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La storia del Castello Aragonese dell'Isola d'Ischia è letta nella triplice ottica dei contenuti architettonici, tecnologici e del possibile riuso in un quadro più ampio che comprende le altre emergeneze monumentali dell'isola.

The erythrocyte activities of glucose 6-phosphate dehydrogenase, pyruvate kinase and glucose phosphate isomerase decrease during the first days of life. Furthermore the level of these enzymatic activities is higher in newborn infants with higher percentage of carboxyhemoglobin. It is likely that a premature and rapid fall of reticulocytes causes a decrease in enzymatic activities sensitive to aging and that the higher hemolysis can represent a disappearance of oldest erythrocytes which present lower enzymatic activities. These data therefore confirm the block in erythropoiesis in the first hours of life.

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.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological As- sociation [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the re- sponses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identi- fied where no guidelines are available. Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male in- fertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical prac- tice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

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. post-print 1243 KB

Background andObjective: Plaque formation ordinarily takes place in the acute phaseof Peyronie’s disease. There is no unanimous consent regarding the management of the acute phase ofPeyronie’s disease.The objective of this study was to evaluate the advantages of using a single intralesional injection of collagenase Clostridium histolyticum in patients with the active phase of Peyronie’s disease and to assess its effect on disease progression by reducing penile curvature and ameliorating pain during sexual intercourse. Methods: Sexually active men aged older than 18years with the acute phase of Peyronie’s disease were enrolled. All patients received treatment with a single intralesional injection of collagenase Clostridium histolyticum. The primary outcome of the study was the change in penile curvature after treatment while secondary outcomes were the change in sexual function (International Index of Erectile Function [IIEF-5]) and in the Peyronie Disease Questionnaire (PDQ) and its sub-scores, PDQ-PS (psychological symptoms), PDQ-PP (penile pain) and PDQ-BD (bother disease). Results: Overall, 74 patients were enrolled. Mean penile curvature at baseline was 41.1° ± 12.2°. The mean changes before and at the 3-month evaluation in terms of penile curvature, Visual Analog Scale score at rest, and Visual Analog Scale score during intercourse were − 19.3 ± 8.4 (p < 0.0001), − 0.8 ± 1.1 (p < 0.0001) and − 3.8 ± 0.9 (p < 0.0001) with the benefit persisting also after 6months. Moreover, improvements of mean IIEF-5 score (1.1 ± 0.9, p = 0.03; 0.9 ± 0.5, p = 0.02), PDQ-PS (− 2.7 ± 2.2; − 2.5 ± 2.0, p = 0.01), PDQ-PP (− 1.2 ± 1.6; − 1.1 ± 1.2, p = 0.02) and PDQ-BD (− 3.8 ± 3.4; − 3.5 ± 3.1, p = 0.001) were observed 3 and 6months after the end of treatment, respectively. At the multivariable regression analysis, the time since disease onset (modelled with non-linear terms) and baseline curvature were independently associated with the degree of curvature improvement (coefficient: 0.30; 95% confidence interval 0.16–0.44) after a single intralesional injection (all p < 0.03). Conclusions: Although intralesional therapy with collagenase Clostridium histolyticum is not yet indicated for the acute phase of Peyronie’s disease, thesepreliminary results suggest the effectiveness of this minimally invasive option by improving penile curvature and IIEF-5 and PDQ scores.

Purpose: The aim of this article is to describe our modified surgical technique for the reconfiguration of the glans in the clitoris and the labia minora, known as the “M-shape neoclitorolabioplasty”. Methods: The glans with all its neurovascular bundle is isolated from the corpora cavernosa, incised in Y-shape mode and spread in order to obtain an M-shape glandular flap. The “belly” of the M-shape glans will constitute the triangular neoclitoris meanwhile the lateral flaps will constitute the labia minora. The inferior apex of the neoclitoris is fixed to the superior apex of the previously spatulated urethra. The two glans flaps are incised transversally to increase their length and sutured to the sides of the spatulated urethra forming the labia minora. Our technique permits to create an aesthetically pleasing neovagina preserving all the glandular erogenous sensitivity. Results: 94 patients have been treated with our modified technique of male-to-female (MtoF) gender affirming surgery. At median follow-up of 27.57 months, 81 (86.1%) patients reported vaginal intercourse and 78 (82.9%) patients referred presence of erogenous sensitivity during dilatations, intercourse or masturbations. All the glandular tissue is preserved and reconfigured forming the neoclitoris and the labia minora. The M-shape reconfiguration permit to create an aesthetically pleasant neoclitoris. Conclusions: This technique could be applied safely and easily to patients undergoing gender affirming surgery, allowing the creation of a neovagina with the best possible erogenous sensitivity without losing aesthetical results.

Pre-clinical studies on human isolated bronchi have relevant translational value in human in vivo, conversely no investigation has been performed to assess whether data resulting from equine isolated airways can have any translational application in asthmatic horses. Thus, a meta-regression analysis via random-effect method was carried out to correlate the pharmacological characteristics of bronchodilators resulting from experiments performed in equine isolated bronchi with their impact on the lung function outcomes in asthmatic horses. Data on the potency of different bronchodilators were extracted from four ex vivo studies involving 68 horses, and related with the maximum change in transpulmonary pressure (ΔPpl max ), pulmonary resistance (R L), and dynamic lung compliance (Cdyn ) resulting from the meta-analysis of clinical trials aimed to assess the effect of different bronchodilator classes, namely antimuscarinic agents and β 2-adrenoreceptor (β2-AR) agonists, on lung function of asthmatic horses. The potency (pEC50) detected in equine isolated bronchi for each specific bronchodilator did not significantly (P > 0.05) influence the bronchorelaxant effect resulting from clinical trials. RL was characterized by a flatter meta-regression line (slope 0.01, 95%CI -0.25 – 0.28) with respect to ΔPplmax (slope 0.90, 95%CI -4.06 – 2.26) and Cdyn (slope 0.09, 95%CI -0.21 – 0.04). The quality of evidence was moderate for RL and ΔPplmax and low for Cdyn. This quantitative synthesis provides the indirect evidence that pre-clinical investigations performed by using equine isolated airways may produce useful data to predict the impact of bronchodilators on the RL of asthmatic horses. Further translational studies are needed to directly confirm the results of this research.

Introduction The aim of this study is to accomplish a systematic review on the surgical techniques available for male-to-female gender assignment surgery (MtoF GAS) published in the last 15 years, from January 2002 to May 2017, assessing advantages and disadvantages. Evidence acquisition A specific search on MEDLINE, Scopus and Web of Science databases included vaginoplasty for gender exchange. Preoperative (age, gender, body mass index, prior surgery), intraoperative (mean operating time, intraoperative complications, transfusion rate, conversion rate), postoperative (hospital stays, readmission rate, early and late complication rate), postoperative sexual activity, subjective satisfaction, vaginal depth, and long-term outcomes (vaginal stenosis, prolapse, dyspareunia and labial abscess) data of vaginoplasty for sexual exchange were collected. 29 articles were included (2.402 patients). Evidence synthesis Out of the 29 papers, 19 studies assessed penile skin inversion and 10 evaluated intestinal vaginoplasty. No comparative studies were found. Penile skin inversion vaginoplasty reported slightly shorter operative time compared to intestinal vaginoplasty (109-420 vs 145-420 minutes). Intraoperative complications for penile skin inversion vaginoplasty not exceeded an incidence of 10%. No significant differences in terms of postoperative complications or hospitalization time were reported. Intestinal vaginoplasty provides a deeper neovagina. Female Sexual Function Index score was significantly higher in patients undergoing intestinal vaginoplasty. Conclusions A standardized data collection may allow a better understanding of effectiveness and outcomes of different techniques.

Introduction The effectiveness of phosphodiesterase type 5 (PDE5) inhibitors over the conservative management of Peyronie’s disease (PD) has been widely questioned. Aim To determine the role of sildenafil 25 mg film formulation twice a day (S25 b.i.d.) in the improvement of curvature after treatment of collagenase of Clostridium hystoliticum (CCH) in penile curvature owing to PD. Methods From April 2017 to April 2018, 161 consecutive patients were treated with S25 b.i.d. + CCH or CCH alone. Adjustment variables consisted of age, penile curvature, and the 15-question International Index of Erectile Function (IIEF-15) questionnaire at baseline using 1:1 propensity-score matching. Overall, 50 patients were considered subdivided into the following: 25 patients who received S25 b.i.d. + CCH (group A) and 25 who received CCH alone (group B). Patients received CCH injection using a shortened protocol and vacuum device in both groups. Main Outcome Measure The primary outcome of the study was the change in penile curvature after treatment, and secondary outcomes were the change in sexual function (IIEF-15) and in the Peyronie’s Disease Questionnaire (PDQ) and its subscores, PDQ-PS (psychosexual symptoms), PDQ-PP (penile pain), and PDQ-SB (symptom bother). Results Overall, mean penile curvature was 47.0° (SD 21.88), the mean IIEF-EF (erectile function) was 23.56 (SD 4.10), and the mean PDQ was 27.06 (SD 13.55). After the treatment, we observed a mean change for penile curvature of 25.6 (SD 9.05) in group A and –25.6 (SD 9.7) in group B (P < .01), for IIEF-EF of 2.28 (SD 2.33) in group A and 1.36 (SD 1.77) in group B (P = .03), for PDQ-PS of –3.04 (SD 2.95) in group A and of –2.12 (SD 2.06) in group B (P = .11), for PDQ-PP of –1.0 (SD 4.48) in group A and of –0.88 (SD 2.04) in group B (P = .60), for PDQ-SB of –5.84 (SD 4.58) in group A and of –4.16 (SD 4.45) in group B (P = .60), and for Female Sexual Function Index of 3.8 (SD 2.45) in group A and of 2.72 (SD 2.28) in group B (P = .14). We found a rate of global satisfaction of 70.83% in group A and of 84.0% in group B (P = .27). Clinical Implications Addition of S25 b.i.d. to CCH is superior to CCH alone for improving penile curvature and erectile function. Strength & Limitations This is the first study comparing sildenafil + CCH vs CCH alone for the treatment of PD. Lack of randomization and direct verification of appropriate use of penile modeling could be considered limitations. Conclusion In this study, combination therapy was superior in terms of penile curvature and erectile dysfunction improvement.

Background A new oro-dispersible film (ODF) formulation of sildenafil has been developed for the treatment of erectile dysfunction (ED) to overcome the drawbacks that some patients experience when taking the conventional film-coated tablet (FCT). Aim To assess the effectiveness and safety of sildenafil ODF formulation in patients with ED who were using the conventional FCT. Methods From May 2017 through July 2017, 139 patients with ED were enrolled. Data from penile color-duplex ultrasound, medical history, hormonal evaluation, and patient self-administered questionnaires were collected. All patients were administered sildenafil 100-mg FCT for 4 weeks. Thereafter, they underwent a 2-week washout period and subsequently took sildenafil 75-mg ODF for 4 weeks. Outcomes The International Index of Erectile Function (IIEF-15), Hospital Anxiety and Depression Scale (HADS), Patient Global Impressions of Improvement (PGI-I), and Clinician Global Impressions of Improvement (CGI-I) questionnaires were administered and severity of ED was classified as severe (IIEF-15 score ≤ 10), moderate (IIEF-15 score 11–16), or mild (IIEF-15 score = 17–25). Results All patients completed the final protocol. Differences in mean IIEF scores for erectile function, orgasmic function, sexual desire, and intercourse satisfaction were significantly in favor of sildenafil 100-mg FCT, whereas the mean score for overall satisfaction was in favor of sildenafil 75-mg ODF. A significant difference in changes in HADS score was found from washout to final follow-up (mean difference = −0.19; P < .01). For the ODF formulation, the median CGI-I score was 3.5 (interquartile range [IQR] = 2.5–4.5) and the median PGI-I score was 3.0 (IQR = 2.0–4.0). The median action time was 20.0 minutes (IQR = 15.0–30.0) and the median mouth time was 60.0 seconds (IQR = 30.0–120.0). Clinical Implications The ODF formulation of a widely known drug, with the same safety and effectiveness of the FCT, was better appreciated by patients in overall satisfaction. Strengths and Limitations This is the first clinical trial to assess the efficacy of a new formulation of sildenafil in patients with ED. The limitations of the study are related to the methodology used: it was not a case-control study and the patients were not drug-naïve for ED treatment. Therefore, only the “additional” side effects of the ODF formulation compared with FCT are reported. Conclusion The new ODF formulation is as efficient and safe as the FCT formulation and offers a new choice of treatment to specialists for more precisely tailored therapy.

Background Although the mouse is the animal model most widely used to study the pathogenesis and treatment of human diseases, reference values for biochemical parameters are scanty or lacking for the most frequently used strains. We therefore evaluated these parameters in the C57BL/6J, 129SV/EV and C3H/HeJ mice. Methodology/Principal Findings We measured by dry chemistry 26 analytes relative to electrolyte balance, lipoprotein metabolism, and muscle/heart, liver, kidney and pancreas functions, and by automated blood counter 5 hematological parameters in 30 animals (15 male and 15 female) of each mouse strain at three age ranges: 1–2 months, 3–8 months and 9–12 months. Whole blood was collected from the retro-orbital sinus. We used quality control procedures to investigate analytical imprecision and inaccuracy. Reference values were calculated by non parametric methods (median and 2.5th and 97.5th percentiles). The Mann-Whitney and Kruskal-Wallis tests were used for between-group comparisons. Median levels of GLU, LDH, Chol and BUN were higher, and LPS, AST, ALP and CHE were lower in males than in females (p range: 0.05–0.001). Inter-strain differences were observed for: (1) GLU, t-Bil, K+, Ca++, PO4− (p

Il contributo si esplicita in 17 schede tecniche su interventi di recupero delle coperture nel volume "Il recupero delle coperture" di B. de Sivo G. Cito, G. Giordano, R. Iovino, per i tipi di Dario Flaccovio Editore.