[Congenital penile curvature: Guidelines from the Andrology and Sexual Medicine Committee of the French Association of Urology (CAMS-AFU)]. / Courbures congénitales du pénis : recommandations du Comité d'andrologie et de médecine sexuelle de l'Association française d'urologie.

INTRODUCTION: Guidelines regarding congenital penile curvature (CPC) are lacking, and this pathology has not been the subject of French recommendations to date. The Andrology and Sexual Medicine Committee (CAMS) of the French Association of Urology (AFU) propose a series of clinical practice recommendations (CPR) by answering five clinical questions concerning the diagnosis and treatment of this pathology. MATERIALS AND METHODS: After a bibliographic research between 2000 and 2021, followed by a critical reading according to the CRP method. These recommendations were written to answer five questions: (1) What are the different types of CPC? (2) What are the reasons for consultation? (3) What are the assessment methods for CPCs and their consequences? (4) What are the indications for CPCs treatment? (5) What are the corrective modalities for the treatment of CPC? RESULTS: There are two main phenotypes: CPC type 4 (the most common) and chordee without hypospadias. The diagnosis of CPC is clinical and established through enquiry and clinical examination associated with photos of the erect penis. Support can be offered if the curvature is responsible for a disability and/or sexual dissatisfaction linked to a deformation making penetration difficult and/or in the event of significant psychological impact. Only surgical treatments have demonstrated their effectiveness. For type 4 CPCs, corporoplasty (excisional, incisional, or incisionless techniques) is the gold standard. CONCLUSION: These recommendations provide support for the management of patients consulting with CPC.

Plasmonic Metasurfaces for Specific SERS Detection of Shiga Toxins.

The interest in the development of nanoscale plasmonic technologies has dramatically increased in recent years. The photonic properties of plasmonic nanopatterns can be controlled and tuned via their size, shape, or the arrangement of their constituents. In this work, we propose a 2D hybrid metallic polymeric nanostructure based on the octupolar framework with enhanced sensing property. We analyze its plasmonic features both numerically and experimentally, demonstrating the higher values of their relevant figures of merit: we estimated a surface-enhanced Raman spectroscopy (SERS) enhancement factor of 9 × 107 and a SPR bulk sensitivity of 430 nm/RIU. In addition, our nanostructure exhibits a dual resonance in the visible and near-infrared region, enabling our system toward multispectral plasmonic analysis. Finally, we illustrate our design engineering strategy as enabled by electron beam lithography by the outstanding performance of a SERS-based biosensor that targets the Shiga toxin 2a, a clinically relevant bacterial toxin. To the best of our knowledge, this is the first time that a SERS fingerprint of this toxin has been evidenced.

[French Urological Association (AFU) guidelines for Peyronie's disease assessment and treatment]. / Recommandations pour l'évaluation et la prise en charge de la maladie de Lapeyronie : rapport du comité d'andrologie et de médecine sexuelle de l'AFU.

INTRODUCTION: Peyronie's disease is a common cause for consultation in urology. Many controversies surround its treatment. No French Guidelines have been published so far. The Committee of Andrology and Sexual Medicine of the French Association of Urology therefore offers a series of evidence-based recommendations. MATERIALS AND METHODS: These recommendations are made according to the ADAPTE method, based on European (EAU, ESSM), American (AUA, ISSM) and Canadian (CAU) recommendations, integrating French specificities due to the availability of treatments, and an update of the recent bibliography. RESULTS: The assessment of the disease is clinical. Patients with functional impairment or significant psychological repercussions may be offered treatment. The benefits and drawbacks of each treatment should be explained to the patient. Regarding non-surgical treatments, no available treatment has market authorization in France. Vitamin E is not recommended. Analgesic (oral or low-intensity shock waves) or proerectile treatments may be offered as needed, as well as traction therapy. Due to the unavailability of collagenase injections, verapamil injections may be offered. Surgical treatments are to be considered in the stabilized phase of the disease, and consist of performing a plication, an incision-graft or the placement of a penile implant according to the patient's wishes, the curvature and the penis size, as well as erectile function. Combination treatments can be offered. CONCLUSION: The management of Peyronie's disease is complex, and the levels of evidence for treatments are generally low. The success of treatment will depend on the quality of the initial assessment, the patient's information and understanding of the expected effects, and the practitioner's experience.

[Recommendations of the Committee of Andrology and Sexual Medicine of the AFU concerning the management of andrological and sexual medicine pathologies during the COVID-19 crisis]. / Recommandations du Comité d'andrologie et de médecine sexuelle de l'AFU concernant la prise en charge andrologique et en médecine sexuelle en contexte et en sortie de crise sanitaire liée au COVID-19.

OBJECTIVE: To assist urologists in the management of andrological and sexual medicine pathologies during the COVID-19 crisis. MATERIAL AND METHOD: Use of the formalized consensus method. RESULTS: The medical and surgical management of patients in andrology and sexual medicine must be adapted. Consultations should, as far as possible, be carried out by tele-consultation. For operative procedures, the delay between the operative decision and the date of (re)scheduling of the procedure will depend on: (1) the level of criticality of the clinical situation; (2) the type of intervention; (3) the functional and psychological repercussions, including quality of life while waiting for the procedure; (4) the notion of losing the chance of having an optimal outcome; (5) the risk of potential complications from delaying a procedure for too long; and (6) taking into account the patient's risk factors for severe forms of COVID-19. The protection of urologists from COVID-19 should be considered. Each urologist must make the best decision for the patient, taking into account the acceptable time frame and quality of life impact before surgical management, the COVID risk parameters, the technical and anesthetic feasibility and the structural possibility of the health care institution to ensure a specific dedicated pathway during the COVID-19 health crisis. CONCLUSION: The management of andrological and sexual medicine pathologies must be adapted to the COVID-19 crisis context. Some patients may require surgery, including in emergency. These recommendations are transitional and will end with the COVID-19 crisis.

[Recommendations of the Committee of Andrology and Sexual Medicine of the AFU concerning the management of Varicocele]. / Recommandations du Comité d'Andrologie et de Médecine Sexuelle de l'AFU concernant la prise en charge de la Varicocèle.

The diagnosis of varicocele is clinical, carried out in supine and standing position and in Valsalva maneuver. Only clinical varicoceles have to be treated. A scrotal ultrasound with Doppler is generally performed as part of the infertile man's evaluation or in case of examination difficulties. The main indication for varicocele treatment is the adult man with clinical varicocele and abnormalities of sperm parameters, in a context of infertility of couple, with a partner having a satisfactory ovarian reserve and no cause of female infertility or a curable infertility cause. The decision to treat varicocele must therefore be taken after evaluation of the two partners of the couple. Adults with symptomatic varicocele and those with spermogram abnormalities may also be offered a cure for their varicocele even in the absence of a paternity plan, as well as adolescents with reduced testicular growth, an ipsilateral decrease testicular volume, or a size gradient between the 2 testes. The cure of varicocele can be carried out by surgery or by percutaneous embolization. Microsurgery (inguinal or subinguinal) offers lower rates of recurrence and complications than high surgical approaches (laparoscopic or not) and surgeries without magnification. It is therefore the reference surgical technique. Percutaneous retrograde embolization is a minimally invasive alternative to microsurgery offering satisfactory outcomes with rare and often benign complications. The cure for varicocele results in an improvement in sperm parameters and recent data seem to confirm that it increases the natural pregnancy rate. These results appear after a delay of 3 to 9 months (at least 1 to 2 cycles of spermatogenesis). When the sperm involvement was severe (azoospermia, severe oligospermia), the improvement of the spermogram allow (1) to avoid surgery testicular sperm extraction or (2) perform intrauterine insemination rather than ICSI.

[Biotherapies for erectile dysfunction and Peyronie's disease: Where are we now?] / Biothérapies pour les troubles de l'érection et la maladie de la Peyronie : ou en est-on ?

INTRODUCTION: Clinical trials of cell therapy for erectile dysfunction (ED) and Peyronie's disease (PD) were recently conducted after preclinical studies. AIMS: The aims of this study are to give an update on biotherapy for ED and PD and to describe the regulatory framework for these therapies. MATERIALS AND METHODS: A literature review was performed through PubMed and Clinical.trials.gov addressing cell therapy for ED and PD and using following keywords "erectile dysfunction", "Peyronie's disease", "stem cell", and "platelet-rich plasma". RESULTS: Preclinical studies in rodent models have shown the potential benefit of cell therapy for ED after radical prostatectomy or caused by metabolic diseases, and PD. The tissues used to obtain the therapeutic product were bone marrow, adipose tissue and blood (PRP, platelet-rich plasma). Mechanism of action was shown to be temporary and mainly paracrine. Four clinical trials were published concerning ED after radical prostatectomy and in diabetic patients and one for PD. Eleven clinical trials including three randomized trials are currently going on. Preclinical and preliminary clinical results suggested the possibility to improve spontaneous erectile function and response to pharmaceutical treatment in initially non-responder patients. This effect is mediated by an improvement of penile vascularization. A reduction of penile curvature without side effect was noted after injections into the plaque of PD patients. Most of these therapeutic strategies using autologous cells were considered as "Advanced Therapy Medicinal Products" with strict regulatory frameworks imposing heavy constraints, in particular in case of "substantial" modification of the cells. The regulatory framework remains unclear and more permissive for PRP and cell therapy processes with extemporaneous preparation/injection and no "substantial" modifications. CONCLUSIONS: First results on cell therapy for ED and PD are promising. The regulatory framework can significantly change according to cell preparations and origins leading to various constraints. This regulatory framework is crucial to consider for the choice of the procedure.

[Priapism: Diagnosis and management]. / Le priapisme : diagnostic et prise en charge.

OBJECTIVE: Our aim was to present a synthesis on the diagnosis and treatment of priapism. METHODS: For this purpose, a literature search was performed through PubMed to analyze literature reviews and guidelines regarding priapism. RESULTS: Priapism is an erection that persists more than 4hours. There are 3 types of priapism: ischemic priapism, non-ischemic priapism and recurrent (stuttering) priapism. Ischemic priapism, often idiopathic, is the most frequent. When diagnosed, an urgent management is required to limit erectile dysfunction. Sickle-cell patients are prone to have ischemic and stuttering priapism. Non-ischemic priapism usually occurs after perineal trauma. Priapism management depends on the type of priapism. Medical treatment (corporal aspiration and injection of sympathomimetics) then if failed, surgery are indicated for ischemic priapism. The persistence of a non-ischemic priapism most likely requires a radiologic embolization. CONCLUSION: Priapism is a condition that often requires emergency treatment to spare erectile function. It appears crucial to know this condition and its management.

Open prostatectomy versus 180-W XPS GreenLight laser vaporization: Long-term functional outcome for prostatic adenomas>80 g.

INTRODUCTION: GreenLight photoselective vaporisation of the prostate (PVP) offers an endoscopic alternative to open prostatectomy (OP) for treatment of large adenomas. This study compares long-term functional outcome of both techniques in patients with Benign prostatic obstruction (BPO)>80g. MATERIAL AND METHOD: Data from patients who underwent surgical treatment for BPO>80g from January 2010 to February 2015 at our institution were retrospectively collected and compared according to surgical technique. Patient's demographics, surgeon's experience, operative data and long-term functional results were analyzed, using IPSS and International continence society (ICS) male questionnaire associated with Quality of life scores (IPSS-QL and ICS-QL). Predictors of long-term outcome were also assessed. RESULTS: In total, 111 consecutive patients, 57 PVP and 54 OP, were included in the study with a mean follow-up of 24 and 33 month respectively. Patient's age, Charlson score, preoperative IPSS and urinary retention rates were similar. Mean prostatic volume was superior in the OP group (142 versus 103g, P<0.001). Transfusion rate was lower after PVP (P=0.02), despite a more frequent anticoagulant use. Length of hospital stay and urinary catheterization were shorter after PVP (P<0.001), with however a higher rate of recatheterization (RR=4.74) and rehospitalization (RR=10.42). Long-term scores were better after OP for IPSS (1 versus 5, P<0.001), IPSS-QL, ICS, ICS-QL. On multivariate analysis, prostatic residual volume was the only predictor of long-term IPSS but not ICS. CONCLUSION: Long-term functional outcome are better after OP compared to PVP. However, PVP offers good results, allowing to safely operate patients taking anticoagulants, regardless of prostatic volume. Endoscopic enucleation may the compromise between both techniques. LEVEL OF EVIDENCE: 4.

[Penile prosthesis implantation: Indications and outcomes]. / Indications et résultats des implants péniens.

OBJECTIVE: Our aim was to present the indications and the outcomes of penile prosthesis implantation. METHODS: A literature review was performed through PubMed using the following keywords: penile implantation ; penile prosthesis; erectile dysfunction. RESULTS: Evolution of penile prosthesis devices led to get a fiable and effective treatment for men with erectile dysfunction who do not respond to less invasive therapy. Penile implant can also be useful in the treatment of Peyronie's disease, priapism and transgender surgery. Precise information related to this surgery, especially complications, permits to obtain high satisfaction scores. CONCLUSION: Penile implant is a reliable and safe solution for the management of erectile dysfunction resulting to high couple satisfaction ratings.

[Biochemical recurrence after curative treatment for localized prostate cancer: Performance of choline PET/CT in the assessment of local recurrence]. / Récidive biochimique après traitement curatif d'un adénocarcinome prostatique localisé: intérêt de la TEP à la choline dans l'évaluation de la récidive locale.

OBJECTIVE: To establish 18 fluorocholine-positron emission tomography/computed tomography (F-PET/CT) performances for the detection of local recurrence in a population of patients with biochemical failure after primary curative treatment for localized prostate carcinoma. MATERIAL AND METHOD: From February 2011 to February 2014, 55 patients underwent a F-PET/CT for biochemical relapse after primary radical therapy for prostate cancer localized or locally advanced. Primary therapies for prostate cancer were 19 radical prostatectomy, 18 radiotherapy, 13 radiotherapy with hormonal treatment, 3 brachytherapy. The median age was 65 years (50-79). The initial staging was 17 T1, 23 T2 and 15 T3, 52 were N0 and N1 3. The median PSA was 12 (3-127). The Gleason score was less than 7, equal to 7 and greater than 7 at 21, 25 and 9 patients respectively. The average time to recurrence was 69.5 months (8-147) with a median PSA of 2.9 ng/mL (0.48-41). RESULTS: In 42 cases, F-PET/CT showed uptake, suggesting a recurrence, metastatic (6), nodal (26) or local isolated (10). The focal uptake in PET commissioned in 5 cases prostate biopsy, confirming the histological recurrence of prostate cancer in 4 cases. Among the 10 patients with isolated local recurrence, 8 underwent salvage radiotherapy. Of the 13 cases where the (F-PET/CT) showed no recurrence, 7 multiparametric MRI were performed. The MRI showed a local recurrence in 3 patients, the diagnoses were confirmed with prostate biopsy for two of them. CONCLUSION: In our study, for the patients with biochemical relapse of prostate adenocarcinoma localized or locally advanced, (F-PET/CT) was able to detect local recurrence isolated in nearly half the cases but did not show sufficient sensitivity to exclude recurrence local if negative. It does not replace MRI or additional prostate biopsy.

Nucleotides U28-A42 and A37 in unmodified yeast tRNA(Trp) as negative identity elements for bovine tryptophanyl-tRNA synthetase.

Wild-type bovine and yeast tRNA(Trp) are efficiently aminoacylated by tryptophanyl-tRNA synthetase both from beef and from yeast. Upon loss of modified bases in the synthetic transcripts, mammalian tRNA(Trp) retains the double recognition by the two synthetases, while yeast tRNA(Trp) loses its substrate properties for the bovine enzyme and is recognised only by the cognate synthetase. By testing chimeric bovine-yeast transcripts with tryptophanyl-tRNA synthetase purified from beef pancreas, the nucleotides responsible for the loss of charging of the synthetic yeast transcript have been localised in the anticodon arm. A complete loss of charging akin to that observed with the yeast transcript requires substitution in the bovine backbone of G37 in the anticodon loop with yeast A37 and of C28-G42 in the anticodon stem with yeast U28-A42. Since A37 does not prevent aminoacylation of the wild-type yeast tRNA(Trp) by the beef enzyme, a negative combination apparently emerges in the synthetic transcript after unmasking of U28 by loss of pseudourydilation.

Shiga toxin 1: damage to DNA in vitro.

Shiga toxins share with plant ribosome-inactivating proteins the same enzymatic mechanism of action: the removal of a specific adenine from 28S RNA when acting on ribosomes and the removal of multiple adenines when acting on DNA in vitro. The activity on DNA, only recently reported, is particularly evident, and has been studied mostly at acidic pH. For the in vitro activity, on both ribosomes and DNA, Shiga toxins require activation by trypsin, urea and dithiothreitol which release the enzymatically active A(1) fragment. Activation by the classical procedure leaves large amounts of urea and DTT which interfere in the DNA depurination assay and completely abolish depurination at physiological pH. A consistent release of [3H]adenine from DNA at neutral pH is instead observed when the toxin is activated in vitro by an improved method which removes most of the drastic reagents required for proteolytic cleavage and reduction. Damage to single-stranded DNA by Shiga toxin 1 (Stx1) primarily involves depurination. A spontaneous DNA breakdown appears in fact only after extensive base removal, a behavior similar to that observed with uracil-DNA glycosylase, a simple glycosylase devoid of lyase activity. NaCl inhibits the activity of Stx1, probably by minimizing the sliding distance traveled by the enzyme along DNA in search of its target sites and promoting dissociation of the substrate-enzyme complex.

4-Aminopyrazolo[3,4-d]pyrimidine (4-APP) as a novel inhibitor of the RNA and DNA depurination induced by Shiga toxin 1.

Shiga toxin 1 (Stx1) catalyses the removal of a unique and specific adenine from 28S RNA in ribosomes (RNA-N-glycosidase activity) and the release of multiple adenines from DNA (DNA glycosylase activity). Added adenine behaves as an uncompetitive inhibitor of the RNA-N-glycosidase reaction binding more tightly to the Stx1-ribosome complex than to the free enzyme. Several purine derivatives and analogues have now been assayed as inhibitors of Stx1. Most of the compounds showed only minor differences in the rank order of activity on the two enzymatic reactions catalysed by Stx1. The survey highlights the importance of the amino group in the 6-position of the pyrimidine ring of adenine. Shifting (2-aminopurine) or substituting (hypoxanthine, 6-mercapto-purine, 6-methylpurine) the group greatly decreases the inhibitory power. The presence of a second ring, besides the pyrimidine one, is strictly required. Substitution, by introducing an additional nitrogen, of the imidazole ring of adenine with triazole leads to loss of inhibitory power, while rearrangement of the nitrogen atoms of the ring from the imidazole to the pyrazole configuration greatly enhances the inhibitory power. Thus 4-aminopyrazolo[3,4-d]pyrimidine (4-APP), the isomer of adenine with the five-membered ring in the pyrazole configuration, is by far the most potent inhibitor of both enzymatic reactions catalysed by Stx1. This finding opens perspectives on therapeutic strategies to protect endothelial renal cells once endocytosis of Stx1 has occurred (haemolytic uraemic syndrome). In the RNA-N-glycosidase reaction 4-APP binds, as adenine, predominantly to the Stx1-ribosome complex (uncompetitive inhibition), while inhibition of the DNA glycosylase activity by both inhibitors is of the mixed type.

A survey of adenine and 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) as inhibitors of ribosome-inactivating proteins (RIPs).

The inhibitory power of adenine and 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) on the RNA-N-glycosidase activity catalyzed by bacterial (Shiga toxin 1) and plant (ricin, gelonin, momordin, bryodin-R, PAP-S, luffin, trichosantin, saporin 6 and barley) RIPs has been compared. The behavior of the two inhibitors is largely variable. While Shiga toxin 1 is preferentially inhibited by 4-APP, plant RIPs are either preferentially inhibited by adenine, or equally inhibited by the two compounds or, finally, only slightly more by 4-APP. Sequence variabilities involved in these different behaviors are discussed. The experimental data clearly indicate that, in spite of the same mechanism of action, RIPs differ widely in the ability to fit small ring molecules in the active cleft. While the strong inhibitory power of 4-APP on Shiga toxin 1 opens perspectives of therapeutic interventions, the ineffectiveness of the compound on ricin precludes its use as a suitable antidote in poisoning.