The Anatomical Relationships in the Space of Retzius for Penile Implants: An MRI Analysis.

BACKGROUND: The 3-piece inflatable penile prosthesis includes an easy-to-use pump and fluid filled reservoir which is placed in either the space of Retzius (SOR) or in an alternative ectopic location. Reservoir placement in the SOR is a blind procedure despite the SOR being surrounded by many critical structures. To date only a handful of cadaveric studies have described the relevant anatomy. AIM: To use magnetic resonance imaging (MRI) as an in-vivo model to study relevant retropubic anatomy critical for SOR reservoir placement. METHODS: The study population included men with elevated prostate specific antigen or biopsy proven prostate cancer who (i) underwent pelvic MRI, (ii) without prior pelvic or inguinal surgery, and (iii) without pelvic radiation therapy. All MRIs were completed with a 3-Tesla scanner and endorectal coil. Both T1 and T2 weighted images were captured in both axial and sagittal planes. All images were reviewed by 2 independent reviewers under the supervision of a dedicated body MRI radiologist. Bladder volume was calculated using an ellipsoid formula. OUTCOMES: Relevant measurements included (i) the distance between the external inguinal ring (EIR) at the level of the pubic tubercle to the external iliac vein (EIV), (ii) the distance from the EIR at the pubic tubercle to the bladder (accounting for bladder volume) and (iii) the distance from the midline pubic symphysis to the bladder (accounting for bladder volume). Pearson correlation was used to determine correlated measurements. RESULTS: A total of 24 patients were included. Median participant age was 63 years (interquartile range, 59-66). The mean EIR-EIV distance was 3.0 ± 0.4 cm, the mean EIR-bladder distance was 1.8 ± 1.0 cm and the mean distance from the superior pubic symphysis to bladder was 0.9 ± 0.3 cm. There was a weak correlation between bladder volume and distance between the EIR and bladder (r = -0.30, P = .16). CLINICAL IMPLICATIONS: The use of MRI as an in-vivo model is a high-fidelity tool to study real time unaltered anatomy and allows for surgical preparation, diagnosis of anatomic variants and acts as a valuable teaching tool. STRENGTHS & LIMITATIONS: This is the first in-vivo model to report relevant retropubic anatomy in penile implant surgery. Our study is limited by sample size and inclusion of participants with no history of prior pelvic intervention. CONCLUSION: We demonstrate the utility of MRI as an in-vivo model, as opposed to cadaveric models, for the understanding of relevant retropubic anatomy for implant surgeons. Punjani N, Monteiro L, Sullivan J F et al. The Anatomical Relationships in the Space of Retzius for Penile Implants: An MRI Analysis. J Sex Med 2021;18:1830-1834.

Cumulative dietary risk assessment of chronic acetylcholinesterase inhibition by residues of pesticides.

A retrospective cumulative risk assessment of dietary exposure to pesticide residues was conducted for chronic inhibition of acetylcholinesterase. The pesticides considered in this assessment were identified and characterised in a previous scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the nervous system. The exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2016, 2017 and 2018, and individual food consumption data from 10 populations of consumers from different countries and from different age groups. Exposure estimates were obtained by means of a two-dimensional probabilistic model, which was implemented in SAS ® software. The characterisation of cumulative risk was supported by an uncertainty analysis based on expert knowledge elicitation. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides contributing to the chronic inhibition of acetylcholinesterase does not exceed the threshold for regulatory consideration established by risk managers.

Specific NLRP3 Inhibition Protects Against Diabetes-Associated Atherosclerosis.

Low-grade persistent inflammation is a feature of diabetes-driven vascular complications, in particular activation of the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome to trigger the maturation and release of the inflammatory cytokine interleukin-1ß (IL-1ß). We investigated whether inhibiting the NLRP3 inflammasome, through the use of the specific small-molecule NLRP3 inhibitor MCC950, could reduce inflammation, improve vascular function, and protect against diabetes-associated atherosclerosis in the streptozotocin-induced diabetic apolipoprotein E-knockout mouse. Diabetes led to an approximately fourfold increase in atherosclerotic lesions throughout the aorta, which were significantly attenuated with MCC950 (P < 0.001). This reduction in lesions was associated with decreased monocyte-macrophage content, reduced necrotic core, attenuated inflammatory gene expression (IL-1ß, tumor necrosis factor-α, intracellular adhesion molecule 1, and MCP-1; P < 0.05), and reduced oxidative stress, while maintaining fibrous cap thickness. Additionally, vascular function was improved in diabetic vessels of mice treated with MCC950 (P < 0.05). In a range of cell lines (murine bone marrow-derived macrophages, human monocytic THP-1 cells, phorbol 12-myristate 13-acetate-differentiated human macrophages, and aortic smooth muscle cells from humans with diabetes), MCC950 significantly reduced IL-1ß and/or caspase-1 secretion and attenuated leukocyte-smooth muscle cell interactions under high glucose or lipopolysaccharide conditions. In summary, MCC950 reduces plaque development, promotes plaque stability, and improves vascular function, suggesting that targeting NLRP3-mediated inflammation is a novel therapeutic strategy to improve diabetes-associated vascular disease.

Climacturia After Radical Prostatectomy: MRI-Based Predictors.

BACKGROUND: After radical prostatectomy (RP), climacturia is a prevalent and distressing problem. To date, no specific predictors have been identified. AIM: In this analysis, we sought to find associated pelvic magnetic resonance imaging (MRI) parameters. METHODS: We identified all men in our departmental database who (i) had climacturia post-RP, ≥3 episodes; (ii) underwent a pre-RP endorectal MRI; (iii) had no radiation or androgen deprivation therapy (ADT). Soft tissue and bony dimensions were measured by 2 raters blinded to clinical and pathological data. OUTCOMES: MRI parameters included the following: maximum height, width, and depth of prostate, prostate volume, urethral width and length, lower conjugate of pelvis, bony femoral width, outer and inner levator distances and thickness. Point-biserial correlations were run on univariate associations. Logistic regression was used for the multivariable model. RESULTS: 194 consecutive pre-RP MRI studies were reviewed (56 men with and 138 without climacturia). Mean age was 60 ± 7 years, average time post-RP at assessment, 7 ± 7 months. Of MRI parameters, urethral width (r = 0.13, P = .03) and lower conjugate (r = 0.12, P = .05) were associated with presence of persistent climacturia. 2 others met criteria for multivariable analysis, prostate depth and outer levator distance. Of the non-MRI parameters, none were significantly related to climacturia and only body mass index (BMI) met criteria for multivariable analysis. On multivariable analysis, only urethral width was associated with climacturia (OR = 1.23, 95% CI: 1.01-1.49, P = .04); the wider the urethra, greater the chance of climacturia. CLINICAL IMPLICATIONS: Improved ability to predict the occurrence of orgasm-associated incontinence in the preoperative setting. STRENGTHS AND LIMITATIONS: Limitations include the fact that the MRI endorectal probe may have distorted pelvic tissues during imaging and that our study population size was small. However, prospective data collection, blinded measurements by 2 trained readers, and rigorous statistical analysis should be considered strengths. CONCLUSION: By identifying preoperative risk factors, such as urethral width on MRI, we may be able to better understand the pathophysiology of this condition and furthermore may permit us to better counsel men regarding this postoperative outcome. Sullivan JF, Ortega Y, Matsushita K, et al. Climacturia After Radical Prostatectomy: MRI-Based Predictors. J Sex Med 2020;17:1723-1728.

Management of Climacturia During Inflatable Penile Prosthesis Surgery.

Radical prostatectomy, the preferred treatment option for organ-confined prostate cancer, is associated with a wide variety of sexual dysfunctions including erectile and orgasmic dysfunctions. Climacturia is a type of orgasmic dysfunction that has been reported to occur in 20-60% of men after radical prostatectomy. Several treatment strategies for climacturia have been evaluated and recommended including behavioral changes, use of special devices, medications, specialized therapies, and surgeries. Inflatable penile prosthesis implantation might be the treatment of choice when conservative management approaches fail to treat erectile dysfunction. In this review article, the different options and approaches for the management of climacturia during inflatable penile prosthesis surgery will be discussed.

Clinical predictors and risk factors for vaginal mesh extrusion.

PURPOSES: Our study aims to enhance the accuracy of the clinical diagnosis in patients with vaginal mesh extrusion following transvaginal mesh placement for pelvic organ prolapse using significant clinical parameters and risk factors. METHODS: All patients who underwent vaginal mesh removal were retrospectively reviewed from January 2000 to May 2014. Eligible patients were divided into two groups according to the presence of vaginal mesh extrusion. RESULTS: A total of 862 patients, 798 were included. 357 (44.7%) had evidence of vaginal mesh extrusion, and 441 (55.3%) had no evidence of vaginal mesh extrusion. The mean age of the vaginal mesh extrusion group was slightly higher than in the group without vaginal mesh extrusion (58.7 ± 11.2 vs. 56.4 ± 11.5, respectively; p = 0.002). From multivariate analysis, the significant clinical correlations for vaginal mesh extrusion were vaginal bleeding [60 (16.9) vs. 14 (3.2%), p < 0.001], hispareunia [48 (13.5) vs. 15 (3.4%), OR = 4.163, p < 0.001], and vaginal discharge [45 (12.6) vs. 18 (4.1%), p = 0.001]. The risk factors were multiple mesh implantations [218 (67.06) vs. 175 (39.68%), p < 0.001] and menopause [314 (88) vs. 364 (82.7%), p = 0.145]. Demographic data, including BMI, sexual activity, vaginal atrophy, both local and systemic hormonal use, smoking status, and hysterectomy status, were not significantly different, as well as the clinical symptoms including dyspareunia, vaginal infection, and symptomatic vaginal bulge. CONCLUSIONS: Vaginal bleeding, hispareunia, and vaginal discharge were the most significant clinical predictors for raising suspicion of vaginal mesh extrusion. Multiple mesh implantations were a significant risk factor for extrusion.

The Role of Chronic Mesh Infection in Delayed-Onset Vaginal Mesh Complications or Recurrent Urinary Tract Infections: Results From Explanted Mesh Cultures.

OBJECTIVES: Vaginal mesh complications necessitating excision are increasingly prevalent. We aim to study whether subclinical chronically infected mesh contributes to the development of delayed-onset mesh complications or recurrent urinary tract infections (UTIs). METHODS: Women undergoing mesh removal from August 2013 through May 2014 were identified by surgical code for vaginal mesh removal. Only women undergoing removal of anti-incontinence mesh were included. Exclusion criteria included any women undergoing simultaneous prolapse mesh removal. We abstracted preoperative and postoperative information from the medical record and compared mesh culture results from patients with and without mesh extrusion, de novo recurrent UTIs, and delayed-onset pain. RESULTS: One hundred seven women with only anti-incontinence mesh removed were included in the analysis. Onset of complications after mesh placement was within the first 6 months in 70 (65%) of 107 and delayed (≥6 months) in 37 (35%) of 107. A positive culture from the explanted mesh was obtained from 82 (77%) of 107 patients, and 40 (37%) of 107 were positive with potential pathogens. There were no significant differences in culture results when comparing patients with delayed-onset versus immediate pain, extrusion with no extrusion, and de novo recurrent UTIs with no infections. CONCLUSIONS: In this large cohort of patients with mesh removed for a diverse array of complications, cultures of the explanted vaginal mesh demonstrate frequent low-density bacterial colonization. We found no differences in culture results from women with delayed-onset pain versus acute pain, vaginal mesh extrusions versus no extrusions, or recurrent UTIs using standard culture methods. Chronic prosthetic infections in other areas of medicine are associated with bacterial biofilms, which are resistant to typical culture techniques. Further studies using culture-independent methods are needed to investigate the potential role of chronic bacterial infections in delayed vaginal mesh complications.

Glioblastoma cells induce differential glutamatergic gene expressions in human tumor-associated microglia/macrophages and monocyte-derived macrophages.

Glioblastoma cells produce and release high amounts of glutamate into the extracellular milieu and subsequently can trigger seizure in patients. Tumor-associated microglia/macrophages (TAMs), consisting of both parenchymal microglia and monocytes-derived macrophages (MDMs) recruited from the blood, are known to populate up to 1/3 of the glioblastoma tumor environment and exhibit an alternative, tumor-promoting and supporting phenotype. However, it is unknown how TAMs respond to the excess extracellular glutamate in the glioblastoma microenvironment. We investigated the expressions of genes related to glutamate transport and metabolism in human TAMs freshly isolated from glioblastoma resections. Quantitative real-time PCR analysis showed (i) significant increases in the expressions of GRIA2 (GluA2 or AMPA receptor 2), SLC1A2 (EAAT2), SLC1A3 (EAAT1), (ii) a near-significant decrease in the expression of SLC7A11 (cystine-glutamate antiporter xCT) and (iii) a remarkable increase in GLUL expression (glutamine synthetase) in these cells compared to adult primary human microglia. TAMs co-cultured with glioblastoma cells also exhibited a similar glutamatergic profile as freshly isolated TAMs except for a slight increase in SLC7A11 expression. We next analyzed these genes expressions in cultured human MDMs derived from peripheral blood monocytes for comparison. In contrast, MDMs co-cultured with glioblastoma cells compared to MDMs co-cultured with normal astrocytes exhibited decreased expressions in the tested genes except for GLUL. This is the first study to demonstrate transcriptional changes in glutamatergic signaling of TAMs in a glioblastoma microenvironment, and the findings here suggest that TAMs and MDMs might potentially elicit different cellular responses in the presence of excess extracellular glutamate.

Sex differences in translocator protein 18 kDa (TSPO) in the heart: implications for imaging myocardial inflammation.

Myocarditis is more severe in men than in women and difficult to diagnose due to a lack of imaging modalities that directly detect myocardial inflammation. Translocator protein 18 kDa (TSPO) is used extensively to image brain inflammation due to its presence in CD11b(+) brain microglia. In this study, we examined expression of TSPO and CD11b in mice with coxsackievirus B3 (CVB3) myocarditis and biopsy sections from myocarditis patients in order to determine if it could be used to image myocarditis. We found that male mice with CVB3 myocarditis upregulated more genes associated with TSPO activation than female mice. TSPO expression was increased in the heart of male mice and men with myocarditis compared with female subjects due to testosterone, where it was expressed predominantly in CD11b(+) immune cells. We show that TSPO ligands detect myocardial inflammation using microSPECT, with increased uptake of [(125)I]-IodoDPA-713 in male mice with CVB3 myocarditis compared with undiseased controls.

Deformity stabilization and improvement in men with untreated Peyronie's disease.

OBJECTIVE: To define predictors of the deformity stabilisation and improvement in men with untreated Peyronie's disease (PD). PATIENTS AND METHODS: The study population consisted of patients with PD-associated uniplanar curvature, who opted for no treatment and were followed for at least 12 months. All patients had deformity assessment (DA) performed on initial presentation and at follow-up. Stabilisation of PD was defined as no change between DAs (±10°), while improvement and progression were defined as ≥10° change. Patients were subdivided into different groups based on time to presentation: ≤6 months (A), 7-12 months (B), and 13-18 months (C). Multivariable analysis was used to define predictors of stabilisation and improvement. RESULTS: In all, 176 men met the inclusion criteria. The mean age was 54 years, with a mean (sd) PD duration of 9 (12) months and mean curvature of 42 (27)°. In all, 67% of the entire population had no change in deformity over time, 12% improved with a mean (sd) change of 27 (14)°, and 21% worsened with a mean (sd) change of 22 (11)°. On multivariate analysis, predictors of stabilisation included: time to presentation of >6 months (odds ratio [OR] 2.4, P < 0.01), per decade increase in age (OR 1.5, P < 0.05), and age (r = 0.32, P < 0.05). Predictors of improvement included: time to presentation of ≤6 months (OR 4.1, P < 0.001), and per decade decrease in age (OR 2.1, P < 0.01). CONCLUSIONS: In men with uniplanar curvature, PD stabilisation and improvement rates change with time-to-presentation and patient age. These data may aid in counselling patients with PD.

Comparison of laparoendoscopic single site (LESS) and conventional laparoscopic donor nephrectomy at a single institution.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Most transplant centres harvest living donor kidneys via a conventional laparoscopic surgical approach. Laparoendoscopic single-site donor nephrectomy (LESS-DN) is a relatively novel minimally invasive approach that allows the surgery to be performed via a single incision. This technique may be advantageous in decreasing surgical morbidity and improving cosmetic outcomes, thus plausibly reducing the barriers to kidney donation. The study demonstrates the safety and feasibility of LESS-DN in a large consecutive series of kidney donors. Comparative analysis between LDN and LESS-DN showed that there was a significant decrease in intra-operative blood loss and allograft warm ischaemia time in the LESS-DN group, but also a significant increase in operating time. Other peri-operative outcomes were similar between the two approaches. Evaluation of the LESS-DN cases alone revealed that, the operating times did not significantly change through the course of the series. Using this outcome as a surrogate for technical difficulty suggests a relatively shallow learning curve for LESS-DN. OBJECTIVE: To present a comparative analysis of peri-operative outcomes for >200 cases of conventional laparoscopic donor nephrectomy (LDN) and laparoendoscopic single site donor nephrectomy (LESS-DN). PATIENTS AND METHODS: From 2006 to 2011, 213 donor nephrectomies were performed by two surgeons (R.E.L and W.A.M.) at a tertiary transplant centre. The approach changed from conventional LDN to LESS-DN over the course of the series. The two approaches were compared retrospectively and evaluated for differences in peri-operative outcomes. Statistical significance was assessed using Student's t-test and chi-squared analysis. RESULTS: A total of 111 patients underwent LDN and 102 patients underwent LESS-DN. Total operating time was significantly longer in the LESS-DN group (206.1 vs 181.9 min, P < 0.001), but LESS-DN resulted in less intra-operative blood loss (61.5 mL vs 85.9 mL, P < 0.001) and shorter warm ischaemia times (4.4 vs 5.0 min, P = 0.01). There were no significant differences in analgesic requirements, subjective pain scores, length of hospital stay, postoperative graft function, or donor's postoperative glomerular filtration rate between the two approaches. Complication rates were low regardless of the approach, and there were no major complications (>grade II) in the LESS-DN group. CONCLUSIONS: In experienced hands, LESS-DN results in peri-operative outcomes similar to those of conventional LDN without compromising donor safety, while providing a desirable cosmetic result. For surgeons familiar with LDN, transitioning to the LESS approach using this technique appears to have a relatively short learning curve.

Complex rectovaginal fistulas after pelvic organ prolapse repair with synthetic mesh: a multidisciplinary approach to evaluation and management.

OBJECTIVES: The use of synthetic mesh for transvaginal pelvic organ prolapse (POP) repair is associated with the rare complication of mesh erosion into hollow viscera. This study presents a single-institution series of complex rectovaginal fistulas (RVFs) after synthetic mesh-augmented POP repair, as well as strategies for identification and management. METHODS: Institutional review board approval was obtained for this retrospective study. Data were collected and analyzed on all female patients undergoing RVF repair from 2000 to 2011 at our institution. RESULTS: Thirty-seven patients underwent RVF repair at our multidisciplinary center for restorative pelvic medicine. Of these, 10 (27.0%) were associated with POP repairs using mesh. The POP repairs resulting in RVF were transvaginal repair with mesh (n = 8), laparoscopic sacrocolpopexy with concomitant traditional posterior repair (n = 1), and robotic-assisted laparoscopic sacrocolpopexy (n = 1). Time to presentation was an average of 7.1 months after POP repair. Patients underwent a mean of 4.4 surgeries for definitive RVF repair, with 40% of patients requiring a bowel diversion (3 temporary ileostomies and 1 long-term colostomy). Mean follow-up time after last surgery was 9.2 months. On follow-up, 1 patient has a persistent fistula with vaginal mesh extrusion. One patient has persistent pelvic pain. CONCLUSIONS: This series highlights the significant impact of synthetic mesh complications in the posterior compartment. These complications should be cautionary for synthetic graft use by those with limited experience, particularly when an alternate choice of traditional repair is available. When symptoms of RVF are present, collaboration with a colon and rectal specialist should be initiated as soon as possible for evaluation and definitive repair.

Higher RENAL Nephrometry Score is predictive of longer warm ischemia time and collecting system entry during laparoscopic and robotic-assisted partial nephrectomy.

OBJECTIVE: To investigate the predictive value of the RENAL Nephrometry Score (RNS) on operative outcomes during both laparoscopic partial nephrectomy (LPN) and robotic-assisted partial nephrectomy (RPN). METHODS: We reviewed 67 consecutive patients with suspicious renal lesions and available radiographic data who underwent LPN or RPN by a single surgeon. Data included operative type, body mass index (BMI), gender, age, and side of tumor. RNSs were recorded using either magnetic resonance imaging or computed tomography scans. Warm ischemia time (WIT), estimated blood loss (EBL), and collecting system entry (CSE) were the endpoints for the analyses. RESULTS: Total RNS entered as a continuous or dichotomous variable (<7 or ≥ 7), R-score, and N-score were independent predictors of WIT on multivariable analyses (P <.001, P = .001, P = .026, and P <.01, respectively). The total RNS and N-score were predictive of CSE in univariate analysis (P <.001). Neither total RNS nor its individual components were predictive of EBL. CONCLUSION: Total RNS, as well as the N- and R-scores, can help predict both longer WIT and CSE during LPN and RPN. The RNS and its individual components may be useful in the preoperative planning and counseling of patients undergoing LPN or RPN.

Peyronie's disease in teenagers.

INTRODUCTION: Peyronie's disease (PD) is commonly seen in middle-aged men, and little is known about this condition in teenagers. AIM: To investigate the characteristics of PD in teenagers. METHODS: The findings were compared between patients with the disease who were teenagers with those over 40 years of age. Statistical analyses were conducted to define differentiating features between these two groups. MAIN OUTCOME MEASURES: The demographics, clinical features, and associated comorbidities of patients with PD were reviewed. RESULTS: Thirty-two teenaged males were evaluated for PD in a single institution over a 10-year period. The median age for our cohort was 18 (15-19) years. Forty-five percent of patients had already been seen by another urologist, and 28% had been told they did not have PD. The mean duration of PD before seeking medical care in our cohort was 3 ± 1 months. Sixteen percent of patients reported antecedent penile trauma, half of which happened during coitus or masturbation, and 18% of patients had hemoglobin (Hb) A1c levels > 5%. Dupuytren's contracture was not seen in this population. Twenty-two percent of patients presented with penile pain. Subsequent ED was seen in 37% of patients. Multiple noncontiguous plaques were seen in 37% of patients. Twelve percent were previously treated with vitamin E, while another 12% had previous intralesional verapamil. High distress was reported by 94% of patients. Thirty-four percent sought medical attention for anxiety/mood disorder, and 28% had a negative encounter with a sexual partner related to PD. All of the 32 patients had penile curvature with a mean of 32 ± 12 degrees. Seventy-two percent of the patients had dorsal curvature while 22% had an associated deformity. Using duplex Doppler ultrasound, 12% had a calcified plaque, while none of the patients had abnormal hemodynamics. When compared with PD in adults, teenagers had greater than seven times the prevalence of multiple noncontiguous plaques (37% vs. 5%). Also, the prevalence of HbA1c level > 5% was higher in the teenagers as well (18% vs. 5%). CONCLUSIONS: PD does occur in teenagers often causing high distress levels. Compared to older adults, teenagers often present earlier, and more commonly have elevated HbA1c level and increased number of plaques at presentation.

A single-center experience with prone retroperitoneoscopic versus open renal surgery in children: an age- and procedure-matched comparison.

PURPOSE: We determined how surgical outcomes differ among children undergoing prone retroperitoneoscopic (RP) and open total and partial nephrectomies for benign renal disease. PATIENTS AND METHODS: A retrospective analysis was performed, using medical records of children who were undergoing benign renal surgery at a single institution from 2001 to 2010. Patients were divided into open or RP cohorts, then subdivided into those who were undergoing total or partial nephrectomies. A further breakdown by age (<3 years and ≥3 years) was performed. Bilateral nephrectomies were separately evaluated. Surgical outcomes were compared across groups. RESULTS: There were 308 (333 renal units) children who underwent RP (n=154) or open (n=154) total or partial nephrectomies, 25 of which were bilateral (20 RP, 5 open); 199 patients underwent total nephrectomies (RP n=118, open n=81), and 109 underwent partial nephrectomies (RP n=36, open n=73). After controlling for age and concomitant procedures, operative times were similar for the RP total and bilateral nephrectomy groups, but longer for the RP partial nephrectomy group, compared with their open counterparts. In both total and partial nephrectomies, the RP group had a shorter hospital stay. There were no open conversions in any of the RP groups and no differences in complications in the total, partial, and bilateral analyses. There were 13 patients who previously received peritoneal dialysis (8 bilateral RP, 3 unilateral RP, and 2 unilateral open), all of whom resumed dialysis in a mean of 1.11 days. CONCLUSIONS: This is the largest series to date that compares RP and open renal surgeries in children. The RP and open approaches were comparably safe and efficacious. Hospital stays were significantly shorter in the RP total and partial groups, although operative times were significantly longer in the RP partial nephrectomy group. Prone retroperitoneoscopic surgery should be considered a viable option for renal surgery at any age.

Defining predictors of response to intralesional verapamil injection therapy for Peyronie's disease.

OBJECTIVE: • To assess factors that predict penile curvature responses to intralesional verapamil (ILV) injection therapy for men with Peyronie's disease (PD). PATIENTS AND METHODS: • Men with PD for <1 year were assessed at baseline and after 3 months of bi-monthly ILV-injection therapy. Curvature was assessed at the time of maximum penile rigidity. • Univariate relationships were tested with correlation or chi-square analyses. • Multivariate analyses included logistic and linear regression. • We analysed curvature improvement, defined as a decrease of ≥10 ° from baseline. Additionally, the relationship between curvature outcomes and patient age and degree of baseline penile curvature were assessed. RESULTS: • Data from 131 men were included and the rates of penile curvature change were:26% improved, 12% worsened, and 62% stable. • Age (r=-0.24, P < 0.01) and larger baseline penile curvature (r= 0.33, P < 0.01) were associated with improved curvature on univariate analysis. • On multivariate analysis (logistic regression), both age [odds ratio (OR) 0.93, P < 0.01, 95%CI 0.89-0.97] and larger baseline penile curvature (OR 1.07, P < 0.01, 95%CI 1.04-1.11) were associated with improvements in curvature after ILV-injection therapy. • Improvements in curvature were associated with age (≤40 years vs >40 years; OR 0.27, P < 0.05, 95%CI 0.10-0.75) and degree of penile curvature at baseline (≤30 ° vs >30 °; OR 9.12, P < 0.01, 95%CI 1.94-42.84) when dichotomized as indicated. CONCLUSION: • Younger age and larger baseline penile curvature were predictive of favourable curvature outcomes. • Analysis of dichotomized variables suggests that age and baseline curvature thresholds may be important to consider when deciding on ILV as a therapeutic strategy for PD.

Erectile dysfunction after plaque incision and grafting: short-term assessment of incidence and predictors.

INTRODUCTION: Plaque incision and grafting (PIG) surgery for Peyronie's disease (PD) is a recognized management strategy. One of the recognized complications of PIG surgery is the development of postoperative erectile dysfunction (ED). AIM: To determine the incidence of ED after PIG surgery and attempt to define predictors of ED development. METHODS: All patients underwent preoperative cavernosometry. Grafting was performed with either cadaveric pericardium (Tutoplast) or intestinal submucosa (Surgisis). Prior to 2006, the procedure used an H-type incision, whereas after this date, the Egydio approach has been used. MAIN OUTCOME MEASURES: Men undergoing PIG completed preoperative and 6-month postoperative International Index of Erectile Function (IIEF) questionnaires. RESULTS: 56 patients were analyzed. Mean patient and partner ages were 57 ± 22 and 54 ± 18 years, respectively. Mean duration of PD at the time of PIG was 22 ± 9 months. Seventy-five percent had curvature alone, 11% had hourglass/indentation deformity, and the remainder had combined curvature/indentation. Mean preoperative curvature was 52 ± 23°. Fifty-two had grafting with Tutoplast, while four had grafting with Surgisis. All men at baseline were capable of generating a penetration rigidity erection. Preoperatively, 50% of men had cavernosal insufficiency and 21% had venous leak (baseline and postoperative erectile function [EF] domain scores were 23 ± 4 and 17 ± 9, respectively [P < 0.01]). Forty-six percent of men experienced a ≥6-point decrease in EF domain score after PIG. The predictors of a ≥6-point reduction in IIEF-EF domain score on multivariable analysis were degree of preoperative curvature, type of plaque incision, patient age, and baseline venous leak. Conclusions. Almost one-half of men had significant reduction in their erectile rigidity after PIG. Reduction was predicted by larger baseline curvature, the Egydio plaque incision technique, older patient age, and the presence of venous leak at baseline. Based on these data, we discourage older men, those with venous leak, and those with profound curvature from considering PIG surgery.

Translocator protein (18 kDa)/peripheral benzodiazepine receptor specific ligands induce microglia functions consistent with an activated state.

In the brain, translocator protein (18 kDa) (TSPO), previously called peripheral benzodiazepine receptor (PBR), is a glial protein that has been extensively used as a biomarker of brain injury and inflammation. However, the functional role of TSPO in glial cells is not well characterized. In this study, we show that the TSPO-specific ligands R-PK11195 (PK) and Ro5-4864 (Ro) increased microglia proliferation and phagocytosis with no effect on migration. Both ligands increased reactive oxygen species (ROS) production, and this effect may be mediated by NADPH-oxidase. PK and Ro also produced a small but detectable increase in IL-1ß release. We also examined the effect of PK and Ro on the expression of proinflammatory genes and cytokine release in lipopolysaccharide (LPS) and adenosine triphosphate (ATP) activated microglia. PK or Ro had no effect on LPS-induced increase of pro-inflammatory genes, but they both decreased the ATP-induced increase of COX-2 gene expression. Ro, but not PK, enhanced the LPS-induced release of IL-1ß. However, Ro decreased the ATP-induced release of IL-1ß and TNF-α, and PK decreased the ATP-induced release of TNF-α. Exposure to Ro in the presence of LPS increased the number of apoptotic microglia, an effect that could be blocked by PK. These findings show that TSPO ligands modulate cellular functions consistent with microglia activation. Further, when microglia are activated, these ligands may have therapeutic potential by reducing the expression of pro-inflammatory genes and cytokine release. Finally, Ro-like ligands may be involved in the elimination of activated microglia via apoptosis.

Predicting delay in presentation in men with Peyronie's disease.

INTRODUCTION: Many men with Peyronie's disease (PD) delay presentation to a urologist. The reasons for this are unclear. AIM: To define the differences in men who present early compared to those presenting in a delayed fashion and to determine predictors of delayed presentation. METHODS: A retrospective analysis of all patients presenting for the first medical evaluation of PD. All patients underwent a standard history and physical examination and had a standardized deformity assessment. Demographic and PD parameters were recorded. MAIN OUTCOME MEASURES: Statistical comparison was used to define factors that were different between early and delayed presenters and multivariable analysis was used to define predictors of presentation >12 months. RESULTS: 482 patients were analyzed, 61% presenting ≤12 months, 39% >12 months. Mean patient age was 52 ± 13 years and mean duration of PD was 17 ± 30 months. Mean measured curvature was 42° ± 19°. Multivariable analysis revealed that delayed presentation patients were significantly more likely to be older (odds ratio [OR] = 4.0), to be in long-term relationships (OR = 3.6), to have dorsal curvature (OR = 2.5), to have curvature <45° (OR = 3.3), to be heterosexual (OR = 2.0), and to have simple deformity (OR = 1.5). CONCLUSIONS: One-third of men with PD presented in a delayed fashion and they tended to be older, to be in long-term relationships, to have dorsal curvature, or to have simple deformity.

Silica-based nanoparticle uptake and cellular response by primary microglia.

BACKGROUND: Silica nanoparticles (SiNPs) are being formulated for cellular imaging and for nonviral gene delivery in the central nervous system (CNS), but it is unclear what potential effects SiNPs can elicit once they enter the CNS. As the resident macrophages of the CNS, microglia are the cells most likely to respond to SiNP entry into the brain. Upon activation, they are capable of undergoing morphological and functional changes. OBJECTIVE: We examined the effects of SiNP exposure using primary rat microglia. METHODS: We observed microglial uptake of SiNPs using transmission electron and fluorescence confocal microscopy. Microglial functions, including phagocytosis, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), expression of proinflammatory genes, and cytokine release, were measured after SiNP exposure at different concentrations. RESULTS: Microglia are capable of avidly taking up SiNPs at all concentrations tested. These same concentrations did not elicit cytotoxicity or a change in phagocytic activity. SiNPs did increase the productions of both intracellular ROS and RNS. We also observed a significant decrease in tumor necrosis factor-alpha gene expression at all concentrations tested and a significant increase in COX-2 (cyclooxygenase-2) gene expression at the highest concentration of SiNPs. Analysis of cytokine release showed a detectable level of interleukin-1beta. CONCLUSIONS: This is the first study demonstrating the in vitro effects of SiNPs in primary microglia. Our findings suggest that very low levels of SiNPs are capable of altering microglial function. Increased ROS and RNS production, changes in proinflammatory genes, and cytokine release may not only adversely affect microglial function but also affect surrounding neurons.