Moshe Wald’s research while affiliated with University of Iowa Children's Hospital and other places

Introduction Many factors influence patient and provider decisions to surgically correct vesicoureteral reflux (VUR), including risk of breakthrough febrile urinary tract infections and likelihood of spontaneous resolution. Ureteral diameter ratio has been shown in several studies to be more predictive than reflux grade with regard to breakthrough urinary tract infection (UTI). We developed and investigated the accuracy of a computational model for predicating febrile breakthrough urinary tract infection within 13 months of starting prophylactic antibiotics in children with VUR. Objective The aim of this study was to validate a model for evaluating the impact of distal ureteral diameter ratio (UDR) in predicting early breakthrough urinary tract infections in children with VUR. Study Design Following a retrospective review, we recorded patient demographics, presenting symptoms, VUR grade, laterality, VUR during filling or voiding, initial bladder volume at the onset of VUR, ureteral duplication, voiding dysfunction, distal ureteral diameter ratio, and number of UTIs prior to VUR diagnosis. NeUROn++, a set of C++ programs, was used to model each data set using logistic regression and neural networks with different architectures. Results After exclusions, 136 children (93 girls and 43 boys) diagnosed with primary VUR had detailed VCUG and UDR data available. Fourteen children (10.3%) experienced breakthrough febrile UTI events within 13 months of VUR diagnosis. There was a significant association with UDR and breakthrough UTI (p=0.008). Various computational prediction models for the outcome of breakthrough UTI were developed and evaluated. The computational model that fit best was a model using all variables with an ROC of 0.802. Discussion and Conclusions Clinicians and parents often opt for intervention based on likelihood of spontaneous resolution of VUR as well as clinical course, thereby placing an emphasis on the ability to predict likelihood of breakthrough UTI infections. Our statistical analysis and prediction models further confirm UDR as an important variable predictive of breakthrough UTIs within the first 13 months of beginning prophylactic antibiotics. Furthermore, we developed a neural network model incorporating UDR and grade with an ability to yield the greatest accuracy of any breakthrough UTI predictive calculator to date at 80%.

Objective: This study aimed to determine whether the length of the excised obstructed vas deferens at vasovasostomy (VV) performed for fertility is associated with semen parameters and/or pregnancy outcomes postoperatively. Material and methods: The patients who underwent a VV at our institution from September 2004 to December 2018 were contacted via questionnaire and a chart review was performed. Linear and logistic regression models were used to determine the associations between the length of the obstructed vas deferens removed and postoperative outcomes including sperm concentration, motility, and successful pregnancy after reversal. Results: A total of 83/170 questionnaires were returned. After exclusions, a total of 35 patients were included for analysis. The mean age of the patients at the time of surgery was 40.1 years and the mean time since vasectomy 9.3 years. The mean length of the obstructed vas deferens removed during VV was 2.25 cm. The longer the vas deferens segments removed, the more significant was the increase in sperm motility at 3 and 9 months postoperatively (p=0.011 and 0.008, respectively), but decreased sperm motility at 6 months (p=0.029). In 75.9% of the patients, sperm was present postoperatively, 23.2% achieved pregnancy through natural conception, and 55.8% achieved pregnancy using assisted reproductive techniques. There was no significant relationship between the length of the vas deferens removed and sperm concentration or pregnancy achieved after surgery. Conclusion: In this cohort, the length of the excised obstructed vas deferens at VV was associated with improved sperm motility at 3 and 9 months postoperatively but not with pregnancy outcomes.

A 53-year-old man with a history of colon adenocarcinoma and remote scrotal trauma resulting in a palpable nodule. Gradual increase in the size of this lesion over the year prior to his presentation to our clinic prompted scrotal ultrasound that demonstrated a 1.1 cm solid lesion, which appeared to arise from the right epididymal tail. Subsequent positron emission tomography (PET) scan showed intense focal uptake at the base of the right testicle, suspicious for epididymitis versus underlying neoplasm. Scrotal exploration through an inguinal approach revealed a paratesticular mass. Frozen section from an excisional biopsy was positive for adenocarcinoma. Radical orchiectomy was completed. Final pathology returned as metastatic adenocarcinoma involving soft tissue; testis and spermatic cord were without diagnostic abnormalities and surgical margins were not involved. Subsequent analysis was consistent with colorectal origin. The patient recovered well from surgery and is continuing treatment of metastatic colon cancer per the medical oncology team.

Grafting of the male reproductive tract is an exciting new area of tissue engineering which may allow natural conception for patients with significant lengths of obstructed vas deferens. While stents had a significant and important role in increasing patency and pregnancy rates in the pre-microsurgical era, their role in the modern era of microsurgical two-layered anastomosis remains to be defined. To date, if the vasal obstruction is amenable to a primary watertight, tension-free anastomosis, microsurgical non-stented techniques remain the gold standard. Cases where a tension-free anastomosis is not possible because of the physical length of the obstruction remain problematic, but further research into tissue engineering in the form of implantable conduits holds much promise.

Clomiphene citrate (CC) is used off‐label as a treatment for selected cases of male infertility, acting as a competitive selective‐estrogen receptor modulator. Although CC is used clinically, there have only been a small number of randomized controlled human studies that have yielded inconclusive findings. Here we have used a prospective animal model for studying CC treatment to determine if this drug increases spermatogenesis for treatment of male infertility. We treated sexually mature Sprague‐Dawley rats with CC via oral gavage for either 1 or 2 rat spermatogenic cycles (13 days for 1 cycle or 26 days for 2 cycles) at a dose of 0.6 mg/kg. This dose was chosen as it is a similar dose to what is clinically used in humans. Testes were weighed and sperm counts were measured from rats treated with CC and control animals. Testes were fixed in modified Davidson's solution and stained with HE for histopathological and morphometric analysis. No differences in sperm count and no histomorphologic differences were noted in the testes treated with CC as compared to control. Seminiferous tubule minimum diameter and tubular epithelial height were measured and the number of retained spermatozoa was also scored with no significant differences compared to control. Although previous studies have shown that rats treated with much higher doses of CC (>20 mg/kg) have decreased spermatogenesis, we can conclude that CC treatment at a therapeutic dose of 0.6 mg/kg in rats does not appear to have an effect on spermatogenesis. That said; CC may play a more indirect role in male infertility which may include changes in accessory reproductive organs or alterations in hormonal levels. Support or Funding Information Internal funding; Department of Urology, University of Iowa

Introduction and objective: Factors influencing the decision to surgically correct vesicoureteral reflux (VUR) include risk of breakthrough febrile urinary tract infection (fUTI) or renal scarring, and decreased likelihood of spontaneous resolution. Improved identification of children at risk for recurrent fUTI may impact management decisions, and allow for more individualized VUR management. We have developed and investigated the accuracy of a multivariable computational model to predict probability of breakthrough fUTI in children with primary VUR. Study design: Children with primary VUR and detailed clinical and voiding cystourethrogram (VCUG) data were identified. Patient demographics, VCUG findings including grade, laterality, and bladder volume at onset of VUR, UTI history, presence of bladder-bowel dysfunction (BBD), and breakthrough fUTI were assessed. The VCUG dataset was randomized into a training set of 288 with a separate representational cross-validation set of 96. Various model types and architectures were investigated using neUROn++, a set of C++ programs. Results: Two hundred fifty-five children (208 girls, 47 boys) diagnosed with primary VUR at a mean age of 3.1 years (±2.6) met all inclusion criteria. A total 384 VCUGs were analyzed. Median follow-up was 24 months (interquartile range 12-52 months). Sixty-eight children (26.7%) experienced 90 breakthrough fUTI events. Dilating VUR, reflux occurring at low bladder volumes, BBD, and history of multiple infections/fUTI were associated with breakthrough fUTI (Table). A 2-hidden node neural network model had the best fit with a receiver operating characteristic curve area of 0.755 for predicting breakthrough fUTI. Discussion: The risk of recurrent febrile infections, renal parenchymal scarring, and likelihood of spontaneous resolution, as well as parental preference all influence management of primary VUR. The genesis of UTI is multifactorial, making precise prediction of an individual child's risk of breakthrough fUTI challenging. Demonstrated risk factors for UTI include age, gender, VUR grade, reflux at low bladder volume, BBD, and UTI history. We developed a prognostic calculator using a multivariable model with 76% accuracy that can be deployed for availability on the Internet, allowing input variables to be entered to calculate the odds of an individual child developing a breakthrough fUTI. Conclusions: A computational model using multiple variables including bladder volume at onset of VUR provides individualized prediction of children at risk for breakthrough fUTI. A web-based prognostic calculator based on this model will provide a useful tool for assessing personalized risk of breakthrough fUTI in children with primary VUR.

Although the twentieth century has seen great strides in the development of female contraception, not a single new agent has been introduced as an approved method for common use for male contraception. Condoms (considered uncomfortable by some) and vasectomy (a permanent invasive procedure) are the only options provided to men, leaving an undue burden on women to bear contraceptive responsibility. Significant developments have, however, been made with regard to hormonal and nonhormonal contraception, and minor, reversible, procedural contraception. This article reviews the currently available, soon to be available, and theoretically possible methods of male contraception.

Grafting of the male reproductive tract is an exciting new area of tissue engineering which may allow natural conception for patients with significant lengths of obstructed vas deferens. While stents had a significant and important role in increasing patency and pregnancy rates in the pre-microsurgical era, their role in the modern era of microsurgical two-layered anastomosis remains to be defined. To date, if the vasal obstruction is amenable to a primary watertight, tension-free anastomosis, microsurgical non-stented techniques remain the gold standard. Cases where a tension-free anastomosis is not possible because of the physical length of the obstruction remain problematic, but further research into tissue engineering in the form of implantable conduits holds much promise.