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

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

Risk Factors for Penile Fracture After Intralesional Collagenase Clostridium histolyticum in Peyronie's Disease.

OBJECTIVE: To evaluate risk factors leading to corporal rupture after Collagenase Clostridium histolyticum (CCh). Peyronie's disease (PD) is a fibrotic condition of the penis characterized by abnormal plaque formation. Intralesional CCh is the only FDA-approved medication for PD, however, it can lead to corporal rupture, a potential surgical emergency. METHODS: We retrospectively reviewed medical records from Veterans diagnosed with PD who were under treatment with CCh using the Veterans Administration Informatics and Computing Infrastructure (VINCI). Using International Classification of Diseases and Current Procedural Terminology codes, we identified men who suffered a corporal rupture after CCh. Individual charts were reviewed to determine potential risk factors and events leading to corporal rupture. RESULTS: We identified 17,647 veterans who were diagnosed with PD, of which 8.7% (1541) received at least one injection of CCh for PD. Of them, 0.7% (11/1541) veterans suffered corporal rupture. Within these 11 patients, the median number of CCH injections was 6 with a median initial curvature of 35°. Fracture occurred at a median of 8days after CCH injection. The majority of fractures were secondary to spontaneous erections or sexual intercourse. Finally, six patients had their fracture repaired surgically while the remaining were managed conservatively. CONCLUSION: Most fractures occurred within 2weeks of CCh injections and were associated with sexual intercourse and spontaneous morning erections.

The Discontinuation Rate With Collagenase Clostridium histolyticum for Peyronie's Disease in a High-volume Practice Is Unexpectedly High: Identifying Opportunities for Patient Care Improvement.

OBJECTIVE: To elucidate reasons for premature discontinuation of Collagenase Clostridium histolyticum (CCH) injections for the treatment of penile curvature associated with Peyronie's disease. METHODS: A database of men who underwent CCH injections at a single institution was queried to identify men who completed fewer than 8 injections. Chart review was conducted to identify reasons for treatment discontinuation. When this could not be identified, patients were contacted first via the online patient portal and next by phone. RESULTS: Of 406 patients who underwent CCH treatment, 133 did not complete 8 injections (32.8%). The most common reasons for discontinuation were satisfactory curve reduction (27%), unsatisfactory curve reduction (21%), bothersome side effect (15%), and pursuit of surgery (12%). Other less common reasons included other health concerns, pausing treatment due to the COVID-19 pandemic, high cost, transferring care elsewhere, and lack of awareness that more injections were indicated. CONCLUSION: We present the largest series of patients to date dedicated to evaluation of CCH discontinuation. We find that up to 1/3 of patients who begin CCH injections will not complete the full treatment course. Understanding the reasons for discontinuation can help providers better stratify patients for CCH treatment vs other modalities. In addition, as previous studies indicate curvature improvements are equally likely to be seen in the final four injections as the first four, our data points to the potential impact of improved patient education for individuals who discontinue due to unsatisfactory curve reduction.

Collagenase clostridium histolyticum injection versus limited fasciectomy for the treatment of Dupuytren's disease: a systematic review and meta-analysis of comparative studies.

INTRODUCTION: The aim of the present study is to systematically review the literature on well-selected comparative studies for meta-analysis on outcome differences between collagenase clostridium histolyticum (CCH) injection and limited fasciectomy (LF) for Dupuytren's disease. MATERIALS AND METHODS: PubMed/Medline, Embase, and the Cochrane Library were searched for comparative studies assessing differences in outcomes of CCH and LF. Effect estimates were pooled across studies using random effects models and presented as weighted mean difference (MD) and odds ratio (OR) with corresponding 95% confidence interval (CI). RESULTS: A total of 11 studies encompassing 1'051 patients was included (619 patients in the CCH and 432 in the LF group). The residual contracture at a minimal average follow-up of three months was higher in the CCH group than in the LF group (27.8 vs. 16.2°, MD 11.6°, 95% CI [8.7, 14.5°], p < 0.001). The recurrence rate was significantly higher in the CCH group (25.8 vs. 9.3%, OR 5.2, 95% CI [1.5, 18.8], p = 0.01) while the rate of severe complications was significantly higher in the LF group (0.3 vs. 7.3%, OR 0.12, 95% CI [0.03, 0.42], p = 0.001). CONCLUSIONS: Evidence of the present study confirms that CCH injection has a higher rate of disease recurrence whereas LF carries a higher risk for severe complications. It's imperative that the trade-off between these aspects is considered, keeping in mind that CCH injections may be repeated in case of disease recurrence without increasing procedure related risks, especially in complex cases.

Changes in Point of Maximal Curvature During Collagenase Clostridium Histolyticum Injections for Peyronie's Disease.

OBJECTIVE: To determine change in the point of maximal curvature (POMC) during Collagenase Clostridium histolyticum (CCH) injections for Peyronie's disease (PD). METHODS: A prospective database has been maintained of all men undergoing CCH injections since March 2014. For the current study, data were abstracted on the POMC with each curve assessment and correlated with demographic and clinical factors. Maximal changes were defined as the largest change in POMC from baseline. RESULTS: Six hundred and eighteen men underwent ≥1 series of CCH, with 313 having a baseline and subsequent POMC measurements available. Median baseline curvature was 60.0° and POMC 2.8 cm. Among 189 men who were satisfied or completed 8 CCH injections, the median improvement in penile curvature was -27.5° (40.9%). The median maximal change in POMC during CCH treatment was 1.0 cm (interquartile range, 0.5, 1.8). Overall, 55.6% had changes in POMC of ≥1 cm, 23.6% ≥2 cm, 8.9% ≥3 cm, and 3.8% ≥4 cm. Multivariate logistic regression identified ventral curvature as a predictor of larger change in POMC, after controlling for other variables. Study limitations included the observational, non-randomized study design and potential for intra- and inter-individual measurement variability. Strengths are the inclusion of an all-comer population, large series, prospective database, and routine objective assessments. CONCLUSION: Approximately half of men with PD undergoing CCH experience ≥1 cm of change in POMC during the treatment course, with nearly 1/4 experiencing ≥2 cm. Findings suggest that patients may benefit from repeat curvature assessments with each CCH series to optimize accuracy of drug administration.

New protocol in the treatment of Peyronie's disease by combining platelet-rich plasma, percutaneous needle tunneling, and penile modeling: Preliminary results.

INTRODUCTION: Intra-lesional injections of collagenase (Xiapex®) were the only non-invasive treatment option for Peyronie's disease (PD), until their withdrawal from the European market. OBJECTIVE: To evaluate the feasibility, efficacy, and safety of a combined treatment of percutaneous needle tunnelling (PNT) with penile modelling (PM) and the injection of platelet-rich plasma (PRP) under general anesthesia in the treatment of PD. PATIENTS AND METHOD: A prospective case series study included patients with PD in a stable phase who underwent this procedure between March 2020 and January 2023. The main outcome was an improvement in curvature. RESULT: Thirty-six patients underwent this novel approach for the treatment of PD. The pretreatment mean±standard deviation (SD) curvature degree was 57.5±20.61° (range 20-90°). After the protocol, the mean curvature degree was 40.86±25.13° (range 0-90°). The curvature angle improved significantly (P=0.0001), with a mean improvement difference of 16.85±14.81° (range 0-50°) and a mean improvement percentage of 47.7±40.29% (range 0-100%). CONCLUSION: Our preliminary experience suggests that PNT and PRP injections with PM are effective and safe for the treatment of penile deformity of PD. LEVEL OF EVIDENCE: 4: case series study.

Outcomes of collagenase Clostridium histolyticum in men with ventral curvatures: an updated series.

BACKGROUND: The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie's disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature. AIM: The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD. METHODS: Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures. OUTCOMES: Changes in penile curvature, Peyronie's Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events. RESULTS: A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was -25.0° in the ventral cohort vs -24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was -35.0° in the ventral cohort vs -25.0° in the nonventral cohort (P < .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie's Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort. CLINICAL IMPLICATIONS: Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD. STRENGTHS AND LIMITATIONS: Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study. CONCLUSION: CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.

Long-term clinical outcome of collagenase clostridium histolyticum treatment is independent of Dupuytren Diathesis Score.

Collagenase clostridium histolyticum (CCH) is a pharmaceutical, non-surgical treatment option for Dupuytren Disease. However, recurrence is common, and predictors of treatment outcome of CCH treatment are largely unknown. In this retrospective study, we analysed the possible correlation between Abe's Dupuytren Diathesis Score (DDS) and recurrence after treatment with CCH. In a total of 74 patients, with an average follow-up of 5 years, we found an overall recurrence rate of 67% after 5y but no correlation with DDS. Sub-scale analysis indicated that the presence of knuckle pads was associated with a reduced recurrence risk. Patient satisfaction after CCH was high. Deriving from our data, there is no correlation between DDS and recurrence following CCH treatment. Therefore, at this moment, we do not advocate the use of the DDS when informing patients about recurrence rates after CCH treatment. Level of evidence: IV: therapeutic cohort study.

Delayed vascular complication after collagenase injection for Dupuytren disease.

BACKGROUND: Vascular adverse events after collagenase injection for Dupuytren disease are absent in large trials and systematic reviews. The aim of this study is to present a case series of delayed vascular complications after collagenase treatment. METHODS: A prospective evaluation of 1181 consecutively treated patients at one orthopedic department identified three patients reporting symptoms of possible vascular complication. Baseline demographics and description of symptoms were collected, with a physical examination documenting extension deficit and neurovascular status. All patients completed the Cold Intolerance Symptom Severity (CISS) scale (range 4-100, lower is better) and underwent Doppler sonography examination of the digital arteries. RESULTS: All patients were treated in the small finger and two had an isolated proximal interphalangeal joint contracture. All patients had a delayed presentation of a few months, with episodes of white discoloration of the treated finger relieved within 30 min and associated with variable pain, paresthesia, stiffness and weakness. Two of the patients reported cold exposure as an episode trigger and had a pathological CISS score (40 and 36, respectively). Doppler sonography identified a nonpatent ulnar digital artery in one patient. CONCLUSIONS: Delayed vascular complication after collagenase treatment is rare, but surgeons and patients should be aware of the risk, especially when treating the small finger.

Significant Geographic Variation in Access to Certified Collagenase Clostridium histolyticum Injectors for Peyronie's Disease Throughout the United States.

INTRODUCTION: We characterize the geographic distribution of providers trained to inject Clostridium histolyticum and identify areas with low provider availability. METHODS: We utilized a publicly available search tool to identify clinical sites offering Clostridium histolyticum in the US The data gathered included the provider's name, specialty, address, and whether the site was considered high-volume (ie, administer ≥20 Clostridium histolyticum injections per year). Data were compared to the AUA Census. RESULTS: In total, 2,388 clinical sites offering Clostridium histolyticum were identified. A total of 894 sites (37%) were high-volume sites. The mean number of locations offering Clostridium histolyticum per 100,000 state residents was 0.69 (SD 0.27). Georgia (1.28), Rhode Island (1.13), and Alaska (1.10) had the highest number, whereas New Mexico (0.10), Maine (0.22), and Delaware (0.30) had the lowest. The mean proportion of urologists providing Clostridium histolyticum to total urologists was 0.17 (SD 0.07). The 3 states with the highest proportion were Georgia (0.37), Alaska (0.31), and Utah (0.30), whereas New Mexico (0.03), Maine (0.05), and Vermont (0.06) had the lowest. CONCLUSIONS: States with low numbers of clinical sites offering Clostridium histolyticum per 100,000 residents relative to other states also had a low total ratio of urologists offering Clostridium histolyticum as a treatment. There is room for urologists in these states and others to expand their practice to offer Clostridium histolyticum and improve patient access to this important nonsurgical treatment option.

Comparison of Collagenase Clostridium histolyticum to Surgery for the Management of Peyronie's Disease: A Randomized Trial.

PURPOSE: Since Food and Drug Administration approval of collagenase Clostridium histolyticum for Peyronie's disease, there has been significant debate regarding its role and comparable efficacy to surgery. MATERIALS AND METHODS: A randomized, controlled trial was performed of Peyronie's disease men treated with either collagenase C histolyticum + RestoreX penile traction therapy + sildenafil or penile surgery + RestoreX penile traction therapy + sildenafil, with 3-month data presented. Primary objectives were overall satisfaction, subjective changes in erectile function, penile sensation, penile length, and changes in the International Index of Erectile Function-Erectile Function Domain score. Secondary outcomes included objective changes in length, curve, adverse events, and other standardized and nonstandardized questionnaires. RESULTS: A total of 40 men were enrolled, with 38 (collagenase C histolyticum group = 19, surgery group = 19) completing treatment and having 3-month data available. All demographic and clinicopathological variables were similar between groups. Following treatment, 50% of men in the collagenase C histolyticum group reported being very satisfied (vs 21% in the surgery group, P = .08) and noted better subjective erectile function (100% vs 68%, P = .03) and penile length (88% vs 16%, P < .0001), lesser impacts on penile sensation (75% vs 11% no change, P < .001), and similar International Index of Erectile Function-Erectile Function Domain changes (+1.5 vs +2.5, P = .91). Objectively, men in the surgery group had greater curve improvements (84% vs 54%, P < .01) and higher rates of adverse events (50 vs 13 events, P < .001) but decreased penile length (-0.5 cm vs +1.0 cm, P < .01). CONCLUSIONS: At 3 months posttreatment, collagenase C histolyticum + RestoreX penile traction therapy + sildenafil results in lesser curve improvements but greater penile length and fewer adverse events, including impacts on subjective erectile function and sensation, than men treated with surgery.

Collagenase Treatment Versus Needle Fasciotomy for Single-Digit Dupuytren Contractures: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The objective of this systematic review and meta-analysis was to synthesize the available randomized controlled trial data comparing needle fasciotomy and collagenase treatment for single-digit Dupuytren contractures with a minimum of 3-year follow-up and determine whether one treatment is superior regarding contracture correction and functional outcomes. METHODS: A systematic review and meta-analysis was conducted by searching four databases for randomized controlled trials investigating the single-digit treatment outcomes for Dupuytren contracture comparing collagenase treatment and needle fasciotomy with a minimum of 3-year follow-up. The risk of bias of included studies was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed using a random effects model in anticipation of unobserved heterogeneity. The primary outcome measure was contracture recurrence. Secondary outcome measures included final fixed flexion contracture (FFC), Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) scores, and Unité Rhumatologique des Affections de la Main (URAM) scores. RESULTS: After screening 264 articles, 4 randomized clinical trials were eligible for final inclusion. One trial had a high risk of bias, and two trials had some concern for bias. The final meta-analysis included 347 patients, 169 who underwent collagenase treatment and 178 who underwent needle fasciotomy. No significant differences were noted between the groups in contracture recurrence, FFC, and URAM scores. The pooled data showed a higher QuickDASH score in the collagenase treatment group compared with the needle fasciotomy group, but the observed difference was less than what would be expected to be clinically relevant. CONCLUSIONS: Needle fasciotomy and collagenase treatment have similar outcomes with regards to contracture recurrence, final FFC, QuickDASH scores, and URAM scores for the single-digit treatment for Dupuytren contracture at a minimum of 3-year follow-up. Relevant factors that may be considered during the shared decision-making process for treatment selection include surgeon and patient preferences, costs of treatment, and the disparate complication profiles of these two treatments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Targeting Myofibroblasts as a Treatment Modality for Dupuytren Disease.

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

Collagenase treatment decreases muscle stiffness in cerebral palsy: A preclinical ex vivo biomechanical analysis of hip adductor muscle fiber bundles.

AIM: To determine the dose-response relationship of collagenase Clostridium histolyticum (CCH) on collagen content and the change in muscle fiber bundle stiffness after ex vivo treatment of adductor longus biopsies with CCH in children with cerebral palsy (CP). METHOD: Biopsy samples of adductor longus from children with CP (classified in Gross Motor Function Classification System levels IV and V) were treated with 0 U/mL, 200 U/mL, 350 U/mL, or 500 U/mL CCH; percentage collagen reduction was measured to determine the dose-response. Peak and steady-state stresses were determined at 1%, 2.5%, 5%, and 7.5% strain increments; Young's modulus was calculated. RESULTS: Eleven patients were enrolled (nine males, two females, mean age at surgery 6 years 5 months; range: 2-16 years). A linear CCH dose-response relationship was determined. Peak and steady-state stress generation increased linearly at 5.9/2.3mN/mm2 , 12.4/5.3mN/mm2 , 22.2/9.7mN/mm2 , and 33.3/15.5mN/mm2 at each percentage strain increment respectively. After CCH treatment, peak and steady-state stress generation decreased to 3.2/1.2mN/mm2 , 6.5/2.9mN/mm2 , 12.2/5.7mN/mm2 , and 15.4/7.7mN/mm2 respectively (p < 0.004). Young's modulus decreased from 205 kPa to 100 kPa after CCH (p = 0.003). INTERPRETATION: This preclinical ex vivo study provides proof of concept for the use of collagenase to decrease muscle stiffness in individuals with CP.

Pharmacotherapies in Dupuytren Disease: Current and Novel Strategies.

Dupuytren disease is a benign, progressive fibroproliferative disorder of the hands. To date, only one pharmacotherapy (clostridial collagenase) has been approved for use in Dupuytren disease. There is a great need for additional nonsurgical methods that can be used to either avoid the risks of invasive treatments or help minimize recurrence rates following treatment. A number of nonsurgical modalities have been discussed in the past and continue to appear in discussions among hand surgeons, despite highly variable and often poor or no long-term clinical data. This article reviews many of the pharmacotherapies discussed in the treatment of Dupuytren disease and novel therapies used in inflammation and fibrosis that offer potential treatment options.

Identification of key genes in colorectal cancer diagnosis by co-expression analysis weighted gene co-expression network analysis.

BACKGROUND: The purpose of this study was using bioinformatics tools to identify biomarkers and molecular factors involved in the diagnosis of colorectal cancer, which are effective for the diagnosis and treatment of the disease. METHODS: We determined differentially expressed genes (DEGs) related to colorectal cancer (CRC) using the data series retrieved from GEO database. Then the weighted gene co-expression network analysis (WGCNA) was conducted to explore co-expression modules related to CRC diagnosis. Next, the relationship between the integrated modules with clinical features such as the stage of CRC was evaluated. Other downstream analyses were performed on selected module genes. RESULTS: In this study, after performing the WGCNA method, a module named blue module which was more significantly associated with the CRC stage was selected for further evaluation. Afterward, the Protein-protein interaction network through sting software for 154 genes of the blue module was constructed and eight hub genes were identified through the evaluation of constructed network with Cytoscape. Among these eight hub genes, upregulation of MMP9, SERPINH1, COL1A2, COL5A2, COL1A1, SPARC, and COL5A1 in CRC was validated in other microarray and TCGA data. Based on the results of the mRNA-miRNA interaction network, SERPINH1 was found as a target gene of miR-940. Finally, results of the DGIDB database indicated that Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, and Bevacizumab, could be used as a therapeutic agent for targeting the MMP9. Furthermore, Ocriplasmin and Collagenase clostridium histolyticum could target COL1A1, COL1A2, COL5A1, and COL5A2. CONCLUSION: Taken together, the results of the current study indicated that seven hub genes including COL1A2, COL5A1, COL5A2, SERPINH1, MMP9, SPARC, and COL1A1 which were upregulated in CRC could be used as a diagnostic and progression biomarker of CRC. On the other hand, miR-940 which targets SERPINH1 could be used as a potential biomarker of CRC. More ever, Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, Bevacizumab, Ocriplasmin , and Collagenase clostridium histolyticum were introduced as therapeutic agents for CRC which their therapeutic potential should be evaluated experimentally.

Dupuytren's Contracture Recurrence and Treatment Following Collagenase Clostridium Histolyticum Injection: A Longitudinal Assessment in a Veteran Population.

INTRODUCTION: Dupuytren's contracture is a connective tissue disease characterized by an abnormal proliferation of collagen in the palm and fingers, which leads to a decline in hand function because of progressive joint flexion. In addition to surgical and percutaneous interventions, collagenase clostridium histolyticum (CCH, trade name Xiaflex) is an intralesional enzymatic treatment for adults with palpable cords. The objectives of this study are to evaluate factors predictive of recurrence following treatment with CCH and to review the outcomes of repeat treatments with CCH for recurrent contracture. MATERIALS AND METHODS: An institutional review board-approved retrospective chart review was conducted for patients between 2010 and 2017 who received CCH injections for Dupuytren's contracture at a Veterans Affairs hospital. Demographics, comorbidities, affected finger and joint, pre/posttreatment contracture, time to recurrence, and treatment of recurrence were recorded. Successful treatment was defined as contracture ≤5° following CCH, and improvement was defined as ≥20° reduction from baseline contracture. Study cohorts were followed after their secondary treatment, and time to recurrence was recorded and plotted using a Kaplan-Meier curve. A Cox proportional hazards model was used to compare treatment group risk factors for recurrence with a P-value less than .05 defined as statistical significance. RESULTS: Of 174 injections performed for the correction of flexion deformities in 109 patients, 70% (121) were successfully treated with CCH, and an additional 20% (35) had improvement. There was a recurrence of contractures in 43 joints (25%). Of these, 16 contractures were treated with repeat CCH, whereas another 16 underwent limited fasciectomy. In total, 75% (12 of 16) of the repeat CCH group and 75% of the fasciectomy group were successfully treated. Pre-injection contracture of ≥25° was found to be predictive of recurrence (P < .05). CONCLUSIONS: Initial treatment of contracture with CCH had a 70% success rate with 25% recurrence during the study period. Compared with limited fasciectomy, CCH had decreased efficacy. Based on the findings of this study, we believe that the treatment of primary and/or recurrent Dupuytren's contracture with CCH is a safe and less invasive alternative to fasciectomy in the era of telemedicine. CCH treatment requires no suture removal, which allows the ability to assess motion virtually, and the potential consequences of CCH treatment such as skin tears can be assessed and managed conservatively. In the veteran and active duty population, CCH can facilitate faster recovery and return to service. Strengths of this study include a large series of veteran populations with longitudinal follow-up to determine treatment efficacy for primary Dupuytren's contracture and recurrence. Limitations include a smaller sample size compared to previous trials, a lack of standardized follow-up, and the retrospective nature of our study that prohibits randomization to compare outcomes between CCH treatment and fasciectomy efficacy over time. Directions for future research include stratification of patients by joint and specific digit involvement as well as comparison with percutaneous needle fasciotomy, another minimally invasive technique that could benefit the veteran population at increased risk for developing Dupuytren's disease.