Electrophysiological Impact of SARS-CoV-2 Envelope Protein in U251 Human Glioblastoma Cells: Possible Implications in Gliomagenesis?

SARS-CoV-2 is the causative agent of the COVID-19 pandemic, the acute respiratory disease which, so far, has led to over 7 million deaths. There are several symptoms associated with SARS-CoV-2 infections which include neurological and psychiatric disorders, at least in the case of pre-Omicron variants. SARS-CoV-2 infection can also promote the onset of glioblastoma in patients without prior malignancies. In this study, we focused on the Envelope protein codified by the virus genome, which acts as viroporin and that is reported to be central for virus propagation. In particular, we characterized the electrophysiological profile of E-protein transfected U251 and HEK293 cells through the patch-clamp technique and FURA-2 measurements. Specifically, we observed an increase in the voltage-dependent (Kv) and calcium-dependent (KCa) potassium currents in HEK293 and U251 cell lines, respectively. Interestingly, in both cellular models, we observed a depolarization of the mitochondrial membrane potential in accordance with an alteration of U251 cell growth. We, therefore, investigated the transcriptional effect of E protein on the signaling pathways and found several gene alterations associated with apoptosis, cytokines and WNT pathways. The electrophysiological and transcriptional changes observed after E protein expression could explain the impact of SARS-CoV-2 infection on gliomagenesis.

Is early continence recovery related to the length of spared urethra? A prospective multicenter study comparing preoperative MRI and histologic specimen measurements after robotic radical prostatectomy.

BACKGROUND: Urinary incontinence (UI) is a common complication after radical prostatectomy, significantly affecting patients' quality of life. This study aimed to correlate the length of preserved urethra in robotic radical prostatectomy (RALP) patients with short-term urinary continence rates within 90 days post-surgery. METHODS: A prospective multicentric study enrolled 190 prostate adenocarcinoma patients undergoing RALP. Using preoperative magnetic resonance imaging (mpMRI), urethral length was measured from the external urethral sphincter to the bladder neck. After surgery, histological measurements of the removed urethra were compared to the preoperative mpMRI data. Patients were categorized into two groups at the three-month follow-up based on urinary continence assessed through Urodynamic Study (UDS): Group A (94 patients without UI) and Group B (96 patients with UI). RESULTS: Results revealed a significant difference in mean UI recovery time (Group A: 12.35 days, SD: 3.09 vs. Group B: 93.86 days, SD: 34.8, p < 0.0001). A ROC curve identified a 16.5% cut-off value (p < 0.000, sensitivity 87.5%, specificity 91.8%). Both groups showed a significant negative correlation between preserved urethral percentage and UI recovery time (Group A: r -0.655, p < 0.0001; Group B: r -0.340, p: 0.017). Group A had an average of 21.52% preserved urethra, while Group B had 13.86% (p < 0.0001). At one-year follow-up, 93.2% overall patients reported urinary continence without pads. CONCLUSIONS: This study emphasizes the positive correlation between preserved urethra percentage in RALP and early urinary continence recovery, highlighting its surgical significance.

Fluorescence Confocal Microscopy in Urological Malignancies: Current Applications and Future Perspectives.

Fluorescence confocal microscopy (FCM) represents a novel diagnostic technique able to provide real-time histological images from non-fixed specimens. As a consequence of its recent developments, FCM is gaining growing popularity in urological practice. Nevertheless, evidence is still sparse, and, at the moment, its applications are heterogeneous. We performed a narrative review of the current literature on this topic. Papers were selected from the Pubmed, Embase, and Medline archives. We focused on FCM applications in prostate cancer (PCa), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Articles investigating both office and intraoperative settings were included. The review of the literature showed that FCM displays promising accuracy as compared to conventional histopathology. These results represent significant steps along the path of FCM's formal validation as an innovative ready-to-use diagnostic support in urological practice. Instant access to a reliable histological evaluation may indeed significantly influence physicians' decision-making process. In this regard, FCM addresses this still unmet clinical need and introduces intriguing perspectives into future diagnostic pathways. Further studies are required to thoroughly assess the whole potential of this technique.

Robot-Assisted Sacrocolpopexy versus Trans-Vaginal Multicompartment Prolapse Repair: Impact on Lower Bowel Tract Function.

BACKGROUND: This study evaluated the effectiveness, safety, and possible changes in bowel symptoms after multicompartment prolapse surgery by comparing two different surgical approaches, transvaginal mesh surgery with levatorplasty (TVMLP) and robot-assisted sacrocolpopexy (RSC). METHODS: All patients underwent pelvic (POP-Q staging system) and rectal examination to evaluate anal sphincter tone in the lithotomy position with the appropriate Valsalva test. The preoperative evaluation included urodynamics and pelvic magnetic resonance defecography. Patient Global Impression of Improvement (PGI-I) at follow-up measured subjective improvement. All patients completed Agachan-Wexner's questionnaire at 0 and 12 months of follow-up to evaluate bowel symptoms. RESULTS: A total of 73 cases were randomized into the RSC group (36 cases) and TVMLP group (37 cases). After surgery, the main POP-Q stage in both groups was stage I (RCS 80.5% vs. TVMLP 82%). There was a significant difference (p < 0.05) in postoperative anal sphincter tone: 35%. The TVMLP group experienced a hypertonic anal sphincter, while none of the RSC group did. Regarding subjective improvement, the median PGI-I was 1 in both groups. At 12 months of follow-up, both groups exhibited a significant improvement in bowel symptoms. CONCLUSIONS: RSC and TVMLP successfully corrected multicompartment POP. RSC showed a greater improvement in the total Agachan-Wexner score and lower bowel symptoms.

Sentinel Lymph Node Biopsy in Prostate Cancer: An Overview of Diagnostic Performance, Oncological Outcomes, Safety, and Feasibility.

Sentinel node biopsy (SNB) for prostate cancer (PCa) represents an innovative technique aimed at improving nodal staging accuracy. The routinary adoption of this procedure in patients undergoing radical prostatectomy (RP) might be crucial to identify candidates who could effectively benefit from extensive pelvic lymph nodal dissection (ePLND). Despite some promising results, SNB for PCa is still considered experimental due to the lack of solid evidence and procedural standardization. In this regard, our narrative review aimed to analyze the most recent literature in this field, providing an overview of both the diagnostic accuracy measures and the oncological outcomes of SNB.

The Utility of Inflammatory Serum Markers in the Assessment of Perioperative Morbidity after Radical Cystectomy for Bladder Cancer.

Background and Objectives: To date, sparse evidence exists about the impact of inflammatory serum markers in predicting perioperative complications after radical cystectomy (RC) for bladder cancer (BC). Here, we evaluated the role of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), C-reactive protein (CRP), and plasma fibrinogen in predicting perioperative morbidity and unplanned 30-days readmission after RC for BC. Materials and methods: We relied on a collaborative database of 271 patients who underwent open RC for cT1-4a N0 M0 BC between January 2012 and December 2022. Univariable and multivariable binomial logistic regression analyses were performed to assess the odds ratio (OR) with 95% confidence intervals (CI) testing the ability of each serum marker to predict postoperative complications (any-grade and major complications), and 30-days unplanned readmission. Results: The median age at RC was 73 yr (IQR 67-79). A total of 182 (67.2%) patients were male and the median BMI was 25.2 (IQR 23.2-28.4). Overall, 172 (63.5%) patients had a Charlson Comorbidity Index (CCI) greater than 2 points and 98 (36.2%) were current smokers at the time of RC. Overall, 233 (86.0%) patients experienced at least one complication after RC. Of these, 171 (63.1%) patients had minor complications (Clavien-Dindo grade 1-2) while 100 (36.9%) experienced major complications (Clavien-Dindo grade ≥ 3). According to multivariable analysis, current smoking status, high plasma fibrinogen, and preoperative anemia were independently associated with major complications (OR 2.10, 95%CI 1.15-4.90, p = 0.02), (OR 1.51, 95%CI 1.26-1.98, p = 0.09), and (OR 1.35, 95%CI 1.17-2.57, p = 0.03), respectively. Overall, 56 (20.7%) patients experienced a 30-days unplanned readmission. According to univariable analysis, high preoperative CRP and hyperfibrinogenemia were significantly associated with an increased risk of unplanned readmission (OR 2.15, 95%CI 1.15-4.16, p = 0.02; OR 2.18, 95%CI 1.13-4.44, p = 0.02, respectively). Conclusions: In our study, the preoperative immune-inflammation signature described by NLR, PLR, LMR, SII, and CRP showed a low reliability in predicting perioperative course after RC. Preoperative anemia and hyperfibrinogenemia were independent predictors of major complications. Further studies are pending in order to draw definitive conclusions.

Focus on the Use of Resveratrol in Bladder Cancer.

Bladder cancer is the most common tumor of the urinary system, with a high incidence in the male population. Surgery and intravesical instillations can eradicate it, although recurrences are very common, with possible progression. For this reason, adjuvant therapy should be considered in all patients. Resveratrol displays a biphasic dose response both in vitro and in vivo (intravesical application) with an antiproliferative effect at high concentrations and antiangiogenic action in vivo (intraperitoneal application) at a low concentration, suggesting a potential role for it in clinical management as an adjuvant to conventional therapy. In this review, we examine the standard therapeutical approach to bladder cancer and the preclinical studies that have investigated resveratrol in xenotransplantation models of bladder cancer. Molecular signals are also discussed, with a particular focus on the STAT3 pathway and angiogenic growth factor modulation.

Idiopathic Retroperitoneal Fibrosis: What Is the Optimal Clinical Approach for Long-Term Preservation of Renal Function?

BACKGROUND: The aim of this study was to investigate the long-term effects of ureteral stenting and the exact timing of stent removal in favor of surgery in patients with idiopathic retroperitoneal fibrosis (IRF). SUMMARY: Medline research terms of "idiopathic retroperitoneal fibrosis" AND " medical therapy" OR "ureteral stenting" OR "surgical treatment" were done. Systematic reviews and observational and clinical studies were analyzed to obtain indication regarding the objective of the study for a narrative review. Ninety-two papers were analyzed. The treatment of IRF includes the monitoring of retroperitoneal fibrotic process spread and the prevention of abdominal organs entrapment. Treatment of ureteral obstruction includes medical therapy and ureteral stenting (US) or percutaneous nephrostomy (PNS) to overcome the worsening of renal function. Up to now, the timing of US or PNS removal is not yet clear, both for the complexity of evaluating the efficacy of the medical therapy and demonstrating the resolution of obstructive nephropathy. Moreover, it is not yet clear if the long-term ureteral stent placement or PNS is able to maintain an efficient renal function. Ureterolysis with a laparoscopic robot-assisted approach is now considered as an ultimate treatment for ureteral obstruction, limiting the progression of kidney impairment and improving the quality of life of patients, although nephrologists are generally abdicant regarding the potential switch toward the surgical approach. KEY MESSAGES: Prospective studies regarding the long-term effects of US on the renal function impairment in patients with IRF should be structured to obtain adequate information on the exact timing for the surgical approach.

Procalcitonin as prognostic factor in patients with Fournier's gangrene.

INTRODUCTION: Fournier's Gangrene (FG) has still a mortality rate up to 45%. Several studies identified prognostic factors but there is a knowledge gap concerning procalcitonin (PCT) levels and mortality risk in FG. This study is aimed to assess the role of PCT as prognostic factor in FG. MATERIALS AND METHODS: The medical records of 20 male FG patients admitted at the Department of Urology of "Cattinara" Hospital, University of Trieste between January 2019 and November 2020 were retrospectively reviewed. Clinical, demographic, microbiological data were collected. The Fournier's Gangrene Severity Index (FGSI) was calculated for each patient. RESULTS: Thirteen (65%) of 20 patients survived. Median age was 58 years (IQR 51-88), 15 patients (75%) had a Charlson Comorbidity Index (CCI) score ⩾2, 1 (5%) equal to 0, 4 to 1 (20%). Median FGSI score was 6 (IQR 2-12) and median PCT 0.8 ng/ml (IQR 0.04-2.12). At multivariate analysis PCT levels >0.05 ng/ml were associated with an increased overall mortality risk (OR 2.14, CI 1.25-4.27, p = 0.002). CCI score ⩾2 (OR 1.51, CI 1.01-2.59, p = 0.04), Streptococcical etiology (OR 3.41, CI 2.49-4.61, p = 0.002) and FGSI score >9 (OR 1.41, CI 1.19-2.21, p = 0.004) were associated with unfavorable outcome. CONCLUSION: PCT might be a prognostic factor in FG. CCI and FGSI are useful tools in mortality risk stratification. Streptococcical etiology is associated with unfavorable outcome. Further larger clinical trials are pending.

A single pedicled robotic peritoneal flap in penile inversion vaginoplasty augmentation.

OBJECTIVES: To develop a surgical technique to achieve greater depth of the neovaginal cavity in transgender patients undergoing scrotovaginoplasty, and to propose a method for restoring neovaginal integrity in case of lack of genital skin or reduction of the depth due to scarring after infections or ischaemic processes. METHODS: Eight patients were selected to undergo scrotovaginoplasty with scrotal graft and peritoneal flap augmentation in one operating session as a modification of Zhao's original technique. The age of the patients ranged from 25 to 65 years. The first step of the procedure was standard penile inversion vaginoplasty, avoiding suturing of the superior side of the skin cylinder. The skin cylinder was pushed into the abdominal cavity through the perineal access. Afterwards a laparoscopic/robotic approach was used: a single peritoneal flap was harvested from the posterior bladder surface, incised, dissected, pedicled on the neovaginal dome, overturned and and sutured all-round to the neovagina. The sides were adapted to obtain a 'cul-de-sac'. RESULTS: The average operating time was 6 ± 1.5 h, and patients' hospitalization lasted 6 days. There were no intra- or postoperative complications. Postoperative management was the same as that usually reported in BJUI for patients undergoing standard scrotovaginoplasty. CONCLUSIONS: The use of this technique represents a good solution for increasing neovaginal depth by harvesting a large peritoneal vascularized flap, without significantly affecting postoperative management or increasing complications, as frequently observed using the colovaginoplasty technique.

16 years follow-up evaluation of immediate vs delayed vs. combined hormonal therapy on fertility of patients with cryptorchidism: results of a longitudinal cohort study.

BACKGROUND: To investigate in a longitudinal cohort study, the best treatment to preserve fertility in cryptorchid subjects. Patients treated with immediate hormonal vs. delayed vs. combined (hormone plus surgery) therapy consecutively enrolled during the period 1987-1997, were evaluated. METHODS: Two hundred fifty-five subjects were enrolled and 192 patients completed the follow-upt. One hundred fifty-six patients and 36 out 192 had monolateral and bilateral cryptorchidism, respectively. Twenty-nine out of 192 were previously treated by surgery alone (Group A), 93/192 by hormone therapy alone (Group B), 51/192 received sequential combined hormone therapy plus surgery (Group C) whilst 19/192 refused any type of treatment (Group D). The other 63 patients were considered lost to follow-up. All the patients underwent medical consultation, scrotal ultrasound scan, sperm analysis and Inhibin B, Follicular Stimulating Hormone (FSH) and Testosterone (T) serum level determination. RESULTS: Testicular volume was found decreased in the Group D patients whilst hormone serum levels were comparable in all groups. Statistically significant differences for sperm characteristics were found in patients treated with hormonal therapy alone or combined with surgery (Groups B and C). These two groups reported better semen quality than patients who received surgery alone or no treatment. No differences were observed between monolateral and bilateral cryptorchidism patients. CONCLUSIONS: Early prolonged hormonal therapy is advisable in all patients with cryptorchidism independently from the surgical option of promoting testicular descent to the scrotum. Hormonal therapy provides in our study better chance to obtain adequate sperm quality in adult life.

Antibiotic prophylaxis in patients who had undergone to prostate biopsy in between the EMA warning era: effects of fluoroquinolones in diabetic and non-diabetic patients. Results of an observational cohort study.

PURPOSE: To investigate the effects of different antibiotic prophylaxis regimens in patients with diabetes mellitus (DM) candidates to trans-rectal ultrasound-guided prostate biopsy (TRUSPB). METHODS: 143 outpatients with DM who underwent TRUSPB during the period 2018-2020 were selected from a cohort of 1150 patients in 3 different institutions. Exclusion criteria were allergies, concomitant anti-platelet therapies and uncontrolled DM. Different antibiotic prophylaxis regimens were adopted. Bacterial resistance levels to fluoroquinolones into the different communities were also collected. Univariable and multivariable binomial logistic regression analyses were used to assess the odds ratio (OR) with 95% confidence intervals (CIs) testing the risk of infective complications' occurrence after adjusting for clinical covariates. RESULTS: Overall, DM patients were significantly associated with infective complications' occurrence (p < 0.001). No differences on the event of sepsis were found between diabetic and non-diabetic patients. Clinically relevant infections with fever > 37 °C were found in 9.1% and 1.5% (p < 0.001) in diabetic and non-diabetic patients, respectively. Trimethoprim-sulphametoxazole and fluoroquinolones were six times more efficient than Cefixime in non-diabetic patients. Fluoroquinolones confirmed the same effect in diabetic patients although the level of resistance in the period of study decreased only from 56 to 46%. CONCLUSION: Fluoroquinolones were active in antibiotic prophylaxis of diabetic patients who had undergone to TRUSPB independently from the level of bacterial resistance found in the community. These results conflict with the recent European warning and support the Japanese and American guidelines on the topic.

Comparison of Fluoroquinolones and Other Antibiotic Prophylaxis Regimens for Preventing Complications in Patients Undergoing Transrectal Prostate Biopsy.

Our study aimed to compare the incidence of infective complications after transrectal ultrasound-guided prostate biopsy (TRUSBx) when adopting different antimicrobial prophylaxis regimens. A multi-institutional cohort of 1150 patients who underwent TRUSBx was retrospectively analyzed. Procedures were performed between 2017 and 2019 (before and after the EMA warning about the use of fluoroquinolones for the antibiotic prophylaxis of patient candidates to TRUSBx). The primary endpoint was the occurrence of infective complications, including sepsis and/or fever. The population was stratified according to the antibiotic prophylaxis adopted: fluoroquinolones (levofloxacin, ciprofloxacin, prulifloxacin), cephalosporins (cefixime, ceftriaxone) or trimethoprim/sulfamethoxazole. Univariable and multivariable binomial logistic regression models were used to assess the odds ratio (OR) with 95% confidence interval (CI) testing of the risk of infective complication after adjusting for each prebiopsy covariate. In total, 478 (41.6%) patients received fluoroquinolone-based prophylaxis. Among these, 443 (38.5%), 25 (2.2%) and 10 (0.9%) patients received levofloxacin prophylaxis, ciprofloxacin and prulifloxacin, respectively while 14.6% received cefixime, 20.7% received the comedication of ceftriaxone/fosfomycin and 23.1% received trimethoprim/sulfamethoxazole. The trimethoprim/sulfamethoxazole and fluoroquinolone regimens were significantly associated with a lower risk of infective complications (OR 0.15, 95% CI 0.03−0.48, p = 0.003 and OR 0.17, 95% CI 0.06−0.43, p < 0.001, respectively). The ceftriaxone/fosfomycin (OR 0.21, 95% CI 0.04−0.92, p = 0.04) and fluoroquinolone (OR 0.07, 95% CI 0.00−0.70, p = 0.048) prophylaxis were associated with a lower risk of infective sequelae. Fluoroquinolone-based prophylaxis was associated with a lower risk of infective complications after TRUSBx compared to other prophylaxis regimens although its clinical application was recently forbidden by European Medical Agency restrictions.

Sexual and functional outcomes after prolapse surgery: a randomized prospective comparison of trocarless transvaginal mesh and pelvic organ prolapse suspension.

PURPOSE: Stress urinary incontinence (SUI) related to pelvic organ prolapse represents a common condition that negatively impacts female sexual activity. Laparoscopic pelvic organ prolapse surgery (POPs) and the anterior repair with a trocar-less trans-vaginal mesh (TTMs) represent two different surgical techniques to treat SUI secondary to POP. This study aimed to report the results of these techniques comparing the sexual and functional outcome improvement. MATERIALS AND METHODS: Fifty-nine sexually active female patients, complaining of urodynamic stress incontinence, were enrolled in this prospective study, and simply randomized in two groups: 29 POPs and 30 TTMs. All patients were studied at baseline and 6 months after surgery. Preoperative evaluation included medical history, urodynamic test, Female Sexual Function Index (FSFI), and pelvic magnetic resonance defecography. Six months after surgery, all patients completed the FSFI and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and were investigated with a uroflowmetry test with post-void residual volume (PVR). RESULTS: At 6 months after surgery, 87% of POPs patients and 79% of TTMs subjects resulted dry. No statistically significant results were obtained in terms of urinary outcomes between the two surgical groups. Regarding sexual function, POPs group exhibited a significant greater improvement of global FSFI (mean: 27.4; SD: 4.31) compared to TTMs group (mean FSFI: 23.56; SD: 2.28; p-value ≤ 0.0001). CONCLUSIONS: Our results indicated that POPs and TTMs lead to satisfactory and safe functional outcomes with a good recovery of urinary continence. Furthermore, POPs, when compared to TTMs, led to a greater improvement of sexual function.

Clinical use of hyaluronic acid in andrology: A review.

BACKGROUND: Hyaluronic acid is a glycosaminoglycan widely used in the fields of orthopedics, ophthalmology, and aesthetic medicine due to its significant ability to reduce the synthesis of pro-inflammatory proteins and its activity against oxidative stress, a feature of many degenerative illnesses. OBJECTIVES: The objective of the present review is to provide a comprehensive narrative review of the most recent literature on the use of hyaluronic acid in andrology in order to facilitate the use of this therapeutic device in the common clinical practice of many physicians. Specific conditions covered in the review are Peyronie's disease, premature ejaculation, and penile enlargement. MATERIALS AND METHODS: A broad and comprehensive literature search included Medline, EMBASE, and the Cochrane Libraries, with no time restriction up to December 2020 and restricted to English language publications. Unpublished studies were not included. The study was registered as "The role of hyaluronic acid in andrology: A systematic review and meta-analysis" in PROSPERO with the ID CRD42021223416. DISCUSSION AND CONCLUSION: Hyaluronic acid is a valid choice for the treatment of Peyronie's disease in terms of the resolution of the acute phase of the disease and of contributing to stabilizing the disease as a bridge to potential surgery. Data, furthermore, suggest that hyaluronic acid is frequently associated with an overall clinical improvement, allowing the patient to resume normal sexual activity. With regard to premature ejaculation, data suggests hyaluronic acid-based treatments were effective in prolonging intra-vaginal ejaculation time. Furthermore, hyaluronic acid was found to be safe and well-tolerated, with main adverse events limited to local discomfort, ecchymosis, papule formation, and glans numbness, all of which were reported to resolve spontaneously. Last, with regard to penile enlargement, the overall perception of experts is that hyaluronic acid may be an extremely well-tolerated compound with potential for application in specific areas of male sexual health that are often neglected as compared to more common, and relatively simpler to treat, conditions.

Holmium:YAG Laser for the Treatment of Genital and urethral Warts: Multicentre Prospective Evaluation of Safety and Efficacy.

Introduction: Genital condylomatosis is a highly contagious disease caused by the human papilloma virus (HPV). The aim of this prospective multicentre study was to evaluate the safety and efficacy of the Holmium:YAG (yttrium-aluminium-garnet) laser in the treatment of genital and intra-urethral warts; the secondary aim was to assess the patients' postoperative satisfaction and cosmetic results. Methods: From December 2016 to March 2019, patients with genital warts were prospectively enrolled in three hospitals. The inclusion criteria were male gender, age over 18 years-old and treatment-naïve. External and urethral genitalia warts were treated by the Holmium YAG laser. The follow-up analysis consisted of physical examination, flexible urethro-cystoscopy in case of meatal lesions, and administration of Dermatology Quality of Life Index (DLQI) and Patient Global Impression of Improvement (PGI-I) questionnaires at 1, 3, 6 and 12 months after surgery and subsequently yearly. Results: Sixty patients were enrolled. The single treatment was effective in 57/60 patients (95%). At a mean follow-up of 26 months, recurrences occurred in 8 patients (13.3%). No peri- or post-operative complication occurred. An improvement in pre-operative condition was highlighted with PGI-I and DLQI questionnaires. Conclusion: Our prospective multicentre study showed that holmium laser surgery seems to be a safe and effective treatment for external genital and urethral warts. Good dermatological outcomes aid to further improve patient satisfaction.

Use of Intravesical Injections of Platelet-Rich Plasma for the Treatment of Bladder Pain Syndrome: A Comprehensive Literature Review.

BACKGROUND: Bladder pain syndrome/interstitial cystitis (BPS/IC) or primary bladder pain syndrome (PBPS) is a complex and poorly understood condition. This comprehensive review aimed to discuss the potential application of platelet-rich plasma (PRP) in the treatment of BPS/IC. The pathophysiology of BPS/IC is characterized by urothelial damage that triggers a chain of events leading to chronic inflammation and other conditions. Frequently, in subjects affected by BPS/IC, recurrent urinary tract infection (rUTI) is associated with difficult therapeutic management. For these reasons, many oral and intravesical treatments (e.g., antibiotic therapy and intravesical anesthetic instillations) have been proposed to alleviate the symptoms of IC/BPS. However, the limitation of these treatments is the short duration of improvement. The purpose of this review is to analyze the efficacy of intravesical PRP injections in subjects with PBS/IC and to try to understand the potential therapeutic effects on the pathophysiology of this disease. METHODS: A nonsystematic literature search using Pubmed, EMBASE, Scopus, Web of Science, Medline was performed from January 2000 to August 2021. The following terms were combined to capture relevant publications: "platelet-rich plasma", "interstitial cystitis", "PRP", "bladder pain syndrome", and "painful bladder syndrome". RESULTS: After exclusion of non-pertinent studies/articles, we have analyzed 5 studies. In detail, 2 articles concerned preclinical studies in which animal models were used. The authors showed an improvement in the histological pattern with less bleeding in treated subjects, a lower presence of inflammatory cytokines and an increase in the mitotic index of urothelial cells in animals treated with intravesical PRP. In the three prospective clinical trials analyzed, patients with BPS/IC who underwent monthly intravesical PRP injections were found to have a statistically significant improvement in symptoms with modulation of growth factors and inflammatory proteins. CONCLUSIONS: New evidence suggests that treatment with intravesical PRP could improve urothelial regeneration and reduces chronic inflammation in BPS/IC, modifying the clinical history of its pathology.

Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the "Normobaric Oxygen Paradox".

The term "normobaric oxygen paradox" (NOP), describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as oxygen shortage, and resulting in up-regulation of the Hypoxia-inducible factor 1α (HIF-1α) transcription factor activity. The molecular characteristics of this response have not been yet fully characterized. Herein, we report the activation time trend of oxygen-sensitive transcription factors in human peripheral blood mononuclear cells (PBMCs) obtained from healthy subjects after one hour of exposure to mild (MH), high (HH) and very high (VHH) hyperoxia, corresponding to 30%, 100%, 140% O2, respectively. Our observations confirm that MH is perceived as a hypoxic stress, characterized by the activation of HIF-1α and Nuclear factor (erythroid-derived 2)-like 2 (NRF2), but not Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB). Conversely, HH is associated to a progressive loss of NOP response and to an increase in oxidative stress leading to NRF2 and NF-kB activation, accompanied by the synthesis of glutathione (GSH). After VHH, HIF-1α activation is totally absent and oxidative stress response, accompanied by NF-κB activation, is prevalent. Intracellular GSH and Matrix metallopeptidase 9 (MMP-9) plasma levels parallel the transcription factors activation pattern and remain elevated throughout the observation time. In conclusion, our study confirms that, in vivo, the return to normoxia after MH is sensed as a hypoxic trigger characterized by HIF-1α activation. On the contrary, HH and VHH induce a shift toward an oxidative stress response, characterized by NRF2 and NF-κB activation in the first 24 h post exposure.

Evaluation of Functional Outcomes and Quality of Life in Elderly Patients (>75 y.o.) Undergoing Minimally Invasive Radical Cystectomy with Single Stoma Ureterocutaneostomy vs. Bricker Intracorporeal Ileal Conduit Urinary Diversion.

BACKGROUND: Diversion after radical cystectomy (RC) is crucial when considering elderly subjects. Data on the quality of life (QoL) impact with different diversions is scarce. This study aims to compare complications and QoL in patients aged > 75 y.o., who underwent minimally invasive (MI) RC with Bricker intracorporeal urinary derivation and single stoma ureterocutaneostomy. METHODS: We conducted a retrospective analysis of elderly patients who underwent MIRC and intracorporeal diversion. The 78 subjects were divided into two groups: group A, ileal conduit, and group B, single stoma ureterocutaneostomy. We evaluated the bowel's recovery time and complications rate. We investigated QoL 3 and 6 months after surgery using the Stoma-QoL questionnaire. RESULTS: Mean age was 77.2 in group A and 82.4 in group B. The mean ASA score and Charlson Comorbidity index were comparable between the two groups. Rates of complications were 57.6% and 37.4% in groups A and B, respectively. The mean postoperative Stoma-QoL score 3 months after surgery was 52.2 and 52.4 in groups A and B, respectively. At 6 months of follow-up the Stoma QoL mean score was 63.4, showing homogeneity between the groups. CONCLUSION: MIRC with single stoma ureterocutaneostomy represents an alternative to ileal conduit, with comparable QoL and ostomy management 6 months after surgery, reporting fewer complications.

Resveratrol-Based Multivitamin Supplement Increases Sperm Concentration and Motility in Idiopathic Male Infertility: A Pilot Clinical Study.

BACKGROUND: It is known that a multitude of factors may lead to male factor infertility, but still, in the majority of cases, the cause remains largely idiopathic, reflecting poor understanding of the basic process of spermatogenesis and the mechanisms involved. Resveratrol is a polyphenol compound that displays several cellular aspects mainly associated with SIRT1-pathway activation and promotion of mitochondrial enhancer activities. In several animal models, resveratrol has shown positive effects on mitochondria and membrane potential. This could explain effects on sperm concentration and motility. The aim of this study is to evaluate the effects on the semen parameters of GENANTE®, a multivitamin supplement containing 150 mg of resveratrol/day, in patients with idiopathic infertility. METHODS: This was a prospective single center clinical study. Twenty patients took a multivitamin supplement based on 150 mg of resveratrol (GENANTE®), in the form of an oral tablet every 12 h, and were followed up at 1, 3, and 6 months after treatment. Pre- and post-treatment evaluation included history, clinical examination, semen analysis, hormonal determinations, and scrotal and prostatic ultrasound. RESULTS: Our preliminary pilot study demonstrated that the multivitamin supplement based on resveratrol improves sperm motility (48.3% ± 13.8 vs. 59.0% ± 12.8, p = 0.0001) and concentration (22.6×106/mL ± 9.5 vs. 25.7×106/mL ± 8.1, p = 0.0001) after 3 and 6 months of treatment in men with idiopathic infertility. CONCLUSION: Our data suggest that targeting the metabolic and energetic pathways involved in spermatogenesis and mitochondrial activity could lead to potential effects and counteract subfertility/infertility in men through a mitochondria dynamics mechanism. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registration identifier: NCT03864198, registered on 1 January 2019.