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Adult Acquired Buried Penis (AABP) is a morbid condition that often requires surgical intervention. This retrospective study of 46 patients who underwent AABP surgery from November 2017 to July 2023 evaluates surgical outcomes, functional outcomes, and patient-reported outcomes. The median follow-up (FU) was 46 months. Patients were categorized by surgical complexity using the Pariser classification, with 76.1% undergoing high-complexity procedures (Pariser ≥ III). Common comorbidities included obesity (58.7%), prior circumcision (52.2%), and hypertension (52.2%). The low-complexity group had a shorter hospital stay ( p = 0.02). No other significant differences were noted between groups in terms of Body Mass Index, operative time, or FU. Sexual dysfunction (45.7%) and urinary issues (38.1%) were the main reasons for surgical consultation. Skin grafting was required in 63.0% of patients; partial graft loss was more common in full thicknes skin graft group ( p = 0.04). Postoperative complications occurred in 32.6% of patients, 13.3% of which were classified severe (Clavien ≥ III). The median increase in stretched penile length was 2 cm. The recurrence rate was 21.7%. The 12-month recurrence-free survival rate was 89.1%. All groups saw significant improvements in urinary and sexual function post-surgery ( p < 0.05), and high patient satisfaction was reported (90.3%). Despite the complication rate, AABP surgery significantly improves quality of life, with ongoing advancements in technique anticipated to enhance outcomes further.

Pursuing effective and biocompatible natural compounds to supplant current biocidal antifouling (AF) technologies remains crucial and challenging. Among natural products hosts, cyanobacteria are recognized as producers of bioactive secondary metabolites that are underexplored in terms of anti-biofilm and AF potential. Nocuolin A, a natural oxadiazine previously isolated and known to be produced by different cyanobacterial strains, has demonstrated bioactive potential, particularly against tumor cell lines. Considering this potential and its exquisite chemical structure, here nocuolin A was investigated as a potential natural AF agent through an integrative approach including AF bioactivity testing across distinct levels of biological organization, mode of action assessment, ecotoxicity evaluation, and ecological risk predictions. Nocuolin A was found to inhibit the settlement of mussel (Mytilus galloprovincialis) plantigrades (EC 50  = 3.905 μM) while showing no toxicity to this biofouling species (LC 50  > 100 μM). Additionally, while exhibiting no inhibitory activity against the growth of five marine biofilm-forming bacterial strains, it significantly suppressed the growth of the marine biofilm-forming diatom Navicula sp. (EC 50  = 1.561 μM), and had a lethal effect on this diatom species (>3.1 μM). The AF targets of nocuolin A on mussel plantigrades revealed no correlation with acetylcholinesterase and tyrosinase metabolic processes; however, proteins involved in oxidative stress, muscle regulation, and energy production were highlighted. The results also provide insights into the ecological risk of nocuolin A, including its ecotoxicity against Artemia salina nauplii (LC 50  = 2.480 μM), Amphibalanus amphitrite nauplii (LC 50  = 0.0162 μM), and Danio rerio embryos (LC 50  = 0.0584 μM). When matching these results with simulated environmental values, nocuolin A was deemed a considerable threat to the ecosystems. While this research highlights the AF activity of nocuolin A, it also emphasizes the potential adverse environmental impact when applied in preventive coatings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joana R. Almeida reports was provided by Foundation for Science and Technology. Joana R. Almeida reports financial support was provided by European Union. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations., Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations., Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate., Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

The first-line treatment of penile cancer confined to the glans (Tis-T2) is based on organ-sparing approaches. Our aim is to report functional outcomes of total glans resurfacing (TGR), wide local excision (WLE) and glansectomy. A retrospective analysis was conducted from January 2013 to October 2022. Ninety-nine patients were enrolled (22 TGR, 29 WLE, and 48 glansectomy). Sexual and urinary outcomes were explored using ad hoc and validated questionnaires (IIEF-15 and IPSS). The mean follow-up was 25.28 ± 24.87 months [95% CI: 20.38; 30.18]. 44 patients (12 TGR, 10 WLE, and 22 glansectomy) were assessed for functional outcomes. Overall, 86.36% of patients were satisfied with the surgery. The mean IIEF-15 score pre-operation was 54.91 ± 21.38 [95% CI: 48.41-61.41], and at 12 months post-operation, it was 44.39 ± 23.01 [95% CI: 37.39-51.39], with the change being statistically significant (mean difference: -10.52, (-19.15), p < 0.001). During the 0-12-month interval, IIEF-15 scores decreased across all techniques. Glansectomy and WLE showed significant decreases (Glansectomy: -12.955, -24.14%, [95% CI: -21.52, -4.38], p = 0.002; WLE: -14.1, -22.92%, [95% CI: -26.8, -1.39], p = 0.025 respectively), whereas TGR experienced a non-significant decrease (-3.083, -5.97%, CI: [-14.68, 8.51], p = 1.0). Concerning urinary function, only 18.18% of overall patients reported a negative impact of surgery. At 12-months, patients returned almost to pre-intervention IPSS values. Organ-sparing surgery guarantees a decent preservation of both erectile and voiding functions. TGR seems to provide better sexual outcomes when compared to other organ sparing approaches., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA., Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process., Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit., Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

The aim of this paper was to describe the long-term outcomes of extracorporeal shock wave therapy (ESWT) in patients with acute Peyronie'disease (PD). An observational retrospective study was conducted in men with acute PD who underwent ESWT between 2009-2013 at a single institution. ESWT protocol consisted of 1 session (3000 shock waves, 0.10-0.25 mJ/mm^2, 4-6 Hz) per week for 4 weeks. Penile pain was chosen as the primary outcome. Penile curvature angle, erectile function, and satisfaction with ESWT were selected as secondary long-term outcomes. A total of 194 patients were included. The mean follow-up duration after ESWT was 125.6 months. Mean penile curvature worsened significantly at 3 months (18.3 vs. 21.5 degrees; p = 0.023) and 12 months (21.5 vs. 28.6 degrees; p = 0.001) and stabilized over the long-term (28.6 vs. 28.8 degrees; p = 0.335). Mean penile pain improved significantly at 3 months (6.5 vs. 3.1 points; p < 0.001) and 12 months (3.1 vs. 1.0 points; p = 0.001), remaining stable over time (1.0 vs. 1.0 points; p = 0.074). The mean five-item version of the International Index of Erectile Function (IIEF-5) increased significantly at 3 months (14.5 vs. 17.9 points; p = 0.001), remaining stable at 12 months (17.9 vs. 18.5 points; p = 0.082), and deteriorating in the long-term (18.5 vs. 15.8 points; p = 0.003). A high satisfaction rate with ESWT was recorded at 3 months (92.3%), remaining similar at 12 months (91.2%) and over the long-term (90.2%). No new acute phase and low rate of PD surgery (4.1%) were recorded in the long-term analysis. In patients with acute PD, ESWT seems to be associated with early and persistent relief of penile pain, transient improvement in erectile function, no significant effect on penile curvature, and a high rate of patient satisfaction constant over time., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objective: Nodal metastasis is a major survival and prognostic factor in penile cancer (PeCa). Thus, accurate staging, prognosis, and treatment selection require adequate inguinal lymphadenectomy (ILND). ILND surgery should balance oncologic rigor with morbidity and postoperative complications. Our aim was to compare the feasibility and safety of open ILND (OILND) and videoendoscopic ILND (VEILND) in patients with PeCa., Methods: We conducted a single-center randomized trial with a within-patient design between October 2019 and April 2023. Patients who were undergoing either staging or radical ILND for PeCa were included and randomized to receive either OILND or VEILND on one side, with the other technique then used on the contralateral side. The trial was approved by the local ethics committee and was registered on ClinicalTrials.gov (NCT05887921). The primary outcome was the safety of VEILND. Secondary outcomes included intraoperative and postoperative morbidity rates and surgical outcomes for the two procedures, as well as oncological outcomes according to survival estimates., Key Findings and Limitations: We included 14 patients in the study. Median follow-up was 12 mo (interquartile range [IQR] 12-17). There were no significant differences in operative time and the number of lymph nodes removed between OILND and VEILND. However, the median time to drain removal was significantly shorter in the VEILND group (15 d, IQR 13-17, 95% confidence interval [CI] 12-17) than in the OILND group (27 d, IQR 20-41, 95% CI 24-31; p  = 0.025). No intraoperative complications were observed, but postoperative complications occurred in three cases (21.4%, 95% CI 8.4-37.8%) in the VEILND group and eight (57.1%, 95% CI 18.6-54.3%) in the OILND group ( p  = 0.032)., Conclusions and Clinical Implications: VEILND represents a safe technique to consider for either staging or curative intent in PeCa and seems to have an advantage over OILND in terms of morbidity. Further high-powered studies are warranted to confirm these preliminary results., Patient Summary: We compared the outcomes of two different surgical techniques to remove lymph nodes in patients with penile cancer. We found that a video-assisted keyhole surgery approach seems to result in a lower rate of complications than after open surgery., (© 2024 The Author(s).)

Purpose: Small intestinal submucosa (SIS) graft urethroplasty has been employed to decrease buccal mucosa morbidity and facilitate the procedure. The first published series had a short follow-up, inhomogeneous patient selection, and a lack of a control group. Our purpose is to report treatment outcomes at 13 years in a propensity score-matched cohort comparing bulbar urethroplasty with SIS (SISU) or buccal mucosa (BMU)., Methods: From our institutional database of 1132 bulbar urethroplasties, we used propensity score matching with the nearest-neighbor method without replacement to generate a study sample of 25 BMU and 25 SISU. Failure was defined as any treatment after urethroplasty. Survival analyses were used to analyze treatment failure occurrence with data censored at 156mo., Results: Matching resulted in a complete correction of bias between the two samples except for the follow-up duration, which was slightly longer in the SIS group. The cumulative treatment success probability of BMU and SISU at 156mo was 83.4% and 68%, respectively. At multivariable Cox regression, SIS graft, previous urethrotomy, stricture length, and lower postoperative Qmax (within 2mo after catheter removal) were predictors of failure. Stricture length had a more remarkable effect in SISU, with estimated survival probabilities from the Cox model lower than 80% in strictures > = 3 cm., Conclusion: SIS has poorer outcomes compared to BM but may still be useful when BM grafting is not possible. The best candidates for SISU, with similar success to BMU, are patients with strictures shorter than 3 cm, preferably without a history of DVIU., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Peyronie's disease, a fibroinflammatory disorder, detrimentally impacts the sexual well-being of men and their partners. The manifestation of fibrotic plaques within penile tissue, attributed to dysregulated fibrogenesis, is pathognomonic for this condition. The onset of fibrosis hinges on the perturbation of the equilibrium between matrix metalloproteinases (MMPs), crucial enzymes governing the extracellular matrix, and tissue inhibitors of MMPs (TIMPs). In the context of Peyronie's disease, there is an elevation in TIMP levels coupled with a decline in MMP levels, culminating in fibrogenesis. Despite the scant molecular insights into fibrotic pathologies, particularly in the context of Peyronie's disease, a comprehensive literature search spanning 1995 to 2023, utilizing PubMed Library, was conducted to elucidate these mechanisms. The findings underscore the involvement of growth factors such as FGF and PDGF, and cytokines like IL-1 and IL-6, alongside PAI-1, PTX-3, HIF, and IgG4 in the fibrotic cascade. Given the tissue-specific modulation of fibrosis, comprehending the molecular underpinnings of penile fibrosis becomes imperative for the innovation of novel and efficacious therapies targeting Peyronie's disease. This review stands as a valuable resource for researchers and clinicians engaged in investigating the molecular basis of fibrotic diseases, offering guidance for advancements in understanding Peyronie's disease., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Addressing pressing health concerns, modern medical research seeks to identify new antimicrobials to combat drug resistance, novel molecules for cancer treatment, and antioxidants for inflammation-related diseases. Pisolithus (Basidiomycota) is a ubiquitous and widely distributed fungal genus in forest ecosystems, known for establishing ectomycorrhizal associations with a range of host plants, enhancing their growth, and conferring protection against biotic and abiotic stresses. Beyond ecological applications, Pisolithus yields bioactive compounds with medicinal potential. This comprehensive review explores the transversal biological activity of Pisolithus fungi, aiming to provide a thorough overview of their antimicrobial, anticancer, and antioxidant potential. The focus is on elucidating bioactive compounds within Pisolithus to trigger further research for innovative applications. Compounds from Pisolithus displayed antimicrobial activity against a broad spectrum of microorganisms, including antibiotic-resistant bacteria. The efficacy of Pisolithus -derived compounds matched established medications, emphasizing their therapeutic potential. In anticancer research, the triterpene pisosterol stood out with documented cytotoxicity against various cancer cell lines, showcasing promise for novel anticancer therapies. Pisolithus was also recognized as a potential source of antioxidants, with basidiocarps exhibiting high antioxidant activity. In vivo validation and comprehensive studies on a broader range of compounds, together with mechanistic insights into the mode of action of Pisolithus -derived compounds, are compelling areas for future research.

Vitamin K isoforms are known as co-factors for the synthesis of blood-clotting proteins, but several other bioactivities were reported. In this work, we isolated a vitamin K1-analogue (OH-PhQ) from the cyanobacterium Tychonema sp. LEGE 07196 with lipid reducing activity. OH-PhQ reduced neutral lipid reservoirs with an EC 50 value of 31 μM after 48 h exposure in zebrafish larvae, while other vitamin K isoforms had EC 50 values of 21.1 μM (K2) and 1.2 μM (K3). No lipid reducing activity was observed for K1 up to 50 μM. The presence of vitamin K isoforms was studied in zebrafish after exposure (OH-PhQ, K1, K2 and K3), and a clear preference for bioconversion was observed to retain K1 and OH-PhQ. Untargeted metabolomics revealed different biological effects for vitamin K isoforms on the subclass and metabolite level, but similarities were present on the compound class level, particularly on the regulation of glycerophospholipids. Our data showed for the first time a lipid reducing activity of OH-PhQ and performed a comparative analysis of vitamin K isoforms, which could be important for the development of future nutraceuticals or food supplements.

Adult Acquired Buried Penis (AABP) is a pathological condition necessitating surgical correction, ranging from simple to complex procedures involving the utilization of full-thickness (FTSG) or split-thickness (STSG) skin grafts especially in cases of substantial viable penile skin loss. In this retrospective study, we aimed to compare the surgical, functional, and patient-reported outcomes (PROs) of graft types that were utilized to treat AABP among 39 patients at a single center between November 2017 and May 2023. Among these patients, 22 needed skin grafts, with 9 undergoing FTSG and the remainder receiving STSG. Lichen Sclerosus (LS) was the primary cause (54.6%) of AABP requiring skin grafts. Patients primarily presented with voiding (63.6%) and sexual (27.3%) dysfunction. The STSG group had a lower mean age (64.7 ± 11.6) than the FTSG group (66.7 ± 11.6; P = 0.015), with no significant differences in BMI (p = 0.643). Complex repairs (Santucci grade ≥3) were performed in 81.0% of cases, with 88.9% in the FTSG group and 75.0% in the STSG group. Operative times were similar (160.2 ± 31.7 vs 161.5 ± 50.3, p = 0.945). No significant differences in preoperative penis length were found between the FTSG and STSG groups (P = 0.918). Postoperative complications occurred in 36.4% of patients, with severe complications (Clavien grade ≥3) in 9.1%. General postoperative complications and recurrence rates did not significantly differ between groups (P = 0.397 and 0.375; respectively). Functional outcomes, evaluated using the International Index of Erectile Function and the International Prostate Symptom Score, improved significantly in both groups after surgical procedures (P < 0.001 for all). Patient-reported satisfaction for the operation was 81.3% calculated by ad-hoc questionnaire. In conclusion, no discernible differences in outcomes were observed between STSG and FTSG. Larger comparative studies with extended follow-up periods and validated questionnaires are warranted for confirmation. Physicians should consider specialized centers for AABP surgical repair due to its intricacies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Penile shortening, frequently resulting from end-stage Peyronie's disease (PD), has a negative impact on patients' sexual activity and overall quality of life, especially when accompanied by Erectile dysfunction (ED). Various surgical techniques have been described to manage concomitant ED and penile shortening through penile prosthesis (PP) implantation., Objectives: To evaluate the benefits and risks of different penile length preservation techniques during PP implantation., Design: A systematic review of the available literature on the use of penile length preservation maneuvers in conjunction with PP implantation was conducted., Data Sources and Methods: For this systematic review, three databases (Medline, Embase and Cochrane) and clinical trial.gov were queried for relevant publications from 1 January 1990 to 1 September 2022. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines., Results: The qualitative analysis included 15 relevant articles involving 1186 adult patients who underwent penile length preservation techniques during PP implantation. Penile lengthening of 1-7 cm was reported. Overall, postoperative complications were described in up to 21.7% of cases. Only five studies reported functional outcomes, showing a significant improvement in postoperative period based on the administered questionnaire (e.g. IIEF - International Index of Erectile Function, EDITS - Erectile Dysfunction Inventory of Treatment Satisfaction)., Conclusion: Penile length preservation procedures appear to offer a viable option for managing acquired penile shortening, particularly in cases of PD. However, they are associated with a significant risk of complications. Proper patient selection, thorough discussion of risks and benefits, and referral to high-volume centers are mandatory to achieve optimal outcomes and minimizing complications., Trial Registration: PROSPERO database registration CRD42022360758., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice., Materials and Methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured., Results: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%)., Conclusions: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Functional and surgical outcomes after surgical correction of adult acquired buried penis (AABP) are limited in the current literature. We retrospectively recruited patients underwent surgical treatment of AABP in a single institution from 2017 to 2021. Surgical repair was classified according to surgical complexity following Pariser-Santucci's classification. The primary endpoint of the study was the recurrence-free rate survival. The secondary endpoints were surgical, functional and patients' reported outcomes. Overall 28 patients were included in the study. Median follow-up was 27.5 (18.5-34.5). The most common complaints at presentation were sexual (53.6%) and voiding (39.3%) dysfunction. Surgical management steps ranged from circumcision to more complex procedures, such as suprapubic fat pad excision, abdominoplasty and/or penile shaft skin grafting. Overall postoperative complications were recorded in 32.1%. High-grade complications (Clavien≥3) occurred in 7.1%. One-year recurrence-free survival was 88.7%. Postoperatively IPSS and IIEF-15 questionnaires showed a significant improvement in urinary 8 (0-12) vs 2 (0-3), p = 0.03 and sexual function 37 (23-68) vs 68 (45-72), p = 0.001 respectively. Overall, patients reported functional improvement and 93.8% experienced a positive impact of QoL. AABP surgical repair, despite the high incidence of complications, seems to allow satisfactory outcomes and a significant improvement in patients' QoL., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Like all surgeries, penile prosthesis implantation (PPI) has the potential for both postoperative complications and suboptimal patient satisfaction. In order to assess risk factors for poor satisfaction, we reviewed patients who had been prospectively recruited in a national multi-institutional registry of penile prostheses procedures (INSIST-ED) from 2014 to 20121. Patient baseline characteristics and postoperative complications were recorded. The primary endpoint of this study was unfavorable outcomes after inflatable PPI, defined as significant postoperative complications (Clavien-Dindo ≥2) and/or Sexuality with Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) scores below the 10th percentile. A total of 256 patients were included in the study. The median age was 60 years (IQR 56-67). The most common cause of erectile dysfunction (ED) was organic (42.2%), followed by pelvic surgery/radiotherapy (39.8%) and Peyronie's disease (18.0%). Postoperative complications were recorded in 9.6%. High-grade complications (Clavien ≥2) occurred in 4.7%. At 1-year follow-up, the median QoLSPP total score was 71 (IQR 65-76). In all, 14.8% of patients were classified as having experienced unfavorable outcomes because of significant postoperative complications and/or QoLSPP scores below the 10th percentile. Logistic regression analysis demonstrated patient age to be non-linearly associated with the risk of experiencing unfavorable outcomes. A U-shaped correlation showed a lower risk for younger and older patients and a higher risk for middle-aged men. ED etiology and surgical volume were not associated with PPI outcomes. Physicians should, therefore, be aware that middle-aged men may be at higher risk of being unsatisfied following PPI compared to both younger and older patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Total phallic construction with radial artery forearm free-flap (RAFFF) is widely regarded as the gold standard approach for phalloplasty. However, donor-site morbidity remains a significant concern, which is typically managed by using a full-thickness skin graft (FTSG) on the forearm. Split thickness skin grafts (STSG) have been proposed as an alternative, along with the use of an acellular dermal matrix substitute. A retrospective comparative analysis was performed to assess the differences in operative, functional and cosmetic outcomes between FTSG (Group A) and the combination of acellular dermal matrix with STSG (Group B). A retrospective cohort study was conducted on all patients who underwent total phallic construction with RAFFF, between 2016 and 2021. Post-operative surgical and functional outcomes were evaluated using validated tools. A total of 34 patients were included in the study, with 18 patients (52.9%) in Group A and 16 patients (47.1%) in Group B. Group B demonstrated a significant advantage in terms of healing time (24 days vs. 30 days, p = 0.003) and complete graft take (93.8% vs. 27.8%, p = 0.001). Group B also had significantly shorter operative times (310 min vs. 447 min, p = 0.001) and a reduced median hospital stay (8 days vs. 10 days, p = 0.001). Satisfaction with cosmesis was significantly higher in Group B (93.8% vs. 66.7%, p = 0.048)., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition., Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method., Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated., Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Introduction: Neurological disease is a known entity for causing erectile dysfunction (ED). Pharmacological therapies are not always effective these patients - penile prosthesis implant (PPI) is an established surgical treatment option. For a variety of reasons, neurological patients may experience differing outcomes of PPI compared to those whose ED arises from other causes. We investigated outcomes of PPI in neurological patients using the Italian multi-institutional national registry of penile prostheses [Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED)]., Methods: Patients undergoing PPI were investigated via the INSIST-ED registry, from 2014 to 2021. Data were prospectively recorded by 45 surgeons on a dedicated website (www.registro.andrologiaitaliana.it) and reviewed by a data manager. We subselected patients with neurological disease undergoing PPI for ED, and these patients were reviewed at 3, 6, and 12 months, and annually thereafter. Postoperative complications and functional outcomes were evaluated through validated questionnaires [International Index of Erectile Function-5 (IIEF-5), Sexual Encounter Profile 2-3, and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS)]. A nonvalidated questionnaire was administered to assess patient satisfaction., Results: A total of 33 patients were included with a median age of 49 [interquartile range (IQR) 41-55]. Median follow-up was 83 months (IQR 67-99.5). A penoscrotal approach for PPI was performed in most cases (90.9%), while infrapubic was used in three cases (9.1%). Inflatable and malleable devices were implanted in 30 (90.9%) and 3 cases (9.1%), respectively. Intraoperative complications occurred in one case (3%). Early postoperative complications (<90 days) were observed in three cases (9.1%): two wound dehiscence (Clavien-Dindo G1 and G3a respectively) and one device infection requiring prosthesis explant (Clavien-Dindo G3a). Mechanical failures of inflatable devices were not observed during the follow-up period. Median IIEF-5 before surgery was 8 (IQR 7-9). At the latest follow-up, IIEF-5 was 22 (IQR 19-23.5), and median EDITS was 79 (IQR 64-88). A total of 28 patients (84.8%) self-reported to be fully satisfied with the PPI., Conclusion: Although PPI in the neurological population has been historically considered to be at increased risk, in our study, PPI complications and infections rates in this cohort did not differ from general population., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Alzheimer's disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial origin, current targeted treatments have only managed to reduce or control symptoms, and to date, only two drugs are close to being able to halt its progression. For decades, natural compounds produced by living organisms have been at the forefront of research for new therapies. Mushrooms, which are well-known for their nutritional and medicinal properties, have also been studied for their potential use in the treatment of AD. Natural products derived from mushrooms have shown to be beneficial in several AD-related mechanisms, including the inhibition of acetylcholinesterase (AChE) and β-secretase (BACE 1); the prevention of amyloid beta (Aβ) aggregation and neurotoxicity; and the prevention of Tau expression and aggregation, as well as antioxidant and anti-inflammatory potential. Several studies in the literature relate mushrooms to neurodegenerative diseases. However, to the best of our knowledge, there is no publication that summarizes only AD data. In this context, this review aims to link the therapeutic potential of mushrooms to AD by compiling the anti-AD potential of different mushroom extracts or isolated compounds, targeting known AD-related mechanisms.

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations., Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus., Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing., Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Background and Objectives : The peak of incidence of testicular cancer (TC) occurs among individuals in their reproductive age, emphasizing the importance of fertility preservation as an integral aspect of disease management. Sperm cryopreservation performed before orchiectomy is ineffective in azoospermic men, necessitating alternative approaches such as microdissection testicular sperm extraction (mTESE) at the time of orchiectomy (onco-mTESE) to obtain viable sperm. This study presents the findings from our institution's experience with onco-mTESE and critically discusses our results in light of the existing body of literature. Materials and Methods : This is a tertiary center retrospective analysis of onco-mTESE procedures performed at a single center between December 2011 and July 2022. The included patients were post-puberal men with testicular tumors requiring orchiectomy, along with concomitant severe oligozoospermia or azoospermia. Bilateral mTESE was performed in all cases. Surgical outcomes, sperm retrieval rates, the usage of preserved viable sperm, assistive reproductive techniques' results, and post-operative serum testosterone were recorded. Results : A total of nine patients were included, with a median age of 34 (IQR 29-36) years. All patients had germ cell tumors (GCTs), with seminomatous and non-seminomatous GCTs accounting for 44.4% ( n = 4) and 55.6% ( n = 5) of patients, respectively. Sperm retrieval occurred in three (33%) patients: one patient in the ipsilateral testis, one in the contralateral testis, and one in both testes. No complications were reported during the procedure, and no post-operative hypogonadism was observed. Among the three patients with successful sperm retrieval, an intracytoplasmic sperm injection (ICSI) was performed in two patients, resulting in two pregnancies, leading to one healthy live birth and one miscarriage. Conclusions : In the context of TC, it is essential to conduct a thorough evaluation of testicular function, including a semen analysis and cryopreservation. Onco-mTESE has proven its safety in preserving fertility in azoospermic cases while ensuring the efficacy of oncological treatment.

Background: The PICS technique (penile implant in combination with the sealing) was recently described as a valuable option to correct residual curvature during inflatable penile prosthesis (IPP) implantation in patients with complex Peyronie disease (PD)., Aim: To report the surgical and functional outcomes of the PICS technique in a multicentric series of patients., Methods: A consecutive series of patients with complex PD who underwent PICS were recruited. Patients were from 2 European tertiary referral centers. Data regarding baseline characteristics and perioperative, postoperative, and functional outcomes were retrospectively evaluated., Outcomes: Complete penile straightness, duration of operative time and hospital stay, as well as postoperative complications (including hematoma, IPP infection, and IPP mechanical failure) were recorded, whereas functional outcomes were evaluated through the administration of validated questionnaires at baseline and 12 months postoperatively: International Index of Erectile Function-5, Sexual Encounter Profile questions 2 and 3 (SEP-2 and SEP-3), and Erectile Dysfunction Inventory of Treatment Satisfaction., Results: Thirty-seven patients with a median age of 62 years (IQR, 57-70 years) were enrolled. Median preoperative curvature was 75° (IQR, 65°-77°). Median residual curvature after IPP implantation was 60° (IQR, 50°-70°). Overall, 31 patients (84%) achieved a totally straight penis. Only 6 patients (16%) experienced a residual penile curvature (<20° in all cases) after the procedure. No intraoperative complications were detected. Nine patients (24%) developed an early postoperative complication, 3 (8%) a transient fever, and 6 (16%) a genital hematoma. A single case of IPP acute infection requiring device explantation was recorded. The survey response rate was 100%. At the 12-month follow-up evaluation, the median IIEF-5 score was 23.5 (IQR, 22.2-25) with evident improvement vs the baseline value of 10 (IQR, 8-12). Accordingly, 92% of the patients responded positively to SEP-2 and SEP-3. For the Erectile Dysfunction Inventory of Treatment Satisfaction, patients recorded a median postoperative value of 25 (IQR, 21-30) 1 year after PICS., Clinical Implications: Complex PD is an end-stage disease featured by severe penile curvature, penile shortening, and erectile dysfunction: the gold standard approach is deemed to be penile prosthesis implantation, aiming to address penile curvature and erectile dysfunction, but in a limited percentage of cases, additional maneuvers are deemed necessary to manage residual penile curvature., Strengths and Limitations: Our study has some limitations: the retrospective nature, relatively short follow-up, and limited number of patients., Conclusion: The PICS technique may represent a reliable and effective treatment option to address significant residual curvature after IPP implantation., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Two-sided dorsal plus ventral oral graft urethroplasty is a new urethra-sparing technique suggested in tight bulbar strictures which are too severe for a simple one-side grafting. The aim of this study was to evaluate long-term outcomes and the success predictive factors of this technique., Methods: A descriptive retrospective study was conducted on 216 patients undergoing dorsal plus ventral graft urethroplasty for bulbar strictures between 2002 and 2018 in a single high-volume center by a single surgeon (EP). The primary outcome measure was stricture recurrence at follow-up. Surgical procedure was considered failed when any postoperative instrumentation was needed. Univariable and multivariable logistic regression analysis were performed., Results: Median follow-up was 98 months (IQR: 41-131). Among the 216 patients, 188 (87%) were successful and 28 (13%) were failures. Most of the failures (78.4%) were observed during the first 7 years of follow-up, afterward failures were less frequently recorded. Stricture length <1.5 cm and the absence of previous treatments resulted as independent success predictors (respectively P=0.04, OR=0.55 (0.29-0.99) and P=0.02, OR=0.23 (0.06-0.79). Age and stricture etiology were not significant predictors of surgical outcome. The limitation of our survey is that it is a retrospective single center experience. Multicentric experiences from different centers should be performed., Conclusions: After long-term follow-up in our wide series, the two-sided dorsal plus ventral oral graft bulbar urethroplasty showed a high success rate. Stricture length <1.5 cm and the absence of previous treatments resulted as independent success predictors.

Microdissection testicular sperm extraction (mTESE) has been proposed as a salvage treatment option for men with a previously failed classic TESE (cTESE), but data are scarce. We aimed to assess the outcome of and potential predictors of successful salvage mTESE in a cohort of men previously submitted to unfruitful cTESE. Data from 61 men who underwent mTESE after a failed cTESE between 01/2014 and 10/2020, at 6 tertiary-referral centres in Italy were analysed. All men were investigated with semen analyses, testicular ultrasound, hormonal and genetic blood testing. Pathological diagnosis from TESE was collected in every man. Descriptive statistics and logistic regression models were used to investigate potential predictors of positive sperm retrieval (SR+) after salvage mTESE. Baseline serum Follicle-Stimulating hormone (FSH) and total testosterone levels were 17.2 (8.6-30.1) mUI/mL and 4.7 (3.5-6.4) ng/mL, respectively. Sertoli-cell-only syndrome (SCOS), maturation arrest (MA) and hypospermatogenesis were found in 24 (39.3%), 21 (34.4%) and 16 (26.2%) men after cTESE, respectively. At mTESE, SR+ was found in 30 (49.2%) men. Patients with a diagnosis of hypospermatogenesis had a higher rate of SR+ (12/16 (75%)) compared to MA (12/21 (57.1%)) and SCOS (6/24 (25%)) patients at mTESE (p < 0.01). No clinical and laboratory differences were observed between SR+ and SR- patients at mTESE. There were no significant complications after mTESE. At multivariable logistic regression analysis, only hypospermatogenesis (OR 9.5; p < 0.01) was independently associated with SR+ at mTESE, after accounting for age and FSH.In conclusion, salvage mTESE in NOA men with previous negative cTESE was safe and promoted SR+ in almost 50%. A baseline pathology of hypospermatogenesis at cTESE emerged as the only independent predictor of positive outcomes at salvage mTESE., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To report our experience with the non-transecting dorsal mucosal anastomosis plus ventral oral graft urethroplasty (NTAVOG) for the repair of tight bulbar urethral strictures., Methods: Data of 68 men with tight bulbar strictures underwent NTAVOG urethroplasty between 2012 and 2019 were retrospectively revised. The urethra was opened ventrally; the dorsal scarred mucosa was excised preserving the spongiosum; the mobilized mucosal edges were anastomosed to recreate the dorsal urethral plate; the repaired urethral plate was augmented by the ventral oral graft and the spongiosum was closed over it. Successful urethral reconstruction was defined as normal voiding without the need for any postoperative procedure. Sexual function was investigated using a validated questionnaire., Results: Median follow-up was 58 months (IQR 38-63) and mean stricture length was 1 cm (IQR 1-1.5). Of 68 cases, 56 (82.4%) were successful and 12 (17.6%) were failures requiring re-treatment. At multivariable analysis, no preoperative factor was significantly associated with recurrence. None of the preoperatively sexually active 53 patients reported postoperative erectile impairment and all were satisfied with their sexual life. The main limitation is the retrospective design., Conclusions: In cases of tight bulbar stricture, the NTAVOG urethroplasty provides adequate urethral augmentation by preserving the spongiosum and avoiding postoperative sexual complications. We presented a series of patients undergone non-transecting dorsal anastomosis plus ventral oral graft urethroplasty for tight bulbar stricture. This treatment seems to be safe and with limited postoperative complications thanks to the preservation of the corpus spongiosum., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: One-stage buccal mucosa graft urethroplasty (BMGU) is advised for non-obstructing, simple penile strictures due to lichen sclerosus (LS), while a multistage approach is preferred for most complex cases. Our study aims to evaluate long-term treatment outcomes and patient-reported outcomes (PROs) in patients undergoing multistage BMGU for LS-associated penile strictures., Methods: This is a retrospective analysis of prospectively collected data on multistage penile BMGU from 2001. All patients underwent a 2-stage (2St) or 3-stage (3St) BMGU with the final closure of the urethral plate. PROs were collected from a pre-defined questionnaire., Results: Twenty patients were successfully treated, while five experienced recurrence. If a first-stage Johanson was only performed, a 3St-BMGU was more likely, and higher treatment success was observed. A time course between the first and last stages shorter than 12 m was an independent predictor of treatment failure. Patients reported high overall satisfaction and urinary flow improvement. Sexual life was not significantly affected, while aesthetic appearance was the most affected dimension., Conclusions: Staged approaches have satisfactory treatment success rates, likely depending on the duration from the first to the last stage. PROs do not differ based on the number of stages performed, and overall satisfaction with the procedure is high.

Microginins are a large family of cyanobacterial lipopeptide protease inhibitors. A hybrid polyketide synthase/non-ribosomal peptide synthetase biosynthetic gene cluster (BGC) found in several microginin-producing strains─ mic ─was proposed to encode the production of microginins, based on bioinformatic analysis. Here, we explored a cyanobacterium, Microcystis aeruginosa LEGE 91341, which contains a mic BGC, to discover 12 new microginin variants. The new compounds contain uncommon amino acids, namely, homophenylalanine (Hphe), homotyrosine (Htyr), or methylproline, as well as a 3-aminodecanoic acid (Ada) residue, which in some variants was chlorinated at its terminal methyl group. We have used direct pathway cloning (DiPaC) to heterologously express the mic BGC from M. aeruginosa LEGE 91341 in Escherichia coli , which led to the production of several microginins. This proved that the mic BGC is, in fact, responsible for the biosynthesis of microginins and paves the way to accessing new variants from (meta)genome data or through pathway engineering.

Background: Low-chance retrieval non-obstructive azoospermic (NOA) patients are a subpopulation of NOA patients. The objective of this study is to compare the surgical outcome of microsurgical-assisted testicular sperm extraction (M-TeSE) and combined trifocal/M-TeSE in low-chance retrieval NOA patients. Material and Methods: A single-center retrospective analysis of NOA patients who underwent testicular sperm extraction was performed. Low-chance retrieval NOA (testicular volume < 10 cc and FSH > 12.4 UI/L) was set as the inclusion criteria. Re-do TeSE procedures were excluded from the current analysis. Data were extrapolated from clinical records and operative notes. We compared data from patients who underwent classic M-TeSE (group A) with that from patients submitted to combined trifocal/M-TeSE (group B). Sperm retrieval rate (SRr) was the primary outcome of the study. Surgical outcomes and postoperative complications were evaluated. A multivariate analysis was conducted to investigate predictive factors for positive SR. Results: Overall, 80 patients (60 patients in Group A and 20 patients in Group B) fulfilled the inclusion criteria. The average (SD) age was 35 (8.2) years. The average preoperative FSH was 27.5 (13) UI/L. The average testicular volume was 6.3 (3) cc on the left side and 6.8 (2.5) cc on the right. Groups were similar in terms of preoperative parameters. The overall SRr was 28%. Patients in group B had higher SRr than those in group A (29.4% vs. 26.9%, p < 0.03). We identified a significant association between testicular histopathology and positive SR (hypospermatogenesis 100%, spermatogenic arrest 32%, and Sertoli cell-only syndrome 22%). The histopathology report was the only significant predicting factor for SR in the multivariate analysis. Conclusion: The combined trifocal and M-TeSE approach is safe and may represent a valuable approach to enhance the SRr in low-chance retrieval NOA. The histopathology report is confirmed to be the only valuable predicting factor for a positive SR.

Objective: To report surgical, functional and patient reported outcomes(PROs) of glansectomy(GS), and split-thickness skin graft(STSG) reconstruction in case of locally invasive penile cancer(PC) MATERIALS AND METHODS: A retrospective analysis from May 2015 to August 2019 was conducted. Inclusion criteria were age<80, a "de novo" malignancy, clinically confined PC (≤T2) with histologic confirmation. Complications, recurrence-free(RFS), cancer-free(CFS) and overall survival(OS) were described. Functional outcomes and PROs were explored using validated questionnaires and "ad hoc" created questionnaire respectively. Kaplan-Meier analysis, t-Student and the Mann-Whitney U test were used to estimate survival and postsurgical functional changes respectively., Results: 34 patients were enrolled. Median follow-up was 12(IQR:12-41) months. Positive surgical margins were detected in 2.9% of cases, requiring salvage surgery. Postoperative complications occurred in 29.4%, most commonly being a graft partial loss (17.6%), meatal stenosis (5.8%) or genital wound infection (5.8%). Disease recurrence occurred in 17.6% of cases with a median elapsed time of 16 months (12-41). 12-month RFS was 88.2%, whilst CSS and OS were 91% at the same time point. Glans sensation was preserved in 91.2% of cases. 88.2% of patients reported to be fully satisfied with the postoperative aesthetic appearance of the penis, 91.2% of patients would recommend the same procedure to someone else. Limitations include retrospective design and the lack of a control group CONCLUSION: GS with STSG minimizes the impact on urinary and sexual functions without jeopardizing oncological control in locally advanced PC., Competing Interests: CONFLICT OF INTEREST None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Patients with Peyronie's disease may experience significat distress. The choice of treatment depends on a variety of factors, including the stage of the disease, the presence of pain, severity and direction of the curvature, penile length and the quality of erectile function., Aim: To review the evidence associated with surgical treatment of Peyronie`s Disease and provide clinical recommendations on behalf of the European Society for Sexual Medicine. 131 peer-reviewed studies and systematic reviews, which were published from 2009 to 2019 in the English language, were included., Methods: MEDLINE, Google Scholar and EMBASE were searched for randomized clinical trials, meta-analyses, open-label prospective and retrospective studies., Main Outcome Measure: The panel provided statements on clinically relevant questions including patient involvement in the decision process, indications for surgery, choice of the approach, and the management of patient expectations. A comparison of the different grafts used in patients who have undergone plaque incision/excision and grafting in order to identify an ideal graft, has been carried out. The prevalence of postoperative complications has been summarized. Levels of evidence were provided according to the Oxford 2011 criteria and Oxford Centre for Evidence-Based Medicine recommendations., Results: In order to allow shared decision making, a patient preoperative counselling regarding the pros and cons of each intervention is recommended. In particular, adverse effects of surgical treatments should be discussed to set realistic understanding and expectations of surgical outcomes and ultimately improve postoperative satisfaction rates. Surgical treatment should be only offered in the chronic phase of the condition, when the deformity and/or degree of erectile dysfunction, prevent patients from engaging in satisfying sexual interaction, or if the deformity is the cause of severe bother., Conclusions: Current European Society for Sexual Medicine recommendations cover several aspects of Peyronie's disease treatment. These recommendations aim both to ensure patients and partners have accurate and realistic expectations of their treatment options, as well as to formulate algorithms to guide clinician management pathways. Osmonov D, Ragheb A, Ward S et al, ESSM Position Statement on Surgical Treatment of Peyronie's Disease. Sex Med 2022;10:100459., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

The Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) holds a vast number of cyanobacteria whose chemical richness is still largely unknown. To expedite its bioactivity screening we developed a natural products library. Sixty strains and four environmental samples were chromatographed, using a semiautomatic HPLC system, yielding 512 fractions that were tested for their cytotoxic activity against 2D and 3D models of human colon carcinoma (HCT 116), and non-cancerous cell line hCMEC/D3. Six fractions showed high cytotoxicity against 2D and 3D cell models (group A), and six other fractions were selected by their effects on 3D cells (group B). The metabolome of each group was organized and characterized using the MolNetEnhancer workflow, and its processing with MetaboAnalyst allowed discrimination of the mass features with the highest fold change, and thus the ones that might be bioactive. Of those, mass features without precedented identification were mostly found in group A, indicating seven possible novel bioactive molecules, alongside in silico putative annotation of five cytotoxic compounds. Manual dereplication of group B tentatively identified nine pheophytin and pheophorbide derivatives. Our approach enabled the selection of 7 out of 60 cyanobacterial strains for anticancer drug discovery, providing new data concerning the chemical composition of these cyanobacteria.

From 2012, the World Professional Association Transgender Health defined a structured therapeutic path and standards of care for transgender patients undergoing genital gender affirming surgery (GGAS). The main goal of GGAS in transgender males is to provide patients with an aesthetically appealing appearance of the neophallus that should allow standing micturition and enabling penetrative intercourse along with erogenous and tactile sensitivity. The optimal procedure should be safe, reproducible and performed in the fewest number of surgical stages. The ideal technique for total phallic construction (TPC) has not yet been demonstrated; TPC remains challenging and, from a functional point of view, it is also make more demanding as yet there are no perfect replacement materials for erectile and urethral tissues. Several procedures and different type of flaps (pedicled and free-flaps) have been proposed and investigated over time to address TPC with significant advances over the years especially after microsurgical procedures introduction. Due to its high complexity TPC is not free from complications. Local tissue ischaemic complications, complete and partial flap loss, donor site morbidity and urethral complications (fistulae and strictures) are reported. This narrative review aims to provide the readers with a contemporary overview of surgical procedures for TPC in transgender males focusing on key surgical steps, as well as surgical and functional outcomes., Competing Interests: Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1340). The series “Controversies and Considerations of Penile Surgery” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Background: Whilst there is a trend away from aggressive nonorgan sparing surgical treatments for malignant penile disease, a variety of penile preservation options exist but functional outcomes and patient reported outcomes (PROs) in this area are poorly reported to date., Aim: The aim of this study is to report functional outcomes and PROs of total glans resurfacing (TGR) in a consecutive series of patients with lichen sclerosis (LS) or localized penile cancer (PC)., Methods: From 2004 to 2018 a consecutive series of patients underwent TGR for the management of LS or localized PC in a tertiary referral network. Patient clinical records and operative notes were retrospectively reviewed. Statistical analysis was conducted with Stata 12., Outcomes: Urinary and sexual outcomes were recorded utilizing both the International Index of Erectile Function (IIEF) and International Prostate Symptom Score (IPSS) validated questionnaires while PROs were extrapolated from a 5-item "ad hoc" telephone questionnaire administered at 1 year post procedure., Results: 37 consecutive patients were enrolled. Histology results demonstrated LS in 16 patients, with the remaining 21 having a diagnosis of PC. The most common reasons for patient presentation were local pain (32.4%), pruritus (37.8%) and bleeding (29.7%). Median follow-up was 22 (IQR 13-77) months. Median age was 62 (IQR 55-68). Neither of the questionnaires assessing urinary and sexual function showed any significant deterioration after surgery. Glans sensitivity was fully maintained in 89.2% of cases. 94.5% of patients reported to be fully satisfied with the aesthetic appearance of the penis and would consider undergoing the same procedure again if necessary. 91.9% of patients would recommend the same procedure to someone else. An overall improvement of the quality of life was reported by 86.4% of patients., Clinical Implications: TGR should be considered a treatment of choice for selected cases of benign or malignant penile lesions STRENGTHS AND LIMITATIONS: Our study has some limitations, the first being its retrospective nature. Furthermore, despite being one of the largest series to date, follow-up duration is somewhat limited and a control group is lacking., Conclusion: TGR represents an excellent surgical option ensuring satisfactory voiding and sexual function, as well as cosmesis for selected cases of penile lesions. M. Preto, M. Falcone, G. Blecher, et al. Functional and Patient Reported Outcomes Following Total Glans Resurfacing. J Sex Med 2021;18:1099-1103., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

In recent years, extensive sequencing and annotation of bacterial genomes has revealed an unexpectedly large number of secondary metabolite biosynthetic gene clusters whose products are yet to be discovered. For example, cyanobacterial genomes contain a variety of gene clusters that likely incorporate fatty acid derived moieties, but for most cases we lack the knowledge and tools to effectively predict or detect the encoded natural products. Here, we exploit the apparent absence of a functional β-oxidation pathway in cyanobacteria to achieve efficient stable-isotope-labeling of their fatty acid derived lipidome. We show that supplementation of cyanobacterial cultures with deuterated fatty acids can be used to easily detect natural product signatures in individual strains. The utility of this strategy is demonstrated in two cultured cyanobacteria by uncovering analogues of the multidrug-resistance reverting hapalosin, and novel, cytotoxic, lactylate-nocuolin A hybrids-the nocuolactylates., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

In the present study we aimed to investigate the surgical outcomes of patients with persistent penile curvature (PC) after Collagenase Clostridium histolyticum (CCH) intraplaque injections. Data from 90 patients with persistent PC after CCH in a multicentre study from 6 andrological centres were retrospectively reviewed. Three standardized surgical techniques were performed. Group 1: plaque incision grafting (PIG) with penile prosthesis implant (PPI); Group 2: PIG without PPI; Group 3: Nesbit technique. Hospital stay, operative time, postoperative complications and PC persistency/recurrence (> 20°) were evaluated. Overall satisfaction and functional outcomes were assessed through International Index of Erectile Function-Erectile Function (IIEF-EF), Peyronie's Disease Questionnaire (PDQ), Female Sexual Function Index (FSFI) administered pre and 3 months postoperatively. Of all, 25 (27.8%) patients received grafting procedure + PPI (Group 1), 18 (20.0%) patients belonged to Group 2, and 47 (52.2%) to Group 3. Bovine pericardium graft and collagen fleece have been used in in 22 (51.2%) and 21 (48.8%) patients, respectively. Median penile length after surgery was 13.0 cm (IQR 12.0-15.0). After surgery, Group 1 showed higher increase in penile length after surgery and better improvements in terms of PDQ-PS. In contrast, both IIEF-EF and FSFI scores did not differ among groups. Overall, 86 (95.6%) did not report any complication. 4 (4.4%) patients had PC recurrence; of those, 2 (8.0%), 1 (5.6%) and 1 (2.1%) cases were observed in Group 1, Group 2 and Group 3, respectively. In case of persistent PC after CCH, surgical correction by grafting with or without concomitant PPI or Nesbit technique emerged as a technically feasible, effective and safe procedure, with no significant postoperative complications.

A variety of approaches are available to address a genital gender affirming surgery (GGAS) in transgender men. The aim of the present study is to report surgical and functional outcomes after a suprapubic pedicled phalloplasty (SPP). From November 2008 to August 2018, a consecutive series of 34 patients underwent an SPP in two tertiary referral centers. GGAS was conducted as a multistaged procedure, consisting (1) SPP with subsequent radial artery-based forearm free-flap urethroplasty, (2) glans sculpting, urethral anastomosis, and scrotoplasty, and (3) penile prosthesis implantation. The duration of surgery, intra and postoperative complications, and hospital stay were selected as variables for surgical outcomes. Functional outcomes were extrapolated from a four-item questionnaire.A partial necrosis of phallus was detected in two cases (5.8 %). Two cases of seroma formation with wound dehiscence (5.8%) were detected. Overall, 89% of patients declared to be fully satisfied of the SPP, 83% would recommend the procedure to someone else, and 89% would undergo the same procedure again. Overall, 66% of patients could achieve an orgasm during sexual penetrative intercourses. The retrospective design, the lack of randomization and validated questionnaire for outcomes reporting, and the limited follow-up represent the main drawbacks of our study. Our evidences suggest that SPP represents as an acceptable option for GGAS., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To report surgical and oncological outcomes of total glans resurfacing in a consecutive series of superficial penile cancers., Design, Settings and Partecipants: 26 patients were enrolled in the present trial. A retrospective analysis was conducted. Inclusion criteria were age < 80, "de novo" malignancy, clinically suspected superficial disease and disease confirmation by a penile biopsy. Clinically palpable corporeal or urethral involvement, high histological grade, clinically palpable nodes on physical examination and unwillingness to comply with follow-up were considered as exclusion criteria., Outcome Measurements and Statistical Analysis: Descriptive features and surgical outcomes were extrapolated from the clinical records. The categorical variables were described using frequency and percentage, and the continuous variables were described using median and interquartile range (IQR) value. Kaplan-Meier analysis was used to estimate survival over time., Results and Limitations: Median follow-up was 38 (IQR 13-86) months. Median age was 65 (IQR 55-68). An history of lichen sclerosus was reported by 50% of patients. No intraoperative complications were reported. Median hospital stay was 5 (IQR 2-6) days. Final histology confirmed superficial disease in 42.4% and T1 in 53.8%. T2 was detected in a single case. Postoperative complications were minimal (3.8%). No regional nodal recurrence was reported. At Kaplan-Meier analysis, overall survival rate was 100% at 1 year, 1-year recurrence free survival was 96.1% and 2-year recurrence free survival was 88.5%., Conclusion: Total glans resurfacing may represent an excellent option for organ preserving surgery in patients with a superficial penile cancer. Surgical and oncological outcomes proved to be satisfactory., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Radial artery forearm free-flap (RAFFF) phalloplasty is considered by most authors as the gold-standard technique for genital gender-affirming surgery (GGAS). RAFFF surgical complications have rarely been investigated, and the aim of this study and literature review is to analyse and focus on the surgical technique and its postoperative vascular complications. From May 2016 to January 2020, a consecutive series of 25 transgender men who underwent GGAS were enrolled in the present study. Age, BMI and smoking habits were recorded for all patients. Overall, vascular flap complications occurred in 20% of cases. Complete flap loss due to acute arterial thrombosis was recorded in a single case (4%). In 8% of cases, limited ventro-proximal arterial ischaemia was detected, while in the remaining 8% of cases, venous ventral ischaemia was reported. These results were compared with the current literature results. Indeed, from our analysis, the number of flap veins (<2) was the only predictive factor for vascular complications. In conclusion, RAFFF represents a reliable option for total phallic construction, leading to satisfactory results in terms of flap survival. To optimize the surgical outcomes, venous vascular drainage should be recommended., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Introduction and Objectives: Adult patients with Klinefelter syndrome (KS) may present with testicular volume loss and a decrease in circulating testosterone (T) levels. However, the actual rate of hypogonadism in adult KS men is unknown. We aimed to (a) assess the prevalence of different forms of hypogonadism in a cohort of KS patients with non-obstructive azoospermia (NOA); and (b) investigate potential preoperative predictor of positive sperm retrieval (SR) at surgery in the same cohort of men., Methods: Complete data from 103 KS men with NOA who underwent testicular sperm extraction (TESE) between 2008 and 2019 at five centers were analyzed. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients were categorized into four groups of hypogonadism as follows: eugonadism [normal total T (tT) (≥3.03 ng/mL) and normal luteinizing hormone (LH) (≤9.4 mUI/mL)], secondary hypogonadism [low tT (≤3.03 ng/mL) and low/normal LH (≤9.4 mUI/mL)], primary hypogonadism [low tT (≤3.03 ng/mL) and elevated LH (≥9.4 mUI/mL)], and compensated hypogonadism [normal tT (≥3.03 ng/mL) and elevated LH (≥9.4 mUI/mL)]. Descriptive statistics tested the association between clinical characteristics and laboratory values among the four groups., Results: Median (IQR) patients age was 32 (24, 37) years. Baseline follicle-stimulating hormone and tT levels were 29.5 (19.9, 40.9) mUI/mL and 3.8 (2.5, 11.0) ng/mL, respectively. Eugonadism, primary hypogonadism, and compensated hypogonadism were found in 16 (15.6%), 34 (33.0%), and 53 (51.4%) men, respectively. No patients had secondary hypogonadism. Positive SR rate at TESE was 21.4% (22 patients); of 22, 15 (68.2%) patients underwent assisted reproductive technology and five (22.7%) ended in live birth children. Patients' age, BMI, CCI, FSH levels, and positive SR rates were comparable among hypogonadism groups. No preoperative parameters were associated with positive SR at logistic regressions analysis., Conclusions: Findings from this cross-sectional study showed that 15.6% of adult KS men have normal tT values at presentation in the real-life setting. Most KS patients presented with either compensated or primary hypogonadism. Sperm retrieval rates were not associated with different forms of hypogonadism., (© 2020 American Society of Andrology and European Academy of Andrology.)

The use of natural products in skin care formulations gained interest as a concern for modern societies. The undesirable side effects of synthetic COMPOUNDS, as well as the associated environmental hazards, have driven investigation on photosynthetic organisms as sustainable sources of effective and environmentally friendly ingredients. The use of natural extracts in cosmetics has been highlighted and, along with plants and algae, cyanobacteria have come into focus. Due to their low culture demands, high grow rates and ability to produce a wide variability of bioactive metabolites, cyanobacteria emerged as an economic and sustainable base for the cosmetic industry. In this study, we evaluated the potential of ethanol extracts of picocyanobacteria strains of the genera Cyanobium and Synechocysti s and filamentous strains of the genera Nodosilinea , Phormidium and Tychonema for skin applications, with focus in the field of anti-aging. The extracts were analyzed for their pigment profile, phenolic content, antioxidant potential, cytotoxicity against keratinocytes (HaCat), fibroblasts (3T3L1), endothelial cells (hCMEC/D3) and capacity to inhibit hyaluronidase (HAase). The total carotenoid content ranged from 118.69 to 383.89 μg g -1 of dry biomass, and the total phenolic content from 1.07 to 2.45 mg GAE g -1 . Identified carotenoids consisted of zeaxanthin, lutein, canthaxanthin, echinenone and β-carotene, with zeaxanthin and lutein being the most representative (49.82 and 79.08 μg g -1 , respectively). The highest antioxidant potential was found for Phormidium sp. LEGE 05292 and Tychonema sp. LEGE 07196 for superoxide anion radical (O 2 •- ) scavenging (IC 50 of 822.70 and 924 μg mL -1 , respectively). Low or no cytotoxicity was registered. Regarding HAase inhibition, Tychonema sp. LEGE 07196 and Cyanobium sp. LEGE 07175 showed the best IC 50 (182.74 and 208.36 μg mL -1 , respectively). In addition, an increase in fibroblast proliferation was registered with these same strains. From this work, the ethanol extracts of the species Tychonema sp. and Cyanobium sp. are particularly interesting for their potential application in anti-aging formulations, once they stimulated fibroblast proliferation and inhibit hyaluronic acid digestion.

Background: Nesbit corporoplasty was proposed to address penile curvature (PC), both congenital (CPC) and acquired (APC)., Aim: To evaluate surgical, functional, and patient reported outcomes (PROs) of a modified corporoplasty., Methods: From May 2005 to January 2017, a consecutive series of patients underwent a modified corporoplasty. Data were retrospectively extrapolated. Intra and postoperative complications and hospital stay were recorded as surgical outcomes. 2 validated international questionnaires were administered preoperatively and at 12 months after surgery: International Index of Erectile Function and Sexual Encounter Profile (items 2-3). An "ad hoc" questionnaire was utilized to assess PROs., Outcomes: Postoperative surgical and functional outcomes and PROs were the primary outcomes assessed in this study., Results: 87 out of 145 patients had complete data available and were included in the study. CPC was noted in 61 patients whilst APC, secondary to Peyronie's disease, was present in 26 patients. Median preoperative PC was 60° (interquartile range [IQR] 45-70). Functional and PROs were evaluated 12 months after surgery for all enrolled patients. Considering surgical outcomes, the median follow-up time was 110 months (IQR 27-132.5). Median operative time was 130 minutes for CPC (IQR 115-150) and 120 minutes for APC (IQR 95-140). Median hospital stay was 2 days for both groups (IQR 1-2). After the median follow-up time of 110 months (IQR 27-132.5), a recurrent curvature was observed in 9.2% of cases. Minor residual curvature (<20°) was detected in 13.8%. International Index of Erectile Function and Sexual Encounter Profile 2-3 scores improved in both groups. Long-term de novo postoperative erectile dysfunction was observed in 3.2% of CPC cases and in 38.5% in APC (P = .001). A multivariate analysis revealed that etiology (APC), patient age (>35 years), and postoperative complications represented independent risk factors for the development of postoperative erectile dysfunction. Postoperative complications, in terms of bleeding, infection, or poor esthetic wound healing, occurred in 12.6% of patients. No Clavien-Dindo grade III-IV intraoperative complications were reported. Postoperative hematoma was more frequent in CPC when compared to APC (P = .003). In relation to PROs, 26.4% of patients responded as being dissatisfied with postoperative penile length, with a higher incidence in the APC group (P = .001). Overall, a significant improvement in everyday and sexual life quality was observed in both categories., Clinical Implications: The modified corporoplasty described showed better residual curvature rates, whilst maintaining similar PROs even if APC patients reported less favorable outcomes when compared to CPC., Strengths & Limitations: The primary limitations of this study are its retrospective nature, no objective evaluation of postoperative curvature, and no penile length assessment., Conclusion: The aforementioned corporoplasty may represent an excellent option for PC correction, with low complication rate and high patient satisfaction. Falcone M, CerutiC, Preto M, et al. Long-Term Surgical, Functional, and Patient Reported Outcomes of a Modified Corporoplasty: A Tertiary Referral Center Experience. J Sex Med 2020;17:1779-1786., (Copyright © 2020 International Society for Sexual Medicine. All rights reserved.)

Objectives: To compare segmental ureterectomy (SU) and radical nephroureterectomy (RNU) in terms of overall survival (OS) and impact on postoperative renal function in patients treated for upper tract urothelial carcinoma (UTUC) of the ureter with preoperatively reduced estimated glomerular filtration rate (eGFR)., Materials and Methods: We retrospectively collected the data of consecutive patients treated for UTUC, in 6 Italian tertiary referral centers, from 2003 to 2013, and analyzed those treated with RNU or SU for ureteral cancer and with a preoperative eGFR <90 ml/min/1.73m 2 . The primary outcome was to compare the postoperative eGFR variation and the OS according to the surgical technique chosen., Results: Out of 521 patients with UTUC, 228 patients had preoperative reduced eGFR. Out of these patients, 93 had ureteral cancer and were included in the primary analyses - 67 (72.0%) treated with RNU and 26 (28.0%) with SU. Preoperative characteristics were similar in the 2 groups. The overall median follow-up period was 26.5 months. A nonsignificant postoperative eGFR decrease of 3.0 ml/min/1.73m 2 was found overall (P = 0.094), with nonsignificant difference between the 2 groups (P = 0.735). A comparable 5-year OS was calculated for RNU and SU patients (P = 0.99)., Conclusions: The type of surgery (SU vs. RNU) has a low impact on postoperative renal function and OS in patients with ureteral cancer and preoperative eGFR <90 ml/min/1.73m 2 . The indications for kidney sparing surgery for UTUC should be based on the surgical and oncological risks in these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)