BACKGROUND: Peyronie\'s disease is characterized by the formation of fibrotic plaques in the penile tunica albuginea. Effective treatments are limited, warranting the investigation of new promising therapies, such as the application of microRNAs that regulate fibrosis-related genes.
OBJECTIVE: We aimed to investigate the therapeutic potential of mimicking microRNA-29b in a fibrin-induced rat model of Peyronie\'s disease.
METHODS: The study was designed in two phases. To establish an optimal Peyronie\'s disease model, rats received either human fibrin and thrombin or saline solutions into the tunica albuginea on days 0 and 5. The animal model validation was done through expression and histopathological analyses, the latest by an experienced uropathologist. After validation, we performed microRNA-29b treatment on days 14, 21, and 28 of the study. This phase had control (normal saline) and scramble (microRNA scramble) groups. The mid-penile shaft was removed on day 30 for histological examination and molecular analyses in both study stages.
RESULTS: The control group displayed typical tunica albuginea histologic architecture in the animal model validation. In Peyronie\'s disease group, the Hematoxylin and eosin and Masson Trichrome staining methods demonstrated an interstitial inflammatory process with concomitant dense fibrotic plaques as well as disarrangement of collagen fibers. Additionally, we found out that reduced microRNA-29b (p = 0.05) was associated with significantly increased COL1A1 and transforming growth factor β1 genes and proteins (p > 0.05) in the Peyronie\'s disease group. After treatment with mimic microRNA-29b stimulation, the Hematoxylin & eosin and Masson Trichrome staining revealed a discrete and less dense fibrotic plaque. This result was associated with significantly decreasing expression of COL1A1, COL3A1, and transforming growth factor β1 genes and proteins (p < 0.05).
CONCLUSIONS: The fibrin-induced animal model showed significant histopathological and molecular changes compared to the Control group, suggesting that our model was appropriate. Previous findings have shown that increased expression of microRNA-29b was associated with decreased pathological fibrosis. In the present study, treatment with microRNA-29b decreased the gene and protein expression of collagens and transforming growth factor β1. This study reveals the therapeutic potential for Peyronie\'s disease involving molecular targets.
CONCLUSIONS: MicroRNA-29b application on the rat\'s tunica albuginea attenuated fibrosis, arising as a novel potential strategy for Peyronie\'s disease management.

UNASSIGNED: Penile plication is commonly performed for Peyronie\'s disease under general or spinal anesthesia. Conscious sedation (CS) offers decreased anesthetic risks, cost-effectiveness, and the ability to perform the procedure in outpatient settings with shorter wait times. We sought to compare tolerability of penile plication under deep intravenous sedation (DIS) administered by anesthesiologists and nursing-administered CS (NACS).
UNASSIGNED: Tolerability for penile plication was prospectively evaluated, excluding revision surgeries and those with hourglass or hinge deformities. DIS included midazolam and ketamine with infusion of propofol and remifentanil. NACS consisted of midazolam and fentanyl. Baseline characteristics, procedural information, and patient- and surgeon-reported pain assessments were collected. Patients were administered a standardized tolerability questionnaire on follow-up.
UNASSIGNED: Forty patients were enrolled (23 DIS; 17 NACS) with similar baseline characteristics. Median curvature of the DIS cohort was 55° (interquartile range = 43.75-76.25) and 45° (interquartile range = 45-60) in NACS. There was a 100% success rate with no procedure abortion or conversion to general anesthetic. On follow-up, all patients had functional curvature (<20°), and 100% of patients in the DIS and NACS cohorts reported that they would recommend CS to others. Over 93% of patients in both cohorts would choose CS over general anesthetic in the future, with no differences in perioperative and postoperative pain between groups.
UNASSIGNED: Penile plication with CS, whether administered by an anesthesiologist or nursing, is well tolerated with no differences in pain or complications. This indicates that outpatient penile plication with trained nursing staff administering CS can safely reduce costs, risks, and wait times.

OBJECTIVE: Peyronie\'s disease is an acquired fibrosis of penile albuginea which modifies the penile morphology. Few studies described the consequences of Peyronie\'s disease on the intimate environment. We studied consequences on the patient and on the partner(s).
METHODS: We questioned last patients followed in our center and more specifically the partners in a direct way, through an online questionnaire, integrating a validated score (HAD score).
RESULTS: Fifty-five patients and 41 partners gave their agreement by answering the questionnaire. Median age was 51.8 years, with a median duration of symptoms of 15 months. Patients described penile deformation (96%), erectile pain (80%) and erectile dysfunction (40%). Patients had penile pain at rest (26%) or sleep disorders (60%). The level of sexual desire was lower in 86%, Penetrative sex was possible in 87%, couple relationship was deteriorated in 40%. Penile deformation bothers 61% of partners. During the stable phase, 60% of patients underwent surgery. HAD score in the general population was 20.24. The 0-60° subgroup was statistically less anxious (10.06 vs. 13.25) and depressed (7.68 vs. 10.05) than the > 60° subgroup (P<0.05). Partners made research on the disease in 51% of cases; the feeling of having been involved in disease management was found in 66% of cases. Most of partners felt powerless or frustrated.
CONCLUSIONS: Peyronie\'s disease has a certain psychological impact on the couple. It combines depressive and social disorders, a devaluation of patients and an alteration of their intimacy. The role of partners in the management of this pathology is undervalued. This must be a subject of further studies to guarantee optimal overal.
METHODS:

UNASSIGNED: Plaque incision/excision and grafting are surgical techniques used to treat patients with Peyronie\'s disease who are refractory to less invasive interventions, have severe penile curvature, or have an hourglass deformity. However, the procedure carries the risk of penile sensory loss because of the need for dissection of the neurovascular bundle (NVB). The aim of this study was to assess the feasibility of a novel technique for unilateral NVB dissection and its ability to preserve penile sensitivity while maintaining adequate correction of the penile curvature.
UNASSIGNED: Charts of patients who underwent unilateral NVB dissection during Peyronie\'s plaque incision/excision and grafting were retrospectively reviewed. All patients received preprocedural intracavernosal injections of TriMix, and the curvature was measured to be >70 degrees. In 3 cases, an incision and minimal excision of the plaque were performed at the point of maximum curvature on the concave side of the curvature. In 3 cases, Tutoplast allografts (Coloplast US, Minneapolis, MN) were used, whereas autografts were used in 2 other cases. All patients were examined at 1, 3, and 6 months after the procedure when curvature and penile sensation were assessed.
UNASSIGNED: Five patients underwent this procedure. The mean age of patients was 55 years (45-70 years). All plaques were dorsally located. The mean preoperative curvature was 78 degrees (75-90 degrees). At the 6-month follow-up, all patients had <15 degrees residual curvature and were satisfied with their cosmetic results. Only 1 patient continued with phosphodiesterase-5 inhibitors to improve potency at the 6-month follow-up. All patients reported normal penile glans sensation. Four patients experienced decreased sensation at the site of NVB dissection, but this was only detected when compared with the contralateral side. Only 2 patients reported a difference after 6 months, and only a minor area of involvement was noted.
UNASSIGNED: Unilateral NVB dissection is a feasible technique that does not compromise surgical success in curvature correction and helps avoid sensory injury to the penile glans.

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

BACKGROUND: Testosterone plays an important role in collagen metabolism, transforming growth factor-β1 expression, and wound healing, which are all critical factors in pathogenesis of Peyronie\'s disease. Some clinical studies have suggested an association between Peyronie\'s disease and hypogonadism.
OBJECTIVE: We sought to investigate whether baseline total testosterone levels influence response to intralesional collagenase clostridium histolyticum in Peyronie\'s disease.
METHODS: A retrospective review of patients receiving collagenase clostridium histolyticum injections with available total testosterone levels within 1 year of initial injection was conducted at a single institution. Baseline demographics, hypogonadal status, total testosterone, number of collagenase clostridium histolyticum cycles, and pre- and post-treatment degrees of curvature were collected. Hypogonadism was defined as total testosterone <300 ng/dL.
CONCLUSIONS: Thirty-six men were included with mean age of 58.2 years (SD 10.4) and mean body mass index 26.8 (SD 3.2). The mean total testosterone was 459.2 ng/dL (SD 144.0), and four (11.1%) were hypogonadal. Mean pre-treatment curvature was 47.6°, and mean post-treatment curvature was 27.8°, with mean improvement of 19.9° (40.1%). Hypogonadal status was not significantly associated with more severe curvature, 46.4° among hypogonadal men as to 57.5° among eugonadal men (p = 0.32). On linear regression analysis, total testosterone did not significantly predict improvement in degrees (β = -0.02; R2 = 0.06; p = 0.14) or percent (β = 0.0; R2 = 0.05; p = 0.18). Improvement in neither degrees nor percent differed significantly by hypogonadal status (p = 0.41 and 0.82, respectively). The cycle number did significantly predict greater improvement in curvature on both univariate and multivariate analyses (β = 5.7; R2 = 0.34; p < 0.01).
CONCLUSIONS: Neither total testosterone nor hypogonadism is associated with a degree of improvement after collagenase clostridium histolyticum treatment.

BACKGROUND: Little is known about patients\' pre-treatment expectations in Peyronie\'s disease (PD).
OBJECTIVE: To evaluate in detail patients\' expectations of conservative therapy and surgery.
METHODS: This multi-center study prospectively enrolled 317 PD patients, who were scheduled to receive conservative therapy or surgery between 2019 and 2022 at the Department of Urology of the University Medical Center Hamburg-Eppendorf, and the Center of Reproductive Medicine and Andrology, University Medical Center Muenster, both Germany. The primary end-point was patients\' pre-treatment expectations of conservative therapy and surgery, measured with the Stanford Expectations of Treatment Scale (SETS). Secondary end-points included patient-reported psychological and physical symptoms, penile pain, symptom bother and erectile function, measured with the Peyronie\'s disease questionnaire (PDQ) and International Index of Erectile Function Erectile Function Domain (IIEF-EF).
RESULTS: In total, 239 (75%) and 78 (25%) patients were scheduled for the conservative therapy and surgery, respectively. Patients undergoing surgery had higher positive and negative mean SETS expectations scores (14 vs. 11, p < 0.001; 9.6 vs. 6.0, p < 0.001). In multivariable analysis, surgery was an independent predictor of positive and negative patients\' pre-treatment expectations (all p ≤ 0.001). In thematic analysis, patients undergoing surgery emphasized distinct themes of pre-treatment expectations. Patients undergoing surgery had higher mean PDQ symptom bother as well as higher psychological and physical symptom scores (14 vs. 10, p < 0.001; 9.2 vs. 7.1, p = 0.001). There were significant positive correlations between SETS negative expectation score and PDQ symptom bother (|ρ| = 0.25; p < 0.001) as well as PDQ psychological and physical symptoms score, respectively (|ρ| = 0.21; p = 0.001).
CONCLUSIONS: PD patients expect both more benefit and more harm from surgery. In addition, patients undergoing surgery have more psychological and physical symptoms and more symptom bother. To set realistic expectations, it is of pivotal importance to assess patients\' expectations before starting treatment.

Peyronie\'s disease (PD) is a connective tissue disorder affecting the tunica albuginea. It can cause pain and penile deformation, and its prevalence increases with age. Although surgery is the gold standard for the chronic phase of the disease, there are several conservative treatment methods available, and the optimal management of the acute phase of the disease remains a matter of debate. In this article, we aim to summarize the recent trends in research on the subject of non-surgical treatment of PD. The search was performed in PubMed, Scopus, and Web of Science databases and included studies in English published between 2012 and 2022 investigating the clinical outcomes of non-surgical PD management in humans. We have identified 20 distinct conservative treatment strategies. Among the oral therapeutics, only the use of phosphodiesterase type 5 inhibitors is currently recommended for clinical use in patients with concomitant erectile dysfunction. The use of collagenase from Clostridium histolyticum is supported by the best quality evidence in terms of intralesional injections for patients suffering from significant penile curvature; however, interferon alpha-2b can also be an option in such patients. Among other non-invasive methods, extracorporeal shockwaves can be useful for pain reduction, and penile traction therapy can lead to a reduction in penile curvature and plaque size. Despite a wide range of non-surgical methods available for PD treatment, the majority are not supported by sufficient scientific evidence, and the treatment efficacy is underwhelming. Further research on the subject of non-surgical management of PD is highly warranted.

The tunica albuginea (TA) of the penis is an elastic layer that serves a structural role in penile erection. Disorders affecting the TA cause pain, deformity, and erectile dysfunction. There is a substantial clinical need for engineered replacements of TA, but data are scarce on the material properties and biochemical composition of healthy TA. The objective of this study was to assess tissue organization, protein content, and mechanical properties of porcine TA to establish structure-function relationships and design criteria for tissue engineering efforts. TA was isolated from six pigs and subjected to histomorphometry, quantification of collagen content and pyridinoline crosslinks, bottom-up proteomics, and tensile mechanical testing. Collagen was 20 ± 2%/wet weight (WW) and 53 ± 4%/dry weight (DW). Pyridinoline content was 426 ±131 ng/mg WW, 1011 ± 190 ng/mg DW, and 45 ± 8 mmol/mol hydroxyproline. Bottom-up proteomics identified 14 proteins with an abundance of >0.1% of total protein. The most abundant collagen subtype was type I, representing 95.5 ± 1.5% of the total protein in the samples. Collagen types III, XII, and VI were quantified at 1.7 ± 1.0%, 0.8 ± 0.2%, and 0.4 ± 0.2%, respectively. Tensile testing revealed anisotropy: Young\'s modulus was significantly higher longitudinally than circumferentially (60 ± 18 MPa vs. 8 ± 5 MPa, p < 0.01), as was ultimate tensile strength (16 ± 4 MPa vs. 3 ± 3 MPa, p < 0.01). Taken together, the tissue mechanical and compositional data obtained in this study provide important benchmarks for the development of TA biomaterials. STATEMENT OF SIGNIFICANCE: The tunica albuginea of the penis serves an important structural role in physiologic penile erection. This tissue can become damaged by disease or trauma, leading to pain and deformity. Treatment options are limited. Little is known about the precise biochemical composition and biomechanical properties of healthy tunica albuginea. In this study, we characterize the tissue using proteomic analysis and tensile testing to establish design parameters for future tissue engineering efforts. To our knowledge, this is the first study to quantify tissue anisotropy and to use bottom-up proteomics to characterize the composition of penile tunica albuginea.

Peyronie\'s disease is an acquired connective tissue disease of the tunica albuginea of the penis which usually presents with penile curvature/deformity and a palpable penile plaque. It is more common in Caucasian men over the fifth decade of life, but it is an under-reported disease. Conservative and non-surgical options are supported by limited evidence except for intralesional injection of collagenase clostridium histolyticum and have limited success. The improved outcome of surgical treatment is accompanied by the risk of erectile dysfunction. This is a brief overview of Peyronie\'s disease, its impact on the patient, and the available treatment options.