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.

Emerging Strategies on Adjuvant Therapies for Nerve Recovery.

Current strategies for promoting faster and more effective peripheral nerve healing have utilized a wide variety of techniques and approaches. Nerve grafts, conduits, and stem cell therapy all have their respective advantages. However, there are still some difficulties in attaining complete functional recovery with a single treatment modality. The utilization of adjuvant treatments, in combination with current standard-of-care methods, offers the potential to improve patient outcomes. This paper highlights the current landscape of adjuvant treatments for enhancing peripheral nerve repair and regeneration.

Efficacy and safety of collagenase clostridium histolyticum in the treatment of proximal interphalangeal joints in dupuytren contracture: combined analysis of 4 phase 3 clinical trials.

PURPOSE: To examine the results of proximal interphalangeal (PIP) joint contractures from 4 phase 3 clinical trials of collagenase clostridium histolyticum (CCH) injection for Dupuytren contracture. METHODS: Patients enrolled in Collagenase Option for Reduction of Dupuytren I/II and JOINT I/II with one or more PIP joint contractures (20° to 80°) received CCH 0.58 mg/0.20 mL or placebo (Collagenase Option for Reduction of Dupuytren I/II only) injected directly into a palpable cord. The percentage of PIP joints achieving clinical success (0° to 5° of full extension), clinical improvement (50% or more reduction in baseline contracture), and range of motion improvement at 30 days after the first and last CCH injections was assessed. The PIP joint contractures were classified into low (40° or less) and high (more than 40°) baseline severity. Adverse events were recorded. RESULTS: A total of 506 adults (mean age, 63 ± 10 y; 80% male) received 1,165 CCH injections in 644 PIP joint cords (mean, 1.6 injections/cord). Most patients (60%) received 1 injection, with 24%, 16%, and 1% receiving 2, 3, and 4 injections, respectively. Clinical success and clinical improvement occurred in 27% and 49% of PIP joints after one injection and in 34% and 58% after the last injection. Patients with lower baseline severity showed greater improvement and response was comparable between fingers, as were improvements in range of motion. Adverse events occurring in more than 10% of patients were peripheral edema (58%), contusion (38%), injection site hemorrhage (23%), injection site pain (21%), injection site swelling (16%), and tenderness (13%). This incidence was consistent with data reported in phase 3 trials. Two tendon ruptures occurred. No further ruptures occurred after a modified injection technique was adopted. CONCLUSIONS: Collagenase clostridium histolyticum was effective and well tolerated in the short term in patients with Dupuytren PIP joint contractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

The Efficacy and Safety of Concurrent Collagenase Clostridium Histolyticum Injections for 2 Dupuytren Contractures in the Same Hand: A Prospective, Multicenter Study.

PURPOSE: To evaluate efficacy and safety of concurrent administration of 2 collagenase clostridium histolyticum (CCH) injections to treat 2 joints in the same hand with Dupuytren fixed flexion contractures (FFCs). METHODS: Patients with 2 or more contractures in the same hand caused by palpable cords participated in a 60-day, multicenter, open-label, phase 3b study. Two 0.58 mg CCH doses were injected into 1 or 2 cords in the same hand (1 injection per affected joint) during the same visit. Finger extension was performed approximately 24, 48, or 72 or more hours later. Changes in FFC and range of motion, incidence of clinical success (FFC ≤ 5°), and adverse events (AEs) were summarized. RESULTS: The study enrolled 715 patients (725 treated joint pairs), and 714 patients (724 joint pairs) were analyzed for efficacy. At day 31, mean total FFC (sum of 2 treated joints) decreased 74%, from 98° to 27°. Mean total range of motion increased from 90° to 156°. The incidence of clinical success was 65% in metacarpophalangeal joints and 29% in proximal interphalangeal joints. Most treatment-related AEs were mild to moderate, resolving without intervention; the most common were swelling of treated extremity, contusion, and pain in extremity. The incidence of skin lacerations was 22% (160 of 715). Efficacy and safety were similar regardless of time to finger extension. CONCLUSIONS: Collagenase clostridium histolyticum can be used to effectively treat 2 affected joints concurrently without a greater risk of AEs than treatment of a single joint, with the exception of skin laceration. The incidence of clinical success in this study after 1 injection per joint was comparable to phase 3 study results after 3 or more injections per joint. Two concurrent CCH injections may allow more rapid overall treatment of multiple affected joints, and the ability to vary the time between CCH injection and finger extension may allow physicians and patients greater flexibility with scheduling treatment.

Contemporary management of dupuytren contracture.

Dupuytren contracture is a condition that affects the palmar fascia. It most commonly affects men of northern European ancestry and initially presents at middle age. The diseased fascia may form cords that extend into the digits, resulting in limited motion and function. Treatment is aimed at either releasing or removing the diseased cord so that the finger can extend fully. Common interventions include surgery, needle aponeurotomy, and collagenase injection. Surgery remains the gold standard in treatment and most commonly includes a limited fasciectomy. Although often successful, surgery carries inherent risks and may involve a lengthy recovery with extensive therapy. Needle aponeurotomy and collagenase injections are office-based alternatives that aim to weaken the cord and release the contracture. Needle aponeurotomy involves repeated needling along the cord in intervals and collagenase injections to dissolve a portion of the cord. Despite being less invasive, problems such as nerve and/or tendon injury, skin tears, and autoimmune reactions have been reported. Regardless of treatment, recurrence remains a concern.

The prevalence of Dupuytren's disease in patients with diabetes mellitus.

BACKGROUND: Dupuytren's disease (DD) is a fibroproliferative hand disorder associated with various medical conditions, including diabetes mellitus (DM). The reported prevalence of DM among DD patients varies widely, primarily due to small sample sizes in previous studies. METHODS: This was a retrospective cohort study using data from the TriNetX Research Database. We analyzed the overall prevalence of DD between 2010 and 2020, comparing the DM, type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) cohorts. Within the DM group, patients were further categorized based on hemoglobin A1c (HbA1c) values and prescribed anti-diabetic agents (insulin or metformin). We compared the prevalence of DD diagnosis in each group using prevalence ratios and differences. RESULTS: There is a higher prevalence of DD in patients with T2DM than in patients with T1DM (relative risk [RR]: 1.641; 95% confidence interval [CI]: [1.356, 1.986]). Among patients with diabetes, there is a higher prevalence of DD in those taking insulin compared to those taking metformin (RR: 0.801, 95% CI: [0.774, 0.83]). The prevalence of DD varies depending on HbA1c levels, with a prevalence of 0.463% in patients having levels within the diabetic range, while lower prevalences of 0.392% and 0.416% are found in patients with prediabetes or uncontrolled diabetes, respectively. CONCLUSIONS: This study provides further insight into the relationship between DM and DD. These findings may be attributed to the increased accumulation of advanced glycosylated end products (AGEs) in patients with diabetes. Future research exploring the connection between AGE accumulation and DD development may enhance our understanding of the relationship between DD and DM.

Dupuytren's disease (DD), commonly known as Dupuytren's contracture, is a disorder of the hand that has been associated with various conditions including diabetes. The relationship between the two has not been studied in large populations; therefore, we used a large electronic medical record database to better understand the association between these two conditions. Our analyses show that within the population of patients with diabetes, DD is more common in patients with adult-onset diabetes and patients with blood sugar levels corresponding to moderate diabetes. This finding may be related to biochemical changes in the body as a result of elevated blood sugar levels found in these patients. Future investigation into this biochemical change may contribute further to our understanding of the relationship between these two conditions.

Injectable collagenase clostridium histolyticum for Dupuytren's contracture.

BACKGROUND: Dupuytren's disease limits hand function, diminishes the quality of life, and may ultimately disable the hand. Surgery followed by hand therapy is standard treatment, but it is associated with serious potential complications. Injection of collagenase clostridium histolyticum, an office-based, nonsurgical option, may reduce joint contractures caused by Dupuytren's disease. METHODS: We enrolled 308 patients with joint contractures of 20 degrees or more in this prospective, randomized, double-blind, placebo-controlled, multicenter trial. The primary metacarpophalangeal or proximal interphalangeal joints of these patients were randomly assigned to receive up to three injections of collagenase clostridium histolyticum (at a dose of 0.58 mg per injection) or placebo in the contracted collagen cord at 30-day intervals. One day after injection, the joints were manipulated. The primary end point was a reduction in contracture to 0 to 5 degrees of full extension 30 days after the last injection. Twenty-six secondary end points were evaluated, and data on adverse events were collected. RESULTS: Collagenase treatment significantly improved outcomes. More cords that were injected with collagenase than cords injected with placebo met the primary end point (64.0% vs. 6.8%, P < 0.001), as well as all secondary end points (P < or = 0.002). Overall, the range of motion in the joints was significantly improved after injection with collagenase as compared with placebo (from 43.9 to 80.7 degrees vs. from 45.3 to 49.5 degrees, P < 0.001). The most commonly reported adverse events were localized swelling, pain, bruising, pruritus, and transient regional lymph-node enlargement and tenderness. Three treatment-related serious adverse events were reported: two tendon ruptures and one case of complex regional pain syndrome. No significant changes in flexion or grip strength, no systemic allergic reactions, and no nerve injuries were observed. CONCLUSIONS: Collagenase clostridium histolyticum significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytren's disease. (ClinicalTrials.gov number, NCT00528606.)

The impact of fiberwire, fiberloop, and locking suture configuration on flexor tendon repairs.

PURPOSE: Suture technique, suture material, and the number of strands all play critical roles in achieving optimal strength of flexor tendon repairs. We evaluated the contribution to the tensile strength of flexor tendon repair using the strongest suture material, Fiberwire, and the best surgical technique (locking configuration) using 2- and 4-strand core repair to see what factor played the most important role in tendon repair. METHODS: Human cadaver flexor tendons were harvested and repaired in a randomized fashion using locking configuration as derived from Pennington's report. Ten tendons per group were repaired using either 4-0 Fiberloop, 4-0 Fiberwire, or 2-0 Fiberwire. During load-to-failure testing, visible gap force and maximum tensile strength were statistically analyzed. RESULTS: All flexor tendon repairs failed by suture pullout. The 4-strand 4-0 Fiberwire double-Pennington repair was found to be significantly stronger than the 4-strand 4-0 Fiberloop single-Pennington repair. When the 2-strand repair (2-0 Fiberwire) was compared to the 4-strand single-Pennington repair (4-0 Fiberloop), there was no significant difference found. CONCLUSIONS: The suture strand configuration rather than the strict number of strands or the strength of the suture material yielded the maximum tensile strength with reduced gapping at the repair site.

Leupeptin accelerates recovery after sciatic transection and repair, but not crush injuries in rats.

We aimed to explore previously reported discrepancies in success with leupeptin by comparing outcomes of two types of injury: transection and crush. Male rats were randomized into vehicle and leupeptin treatment groups (n = 6/transection group; n = 10/crush group). Leupeptin (12 mg/kg) was administered via intramuscular injection into the gastrocnemius muscle twice a week for the duration of the study. Rats were monitored on a weekly basis for electromyographic function and gait for 8 weeks. A total of 83.3% of the rats that were treated with leupeptin began to recover electromyographic activity 1 week after transection, versus 0% that were treated with leupeptin after crush (P < 0.0001). Rats that were treated with leupeptin also had less functional debilitation, as indicated by a greater sciatic functional index at five of the eight time-points after transection versus one of eight after crush (P ≤ 0.05). Leupeptin aids in the rate of recovery after transection and repair but not crush injuries. These findings suggest there may be differences in pathology and recovery associated with these two types of peripheral nerve injury.

Antithrombotic Use with Collagenase Clostridium Histolyticum Injection to Treat Dupuytren Disease.

Background: Collagenase Clostridium histolyticum (collagenase) is an injectable treatment option for Dupuytren disease. The current study was designed to investigate the safety and ensure the effectiveness of collagenase for the treatment of Dupuytren disease, with or without concomitant antithrombotic usage. Methods: One hundred and forty-eight patients with Dupuytren disease were treated with collagenase during this period; 49 taking antithrombotics and 99 not taking antithrombotics. The primary outcomes were clinical success (a reduction in joint contracture to < 5°) and clinical improvement (a reduction in joint contracture by equal to or more than 50%). Results: No statistically significant difference in either clinical success or clinical improvement was found between those taking and those not taking antithrombotics. No significant difference was found in the incidence of any adverse effects or skin splits between the two cohorts. Conclusions: Collagenase can be safely and effectively used to treat patients with Dupuytren disease who take antithrombotics.

Rapid Gout Detection Method and Kit.

Gout is a form of arthritis characterized by buildup of uric acid in synovial fluid, which causes severe swelling and can harm joints, tendons, and other tissues. It affects approximately 4% of the United States population, or approximately 8.3 million people nationwide and is therefore a topic of epidemiologic consideration due to its prevalence. Gout is typically diagnosed via polarized microscopy of arthroscopically-aspirated synovial fluid, which is a costly, time-consuming, labor-intensive, and technically complex procedure, warranting a simpler and less complex method for diagnosis. Here, we propose and validate a colorimetric method which is based on the ability of uric acid to reduce silver nitrate. We also assessed how the colorimetric change can be accelerated by changing the concentration of silver nitrate or adding different silver catalysts, as well as develop a matrix bed for improved handling and ease of use. When translated to the clinic, this diagnostic method for gout will have the potential to increase diagnostic efficiency and accelerate patient care at the bedside.

Development of Collagenase Treatment for Dupuytren Disease.

Proof-of-principle, basic-science studies, using a rat-tail tendon model and surgically removed Dupuytren cords, began collagenase Clostridium histolyticum (CCH) development. Clinical studies in humans were then conducted, where the primary endpoint was reduction in contracture to within 0° to 5° of extension. Phase 2 studies, which confirmed the optimal dose of collagenase as 0.58 mg, showed injectable CCH reduced contractures in MP and PIP joints to within 0° to 5° in many joints and was well tolerated. Clinical results from phase 3 studies confirmed the efficacy and safety of injectable CCH as a viable nonsurgical intervention.

The Optimal Location to Measure Scapholunate Diastasis on Screening Radiographs.

BACKGROUND: Lack of a universally accepted location and normal value limits the utility of measuring scapholunate diastasis. The primary purpose of this study was to define the optimal location to measure the scapholunate gap throughout sequential ligament transections. Secondary purposes were to compare plain radiographs with fluoroscopy and to evaluate interrater reliability in measuring scapholunate diastasis. METHODS: Five cadaver forearms were imaged with intact carpal ligaments and after sequentially transecting the scapholunate, radioscaphocapitate, and scaphotrapezium-trapezoid ligaments. Plain radiographs and static fluoroscopic images were obtained with wrists in neutral and 30° ulnar deviation for each stage. Multiple reviewers performed measurements of the scapholunate interval at 3 separate locations. Mean distances were calculated and pairwise comparisons between groups were made. Intraclass correlation was calculated to determine interrater reliability. RESULTS: Overall, measurements made in the middle of the scapholunate joint had the smallest margins of error for all imaging modalities, ligament disruptions, and wrist positions. For normal wrists, the mean scapholunate measurements were all less than 2.0 mm at the middle of the joint, regardless of imaging modality or wrist position. Fluoroscopy detected significance between more stages of instability than plain radiographs at the middle of the joint. CONCLUSIONS: Measurements in the middle of the scapholunate joint in neutral and 30° of ulnar deviation under fluoroscopic imaging best capture all stages of ligamentous disruptions. Measurements less than 2.0 mm at the middle of the scapholunate interval may be considered within normal range.

Percutaneous release of A1 pulley.

We performed 100 percutaneous releases of the trigger digits in a cadaveric model using an 18-gauge needle. Successful percutaneous release was achieved for only 59 digits (59%). No neurovascular injury occurred. We found that a percutaneous trigger digit release resulted in high percentage of incomplete releases of A1 pulley, especially in the thumb, index, and little fingers.

Collagenase Clostridium histolyticum: emerging practice patterns and treatment advances.

OBJECTIVE: This study aims to provide a comprehensive review of the role of Collagenase Clostridium histolyticum (CCH). METHODS: This review is based on a literature review and practical experience. RESULTS: This review provides practical management strategies for using collagenase by sharing clinical experiences over the past few years; logistical aspects of in-clinic treatment, lessons learned, and novel approaches to correct traditionally hard-to-treat contractures are discussed. In addition a brief, yet comprehensive overview is provided on the pathophysiology of the disease, the mechanism of collagenase action and results of clinical studies. CONCLUSION: CCH has an evolving role as one of the tools available for treating Dupuytren's disease.

Microsurgical Simulation Exercise for Surgical Training.

OBJECTIVE: Initial training for orthopedic surgical residents (postgraduate years 1-5) in microsurgery using the turkey wing model and evaluation of their proficiency. DESIGN: Residents were given a questionnaire on their comfort level with microsurgery and microsurgical knowledge, followed by a lecture on the subject. They watched a surgical dissection and repair of the turkey wing's neurovasculature. Residents performed the dissection and repairs of the artery, vein, and nerve. A postquestionnaire was administered following the simulation exercise. Their performances on repairs were graded and results compared by academic year. SETTING AND PARTICIPANTS: A total of 21 orthopedic surgery residents were recruited from Stony Brook University Medical Center, Stony Brook, NK. RESULTS: This training activity resulted in significant improvements in both microsurgical knowledge (41%) and comfort (37%). Senior residents scored significantly higher than juniors on 6 microsurgical parameters. The largest effect was in nerve repair showing 4 parameters that differed significantly between groups. CONCLUSION: Microsurgical techniques require extensive training to master. The turkey wing model for repair of the artery, vein, and nerve represents a realistic simulation of a human hand artery, vein, and nerve. It provides an inexpensive method for residents to practice on real tissue for improving microsurgical technique.

Delayed manipulation after collagenase clostridium histolyticum injection for Dupuytren contracture.

BACKGROUND: Collagenase clostridium histolyticum (CCH) injection for Dupuytren contracture was approved in the USA in 2010. Current FDA guidelines stipulate that finger manipulation occurs the day following injection. To investigate the safety and efficacy of delaying manipulation to 2 or 4 days following CCH injection, we conducted a prospective, randomized trial at two sites. METHODS: Patients with Dupuytren contracture involving the metacarpophalangeal (MCP) joint ≥20° caused by a palpable cord participated. All patients received one dose of CCH (0.58 mg/0.25 ml) and were followed for 90 days. The primary end point was the percent of patients maintaining clinical success (reduction of contracture to 0°-5°) at 90 days post-injection. Adverse events and change in Michigan Hand Questionnaire (MHQ) score were recorded as secondary end points. RESULTS: Thirty-seven patients enrolled; 13 were manipulated on day 1, 11 on day 2, and 13 on day 4. At 30 days after injection, the percentage of patients obtaining reduction of contracture to <0°-5° extension was 92, 82, and 85 % in groups 1, 2, and 3, respectively, with no significant difference. At 90 days follow-up, the percentage of patients maintaining 0°-5° extension was 91, 82, and 83 % in groups 1, 2, and 3, respectively, with no significant difference. Adverse events were comparable to rates in prior studies. There were no serious adverse events. There was no statistical difference in MHQ scores between groups at any time point. CONCLUSIONS: Delaying manipulation to day 2 or 4 following CCH injection for MCP joint contractures does not increase adverse events or result in loss of efficacy. LEVEL OF EVIDENCE: Therapeutic, Level II.

Synovial chondromatosis of the distal radioulnar joint.

Synovial chondromatosis is a rare lesion in the wrist and it is extremely uncommon in the distal radioulnar joint. This case presented with wrist pain, swelling and locking secondary to synovial chondromatosis of distal radioulnar joint.