears found in displaced distal radial fractures. METHODS Between 1995 and 1997, 51 patients (24 men, 27 women; age, 20-57 y) with a displaced distal radius fracture had wrist arthroscopy to identify associated injuries. Forty-three patients had complete or partial tears of the TFCC, which were not treated. All patients were contacted in 2010, 13-15 years after the injury. One patient had had a TFCC reattachment due to painful distal radioulnar joint instability and was excluded. Thirty-eight patients returned for a radiographic and clinical follow-up that recorded strength, distal radioulnar joint laxity, range of motion, pain scale score, and subjective and objective outcome scores. RESULTS After 13-15 years, 17/38 patients were lax in the distal radioulnar joint. The mean grip strength was worse in the patients with a lax distal radioulnar joint (83%, SD 15 of the contralateral side vs 103%, SD 33). The median Gartland and Werley score was 5 (good; range, 0-15) in the lax group compared to 1 (excellent; range, 0-9) in the non-lax group, and the median Disabilities of the Arm, Shoulder, and Hand scores were 14 (range, 0-59) and 5 (range, 0-70) respectively. CONCLUSIONS In this 13-15 year, prospective, longitudinal outcome study of the natural course of TFCC tears associated with distal radius fracture, only 1 patient had been operated on for painful instability since the injury. The subjective and objective results did not provide evidence that a TFCC injury would influence the long-term outcome. However, trends were found and, by speculation, the low number of patients in the series and the risk for a type II error could be the cause of absent statistically significance. Larger, preferably prospective, randomized studies are needed to find out whether a more aggressive treatment is beneficial. TYPE OF STUDY/LEVEL OF EVIDENCE Diagnostic I.

Identification of Biomarkers in Dupuytren's Disease by Comparative Analysis of Fibroblasts Versus Tissue Biopsies in Disease-Specific Phenotypes

PURPOSE Biomarkers are molecular mediators that can serve as indicators of normal biological processes, pathologic processes, and therapeutic interventions. This study aims to identify potential biomarkers in Dupuytrens disease (DD), a fibroproliferative benign tumor with an unknown etiology and high recurrence after surgery. METHODS Bioinformatic analytical techniques were employed to identify candidate genes that may be differentially expressed in DD, which included gene expression analysis of microarray data and thorough literature searches in genetic linkage and other related biomolecular studies. All DD cases were males with advanced DD (n = 5, 66 years +/- 14). RNA was extracted from biopsies and corresponding cultures of normal fascia (unaffected transverse palmar fascia), palmar nodule and cord from each patient. Real-time reverse transcription-polymerase chain reactions were performed to determine the gene expression levels for disease-related transcripts. RESULTS The bioinformatic analysis revealed 25 candidate genes, which were further short-listed to 6 genes via functional annotation. The 6 selected candidate genes included: A disintegrin and metalloproteinase domain (ADAM12), aldehyde dehydrogenase 1 family member (ALDH1) A1, Iroquois homeobox protein 6 (IRX6), proteoglycan 4 (PRG4), tenascin C (TNC), and periostin (POSTN). The culturing treatments were shown to have significant impact on the gene expression for ALDH1A1, PRG4, and TNC. In tissue biopsies, significant fold changes were observed for ADAM12, POSTN, and TNC in the cord and/or nodule when compared with that of normal fascia. ADAM12 and POSTN are associated with accelerated or abnormal cell growth, whereas TNC has been associated with fibrotic diseases and cell migration. CONCLUSIONS This study demonstrated differential gene expression results in DD tissue biopsies compared with that of their corresponding cultures. ADAM12, POSTN, and TNC were identified from the cord and nodule biopsy samples as potential biomarkers in relation to DD development.

Differential gene expression analysis of subcutaneous fat, fascia, and skin overlying a Dupuytren's disease nodule in comparison to control tissue.

Dupuytren’s disease (DD) is a benign fibroproliferative tumor with an unknown etiology and high recurrence postsurgery. Several observations suggest the possible involvement of skin overlying nodule (SON) and the subcutaneous fat in the pathogenesis of DD. This study aims to (1) compare the gene expression levels of SON and subcutaneous fat in DD and normal subjects and (2) to compare transverse palmar fascia (Skoog’s fibers) from DD patients as internal control tissue, with palmar fascia (transverse carpal ligament) from patients undergoing carpal tunnel release as external control. Skin, fat, and fascia were obtained from five DD patients of Caucasian origin (age = 66 ± 14) and from five control subjects (age = 57 ± 19) undergoing carpal tunnel release. Total ribonucleic acids was extracted from each sample and used for complementary deoxyribonucleic acid synthesis. Real-time quantitative polymerase chain reaction was used to assess the gene expression levels of six candidate genes: A disintegrin and metalloproteinase domain (ADAM12), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), iroquois homeoboxprotein 6 (IRX6), periostin, osteoblast specific factor, proteoglycan 4, and tenascin C. Using independent t test, ADAM12, ALDH1A1, and IRX6 expression levels in DD fats were significantly (p < 0.05) higher than those in the controls. There is no significant difference in the gene expression levels of all six genes when comparing disease and control fascia and skin. Interestingly, ADAM12 up-regulation has also been observed in several other fibrotic and proliferative disorders. In conclusion, this study demonstrates potential roles for subcutaneous fat in DD pathogenesis as well as supports the use of transverse palmar fascia as appropriate control tissues in DD research.

The benefit of radiologically-guided steroid injections for trapeziometacarpal osteoarthritis.

INTRODUCTION Osteoarthritis of the trapeziometacarpal joint (TMJ) is a common condition causing significant disability. Conservative treatments include intra-articular steroid injections. PATIENTS AND METHODS This clinical, observational study prospectively reviewed the longevity of benefit of steroid injections into the TMJ. Eighty-three patients were recruited with a median age of 62 years and injected with steroid and local anaesthetic under radioscopic guidance. They were followed up until the analgesic effects ceased with a questionnaire including visual analogue scores. RESULTS Two-thirds of patients were improved at 2 months, with nearly half having a 3-month improvement. One in six patients had a 6-month benefit, with some patients still improved 2 years after injection. Previously injected patients had a reduced duration of benefit compared to their previous injection. Severity of osteoarthritis did not affect the injection efficacy. CONCLUSIONS Based on this study, we recommend steroid injections in all degrees of TMJ osteoarthritis.

Grip strength ratio: a grip strength measurement that correlates well with DASH score in different hand/wrist conditions

BackgroundGrip strength correlates with personal factors such as gender, age and nutritional status and has a good inter-rater reliability. It reflects fairly well how much people can use their hands.The Disabilities of the Arm, Shoulder and Hand (DASH) Outcome Measure 3 is a 30-item, self-report, questionnaire that reflects the patients’ opinion on their disability due to upper-limb disorders. We assessed if grip strength and grip strength ratio correlate with DASH score.MethodsIn 3 groups (20 healthy volunteers, 17 patients after distal radius fractures, 12 patients with different hand/wrist conditions) grip strength and DASH scores (items 1–21, 22–30 and total) were assessed. To exclude personal factors grip strengths in the injured or non-dominant hand and grip strength ratios (grip strength in the injured or non-dominant hand divided by grip strength in the non-injured or dominant hand) were assessed too. Results were analyzed groups using Pearson Correlation Coefficients and with a multivariate ANOVA.ResultsGrip strength ratio was 0.97 in healthy volunteers, 0.52 in patients after distal radius fracture and 0.74 in patients with various other hand/wrist disorders.Significant correlations were found between the grip strength ratio and DASH as well as DASH subsections in all groups and between DASH scores and grip strength in some. The correlations between the ratio of the grip strength (GSR) and DASH were much stronger than the correlation between grip strength and DASH. This emphasizes the value of the GSR. Age showed no correlation with grip strength ratio using a multivariate ANOVA.ConclusionGrip strength ratio correlates well with the DASH score in different hand and wrist conditions. It is a valuable tool to assess patients that speak a different language and have problems with the non-dominant hand and probably easier to follow over time than the DASH score, which is time consuming to fill in and process.

Clinical scaphoid score (CSS) to identify scaphoid fracture with MRI in patients with normal x-ray after a wrist trauma.

Introduction The aim of this study was to compare a combination of three commonly used tests to identify scaphoid fractures with MRI in patients with normal x-ray after a wrist trauma. Patients and methods This prospective MRI study included patients between 18 years and 49 years, who attended the Emergency Department, Bergen, Norway after sustaining an acute wrist trauma within the previous week. Initial x-rays of the wrist were normal. MRI was done within a median of 1 day after the trauma. The study period lasted 1 year. The patients were examined with three commonly used clinical scaphoid tests; tenderness in the anatomical snuffbox with the wrist in ulnar deviation (3 points), tenderness over the scaphoid tubercle (2 points) and pain upon longitudinal compression of the thumb (1 point). The clinical scaphoid score (CSS) is a sum of these points, which was compared with MRI verified fracture of the scaphoid. Results We included 154 patients with wrist sprain and normal x-rays; 13 had occult scaphoid fracture. A CSS of 4 or more was the only statistically significant ‘cut-off’ value to identify occult scaphoid fractures (p<0.05). Diagnostic sensitivity increased with more experienced Emergency Department doctors. Conclusions If a patient with wrist pain after injury and normal x-ray has a CSS≥4 (pain in the anatomical snuffbox in addition to pain at scaphoid tubercle or longitudinal compression or both) we recommend MRI. A CSS <4 has a negative predictive value of 96%, which makes scaphoid fracture unlikely.

Levine-Katz (Boston) Questionnaire analysis: means, medians or grouped totals?

were prescribed oral antibiotics on discharge. Those patients who were admitted (n1⁄4 12) were admitted to the plastic surgery or orthopaedic surgery units, with a majority being received in plastic surgery (50 from 51 patients). This is mainly attributable to the proportion of days on call for hand trauma (6:1). Of those patients who were admitted, two were transferred to the children’s hospital due to their age. Surgical exploration was performed exclusively in the emergency theatres, under general anaesthesia and tourniquet. Specialist registrars performed 100% of cases. Structural damage was revealed in 83% of cases. The injuries were flexor tendon laceration (n1⁄4 6), digital nerve damage (n1⁄4 4) or both tendon and nerve damage (n1⁄4 2). The majority of admissions were for injuries to zones II and III (5 and 6 admissions respectively). One patient presented with a laceration to the skin overlying the mandible. Oral antibiotics were prescribed on discharge to 10 patients; all were admitted patients who underwent surgery during their admission, with amoxicillin clavulanic acid (Augmentin Duo ) the antimicrobial of choice (n1⁄4 9). Fourteen patients were reviewed at least once postoperatively. Mean follow up was 8.4 weeks (range 1 to 36 weeks). Five of these patients dropped out of follow up and the remaining nine were discharged by the reviewing doctor. Six individuals, all with flexor tendon injury, were referred for physiotherapy. Longterm subjective complaints were seen in two individuals. One patient complained of stiffness and one patient complained of numbness associated with severed superficial digital nerve branch. Two flexor tendon repairs were lost to follow up. Longer follow up will be required for any meaningful conclusion to be drawn. To our knowledge, this is the first large study to clinically document the epidemiology and pathology of hand injuries caused by corrugated iron fences. The results indicate that the majority of the injuries are of a superficial nature, not particularly different from those caused by knives, glass and saws. Such injuries require similar treatment, consisting in repair of damaged structures. The majority of cases can be managed on an outpatient basis.

Arthroscopically Diagnosed Scapholunate Ligament Injuries Associated With Distal Radial Fractures: A 13- to 15-Year Follow-Up

PURPOSE To evaluate the natural history of untreated complete or partial scapholunate (SL) ligament tears associated with displaced distal radius fractures. METHODS Between 1995 and 1997, 51 consecutive patients aged < 60 years with displaced distal radius fractures were examined arthroscopically to assess for concomitant soft tissue injuries. Thirty-two of 51 patients had an SL ligament tear, 10 had a complete tear (Lindau grade 3), and 22 had a partial tear (Lindau grades 1 and 2). Thirty-two patients had AO type-C fractures, 3 had type-B fractures, and 16 had type-A fractures. In 2010, 47 of the 51 patients were still alive, and they were invited for an interview, clinical examination, and radiography. RESULTS Thirty-eight of the 51 original patients participated in the long-term follow-up. Mean grip strength was 83% relative to the contralateral hand in patients with a complete tear, as compared with 92% in patients with partial or no SL tears (nonsignificant). Median Disabilities of the Arm, Shoulder, and Hand questionnaire score was 2 (range, 0‒55) for complete SL tears, compared with 9 (range, 0‒70) for the others (nonsignificant). No differences were found regarding visual analog scale pain or wrist motion/forearm rotation. None of the patients developed a static SL dissociation or a SL advanced collapse wrist. CONCLUSIONS No major differences were found in the subjective, objective, or radiographic outcome after a complete (grade 3) or partial (grade 1 or 2) SL untreated tear associated with displaced distal radius fracture. It should be noted that none of the patients had a grade 4 SL tear, which may have a different outcome. TYPE OF STUDY/LEVEL OF EVIDENCE Prognostic II.