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Background: Treatments for Dupuytren's contracture include limited fasciectomy and collagenase injection. Comparisons of the effectiveness of these treatments have been limited., Methods: We performed an unblinded, multicenter, pragmatic, two-group, randomized, controlled noninferiority trial comparing collagenase injection with limited fasciectomy in persons with moderate Dupuytren's contracture. The primary outcome was the score on the Patient Evaluation Measure-Hand Health Profile (PEM), a questionnaire for assessing hand health as reported by the patient, at 1 year after treatment. Scores on the PEM range from 0 to 100, with higher scores indicating worse outcomes. The prespecified noninferiority margin was 6 points., Results: A total of 672 persons (336 per group) were assigned to receive collagenase injection or to undergo limited fasciectomy. The primary analysis included 599 persons: 314 in the collagenase group and 285 in the limited-fasciectomy group. The mean score on the PEM at 1 year was 17.8 among the 284 patients with available data in the collagenase group and 11.9 among the 250 patients with available data in the limited-fasciectomy group (estimated difference, 5.9 points; 95% confidence interval [CI], 3.1 to 8.8; one-sided P = 0.49 for noninferiority). Among the patients with available data (229 patients in the collagenase group and 197 patients in the limited-fasciectomy group), the estimated difference in the mean score on the PEM at 2 years was 7.2 points (95% CI, 4.2 to 10.9). Moderate or severe complications of treatment occurred in 1.8% of the patients in the collagenase group and in 5.1% of those in the limited-fasciectomy group; recurrent contracture resulted in reintervention in 14.6% and 3.4%, respectively., Conclusions: Collagenase injection was not noninferior to limited fasciectomy with respect to the score on the PEM at 1 year after treatment. (Funded by the National Institute for Health and Care Research Health Technology Assessment Programme; DISC ISRCTN Registry number ISRCTN18254597.)., (Copyright © 2024 Massachusetts Medical Society.)

Peyronie's disease (PD) is defined by penile plaque formation and curvature causing sexual dysfunction. The only FDA-approved intralesional treatment is Collagenase Clostridium histolyticum (CCh). CCh contains two collagenases, AUX1 and AUXII, that break down the type I and type III collagen contained in plaques, leading to plaque dissolution and reduction in penile curvature. Peyronie's plaques, however, also contain fibrin and calcium, which CCh cannot digest. It is unclear if plaque calcification prevents CCh from breaking down plaques. We collected ten tissue samples: five calcified penile plaques and five control samples of corpus cavernosum. They were incubated in CCh or PBS. Soluble collagen measurements and collagen staining assays were completed to measure tissue breakdown. Calcified plaques incubated in CCh showed significantly higher levels of soluble collagen (301.07 ug ± 21.28 vs. PBS: 32.82 ug ± 3.68, p = 0.02), and significantly lower levels of collagen (type I and III) compared to tissues incubated in PBS (0.12 ± 0.08, vs. 0.44 ± 0.17, p = 0.002). When comparing different tissues (calcified vs. control) incubated in CCh and PBS solutions, there were no significant differences in collagen staining or breakdown. Although higher collagen staining was seen in the calcified group, soluble collagen showed no significant differences between control and calcified tissues in the CCh group (control: 0.08 ± 0.02 vs. calcified: 0.17 ± 0.09, p = 0.08) or the PBS group (control: 0.50 ± 0.23 vs. calcified: 0.39 ± 0.39, p = 0.23). CCh exposure led to significantly more tissue breakdown in both tissue groups when compared to PBS however, there was no significant difference in plaque digestion found between calcified and control tissue exposed to CCh or PBS. This suggests that plaque calcification does not affect the action of CCh. Further research into CCh for calcified plaques is necessary to inform clinicians as to the optimal management of this population., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The purpose of this study was to determine the perioperative complication rate of surgical fasciectomy following previous treatment with collagenase clostridium histolyticum (CCH) treatment in patients with Dupuytren disease., Methods: A retrospective review of all patients at a large health system undergoing CCH treatment and subsequent limited surgical fasciectomy for recurrence on the same digit between 2010 and 2020 was performed. Fifty-two patients with 62 affected digits met inclusion criteria, and cases were reviewed for preoperative demographics, treatment characteristics, clinical outcomes, and perioperative complications., Results: Fifty-five digits in 48 patients were treated with CCH and underwent subsequent limited surgical fasciectomy. Of all digits in the present study, 3 (6.3%) had a documented surgical complication following open surgical fasciectomy. There were zero postoperative infections, vascular injuries, or tendon injuries. The rate of nerve injury was 2.1%. The rate of postoperative skin necrosis was 4.2%. These rates were comparable or lower than those of historical published data., Conclusions: The rate of perioperative complications in patients undergoing limited surgical fasciectomy after previous CCH treatment is low. The findings of this study will aid the counseling of Dupuytren patients in deciding whether to pursue treatment with CCH versus open surgical fasciectomy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In patients with a high recurrence risk after treatment for Dupuytren contracture (DC) by Collagenase Clostridium histolyticum (CCH), adjuvant medical therapy may improve the outcome. Non-steroidal anti-inflammatory drugs have been used in the treatment of similar fibroproliferative processes. The aim of this study was to investigate if adjuvant anti-inflammatory medication could improve the outcome of CCH treatment for DC. Methods: In a prospective double blinded randomised trial, the effect of adjuvant peroral celecoxib on the outcome of DC treated with CCH was investigated in 32 patients with a high fibrosis diathesis. Primary outcome was the increase in Total Passive Extension Deficit (TPED)/ray. Secondary outcomes were the TPED of the individual finger joints, Tubiana index, Disability of Arm, Shoulder and Hand score (DASH) and visual analogue scale (VAS) for pain and satisfaction. Results: A significantly greater improvement in the celecoxib group for TPED and metacarpophalangeal contracture was found. For the proximal interphalangeal joint, the effect was much less pronounced. The VAS for pain and satisfaction were better at 6 and 12 weeks in the celecoxib group. The other outcome parameters did not significantly differ between both groups. Conclusions: Adjuvant peroral administration of celecoxib might improve the gain in TPED after treatment with CCH in patients with DC and a high fibrosis diathesis, with a beneficial effect up to 24 months. Level of Evidence: Level II (Therapeutic).

Introduction: Peyronie's disease (PD) is a common penile disorder characterized by the formation of fibrous noncompliant hard nodules in the tunica albuginea of the penis. Collagenase Clostridium histolyticum (CCH) is an injectable drug that treats PD by enzymatically degrading plaque interstitial collagen. CCH has been used in patients with varying curvature, as well as in the acute and stable phases of the disease, through a variety of treatment regimens and combinations. We carried out a systematic review and meta-analysis to assess the efficacy of CCH combination therapies for PD., Methods: We selected 4 observational comparative studies and 3 randomized controlled trials including 532 participants from the PubMed, Embase, and Cochrane databases (until December 2023) to evaluate the efficacy of CCH combination therapies for PD. The primary outcome was clinical efficacy as evaluated by improvement in penile curvature and penile length, as well as by scores on the Peyronie's Disease Questionnaire (PDQ) for symptom bother, penile pain, and psychological symptoms. Continuous data were represented by mean difference (MD) and 95% CI. All data were analyzed by Review Manager version 5.3., Results: For penile length (MD, 0.81 cm; 95% CI, 0.17-1.45; P = .01), PDQ symptom bother (MD, -1.02; 95% CI, -1.83 to -0.21; P = .01), and PDQ penile pain (MD, -0.93; 95% CI, -1.50 to -0.36; P = .001), CCH combination therapy showed significantly greater improvements vs CCH monotherapy. However, in the other indicators, penile curvature and PDQ psychological symptoms, there was no significant difference between the therapies., Conclusion: This meta-analysis supports that CCH combination therapies can partially increase penile length and ameliorate symptom bother and penile pain to some extent. However, CCH combination therapies still need to be evaluated through more high-quality research., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: Dupuytren disease (DD) is one of the most common disorders of the hand, affecting 5.7% to 11.7% of the global population. This study seeks to evaluate the 10-year efficacy of the 2 most prominent treatment modalities for DD in Veterans Affairs hospitals, injectable collagenase Clostridium histolyticum versus open fasciectomy., Methods: A retrospective review was conducted of all electronic medical records of patients who underwent open fasciectomy or collagenase injection to treat their persistent Dupuytren contracture between April 2011 and April 2021. All procedures were performed by 1 of 5 senior surgeons at the same Veterans Affairs Hospital., Results: A total of 232 patients were treated for DD, with 247 collagenase injections and 44 open fasciectomies performed in this sample. Collagenase patients were, on average, 6.51 years after intervention at the time of review. Open fasciectomy patients were, on average, 4.56 years after operation at the time of review. Collagenase decreased contractures, on average, by 29.40 degrees, whereas open fasciectomy decreased contractures, on average, by 38.59 degrees. Of the contractures that were initially classified as resolved, 50 of 155 (32.2%) treated with collagenase and 6 of 56 (10.7%) treated with open fasciectomy recurred. The use of open fasciectomy compared with collagenase injections to treat contracture was associated with a 74.2% decrease in the likelihood of recurrence., Conclusions: This study found that treatment of DD with collagenase injection is associated with a significantly lower degree of deformity correction, lower rate of resolution, and increased rate of recurrence when compared with open fasciectomy., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflict of interest and received no funding to conduct this study. Because this is a retrospective review, this article does not contain any studies with human or animal subjects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease., Methods: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic., Results: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified., Conclusions: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To present the functional results obtained and the possible surgical difficulties after the surgical treatment of Dupuytren's disease (DD) recurrence in patients previously treated with Clostridium histolyticum (CCH) collagenase., Materials and Methods: In this prospective study, 178 patients with DD were treated with CCH from 2011 to 2018; During long-term postoperative follow-up, 34 patients (19.1%) had recurrence of DD. In all patients injected in the IFP the disease recurred; In patients injected in the MCP, recurrence was highest in grade III and IV of the Tubiana classification, with involvement of the 5th finger and the two-finger Y-chord. Fourteen patients (7,8%) required surgery by partial selective fasciectomy due to recurrence of cord DD infiltration. The clinical and functional results of the patients, the difficulty of the surgical technique and the anatomopathological analysis of the infiltrated cords were evaluated in comparison with those of cords and patients who had had no previous CCH treatment., Results: In all patients, cord rupture was achieved after injection, reducing joint contracture. In 14 patients, we observed during the follow-up the existence of DD recurrence that required surgical treatment by selective partial fasciectomy. There were no major difficulties in surgery and good clinical and functional results at 6 months of follow-up. The anatomopathological study of the resected tissue did not present histological alterations with respect to the samples obtained from patients initially treated by selective partial fasciectomy., Conclusions: Selective fasciectomy after CCH injection does not lead to important operative difficulties, as long as the CCH injection is performed according to the recommendations. There were no histological changes in the tissue after CCH injection., Level of Evidence: III., (© 2024. The Author(s).)

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., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate cumulative and incremental changes in penile curvature after each treatment cycle of collagenase clostridium histolyticum (CCH) in men with Peyronie's disease (PD)., Methods: Data from 2 phase 3, randomized, placebo-controlled trials were analyzed post hoc. Treatment was administered in up to 4 treatment cycles (per cycle: 2 injections, 1-3 days apart, of CCH 0.58 mg or placebo; subsequent penile modeling) at 6-week intervals. Penile curvature was measured at baseline and after each treatment cycle (weeks 6, 12, 18, and 24). Successful response was defined as ≥20% reduction from baseline penile curvature., Results: Overall, 832 men (CCH, n = 551; placebo, n = 281) were included in the analysis. After each cycle, mean cumulative percent reduction from baseline penile curvature was significantly greater with CCH vs placebo (P <.001). Following one cycle, 29.9% of CCH recipients exhibited a successful response. Among nonresponders, additional cycles of injections led to further successful responses: 60.8% of first cycle failures achieved response after fourth cycle (8 injections), 42.7% of cycle 1-2 failures achieved response after fourth cycle, and 23.5% of cycle 1-3 failures achieved response after fourth cycle., Conclusion: Data showed incremental benefits from each of the 4 CCH treatment cycles. Completion of a full series of 4 CCH treatment cycles may optimize improvements in penile curvature in men with PD, including among those who did not clinically respond to previous treatment cycles., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The safety label for collagenase Clostridium histolyticum was updated to include postinjection acute lower back pain as an adverse event observed with intralesional therapy for Peyronie's disease. Incidence and causality are unknown. We assessed frequencies and temporal associations for this adverse event in a large cohort., Materials and Methods: Data on all men undergoing collagenase injections for Peyronie's disease at our institution from October 2015 through December 2020 were retrospectively assessed. The study included 330 patients, 300 completing at least 1 full course (8 injections). Measured outcomes included incidence and timing of back pain, and associations with demographics and comorbidities., Results: Of 330 patients, 19 (5.8%) experienced at least 1 episode of postinjection acute lower back pain. Of 300 who completed at least 1 full course of 8 injections, 4 (1.3%) reported back pain within the 8-injection course. A subset underwent additional rounds (16 or 24 injections). Back pain increased to 8.7% (13/149) during a second round, 6.9% (3/43) during a third. No association was found with age, diabetes or back pain history. Most cases occurred shortly after injection; all were self-limited or resolved with a single dose of ketorolac., Conclusions: This single-center, retrospective analysis suggests that intralesional collagenase injections for Peyronie's disease may cause acute lower back pain in up to 6% of patients. Patients may benefit from counseling regarding this risk. Incidence rises with additional rounds of treatment. Prospective safety data regarding >8 injections do not exist. No patient had long-term sequelae of back pain.

Summary: Treatment of boutonniere Dupuytren disease is rare and is resistant to treatment because of altered tendon dynamics. The authors used a small dose of collagenase clostridium histolyticum for an enzymatic tenotomy of the distal interphalangeal joint and showed that hyperextension at the distal interphalangeal joint improved significantly. Fifteen patients with boutonniere Dupuytren disease with severe proximal interphalangeal joint contractures averaging -69 degrees of extension were included in the study. Ten patients had at least one previous intervention, including surgical fasciectomy, Digit Widget treatment, and needle aponeurotomy. Collagenase clostridium histolyticum enzymatic tenotomy was performed in-office as a wide-awake procedure. All patients received varying doses of collagenase clostridium histolyticum for volar Dupuytren disease enzymatic fasciotomy and 0.1 mg of collagenase clostridium histolyticum into the distal extensor tendon for tenotomy to treat boutonniere deformity at the same time. Collagenase clostridium histolyticum enzymatic tenotomy significantly improved total active motion of the finger by 41.0 degrees (p = 0.001). Loss of extension at both the metacarpophalangeal joint and the proximal interphalangeal joint also improved with gains of 11.7 (p = 0.04) and 20.7 degrees (p = 0.0005) of extension, respectively. The average distal interphalangeal joint hyperextension was improved from 29.7 degrees to 14.0 degrees (p = 0.002). The authors show that collagenase injection led to significant average improvement in joint contracture at all finger joints and significantly increased the arc of motion at the proximal interphalangeal joint and metacarpophalangeal joint. Although collagenase has been previously used for flexion contractures in Dupuytren disease, we believe it has a role in treating the distal interphalangeal joint hyperextension deformity associated with boutonniere deformity in Dupuytren disease as well., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background: The factors typically considered to be associated with Dupuytren disease have been described, such as those in the "Dupuytren diathesis." However, the quality of studies describing them has not been appraised. This systematic review aimed to analyze the evidence for all factors investigated for potential association with the development, progression, outcome of treatment, or recurrence of Dupuytren disease., Methods: A systematic review of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Cumulative Index to Nursing and Allied Health Literature databases was conducted using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant methodology up to September of 2019. Articles were screened in duplicate. Prognostic studies were quality assessed using the Quality in Prognosis Study tool., Results: This study identified 2301 records; 51 met full inclusion criteria reporting data related to 54,491 patients with Dupuytren disease. In total, 46 candidate factors associated with the development of Dupuytren disease were identified. There was inconsistent evidence between the association of Dupuytren disease and the presence of "classic" diathesis factors. The quality of included studies varied, and the generalizability of studies was low. There was little evidence describing the factors associated with functional outcome., Conclusions: This systematic review challenges conventional notions of diathesis factors. Traditional diathesis factors are associated with disease development and recurrence, although they are not significantly associated with poor outcome following intervention based on the current evidence., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Uterine fibroids feature excessive deposition of types I and III collagen. Previous ex vivo studies showed an FDA-approved collagenase (EN3835)-digested types I and III collagen fibers in fibroid tissues; however, collagenase had not been evaluated in vivo for effects on uterine fibroids. The objective was to assess the safety and tolerability of collagenase injection directly into uterine fibroids. This was a prospective, open label, dose escalation study. The study participants were fifteen women aged 35-50 years with symptomatic uterine fibroids planning to undergo hysterectomy. Three subjects received saline and methylene blue, three subjects received a fixed dose of EN3835, and 9 subjects received stepped, increasing dosages of EN3835, all by transvaginal, ultrasound-guided injections. Primary outcome measures were safety and tolerability of the injection and change in collagen content between treated and control tissues. There were no significant adverse events following injection of EN3835 into uterine fibroids. Masson's trichrome stains revealed a 39% reduction in collagen content in treated samples compared to controls (p <0.05). Second harmonic generation (SHG) analysis showed treated samples to have a 21% reduction in density of collagen compared to controls. Picrosirius-stained collagenase-treated fibroids showed collagen fibers to be shorter and less dense compared to controls. Subjects reported a decrease in fibroid-related pain on the McGill Pain Questionnaire after study drug injection in Group 2 at both 4-8 days and 60-90 days post-injection. The findings indicated that injection of collagenase was safe and well tolerated. These results support further clinical investigation of collagenase as a minimally invasive treatment of uterine fibroids. NCT0289848., (© 2021. The Author(s).)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Purpose of Review: To review the current literature on acute management of traumatic penile fracture, with a specific discussion of those injuries following collagenase clostridium histolyticum (CCH) injections for the treatment of Peyronie's disease., Recent Findings: The immediate repair of traumatic penile fracture injury is associated with significantly better prognosis for long-term sexual health. Corporal disruption following CCH administration has several distinct features, and the trend is to manage these patients conservatively in the absence of urethral injury. Traumatic penile fracture repair continues to have excellent results when performed immediately following injury. The post-CCH treatment setting portends increased difficulty during surgical management and can be successfully managed in most cases by conservative measures.

Purpose of Review: To analyze the literature on current conservative treatment options for Peyronie's disease (PD)., Recent Findings: Conservative therapy with intralesional collagenase clostridium histolyticum (CCH) is safe and efficacious in either the acute or chronic phases of PD. Combination treatment with penile traction therapy (PTT) can produce even better results. While most PTT devices require extended periods of therapy up to 8 h per day, the RestoreX® device can be effective at 30-90 min per day. A variety of conservative therapies are available for treatment of PD. The available literature does not reveal any treatment benefit of oral therapies. Intralesional therapy is the mainstay conservative treatment of PD. Intralesional CCH therapy is the first Food and Drug Administration-approved intralesional therapy and represents the authors' preference for medical therapy. The most effective conservative management of PD likely requires a combination of therapies.

Objective: To examine the long-term (5-year) efficacy and safety of collagenase clostridium histolyticum (CCH) therapy in men with Peyronie's disease and varying degrees of plaque calcification., Materials and Methods: CCH-treated adult men from the 12-month Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I/II or 9-month open-label studies were eligible. Degree of plaque calcification (no calcification, noncontiguous stippled calcification, or calcification that did not interfere with CCH injection) was determined by penile x-ray or ultrasound. Penile curvature deformity and Peyronie's Disease Questionnaire responses were assessed annually for up to 5 years, with ≥6 months between consecutive visits., Results: For no calcification group, from baseline to last (Reference) visit during the prior studies (n = 160), mean penile curvature improved by 20.9° ± 16.3° (39.3%) with CCH. Similar improvements with CCH from baseline to Reference were observed in stippled calcification (n = 27; improvement of 24.1° ± 20.2° [42.7%]) and calcification (n = 27; improvement of 21.7° ± 14.8° [43.3%]) subgroups. At Year 5 follow-up in no calcification group (n = 119), an additional 10.0% improvement in mean penile curvature vs Reference (4.3°) occurred. Penile curvature improvements seen at Reference in stippled calcification and calcification groups were maintained through Year 5. Additional numeric improvements in 3 Peyronie's Disease Questionnaire domains were observed at Year 5 visit vs baseline scores. No long-term safety issues were identified., Conclusion: This first report of long-term (5-year) CCH clinical trial outcomes in a population with penile plaque calcification demonstrates that nonsurgical intralesional CCH therapy is an appropriate Peyronie's disease treatment in men with penile plaque calcification that is stippled or does not impede CCH injection., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To study, in a multi-institutional setting, the efficacy/safety outcomes in acute phase Peyronie's disease (PD) of multiple high-volume centers employing CCH to treat PD, which is defined as the abnormal formation of fibrous plaque(s) in the tunica albuginea of the penis. It is a chronic condition that afflicts 3%-13% of the US male population. There is no current multi-institutional research on the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase PD., Methods: Retrospective data were collected for consecutive patients with PD who underwent treatment with CCH between April 2014 and March 2018 at 5 institutions. 918 patients were included. Patients with duration of PD no longer than 6 months at presentation qualified as being in the acute phase of PD. Main outcomes of interest include the change in curvature after receiving CCH therapy, and frequency of serious treatment-related adverse events. Successful improvement in curvature is defined as an at least 20% decrease in penile curvature from baseline after CCH therapy., Results: A total of 918 patients were included in the analysis, of which 134 (14.6%) qualified as acute phase PD (group 1) and the remaining 784 (85.4%) qualified as stable phase (group 2). Mean duration of PD was 4.44 ± 1.68 months for group 1, and 40.8 ± 61.2 months for group 2. There was no significant difference in final change in curvature between acute and stable phase of PD (13.5° vs 15.6°, P = .09). There was no statistically significant difference in frequency of treatment-related adverse events between the acute phase (16 patients, 11.9%) and the stable phase (77 patients, 9.8%; P = .44). In our multivariate analysis, only number of CCH cycles received was predictive of improvement of curvature., Conclusion: This large multi-institutional analysis confirms that CCH therapy is as safe and efficacious in acute phase PD as it is in stable phase PD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The etiology of cellulite is unclear. Treatment of cellulite has targeted adipose tissue, dermis, and fibrous septae with varying degrees of success and durability of response., Objective: Results from clinical trials that target different anatomical aspects of cellulite can provide insights into the underlying pathophysiology of cellulite., Materials and Methods: A search of the PubMed database and ClinicalTrials.gov website was conducted to identify clinical trials that have investigated treatments for cellulite., Results: A lack of trial protocol standardization, objective means for quantification of improvement and reported cellulite severity, and short-term follow-up, as well as variation in assessment methods have made comparisons among efficacy studies challenging. However, the lack of durable efficacy and inconsistency seen in clinical results suggest that dermal or adipose tissue changes are not the primary etiologies of cellulite. Clinical studies targeting the collagen-rich fibrous septae in cellulite dimples through mechanical, surgical, or enzymatic approaches suggest that targeting fibrous septae is the strategy most likely to provide durable improvement of skin topography and the appearance of cellulite., Conclusion: The etiology of cellulite has not been completely elucidated. However, there is compelling clinical evidence that fibrous septae play a central role in the pathophysiology of cellulite.

Objective: To evaluate the efficacy and safety of collagenase Clostridium histolyticum (CCH) for the management of penile deformities in patients presenting with different categories of atypical Peyronie's disease (PD)., Methods: We conducted a retrospective review of charts of patients who presented to a men's health clinic with atypical PD between October 2016 and June 2019. We included patients in the stable phase of the disease, had completed a penile duplex Doppler ultrasound before any intervention, and proceeded with CCH treatment. Gathered data included patient demographics, treatment details, outcomes, and complications. Outcomes collected were both quantitative (curvature assessments) and qualitative using the symptom bother domain (last 6 questions; Q10 to Q15) of the Peyronie's Disease Questionnaire., Results: Twenty-one men with stable PD underwent CCH inject therapy after penile duplex Doppler ultrasound. The mean number of injections was 8.4 (standard deviation [SD] = 3.3), and the mean follow-up was 20.5 months (SD = 5.9). The overall mean change in penile curvature was -19.2° ± 8.3°, which corresponded to a -39% ± 13% improvement in curvature (P = .0079). In men who presented with an indentation or hourglass deformity, 11 of 17 (64%) were satisfied and reported subjective improvement in narrowing/indentation after receiving CCH injections. The average composite symptom bother domain of the Peyronie's Disease Questionnaire decreased by 6.7 (P = .0029)., Conclusion: Our results suggest that CCH appears to be safe and provide significant clinical improvements in men presenting with atypical PD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Clostridium collagenase histolyticum (CCH) is being evaluated in women as a cellulite treatment., Objective: To report preclinical safety and human pharmacokinetics (PK) and safety data for CCH., Methods: Across 3 PK studies, 41 women received 12 subcutaneous injections per thigh/buttock in 1 session (up to 3.36 mg/dose). Blood samples were taken at baseline; at 5, 10, 20, and 30 minutes postdose; and at 1, 2, 4, 8, 12, 24, 48, 168, and 504 hours postdose. In a preclinical study, rats received 0, 0.029, 0.13, or 0.29 mg/dose of CCH intravenously (IV) every other day (QOD) for 16 days (total, 8 doses) and were evaluated for histopathologic changes., Results: In human PK studies, no quantifiable plasma concentrations of AUX-I or AUX-II were observed postdose (n= 39 evaluable). Adverse events were injection site&ndash;related (bruising [97.6%], pain [87.8%], and edema/swelling [46.3%]). Antidrug antibodies were seen in most women at 504 hours postdose. In rats, plasma concentrations of AUX-I and AUX-II (CCH components) were measurable for 30 minutes and 1-2 hours, respectively, after IV administration. At &ge;43&times; proposed human therapeutic dose on a mg/kg basis, rats experienced elevated liver enzyme levels, increased liver weights, and histologic changes that were mostly reversed during a 14-day recovery period., Conclusions: In human studies, no quantifiable circulating CCH levels were observed after a single subcutaneous dose of CCH up to 3.36 mg. Preclinical data indicated that repeat IV dosing (QOD; 8 doses) at &ge;43&times; proposed human dose on a mg/kg basis for CCH was generally well tolerated.J Drugs Dermatol. 2020;19(9):852-856. doi:10.36849/JDD.2020.5048THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Clostridiumhistolyticum collagenase (CHC) is rapidly becoming a mainstream treatment option for Dupuytren's disease for hand surgeons. We performed a retrospective study of the efficacy of this substance at a lower concentration, but a higher total dose than recommended by the manufacturer. Thirty-nine patients with 43 affected hands were treated and analyzed at a mean follow-up of 27 months. Subgroup analysis was done for patients who received treatment in one or two joints (group A), and for patients who received treatment in more than two joints (group B). We found that our CHC solution is safe and effective when simultaneously treating as many as four joints affected by Dupuytren's disease. Patients in group B had a lower (but non-significant) treatment failure rate compared to patients in group A. Also, higher satisfaction rates were observed in group B, again non-significant. No major complications were observed in any group. CHC use is associated with only minor complications. The results are consistent even when up to four joints are treated with one dose. LEVEL OF EVIDENCE: III., (Copyright © 2020 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Clostridial collagenase ointment (CCO) is the only enzymatic agent indicated for debriding chronic dermal ulcers that is approved by the United States Food and Drug Administration., Objective: The objective of this study is to estimate health care spending among patients with Stage 3 and Stage 4 pressure injuries (PIs) and patients with diabetic foot ulcers (DFUs) who experienced early (ie, within 30 days of index diagnosis) versus late (31 to 90 days of index diagnosis) initiation of CCO., Methods: Patients with PIs and DFUs between January 2007 and March 2017 were identified. One-to-one matched cohorts were used to compare all-cause health care spending and disease-related health care spending between the early initiation and late initiation groups., Results: Compared to the early CCO initiation group, all-cause health care spending for the late CCO initiation group was higher in both patients with PIs and in patients with DFUs within the 12-month follow-up period. Compared to the early CCO initiation group, disease-related health care spending for the late CCO initiation group was higher in both patients with PIs and in patients with DFUs within the 12-month follow-up period. All computations were statistically significant., Conclusions: Early initiation of CCO provides both all-cause and disease-related health care savings to payers and persons managing patients with PIs or DFUs. Payers, providers, and facilities should consider mechanisms to encourage the early use of CCO to lower costs.

Background: This study compared the effectiveness of injectable collagenase clostridium histolyticum and percutaneous needle fasciotomy in the treatment of Dupuytren's contracture., Methods: Patients with a total passive extension deficit of 30 degrees or more in a single digital ray were enrolled and assigned randomly to receive either collagenase clostridium histolyticum injections or percutaneous needle fasciotomy. Preoperative severity of proximal interphalangeal joint contracture for Dupuytren's disease was classified according to the British Society for Surgery of the Hand as less than 30 degrees (stage I) or 30 degrees or more (stage II)., Results: Of the 70 patients enrolled, 36 patients with 46 joints received collagenase clostridium histolyticum injections and 34 patients with 48 joints received percutaneous needle fasciotomy. At day 30, successful corrections were obtained in only 50 percent of the injection group and 67 percent of the fasciotomy group for stage II proximal interphalangeal joints. Recurrences were frequent among patients with stage II joint contractures. The mean Quick Disabilities of the Arm, Shoulder and Hand questionnaire score at day 30 was significantly higher in the injection group compared with the fasciotomy group (7.5 versus 4.2, respectively). In the injection group, adverse events were reported for all patients. In the fasciotomy group, complications were reported for 15 percent of patients., Conclusions: The collagenase clostridium histolyticum and percutaneous needle fasciotomy groups had similar outcomes for Dupuytren's contracture with 3 years' follow-up. Recurrences were frequent among patients with stage II proximal interphalangeal joint contractures. The Unité Rhumatologique des Affections de la Main scale and Quick Disabilities of the Arm, Shoulder and Hand questionnaire score decreased significantly for both groups at final follow-up., Clinical Question/level of Evidence: Therapeutic, II.

Objective: To identify patient-specific factors associated with patient-reported improvements in functional outcomes after intralesional Collagenase Clostridium histolyticum (CCH) for Peyronie's Disease (PD)., Methods: We retrospectively explored our prospectively maintained CCH registry. We sought to identify patient-specific factors that prevented the need for surgical straightening and/or improved ability to engage in penetrative intercourse., Results: Eighty-six patients underwent CCH monotherapy and had objective follow-up data available. Mean PD symptom duration was 25 months (SD 44) and baseline curvature was 65 o (SD 24). Prominent indentation/hourglass deformities (defined as girth discrepancy >10%) were present in 40 patients (47%). Mean objective curve improvement was 19 o (SD 20), and 60% achieved improvement ≥15 o . Greater baseline curvature was associated with greater absolute improvements in curvature, although there was no association between baseline curvature and relative (%) improvement. Three of 40 patients (8%) with indentation achieved girth improvement. Patients with baseline indentation/hourglass were less likely to report that CCH prevented the need for surgery (35% vs 64%, P = .018). Patients with curve improvement <15 o were also less likely to report that CCH prevented the need for surgery (25% vs 63%, P = .0086) or improved penetration (54% vs 89%, P = .018). There were no differences in outcomes based on age, BMI, symptom duration, and presence of biplanar curvature., Conclusion: Baseline indentation/hourglass deformity and curve improvement <15 o are associated with less favorable functional improvements such as preventing the need for surgery and improving penetration., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: Treatment of Peyronie's disease with collagenase Clostridium histolyticum (CCh) has gained world-wide adoption following the phase III clinical trials IMPRESS I and II. However, the optimal treatment parameters remain largely unknown. Many groups have made modifications to CCh treatment in Peyronie's disease in recent years. This review aims to discuss the variations in CCh treatment reported and associated outcomes., Recent Findings: Variations in CCh treatment protocols include administering higher CCh doses (0.9 mg) less frequently (q1month), use of home penile modeling, use of angulating penile traction devices, and vacuum therapy devices. Authors have reported different injection techniques to include three-point fans and tunneling techniques. Patient selection has expanded to include and evaluate responses among men with some extent of plaque calcification, and ventral curves., Summary: Since publication of the IMPRESS trials, several variations of CCh treatment have been reported with similar treatment responses to the original trials. However, future studies are required with prospective, randomized comparative designs to identify the optimal treatment strategies for men with Peyronie's disease.

The purpose of this study was to evaluate the effectiveness and safety of the second cycle of Collagenase Clostridium histolyticum injections using the modified shortened protocol. We performed a retrospective analysis on patients who had already undergone the first cycle of injections using the modified shortened protocol and requested more injections to improve the remaining curvature. The International Index of Erectile Function, the Peyronie's Disease Questionnaire and the Global Assessment of Peyronie's Disease questionnaire were self-administered to all patients. All the parameters were recorded at baseline, after the first cycle and after the second cycle of injections. All adverse events were recorded. Seventeen patients completed two cycles of injections. All patients had a reduction of the initial curvature after the first cycle, with a mean improvement of 17.4° (27.4%). After the second cycle, the reduction of the curvature was 7.9° (17.1%), and 29.4% of patients had no further improvement. No severe side effect was recorded. The results of the present study confirm the effectiveness and safety of the modified shortened protocol of Collagenase C. histolyticum injections for Peyronie's disease. However, the second cycle of three injections may be less effective, and patients may not be completely satisfied., (© 2020 Blackwell Verlag GmbH.)

Neuroinflammation significantly contributes to brain injury and neurological deterioration following intracerebral hemorrhage (ICH). MicroRNA-152(miR-152) was reported to be downregulated in ICH patients and to possess anti-inflammatory properties in other diseases. In this study, we aimed to explore the role of miR-152 in ICH, and the underlying mechanisms, using a collagenase-induced rat ICH model and hemin-exposure as a cell model. We first confirmed that miR-152 was consistently downregulated in both models. Overexpression of miR-152 in microglial BV2 cells reduced hemin-induced inflammatory response and reactive oxygen species (ROS) generation, thus protecting co-cultured neuronal HT22 cells. Moreover, overexpression of miR-152 by intracerebroventricular lentivirus injection in ICH rats significantly alleviated neurodecifits, brain edema, and hematoma. These changes were associated with a marked reduction in ICH-induced neuronal death, as detected by co-staining of NeuN and TUNEL, and ICH-induced neuroinflammation, as revealed by inflammatory cytokine levels as well as by the number of Iba1 positive-stained cells in the perihematomal region. Mechanistically, miR-152 significantly inhibited ICH-induced TXNIP expression, and its overexpression blocked the interaction between TXNIP and NOD-like receptor pyrin domain containing 3(NLRP3), thus inhibiting NLRP3-driven inflammasome activation to attenuate neuroinflammation in vivo and in vitro. Moreover, the results of si-TXNIP transfection further confirmed that TXNIP inhibition was involved in the reduction of NLRP3 inflammasome activation by the overexpression of miR-152. Collectively, the present study demonstrates that miR-152 confers protection against ICH-induced neuroinflammation and brain injury by inhibiting TXNIP-mediated NLRP3 inflammasome activation, indicating a potential strategy for ICH treatment., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Peyronie's disease (PD) can affect men of all ages and is associated with penile pain as well as curvature and erectile dysfunction. Treatment modalities for PD include conservative, less invasive and surgical treatments. Choice of treatment depends on the disease's phase. Injection of collagenase Clostridium histolyticum (CCH) is only the Food and Drug Administration approved treatment for the management of the chronic phase of the disease. Only a few limited studies have evaluated its potential benefits during the acute phase., Aim: To evaluate the current evidence on the use of injectable CCH during the acute or active phase of PD., Methods: We performed a PubMed database search for articles published between 2015 and 2018 that investigated the use of CCH for the management of the acute phase of PD. Search keywords included "Peyronie's disease", "collagenase Clostridium histolyticum", and "acute phase"., Main Outcome Measures: Changes in penile curvature after treatment with injectable CCH., Results: Mean curvature decrease ranged between 15.8° and 22.6° corresponding to 27.4-37.4% decrease from baseline after 2.5-4 cycles, corresponding to 5-8 injections, of CCH treatment in patients during the acute phase of PD., Conclusions: Intralesional CCH injection therapy during the acute phase of PD can be both safe and effective and clinically significant improvements in penile curvature may be achieved. Larger multi-institutional studies are, however, still needed to confirm these results and validate this additional indication for CCH.

Purpose: The introduction of collagenase Clostridium histolyticum (CCH) as the first and only FDA-approved non-surgical treatment for Peyronie's disease (PD) has been an important step in its management. Our aim is to provide an overview of the historical origins of CCH and its development through FDA approval and beyond for the treatment of PD., Methods: A PubMed search using the terms Peyronie OR Peyronie's AND collagenase and limited to clinical research studies resulted in 24 articles that were examined for the current review., Results: PD is a connective tissue disorder of the penile tunica albuginea involving fibrotic penile plaques that cause abnormal curvature and, in many cases, erectile pain. Although the exact mechanism and underlying pathophysiology are not well characterized, the known lability of these plaques to exogenous bacterial collagenase combined with a lack of effective medical therapies led to the development of CCH as an evidence-based treatment of PD. The initial discovery of collagenase was followed by in vitro studies on PD plaque tissue and following the phase 3 IMPRESS trial culminated in FDA approval of CCH in 2013. Future directions in CCH therapy include improved patient selection, use in acute phase PD, adjuvant and combination therapies, and novel delivery mechanisms., Conclusion: CCH provides an effective non-surgical treatment option for men with PD. We have traced the development of CCH in the treatment of PD from the earliest in vitro investigations to comprehensive multi-study meta-analyses confirming its highly rated efficacy when compared to other historical non-surgical remedies.

Purpose: The introduction of collagenase Clostridium histolyticum (CCH) has revolutionized the treatment of Peyronie's disease. The efficacy of this therapy has been well demonstrated and the safety profile is favorable. However, post-injection complications are poorly characterized and management of these complications lacks standardization., Methods: This review includes literature published in English and indexed in the PubMed ® , Embase ® or Google Scholar™ databases. What follows is a synopsis of relevant articles, including original research studies, in an attempt to better define CCH complications and their respective management strategies., Results: Adverse effects of therapy are common but generally self-limiting. Penile pain and edema are expected events, and most patients experience hematologic sequelae (bleeding, hematoma, ecchymosis, etc.). The intervention rate for penile hematoma is low. Penile fracture is a morbid complication of therapy that is rare and may be challenging to diagnose given the frequency with which pronounced bruising and swelling are encountered. Imaging is a useful adjunct in situations of diagnostic uncertainty. Alternative injection protocols have been evaluated to limit the cost and morbidity of CCH therapy. Clinical efficacy of these protocols is promising, but prospective evaluation is lacking., Conclusions: No standardized protocols exist for management of post-injection complications of CCH therapy. The majority of these complications are managed conservatively, but suspected penile fracture should be carefully evaluated and imaging employed when needed. Future prospective studies of alternative injection protocols are warranted to decrease morbidity while maintaining efficacy.

Purpose: Early clinical trials of injectable collagenase Clostridium histolyticum (CCh) for Peyronie's disease (PD) demonstrated safety and efficacy. Since then, modified injection protocols have been proposed. Adverse events-such as bruising, swelling, hematoma, and corporal rupture-exceed 50% in many studies, but lack of standardization of hematoma severity limits conclusions about the relative safety of protocols. We propose a modification of the standard injection technique that aims to decrease the rates of adverse events. We further describe a hematoma classification rubric that may standardize safety assessment., Methods: A modified injection procedure, termed the "fan" technique, was employed in the treatment of PD. All men receiving CCh from January 2016 through January 2019 at a single institution were included in an institutional review board (IRB) approved database. Treatment outcomes and adverse events were retrospectively assessed. A three-tiered hematoma classification rubric was devised to standardize reporting of hematoma, which was defined as concurrent bruising and swelling at the site of injection without loss of erection., Results: Using the fan technique, 152 patients received 1323 injections. Eight hematomas (5.3% of all patients, 0.6% of all injections) were observed. The number of grade I, grade II, and grade III hematomas were 3, 2, and 3, respectively. Bruising or swelling not meeting the definition of hematoma was seen in 54.6% and 27.0% of patients, respectively. There were zero corporal ruptures., Conclusion: A modified injection technique results in reduced procedural morbidity. A hematoma classification system provides clarity and standardization to the assessment of safety in PD treatment. Further clinical studies with control arms are required to verify these findings.

Introduction: The initial clinical trials for intralesional collagenase Clostridium histolyticum (CCh) injection therapy for Peyronie disease (PD) excluded men on antiplatelet or anticoagulant medications except those on low-dose aspirin. Men with PD who take such medications present a challenging clinical scenario because of a lack of evidence regarding the safety of CCh while on these drugs., Aim: To evaluate safety outcomes among patients continuing anticoagulant and antiplatelet therapy during ongoing intralesional CCh injection treatment for PD., Methods: An institutional review board approved a database of 187 patients treated with CCh at an academic men's health practice from January 2016 through April 2019 was reviewed. Men on antiplatelet/anticoagulant medications were not instructed to stop these agents. Data on patient demographics, comorbidities, CCh injection details, use or nonuse of antiplatelet/anticoagulant medications, and adverse events were extracted from the electronic medical record. Rates of hematoma formation, bruising, swelling, and corporal rupture were determined. Univariate statistical analysis compared clinical data and adverse events between men on or off antiplatelet/anticoagulant medications., Main Outcome Measure: Statistical comparison of adverse events in those taking or not taking antiplatelet or anticoagulant medications while undergoing intralesional CCh injection therapy for PD., Results: Of 187 men undergoing CCh treatment, 33 (17.6%) were on concomitant antiplatelet or anticoagulant therapy. Aspirin 81 mg alone was the most common pharmacologic agent (58% of men on antiplatelet/anticoagulants); medications also included other antiplatelet drugs, warfarin, and novel oral anticoagulants (NOACs). Men taking blood thinners during intralesional CCh injection therapy experienced no statistical difference in rates of bruising, swelling, or hematoma formation compared with men not on antiplatelet/anticoagulants. No corporal ruptures were observed in either group. Men on antiplatelet or anticoagulant therapy were more likely to be older (64 vs 58 years old, P = 0.005), have hypertension (P = 0.025), and have hyperlipidemia (0.009)., Clinical Implications: Intralesional CCh injection therapy may be offered to men on antiplatelet/anticoagulant medications without increased risk of adverse events., Strength & Limitations: This study evaluated the experience of a single surgeon, with a systematic evaluation of adverse events captured in a robust electronic medical record. The retrospective nature of this study limits conclusions but builds upon work performed in the initial clinical trials for CCh., Conclusion: Our findings suggest that antiplatelet and anticoagulant medications do not increase the risk of adverse events during intralesional CCh injection therapy for PD. Amighi A, Regets KV, Nork JJ, et al. Safety of Collagenase Clostridium histolyticum Injection Therapy for Peyronie Disease in Patients Continuing Antiplatelet or Anticoagulant Therapy. J Sex Med 2020;17:353-356., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate characteristics predictive of successful treatment outcomes of Peyronie's disease (PD) with collagenase clostridium histolyticum (CCH) METHODS: CCH is the only FDA-approved medication for treating PD. We reviewed the literature that addresses pre-treatment clinical characteristics that may predict favorable response to CCH therapy., Results: Despite significant heterogeneity in reporting treatment success, we identified four well-studied characteristics that may be predictive of favorable response to CCH therapy: baseline penile curvature, baseline IIEF, duration of PD, and presence of calcification. CCH demonstrated a favorable response in those with pre-treatment curvature 30°-60°, longer duration of disease, mild to moderate baseline sexual function, and low calcification within plaques. Of all factors, calcification is emerging as the most significant factor likely because CCH is unable to degrade the calcified plaques. There is difficulty interpreting results because of differences in reporting outcomes. Some studies compared treatment groups to placebo, others reported changes in curvature, while others reported > 20% curvature correction as treatment success. Additionally, not all studies reported outcomes after completion of four cycles of CCH, and recent studies utilized a shortened, high dose, modified protocol., Conclusions: The ideal candidate for CCH therapy remains elusive. Based on the available literature, the man with PD who will have the greatest chance of curvature improvement will have curvature between 30° and 60°, longer duration of disease, an IIEF > 17, no calcification, and set to receive all four cycles. For a greater understanding of CCH treatment success in PD, prospectively collected registry reporting standardized outcomes are needed.

Introduction: Penile plication or partial excision with grafting has traditionally been the first-line treatment for stable Peyronie's disease (PD). Numerous injection therapies (ITs) have been introduced over the last few decades. Intralesional collagenase clostridium histolyticum (CCH) was U.S. Food and Drug Administration approved in 2013 for patients with stable disease, curvature ≥30° and ≤90°, and intact erectile function. The impact of the advent of CCH on the surgical management of PD is unknown., Aim: We studied the effect of IT on the surgical management of PD in a population-based analysis., Methods: The Statewide Planning and Research Cooperative System database, which provides statewide level of all-payer data on patients in the outpatient, inpatient, ambulatory, and emergency department setting in New York State was reviewed. Patients undergoing a penile prosthesis for concurrent erectile dysfunction were excluded., Main Outcome Measure: Descriptive statistics and multivariable logistic regression modeling were used to assess factors influencing choice of injection therapy vs surgical therapy (penile plication or partial excision with grafting)., Results: From 2003-2016, 547 patients with PD presented for management. Median age was 56 years and 57% were white. Over the study period, surgical management was used less often as the primary procedure with a concurrent increase in use of IT (P < .001). On multivariable modeling, patients more likely to receive IT as treatment for penile curvature were younger (odds ratio [OR]: 1.26; P = .002; CI: 1.09-1.46), of higher socioeconomic status (OR: 1.14; P = .037; CI: 1.01-1.29), presented in the post-CCH era (OR: 1.17; P = .018; CI: 1.03-1.33) and presented to a surgeon with a high volume practice (OR: 1.25; P = .007; CI: 1.07-1.48). Patients presenting in the post-CCH era were 17% significantly more likely to receive IT., Clinical Implications: ITs like CCH are increasingly displacing surgical management as the primary treatment option of Peyronie's disease., Strengths & Limitations: The Statewide Planning and Research Cooperative System database is particularly useful for this analysis because it is an all-payer database that tracks patients longitudinally across various health care settings-outpatient and inpatient., Limitations: It only includes patients in New York State limiting generalizability. The retrospective nature of the analysis makes it subject to the biases inherent in such reports. Specific disease level characteristics (eg, degree of curvature, duration of disease, and associated deformities) were not available., Conclusion: Since the introduction of CCH, there has been a markedly decreasing trend in the utilization of surgery as the primary modality in the management of PD-associated penile curvature. Sukumar S, Pijush DB, Brandes S. Impact of the Advent of Collagenase Clostridium Histolyticum on the Surgical Management of Peyronie's Disease: A Population-Based Analysis. J Sex Med 2020;17:111-116., (Copyright © 2019. Published by Elsevier Inc.)

Collagenase Clostridium Histolyticum (hereafter referred to as CCH) [Xiaflex ® ; Xiapex ® ] is a mixture of two Clostridium histolyticum collagenases [AUX-I (a Class I clostridial collagenase) and AUX-II (a Class II clostridial collagenase)]. Administered by intralesional injection, it is available in various countries for the treatment of adult men with Peyronie's disease (PD). In two double-blind, multinational, phase III studies, CCH improved the physical (penile curvature) and psychological (patient-reported bother) aspects of PD in adult men. Such beneficial effects were also seen in two open-label, multinational, phase III studies, with potential benefits for patients' partners and maintained efficacy over up to 5 years additionally reported. Moreover, large real-world studies generally supported the therapeutic efficacy of CCH. CCH was generally well tolerated in these patient populations, with most treatment-related adverse events [TRAEs; most commonly penile haematoma (or 'bruising'), pain and swelling] being mild or moderate in severity, not serious and resolving without intervention. Moreover, the use of CCH was not associated with penile length shortening. Current evidence indicates that CCH is an effective, generally well tolerated and, compared with surgery, minimally invasive option for the treatment of adult men with PD.

Purpose: To determine factors associated with skin tearing at the time of manipulation in patients undergoing collagenase Clostridium histolyticum (CCH) treatment for Dupuytren contractures., Methods: We identified 368 digits in 261 patients who underwent a total of 469 CCH treatments at a tertiary care referral center from April, 2010 to December, 2013. Medical records were reviewed for the primary outcome, skin tearing at manipulation. Patient-related and disease-specific explanatory variables were collected. We used bivariate analysis to screen for risk factors and multivariable logistic regression to determine associated risk factors for skin tearing., Results: The overall rate of skin tearing with CCH treatment was 12%. Multivariable logistic regression analysis showed older age (odds ratio = 1.04; 95% confidence interval, 1.00-1.07) and amount of contracture correction (odds ratio = 1.02; 95% confidence interval, 1.01-1.04) to be associated with skin tearing at manipulation., Conclusions: A 10-year increase in age results in a 1.5 times increase in the odds of skin tearing. A 30° increase in contracture correction results in a 1.8 times increase in the odds of skin tearing. Patients can be counseled before CCH treatment that older age and increased contracture correction are risk factors for this common complication., Type of Study/level of Evidence: Prognostic II., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: To compare the efficacy and safety of a combined treatment of percutaneous needle tunnelling (PNT) and a modified collagenase Clostridium histolyticum (CCH) protocol (PNT/CCH) vs the modified protocol alone (CCH) in the treatment of Peyronie's disease (PD)., Patients and Methods: A prospective registry of patients treated with a modified CCH protocol was maintained between June 2014 and February 2018. The last 50 patients received PNT as an adjuvant therapy (PNT/CCH), and their data were compared with those of the other 94 patients treated previously (CCH). PNT involves the creation of multiple holes made percutaneously in the plaque before each injection. The modified protocol consisted of two collagenase injections, at 1-week intervals, followed by penile modelling. Patients used penile traction therapy, tadalafil and pentoxifylline for the next 2 months and were followed up for 6 months. The main outcome was improvement of curvature. Secondary outcomes were improvements in erectile function, PD symptoms, stretched penile length and satisfaction., Results: Improvement in curvature was greater in patients in the PNT/CCH group than in the CCH group (mean ± sd 19.2 ± 6.1° vs 12.7 ± 5.0°; P < 0.001 [36.2 ± 12.5% vs 28.1 ± 14.5%; P = 0.001]). Compared with baseline, both interventions were associated with significant improvement in secondary outcomes. The main complications were ecchymosis, bruising and penile pain, with no significant differences between groups., Conclusions: Treatment of PD with CCH using our modified protocol in combination with PNT is safe and more effective than the modified protocol alone, with the potential for improved cost-effectiveness., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Plantar fibromatosis, also known as Ledderhose's disease, is a rare disorder of benign fibroblast proliferation involving the plantar aponeurosis (i.e., plantar fascia). Traditionally, surgical intervention has been the most common treatment for plantar fibromatosis. However, numerous studies have reported high recurrence rates of plantar fibromatosis after surgical intervention, as well as wound healing difficulties and nerve injury. Plantar fibromatosis often coexists with other superficial fibrous diseases such as Dupuytren's contracture and Peyronie's disease; immunohistochemical and ultrastructural analyses suggest a relationship between Ledderhose's disease and Dupuytren's contracture. The US Food and Drug Administration approved collagenase Clostridium histolyticum for the treatment of Dupuytren's contracture in 2010 and Peyronie's disease in 2013. This case study presents the successful treatment of Ledderhose's disease almost 4 years (45.5 months) after off-label use of collagenase C. histolyticum injection in a 22-year-old white female who had recurrent plantar fibromatosis after surgical intervention., (Copyright © 2019 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

The aim of this paper was to introduce a simple and effective method to aid in isolation and stabilization of Dupuytren cords for collagenase injection. Tongue depressors were used to isolate and stabilize the cord during the injection procedure. The area to be injected was sterilely prepared. An assistant was then directed to place a tongue depressor on both sides of the cord. A total of 35 patients with Dupuytren disease were treated. Follow-up lasted two years. Post-operative Disabilities of the Arm, Shoulder and Hand (DASH) scores was 4±2. Health-related quality of life measured with the EQ-5D index was 0.89±0.4. Recurrence rates of metacarpophalangeal joint and proximal interphalangeal joint were 11% and 14% respectively, using a flexion contracture of 20° to define recurrence. Collagenase treatment using a modified injection method with the aid of tongue depressors are a safe, effective way to treat Dupuytren contractures of the fingers. The technique can isolate the cord, which improves visualization of the cord. It may allow improved accuracy with needle placement and helps to decrease the complications and recurrence., (Copyright © 2019 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Background: Dupuytren disease is characterized by the development of palmar fibrous tissue that can lead to fixed flexion contracture (FFC) and contribute to functional loss of the involved digits. Our goal was to investigate rates of contracture resolution and recurrence in patients who underwent enzymatic fasciotomy for Dupuytren contracture consisting of collagenase clostridium histolyticum (CCH) injection followed by passive manipulation combined with splinting and home-based therapy., Methods: We prospectively enrolled 34 patients (44 metacarpophalangeal [MCP] and 33 proximal interphalangeal [PIP] joints) treated by one orthopaedic hand surgeon between November 2010 and November 2014. On day 1, CCH was injected into a palpable fibrous cord of the involved fingers. The next day, the finger was passively extended to its maximal corrective position. FFC was measured for each joint before injection and immediately after manipulation. Patients were instructed to wear an extension splint at night and perform stretching exercises at home and were re-evaluated at 6 weeks, 4 months, 1 year, and 2 years. Resolution was defined as improvement of contracture to ≤ 5° of neutral. Recurrence was defined as an increase in FCC of ≥ 20° after treatment., Results: Immediate contracture resolution occurred in 42 of 44 MCP joints ( p < 0.001), improving from 50° to 1.5°, and in 14 of 33 PIP joints ( p = 0.182), improving from 44° to 16°. Four joints had recurrence within 6 weeks. Of the 48 joints with minimum 4-month follow-up (mean, 26 months), 12 had recurrence at 2-year follow-up (MCP, 6; PIP, 6). At 2-year follow-up, MCP and PIP contractures measured 17° and 35.5°, respectively. Older age and multiple digit involvement were associated with higher recurrence rates., Conclusions: CCH offers a safe, nonoperative option to correct FCC in Dupuytren disease with greater success for MCP joints compared to PIP joints. There is a tendency of reoccurrence within 2 years of treatment. Further investigation is needed to determine optimal timing of repeat CCH injection to improve upon or extend the period of contracture resolution., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: To evaluate the safety and efficacy of collagenase clostridium histolyticum (CCH) in men with ventral penile curvatures secondary to Peyronie's Disease (PD)., Methods: A prospective registry has been maintained of PD men undergoing CCH at our institution. Curvature assessments and subjective questioning were obtained at baseline and following 2 and 4 injection series. Clinicopathologic data were abstracted including history, exam, ultrasound, and end-point curvature assessments. Primary outcomes were adverse events (AE), and secondary outcomes included improvements in curvature by direction and subjective responses to questionnaires., Results: A total of 228 patients undergoing CCH for PD (mean age 57.2 years, mean PD duration 24.3 months) were identified from March 2014 through March 2018. Baseline curvature directions were individually analyzed (total of 329 measures), including 83%, 50%, and 11% with some degree of dorsal, lateral, and ventral angulation. Mean primary and secondary (where applicable) curvatures were 52.9 and 11.4 degrees, respectively. Following treatment, ventral and lateral curvatures experienced greater relative improvements in curvature compared to dorsal (ventral 29.5 degrees [49%], lateral 11.4 [38%], dorsal 15.0 [25%], P < .05). Ventral and lateral curvatures were also more likely to experience ≥50%, ≥75%, and ≥90% improvements compared to dorsal. AEs were similar among curvature directions, and no urethral complications occurred., Conclusion: Men with ventral PD may be effectively treated with CCH with similar AEs compared to other directions. Ventral and lateral curvatures are more likely to experience significant improvements (50% or more) compared to dorsal., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Intralesional injection of collagenase clostridium histolyticum (CCH) improves Peyronie's disease (PD) symptoms; however, patient perspectives regarding PD and CCH treatment have not been fully elucidated. This cross-sectional qualitative study included heterosexual men with PD who received ≥1 injection of study medication and had ≥1 posttreatment Peyronie's Disease Questionnaire (PDQ) assessment during a prior phase 2b clinical trial. These patients were "responders" if they reported (as part of the Global Assessment of the PDQ) that overall symptoms and effects of PD had at least "improved in a small but important way" after CCH therapy. Among 45 patients interviewed, penile bending or curvature was the most common and bothersome PD symptom reported (by 97.8% and 48.9% of patients, respectively). Patients indicated that multiple alterations were necessary in their sex lives because of penile symptoms and specified that these changes impacted their emotional health and partner relationship. Treatment with CCH improved PD symptoms (44.4%), frequency of or ability to have vaginal intercourse (22.2%) and partner relationship (22.2%), particularly among responders. Given that physical, psychologic and sexual function are impacted by PD, clinical trials that evaluate treatments for PD should include patient-reported outcome measures (e.g., the PDQ) to assess overall well-being after treatment.

Purpose of Review: To explore the potential hurdles surgeons may encounter when preforming surgical correction of penile curvature in patients with Peyronie's Disease following intralesional collagenase clostridium histolyticum injections., Recent Findings: Although limited data exists, retrospective analysis of surgeon experiences in surgical treatment of refractory penile curvature in patients with Peyronie's disease appears to not result in more post-operative complications and may only slightly increase intra-operative difficulty. As the use of intralesional collagenase clostridium histolyticum continues to increase and patients who demonstrate persistent curvature despite treatment seek further management, the role of investigating the feasibility of surgery demonstrates significant importance. Although limited data exists, it appears that surgery following intralesional collagenase clostridium histolyticum is safe without added post-operative complications. At the present time, however, further data on intra-operative findings and post-operative outcomes remain necessary, and as the use of this intralesional therapy continues to rise, further information should become readily available.

Background: Previous studies of penile traction therapy (PTT) devices have demonstrated limited/no efficacy when combined with intralesional therapies for Peyronie's disease (PD). Recently, randomized data have demonstrated the efficacy of a novel PTT device, RestoreX, developed in cooperation with the Mayo Clinic, in men with PD., Aim: To assess the safety and efficacy of treatment with the RestoreX device plus collagenase Clostridium histolyticum (CCH) compared with CCH alone and CCH with other PTT devices., Methods: A prospective registry has been maintained of all men undergoing CCH injections for PD between March 2014 and January 2019. Assessments were performed at baseline, during each series, and after completion of treatment. Those completing therapy (8 injections or sooner if satisfied) were categorized into group 1 (CCH alone), group 2 (CCH plus any PTT device other than RestoreX), or group 3 (CCH plus RestoreX)., Outcomes: Changes in penile length, curvature, and subjective perception and the occurrence of adverse events., Results: Of 287 men with data on PTT use, 113 had completed therapy with all objective data available and compose the current cohort. Baseline demographic and pathophysiological variables were similar among the 3 groups except penile length and previous PD medications. Following treatment, group 3 demonstrated significantly greater improvements in curvature (mean, 20.3°/31% for group 1, 19.2°/30% for group 2, and 33.8°/49% for group 3), length (-0.7 cm/-4%, -0.4 cm/-2%, and +1.9 cm/+17%, respectively), and subjectively estimated curvature improvement (44%, 32%, and 63% respectively), despite shorter daily PTT use (0.9 vs 1.9 hours/day). Group 3 was more likely than the other groups to experience ≥20°, ≥20%, and ≥50% curvature improvements, ≥1 cm length gain, and ≥20% length improvement. All results were statistically significant for group 3 versus groups 1 and 2, but not between groups 1 and 2, even after controlling for baseline features and isolating a subset of ≥3 hours/day PTT use (group 2). Group 3 was 6.9 times more likely to achieve ≥20° curvature improvement, and 3.5 times more likely to achieve ≥50% curvature improvement, and 10.7 times more likely to experience ≥20% length improvement. Adverse events were similar among the 3 groups., Clinical Implications: Use of the RestoreX device enhances mean curvature outcomes by 71% and increases penile length in men with PD receiving CCH therapy., Strengths & Limitations: Study strengths include a prospective registry, consistent assessments, the largest single-site series with complete posttreatment outcomes reported to date, the largest PTT series reported to date, and a true-to-life clinical design. Limitations include the nonrandomized methodology and single-site setting., Conclusion: The combination of RestoreX and CCH is associated with significantly greater curvature and length improvements compared with CCH alone or CCH with other PTT devices. Alom M, Sharma KL, Toussi A, et al. Efficacy of Combined Collagenase Clostridium histolyticum and RestoreX Penile Traction Therapy in Men with Peyronie's Disease. J Sex Med 2019;16:891-900., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Peyronie's disease (PD) is a progressive and devastating penile disorder that often results in severe penile curvature with penile shrinking, making vaginal insertion difficult or even impossible. Until now, in contrast to other penile disorders such as erectile dysfunction, PD is characterized by a paucity of conservative treatment options., Aim: To investigate the current status quo in the management of PD across European experts in sexual medicine., Methods: Members of the European Society of Sexual Medicine and of various andrology and urology societies across Europe, with the majority (78%) being urologists, were contacted via e-mail and newsletters and asked to fill in an online questionnaire. The survey comprised 56 items developed by an expert consensus of the educational committee of the European Society of Sexual Medicine. In the end, 401 participants responded to the entire survey, with 277 reporting treating PD patients themselves and knowing this penile entity very well., Main Outcome Measures: Main outcome measures include description of current strategies regarding diagnosis and treatment of PD as reported by specialists in this field., Results: Of the physicians treating PD patients, 94% performed penile palpation, and 74% perform ultrasonography. 45% assessed the degree of penile curvature by means of intravenous drug testing, but only 17% measured it accurately with a goniometer. Penile length, flaccid or in erect state, was measured by only 39% or 25%, respectively. Only 45% assessed testosterone. Primary treatment options were oral (65%), counseling (57%), and topical/local therapy (30%). Among oral drug users, tadalafil 5 mg was the most commonly used (57%), followed by vitamin E (40%). Regarding intralesional therapy, collagenase clostridium histolyticum was the leading drug (34%), followed by calcium channel blockers (17%). Considering surgical procedures, the original Nesbit technique was the preferred procedure (33%). 36% of the specialists expressed their dissatisfaction with the currently available treatment options, and 64% reported the impression that their patients were mostly dissatisfied with the treatment outcomes., Clinical Implications: Innovative and presumably multi-modal treatment protocols for PD are urgently needed., Strengths & Limitations: The survey represents 1 of the largest studies on the management of PD. The results are representative for the standard management of PD mostly among European Urologists with specialization in sexual medicine and may therefore not be generalizable to regions outside Europe or to other physicians treating PD., Conclusion: Around one-third of experts and, from their perspective, around two-thirds of patients are dissatisfied with the currently available PD treatment options. Porst H, Burri A, the European Society for Sexual Medicine (ESSM) Educational Committee. Current Strategies in the Management of Peyronie's Disease (PD)-Results of a Survey of 401 Sexual Medicine Experts Across Europe. J Sex Med 2019;16:901-908., (Copyright © 2019. Published by Elsevier Inc.)