Real-world practice in Peyronie's disease management: Results from a national survey of urologists.

BACKGROUND: Despite many available treatments for Peyronie's disease (PD), practice patterns of available therapeutics are not well characterized. OBJECTIVE: We conducted a national survey of urologists to characterize real-world practice patterns of PD management and to characterize the use of therapies discouraged by the American Urological Association guidelines on PD management. MATERIALS AND METHODS: A 34-item survey was distributed via RedCap to urologists who treat patients with PD in all American Urological Association sections. Questions elicited demographic information as well as practices in the diagnosis and treatment of PD. Comparisons were made with Pearson's chi-squared test. The primary outcome was reported use of therapies discouraged by the American Urological Association guidelines on PD. RESULTS: A total of 145 respondents completed the survey, of whom 19% were fellowship trained in andrology/sexual medicine, 36% practiced in an academic setting, and 50% had at least 20 years in practice. Only 60% of respondents reporting performing in-office curvature assessment prior to commencing intralesional injection or surgical treatment, with higher prevalence in andrology/sexual medicine fellowship-trained versus non-fellowship-trained urologists (85% vs. 54%, p = 0.003). The most popular treatment modalities were collagenase clostridium histolyticum (61% of respondents), phosphodiesterase-5 inhibitors (54%), and penile traction (53%). Twenty-one percent of respondents reported currently using a treatment that is explicitly discouraged by the American Urological Association guidelines (extracorporeal shockwave therapy for curvature, L-carnitine, omega-3 fatty acids, or vitamin E). DISCUSSION: Patients seeking PD treatment may be offered different therapies, some of which are not evidence-based, depending on the treating urologist. This study is limited by self-selection and response bias. Its strength is that it represents a cross-sectional overview of real-world practice patterns in PD management, which has not been previously described. CONCLUSIONS: A significant proportion of urologists reported PD management practices that are not evidence-based and not guideline-supported.

A systematic review of non-surgical management in Peyronie's disease.

The efficacy of many non-surgical treatments for Peyronie's disease is unclear. This systematic review aims to critically assess the currently available options and provide a recommendation for treatment based on this. A systematic literature search utilising the Medline (Pubmed), Embase, global health and Cochrane library databases was conducted up to May 2021. All randomised controlled trials assessing non-surgical treatment modalities for Peyronie's Disease were included. Individual study risk of bias was evaluated using the Cochrane tool and GRADE was used to assess evidence strength. Outcome measures were the change in penile curvature (degrees), plaque size (volume or size), International Index of Erectile Function score, pain scores and change in penile length. Prospero registration number: CRD42017064618. Amongst the 5549 articles identified, 41 studies (42 reports) were included. Seven different oral treatment options including vitamin E supplementation showed evidence for improving outcomes such as penile curvature and plaque size. Of the intralesional treatments, Collagenase Clostridium Histolyticum showed evidence for improving penile curvature (Range: 16.3-17 degrees, moderate level certainty of evidence). Intralesional Interferon demonstrated some improvement in curvature (Range: 12-13.5 degrees), plaque size (Range: 1.67-2.2 cm2) and pain, whilst intralesional calcium channel blockers such as Verapamil showed variable evidence for changes in the plaque size and pain. Extracorporeal Shockwave Therapy consistently demonstrated evidence for improving penile pain in stable disease, and two mechanical traction devices improved curvature. Iontophoresis, topical medications, and combination therapies did not demonstrate any consistent improvements in outcome measures. Intralesional options demonstrate the best potential. Overall, results varied with few high-quality randomised trials present.

Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids.

BACKGROUND: Uterine fibroids are highly prevalent, collagen-rich, mechanically stiff, fibrotic tumors for which new therapeutic options are needed. Increased extracellular matrix (ECM) stiffness activates mechanical signaling and Hippo/YAP promoting fibroid growth, but no prior studies have tested either as a therapeutic target. We tested the hypothesis that injection of a purified form of collagenase Clostridium histolyticum (CCH) that selectively digests type I and type III collagens would alter ECM stiffness, Hippo signaling, and selectively reduce fibroid cell growth. We also used two FDA-approved drugs, verteporfin and nintedanib, to elucidate the role of Hippo/YAP signaling in uterine fibroid and myometrial cells. METHODS: The clinical trial was registered (NCT02889848). Stiffness of samples was measured by rheometry. Protein expression in surgical samples was analyzed via immunofluorescence. Protein and gene expression in uterine fibroid or myometrial cell lines were measured by real time PCR and western blot, and immunofluorescence. RESULTS: Injection of CCH at high doses (0.1-0.2 mg/cm3 ) into fibroids resulted in a 46% reduction in stiffness in injected fibroids compared to controls after 60 days. Levels of the cell proliferation marker proliferative cell nuclear antigen (PCNA) were decreased in fibroids 60 days after injection at high doses of CCH. Key Hippo signaling factors, specifically the transcriptionally inactive phosphorylated YAP (p-YAP), was increased at high CCH doses, supporting the role of YAP in fibroid growth. Furthermore, inhibition of YAP via verteporfin (YAP inhibitor) decreased cell proliferation, gene and protein expression of key factors promoting fibrosis and mechanotransduction in fibroid cells. Additionally, the anti-fibrotic drug, nintedanib, inhibited YAP and showed anti-fibrotic effects. CONCLUSIONS: This is the first report that in vivo injection of collagenase into uterine fibroids led to a reduction in Hippo/YAP signaling and crucial genes and pathways involved in fibroid growth. These results indicate that targeting ECM stiffness and Hippo signaling might be an effective strategy for uterine fibroids.

Development of Collagenase Treatment for Dupuytren Disease.

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

Update on management of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a serious complication of diabetes that results in significant morbidity and mortality. Mortality rates associated with the development of a DFU are estimated to be 5% in the first 12 months, and 5-year morality rates have been estimated at 42%. The standard practices in DFU management include surgical debridement, dressings to facilitate a moist wound environment and exudate control, wound off-loading, vascular assessment, and infection and glycemic control. These practices are best coordinated by a multidisciplinary diabetic foot wound clinic. Even with this comprehensive approach, there is still room for improvement in DFU outcomes. Several adjuvant therapies have been studied to reduce DFU healing times and amputation rates. We reviewed the rationale and guidelines for current standard of care practices and reviewed the evidence for the efficacy of adjuvant agents. The adjuvant therapies reviewed include the following categories: nonsurgical debridement agents, dressings and topical agents, oxygen therapies, negative pressure wound therapy, acellular bioproducts, human growth factors, energy-based therapies, and systemic therapies. Many of these agents have been found to be beneficial in improving wound healing rates, although a large proportion of the data are small, randomized controlled trials with high risks of bias.

Clostridial collagenase ointment and medicinal honey utilization for pressure ulcers in US hospitals.

AIMS: To describe the utilization of clostridial collagenase ointment (CCO) and medicinal honey debridement methods in real-world inpatient and outpatient hospital settings among pressure ulcer (PU) patients and compare the frequency of healthcare re-encounters between CCO- and medicinal honey-treated patients. MATERIALS AND METHODS: De-identified hospital discharge records for patients receiving CCO or medicinal honey methods of debridement and having an ICD-9 code for PU were extracted from the US Premier Healthcare Database. Multivariable analysis was used to compare the frequency of inpatient and outpatient revisits up to 6 months after an index encounter for CCO- vs medicinal honey-treated PUs. RESULTS: The study identified 48,267 inpatients and 2,599 outpatients with PUs treated with CCO or medicinal honeys. Among study inpatients, n = 44,725 (93%) were treated with CCO, and n = 3,542 (7%) with medicinal honeys. CCO and medicinal honeys accounted for 1,826 (70%) and 773 (30%), respectively, of study outpatients. In adjusted models, those treated with CCO had lower odds for inpatient readmissions (OR = 0.86, 95% CI = 0.80-0.94) after inpatient index visits, and outpatient re-encounters both after inpatient (OR = 0.73, 95% CI = 0.67-0.79) and outpatient (OR = 0.78, 95% CI = 0.64-0.95) index visits in 6 months of follow-up. LIMITATIONS: The study was observational in nature, and did not adjust for reasons why patients were hospitalized initially, or why they returned to the facility. Although the study adjusted for differences in a variety of demographic, clinical, and hospital characteristics between the treatments, we are not able to rule out selection bias. CONCLUSION: Patients with CCO-treated PUs returned to inpatient and outpatient hospital settings less often compared with medicinal honey-treated PUs. These results from real-world administrative data help to gain a better understanding of the clinical characteristics of patients with PUs treated with these two debridement methods and the economic implications of debridement choice in the acute care setting.

Injectable collagenase Clostridium histolyticum as a nonsurgical treatment for Dupuytren's disease.

OBJECTIVE: Nonsurgical treatment of Dupuytren's disease using collagenase Clostridium histolyticum (CCH). INDICATIONS: Metacarpophalangeal (MP) joint (20-100°) and proximal interphalangeal (PIP) joint (20-80°) contractures. CONTRAINDICATIONS: Pregnancy, previous hypersensitivity to collagenase or excipients, anticoagulant use within 7 days prior to treatment. INJECTION TECHNIQUE: CCH injected directly into the Dupuytren's cord weakening the contracted cord. After injection, the patient returns the following day to allow CCH to lyse the collagen within the cord. An extension force is then applied to the involved finger to disrupt the weakened cord. POSTMANIPULATION MANAGEMENT: Use of extension splint at night, movement instructions during the day. RESULTS: A total of 120 patients (107 men; 13 women; mean age 62 years, range 30-84 years) were treated. In 49% the little finger, in 44% the ring finger, in 4% the middle finger, and in 3% the index finger was treated. Full release was achieved in 71%, partial release in 26%, and no change in 3% of patients. The median pretreatment contracture for the MP joint was 37° (range 25-100°) and PIP joint 51° (range 30-97°). At 12 months, the mean contracture for the MP joint was 9° (range 0-25°) and for the PIP joint 21° (range 10-36°). Adverse events observed in 96% of patients for 3 months . No tendon ruptures, anaphylactic reactions, or nerve or ligament injuries observed.

Efficacy and tolerability of Day 2 manipulation and local anaesthesia after collagenase injection in patients with Dupuytren's contracture.

In clinical trials, treating Dupuytren's contracture with collagenase injection involves manipulation the day after injection, without local anaesthesia. We evaluated the efficacy and tolerability of manipulation 2 days after injection with local anaesthesia. Forty-five patients received 50 injections into cords contracting metacarpophalangeal and proximal interphalangeal joints; follow-up visits were at 3 and 14 weeks. For the metacarpophalangeal joints there were >90% reduction in contracture at both visits. The proximal interphalangeal joints that improved spontaneously after metacarpophalangeal injection or received direct injections showed 51-55% reduction in contracture. Changes in scores on the Patient Evaluation Measure suggest that patients perceived improvements in their hand function was good and they were satisfied with the procedure. Collagenase and local anaesthesia injections were well tolerated; adverse events were localized to the injection site and were mild and transient in nature. These findings provide another viable option for practising surgeons and may help with the logistics of patient care.

Use of resources and costs associated with the treatment of Dupuytren's contracture at an orthopedics and traumatology surgery department in Denia (Spain): collagenase clostridium hystolyticum versus subtotal fasciectomy.

BACKGROUND: Our purpose was to analyze and compare the use of direct health resources and costs generated in the treatment of Dupuytren's contracture using two different techniques: subtotal fasciectomy and infiltration with Collagenase Clostridium Histolyticum (CCH) in regular clinical practice at the Orthopedic and Traumatology Surgery (OTS) Department at the Hospital de Denia (Spain). METHODS: Observational, retrospective study based on data from the computerized clinical histories of two groups of patients- those treated surgically using a one or two digit subtotal fasciectomy technique (FSC) and those treated with CCH infiltration, monitored in regular clinical practice from February, 2009 to May, 2012. Demographic (age, sex), clinical (number of digits affected and which ones) and use of resources (hospitalizations, medical visits, tests and drugs) data were collected. Resource use and associated costs, according to the hospital's accounting department, were compared based on the type of treatment from Spain's National Health Service. RESULTS: 91 patients (48 (52.8%) in the FSC group) were identified. The average age and number of digits affected was 65.9 (9.2) years and 1.33 (0.48) digits affected in the FSC group, and 65.1 (9.7) years and 1.16 (0.4) digits in the CCH group.Overall, the costs of treating Dupuytren's disease with subtotal FSC amount to €1,814 for major ambulatory surgery and €1,961 with hospital stay including admission, surgical intervention (€904), examinations, dressings and physiotherapy. As to collagenase infiltration, costs amount to €952 (including minor surgery admission, vial with product, office examination and dressings). Finally, comparing total costs for treatments, a savings of €388 is estimated in favor of CCH treatment in the best-case scenario (patient under MAS system with no need for physiotherapy) and €1,008 in the worst-case scenario (patient admitted to hospital needing subsequent physiotherapy), implying a savings of 29% and 51%, respectively. CONCLUSIONS: This study demonstrates that treating patients with DC by injection with CCH at the OTS department of the Hospital de Denia generates a total savings of 29% and 51% (€388 and €1008) compared with fasciectomy at the time of treatment. Long term evolution of CCH treatment is uncertain and the recurrence rate unknown.

A comparative study of ciprofloxacin and conventional therapy in the treatment of patients with chronic lower leg ulcers infected with Pseudomonas aeruginosa or other gram-negative rods.

Twenty-six elderly patients with chronic leg ulcers infected by Pseudomonas aeruginosa or other aerobic Gram-negative rods were randomised to two treatment groups. The control group (eight patients) received conventional local therapy and the other group (18 patients) was treated with oral ciprofloxacin for three months in addition to conventional local therapy. In the beginning of the study both groups were comparable with the age of the patients and the associated diseases including impairment of arterial and venous circulation in the lower legs. Also the size, duration and the severity of the inflammation reaction in the leg ulcers were comparable before the start of the therapy. Ciprofloxacin was clinically more effective than the standard therapy in reducing the size of the ulcer (p less than 0.05). Also the need of extra systemic antibiotics decreased significantly in the ciprofloxacin group compared with the controls. In three out of eighteen ciprofloxacin treated patients the leg ulcers disappeared completely during the three months' study period compared with none in the control group. However, ciprofloxacin resistant strains, mainly staphylococci, appeared in the leg ulcers in 67% of the ciprofloxacin treated patients compared with 0% in the control group (p less than 0.01). No significant side-effects due to ciprofloxacin except the resistant strains were noticed. We conclude that oral long-term ciprofloxacin therapy is effective in the treatment of chronic leg ulcer infections due to Gram-negative rods but selection of ciprofloxacin resistant strains is a problem in this patient group.

Therapeutic considerations in the podiatric care of ulcerations.

In this excellent article, Dr. McCarthy presents some of the most current concepts in the treatment of lower extremity ulcerations. This common clinical finding is frequently frustrating and difficult to treat effectively. It also requires a high degree of suspicion as to the primary underlying cause and many hours of careful treatment and follow-up to prevent serious secondary complications, such as infection and gangrene. The emphasis on therapeutic approaches lends much useful information in our fight with this condition and its sequelae.

[Anesthesiologic aspects of chemonucleolysis in local anesthesia]. / Anästhesiologische Aspekte bei der Chemonukleolyse in Lokalanästhesie.

After treatment of herniation of a lumbar disc by injection of the enzyme chymopapain, i. e. after chemonucleolysis, anaphylactic reactions can occur in about one per cent of the cases. In order to recognise the pattern of signs associated with such reactions, well in advance, while avoiding the additional risk of general anaesthesia, some authors propagate local anaesthesia. We report on our perioperative procedure in 102 cases of chemonucleolysis under local anaesthesia. Prick's tests were carried out before surgery to exclude sensitization to the substances to be injected. In two cases only due to a positive prick test to chymopapain chemonucleolysis had to be effected with collagenase; as a matter of fact, collagenase is not known to have caused any anaphylactic reactions, but it may be responsible for local side effects, such as destruction of adjacent tissues. The patients were kept under observation by an anaesthetist during and after surgery. No anaphylactic reaction was seen. Chemonucleolysis appears to be a suitable treatment method provided it is carried out under local anaesthesia with the same precautions as applied under regional anaesthesia by the anaesthetist.