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The use of barrier layers between the neourethra and skin is associated with lower rates of post-operative urethrocutaneous fistula (UCF) following hypospadias surgery. Recent studies have evaluated the ability of biologic adjuvant urethral coverings (BAUCs) - namely acellular matrix (AM), tissue adhesives (TAs), and autologous platelet-rich plasma or fibrin (PRP/PRF) - to prevent wound complications following hypospadias surgery. In general, however, these studies are small and conducted at single institutions.To assess the effect of BAUCs on the rate of UCF following single-stage primary hypospadias repair.We conducted a systematic review of studies reporting the rate of postoperative UCF in pediatric patients undergoing single-stage, primary hypospadias repairs using either AM, TA, or PRP/PRF as a layer interposed between the neourethra and skin. We then performed a pooled proportional meta-analysis of post-operative UCF. Patients within each study who underwent comparable surgery but did not receive a BAUC were used as controls.10 studies were included in our review. The meta-analysis included 280 patients from 7 studies who underwent hypospadias repairs with BAUCs. The pooled incidence of UCF was 10% (95% CI 6-14%). Mean follow-up ranged 5-23.5 months in the 5/7 studies reporting specific durations, and ≥6 month and 14-30 months, respectively, in the other two studies. Patients in whom a BAUC was used had significantly lower odds of UCF than control patients (OR 0.39, 95% CI 0.24-0.64, p = 0.0002). In subgroup analyses, significant superiority held for AM and TA; proximal or penoscrotal cases; transverse preputial island flap (TPIF) technique; when both cases and controls had local flaps; and when neither cases nor controls had flaps.The use of BAUCs was associated with decreased rates of post-operative UCF in single-stage primary hypospadias repairs and may be most beneficial in more severe cases and when used in addition to local flaps or when using a flap is not possible. In 2/3 studies of PRP/PRF and 2/4 studies of tubularized incised plate (TIP) technique, dartos flaps were used in controls but not BAUC patients, which may explain the lack of benefit demonstrated for these subgroups. This meta-analysis is limited by the quality of evidence in the included studies, which are not uniformly randomized. Furthermore, the follow-up durations and methods for assessing complications are not standardized between included studies.The meta-analysis herein suggests that using BAUCs may reduce UCF rates following hypospadias surgery. Rigorous prospective evaluation is needed to validate this benefit.

Virilization of the 46,XX infant may be attributed to maternal or fetoplacental origin. Maternal sources may be endogenous, as with an androgen-producing tumor, or drug-related. Iatrogenic virilization by maternal drug exposure is rarely reported, with individual case reports and case series demonstrating the effects of progesterone and other medications affecting the pituitary-ovarian axis.1–3 The class of medications known as aromatase inhibitors are recognized as effective in treating hormone receptor-positive breast cancer by preventing the conversion of androgens into estrogens by aromatase. In fetal development, placental aromatase plays a critical role in preventing virilization of the XX fetus by maternal and fetal androgens during development. In the setting of placental aromatase deficiency, the XX fetus may be virilized. It is conceivable, therefore, that maternal exposure to aromatase inhibitors early in gestation may lead to in utero virilization, though there have been no known reports of this phenomenon to date. We present a case of virilization of a 46,XX infant attributed to pharmacologic aromatase inhibition. The infant’s parents provided informed consent for the reporting of this case.

Congenital megalourethra, first described in 1955, is a rare urethral anomaly resulting from dysgenesis of the penile corpus spongiosum, with or without corpus cavernosum involvement, leading to dilatation of the penile urethra. Presentations come in two forms, scaphoid and fusiform, with the former being more common and resulting from deficient or absent corpus spongiosum. Fusiform types are much rarer, and consist of absence of both the corpus spongiosum and cavernosum.3 Here, we present a case involving the surgical correction of an isolated scaphoid-type congenital megalourethra with significantly improved postoperative cosmetic and functional outcomes.

Nocturia negatively impacts the quality of life and is associated with poor general health, but our understanding of its etiologies is incomplete. Urodynamic studies (UDS) findings in patients with nocturia are not well described and may help guide management. Our objective was to compare UDS findings with age-matched patients with and without nocturia.We retrospectively reviewed UDS findings of 1124 patients (2010-2017). A total of 484 (43%) presented with nocturia and 821 (73%) were female. Female patients were separated into age-matched groups with and without nocturia. Urinary symptoms, past medical diagnoses, demographic information, and UDS findings were compared.A total of 596 female patients were included, 298 (50%) with nocturia and 298 without. Past medical history, including diabetes mellitus and cardiovascular disease, did not differ between groups. Patients with nocturia were more likely to have pelvic pain (p = 0.0014) and other daytime symptoms (frequency, urgency, and urgency incontinence). On UDS, patients with nocturia were more likely to have bladder outlet obstruction (BOO) (p = 0.025) and dysfunctional voiding (DV) (p 0.0001). There was no difference in the frequency of detrusor overactivity (DO). Bladder capacity and postvoid residual volumes were lower, though not significantly, in the nocturia group.When comparing UDS findings in contemporary, age-matched groups of female patients with and without nocturia, we found only BOO and DV to be associated with nocturia. While the treatment of nocturia is often aimed at managing DO, our data suggest that this may not be the primary urodynamic correlation with nocturia. Further studies are needed to assess whether successful treatment of BOO and DV can improve nocturia.

Introduction and ObjectivesThe standardization of fetal sonography has enabled early detection of genitourinary anomalies and referral for prenatal counseling with pediatric urologists. Prenatal urologic consultation can determine the need for antenatal and postnatal intervention, assuage parental anxiety, and establish continuity of care. The COVID-19 pandemic led to a significant increase in virtual visits (VVs). Our aim was to characterize a cohort of patients who underwent prenatal VVs with pediatric urologists and to assess adherence to prenatal recommendations for neonatal urologic care.Materials and MethodsData were collected through retrospective chart review of all patients receiving prenatal virtual consultation for genitourinary anomalies at our institution from July 1, 2020 to September 30, 2021. Data collected include maternal and gestational age at the time of prenatal imaging and VV, diagnosis of the fetus and neonate, and adherence to pediatric urological recommendations.ResultsDuring the study period, there were 70 prenatal VVs for 69 singleton and 1 twin gestation. 84 prenatal genitourinary diagnoses were made in these 71 cases. Of the 56/71 children known to have been born by the time of analysis, there are 63 postnatal genitourinary diagnoses. Postnatal diagnoses were consistent (38/56, 68%) or partially consistent (16/56, 29%) with prenatal diagnoses in 54/56 neonates (96%). There was 100% adherence to the postnatal imaging and antibiotic recommendations. One patient failed to attend the postnatal visit and one patient is due for repeat postnatal imaging to determine the necessity of follow-up.ConclusionsPrenatal VVs promoted effective counseling of genitourinary anomalies and were associated with impressive postnatal adherence to prenatal recommendations. This is, to our knowledge, the first study to assess the impact of prenatal virtual pediatric urological consultation on postnatal adherence to prenatal recommendations. Future study will benefit from survey of the patient VV experience and evaluation of the relative merits of virtual versus in-person prenatal visits in a prospective, randomized fashion.

Radiation-induced hemorrhagic cystitis is a complication of pelvic radiotherapy, with an incidence of up to 5%. The resultant hematuria may be severe and refractory to conservative measures. Our objective was to describe the pattern of inpatient treatments among a cohort of patients with radiation-induced hemorrhagic cystitis requiring pharmacological management.We conducted a retrospective case series to identify all inpatient admissions at a single institution during which patients with radiation cystitis underwent pharmacological intervention for refractory hematuria between 2004 and 2019. Patient demographics, medical history, details of radiation therapy, and relevant admission data were collected. Details of treatment, including the use of pharmacotherapy and surgical treatment, were reviewed and summarized.We identified 21 patients who were treated during 26 admissions. Most were male (91%) with a history of external beam radiation therapy (86%), primarily for prostate cancer (85%), and a median age of 73 (IQR: 67-85). Most patients received continuous bladder irrigation as the first intervention during their admission (65%), for a median duration of 40 hours (IQR: 25-59). Eleven separate pharmacologic agents were used, with variations in initial pharmacotherapy utilization over time. Most patients were treated with a combination of surgical and pharmacological interventions (85%). The median length of stay was 9 days (IQR: 5-17) and the 90-day readmission rate was 35%.Pharmacologic treatment for refractory radiation-induced hemorrhagic cystitis is inconsistent and lacks evidence to support treatment strategies. Further work is needed to determine the optimal management for this morbid complication.

Partial cystectomy (PC) is a bladder sparing option to treat bladder cancer in a carefully selected group of patients. We sought to analyze outcomes of partial cystectomy (PC) in a contemporary cohort of patients at a single institution.Records were reviewed for 43 patients with a primary urothelial carcinoma (UC) who had a partial cystectomy with curative intent at Columbia University Medical Center from 2004 to 2019. Endpoints of interest were noninvasive recurrence (defined as any recurrent nonmuscle invasive disease), advanced recurrence (defined as a muscle invasive recurrence or metastasis), and death. We used unadjusted Cox proportional hazards regressions and log rank tests to estimate the association between clinical characteristics and endpoints of interest.Among 43 patients with bladder cancer treated with partial cystectomy, median patient age was 73 years (interquartile range 67-77.5) and 86% were male. Twenty-three percent of patients received preoperative neoadjuvant chemotherapy (NAC) and 49% of patients were given perioperative intravesical chemotherapy at the time of PC. Pathologic stage wasT2 for 23 (53%) patients and ≥T2 for 20 (47%) patients. Pathology showed 14% of patients had lymph node involvement, and 9% had positive surgical margins. Mean follow-up was 51 months (range 1-176). Five-year overall survival was 78%. Of 43 patients, 23 patients (53%) had no recurrence, 9 patients (21%) experienced noninvasive intravesical recurrence, and 11 patients (26%) experienced advanced recurrences. Two patients (5%) required salvage radical cystectomy and 8 patients (19%) died of bladder cancer. On univariate analysis, lymphovascular invasion (hazard ratio [HR] 4.4, confidence interval [CI] 1.3-14.3), pathological stage (HR 5.9, CI 1.3-27.4), and NAC (HR 6.5, CI 1.9-22.7) were associated with advanced recurrence. Noninvasive recurrence was associated with not receiving perioperative intravesical chemotherapy (HR 0.7, CI 0.1-6.0).In well-selected patients, partial cystectomy offers adequate local control of bladder cancer. The risk of systemic progression is similar to reported case series of RC.

Objective To investigate the outcomes of mixed-grade non-muscle invasive bladder cancer (NMIBC) based on the degree of high-grade predominance. Methods We identified patients in our institutional database who had a transurethral resection of bladder tumor(s) for NMIBC. Tumors with mixed-grade features on pathology report were reanalyzed, assigned the percentage high-grade component, and stratified into ≤ 5% high-grade and > 5% high-grade groups. All others were classified as low-grade or high-grade NMIBC. Differences in recurrence-free survival were assessed by log-rank test. A multivariable Cox regression model was used to evaluate the impact of tumor grade on recurrence, controlling for tumor stage, size, multifocality, and intravesical therapy. Results Two hundred and twenty patients were followed for a median of 2 years; 127 (58%) had low-grade NMIBC, 66 (30%) had high-grade NMIBC, and 27 (12%) had mixed-grade NMIBC. Of the mixed-grade patients, 14 had a ≤ 5% high-grade component, and 13 had a > 5% high-grade component. Recurrence rates across all groups ranged from 42% to 79%. There was no significant difference in intravesical recurrence-free survival among the grade categories as assessed by log-rank test. On multivariable Cox regression analysis, grade category was not significantly associated with likelihood of recurrence. Conclusions The prognosis of mixed-grade histology in NMIBC has not previously been well defined. Although grade category was not found to be an independent significant predictor of recurrence, the recurrence rate for mixed-grade tumors was quite high overall. Further studies are required to better understand appropriate risk stratification and treatment of mixed-grade NMIBC.

Background Bladder-sparing treatment of muscle invasive bladder cancer (MIBC) with systemic chemotherapy plus transurethral resection of bladder tumors (TURBT) is increasingly seen in the literature -both in case series and subanalyses of patients who opt out of or are unfit for radical cystectomy (RC). Survival outcomes among these patients are often impressive, but these are typically small retrospective studies from single institutions and therefore of limited clinical value. Objectives Our aim is to summarize the literature regarding definitive treatment of MIBC with systemic chemotherapy plus TURBT and provide a meta-analysis of survival outcomes for patients who received this treatment. Methods A systematic literature search was performed consistent with the Prisma statement to identify publications reporting the outcomes of patients treated with TURBT and systemic chemotherapy as definitive treatment for locally confined MIBC. Identified studies were screened in a two-stage process: first by title and abstract; then by full-text reading. 18 publications (518 patients) were included in the qualitative systematic review and 10 publications (266 patients) were included in the meta-analysis. The primary objective was overall survival (OS). Results Overall survival ranged from 20% to 87.5% across studies at median follow-up ranging 4 to 120 months. 5-year survival rate for all patients included in the meta-analysis was estimated to be 72% [95% CI: 64%, 82%]. Conclusions Definitive treatment with systemic chemotherapy plus TURBT can lead to favorable survival outcomes in select patients. Further study to improve patient selection for this method of treatment is needed.

Introduction Over 1,500 bladder cancers were diagnosed among US Veterans in 2010, the majority of which were non-muscle invasive bladder cancer (NMIBC). Little is known about NMIBC treatment within the Veterans Health Administration. The objective of the study was to assess the quality of care for Veterans with newly-diagnosed NMIBC within Veterans Integrated Service Network (VISN) 02. Materials and Methods We used ICD-9 and ICD-10 codes to identify patients with newly-diagnosed bladder cancer from 1/2016–8/2017. We risk-stratified the patients into low, intermediate, and high-risk based on the 2016 American Urological Association Guidelines on NMIBC. Our primary objectives were percentages of transurethral resection of bladder tumors (TURBTs) with detrusor, repeat TURBT in high-risk and T1 disease, high-risk NMIBC treated with induction intravesical therapy (IVT), and responders treated with maintenance IVT. We performed logistic regression for association between distance to diagnosing hospital and receipt of induction IVT in high-risk patients. Results There were 121 newly-diagnosed NMIBC patients; 16% low-risk, 28% intermediate-risk, and 56% high-risk. Detrusor was present in 80% of all initial TURBTs and 84% of high-risk patients. Repeat TURBT was performed in 56% of high-risk NMIBC and 60% of T1. Induction IVT was given to 66% of high-risk patients and maintenance IVT was given to 59% of responders. On multivariate logistic regression, distance to medical center was not associated with receipt of induction IVT (OR = 0.99, 95% CI [0.97,1.01], p = 0.52). Conclusions We observed high rates of sampling of detrusor in the first TURBT specimen, utilization of repeat TURBT, and administration of induction and maintenance intravesical BCG for high-risk patients among a regional cohort of US Veterans with NMIBC. While not a comparative study, our findings suggest high quality NMIBC care in VA VISN 02.

There is emerging evidence identifying microRNAs (miRNAs) as mediators of statin-induced cholesterol efflux, notably through the ATP-binding cassette transporter A1 (ABCA1) in macrophages. The objective of this study was to assess the impact of an HMG-CoA reductase inhibitor, pitavastatin, on macrophage miRNAs in the presence and absence of oxidized-LDL, a hallmark of a pro-atherogenic milieu. Treatment of human THP-1 cells with pitavastatin prevented the oxLDL-mediated suppression of miR-33a, -33b and -758 mRNA in these cells, an effect which was not uniquely attributable to induction of SREBP2. Induction of ABCA1 mRNA and protein by oxLDL was inhibited (30%) by pitavastatin, while oxLDL or pitavastatin alone significantly induced and repressed ABCA1 expression, respectively. These findings are consistent with previous reports in macrophages. miRNA profiling was also performed using a miRNA array. We identified specific miRNAs which were up-regulated (122) and down-regulated (107) in THP-1 cells treated with oxLDL plus pitavastatin versus oxLDL alone, indicating distinct regulatory networks in these cells. Moreover, several of the differentially expressed miRNAs identified are functionally associated with cholesterol trafficking (six miRNAs in cells treated with oxLDL versus oxLDL plus pitavastatin). Our findings indicate that pitavastatin can differentially modulate miRNA in the presence of oxLDL; and, our results provide evidence that the net effect on cholesterol homeostasis is mediated by a network of miRNAs.

4522Background: Neoadjuvant platinum-based chemotherapy (NAC) followed by radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer (MIBC). High morbidity and mortal...

Science, technology, engineering and mathematics (STEM) policies in the Gulf Arab States are as diverse as the individual economies and political processes that characterize its member states. During the past decade, a number of expert review groups have argued that science and technology policy needs to be reformed and revitalized in the Gulf Arab States. Several reports and studies have identified the need to develop and adopt more rigorous plans to raise the level of research and development (RD 2) how effective are the science policies enacted by regional governments in the Gulf, and how can these policies be enhanced; 3) what role do regional or international collaborations play in a research and training network system, and how can these regional partnerships be bolstered; and, 4) how can the international community assist to accelerate progress and reduce the science knowledge gap. Our results show that the under-performance of the Gulf region in science and technology appears to be due to a: 1) lack of early exposure of young adults to science, 2) low perception of the societal value of science, 3) lack of institutional (e.g. university) resources, 4) too few scientists who make science their long-term careers, 5) lack of an integrated, international research network of collaboration, and 6) lack of motivation among students. We also report on our findings regarding the state-of-the-art of the research enterprise, and the strengths and weaknesses of the research and training environment as perceived by educators/administrators in the region.

A prospective study of preoperative exercise testing was carried out in 200 patients older than 40 years scheduled for elective major noncardiac surgery under general anesthesia. The exercise test response was electrocardiographically positive in 32 patients (16%) (2 patients had a markedly positive test), equivocal in 11 patients (5.5%) and negative in 157 patients (78.5%). The patients were followed with serial pre- and postoperative electrocardiograms (ECGs) and determinations of serum creatine kinase (CK) and CK-MB. Six patients (3%) had primary endpoints: 3 (1.5%) died postoperatively and 3 (1.5%) had definite postoperative myocardial infarction. Secondary endpoints of suspected postoperative myocardial ischemia/injury diagnosed by ECG or elevation in CK-MB levels occurred in 27 patients (14%). Endpoint events were more common in patients aged 70 years or older. Endpoint events were also more common in patients with an abnormal (positive or equivocal) preoperative exercise test response than in those with a negative response (27% vs 14%); however, preoperative exercise results were not statistically significant independent predictors of cardiac risk. Using multivariate analysis, the only statistically significant independent predictor of risk was the preoperative ECG. Endpoint events were more common in patients with an abnormal than in those with a normal ECG (23% vs 7%, p less than 0.002). Because the results of exercise testing do not appear to add substantially to the risk separation provided by the ECG at rest, exercise testing is not recommended as a routine preoperative method for assessing perioperative risk in older patients who are being evaluated before major elective noncardiac surgery under general anesthesia.

• To determine the cost-effectiveness of routine use of serial SGOT, lactic dehydrogenase (LDH), and LDH isoenzyme determinations in patients with suspected acute myocardial infarction (AMI), 166 consecutive patients admitted to a coronary care unit were prospectively identified and clinical findings analyzed independently using predetermined criteria. Based on chest pain characteristics, ECG, and creatine kinase—MB (CK-MB) results, patients were placed in categories of definite AMI (31%), possible AMI (34%), or AMI excluded (36%). The SGOT and/or LDH patterns were considered positive (ie, suggestive of AMI) in 82% of the patients with definite AMI but only confirmed CK-MB results. Positive SGOT/LDH results yielded new clinically relevant information in only 14 patients (8%). Total charges for SGOT/LDH determinations in these 166 patients totaled $10,938 or approximately $780 for each additional clinically important positive result. When serial ECG and CK-MB results are available,routineserial SGOT/LDH determinations are not justified. (Arch Intern Med1983;143:1541-1543)