Society for fetal urology recommendations for postnatal evaluation of prenatal hydronephrosis--will fewer voiding cystourethrograms lead to more urinary tract infections?

PURPOSE: There is no consensus on the extent and mode of postnatal imaging after a diagnosis of prenatal hydronephrosis. We validated the protocol of our practice, which parallels current Society for Fetal Urology (SFU) recommendations, in limiting voiding cystourethrogram, while examining its impact on the incidence of febrile urinary tract infections. A secondary goal was to examine predictors of postnatal intervention. MATERIALS AND METHODS: We evaluated a cohort of 117 infants with prenatal hydronephrosis and retrospectively reviewed outcomes. Excluded from study were 30 infants with anatomical abnormalities. Third trimester prenatal ultrasound was done to evaluate SFU grade, laterality and anteroposterior diameter. Cox proportional hazard model and chi-square analysis were used to assess predictors of resolution and surgical intervention. RESULTS: A total of 87 infants with a median followup of 33.5 months were included in analysis. Postnatal voiding cystourethrogram was done in 52 patients, of whom 7 had vesicoureteral reflux. In 6 infants (6.9%) a febrile urinary tract infection developed, which was diagnosed with a catheter specimen during followup. In 3 infants a urinary tract infection developed immediately after catheterization. Anteroposterior diameter 9 mm or greater and SFU grade 3 or greater independently predicted the need for postnatal intervention (p = 0.0014 and 0.001, respectively). CONCLUSIONS: With adherence to our protocol, voiding cystourethrogram was avoided in almost half of evaluated infants. No infant diagnosed with vesicoureteral reflux had a urinary tract infection. Catheterization was associated with a urinary tract infection in 50% of cases. An anteroposterior diameter of 9 mm or greater and a SFU grade of 3 or greater were associated with postnatal progression to surgery. Patients with a SFU grade of 4 progressed to surgical intervention at a faster rate than those with a grade of greater than 3.

Posterior urethral valve treatments and outcomes in children receiving kidney transplants.

PURPOSE: We evaluated the impact of surgical approaches to posterior urethral valves on renal transplant survival and compared transplant survival in children with vs without posterior urethral valves. MATERIALS AND METHODS: We reviewed the records of all children who underwent renal transplantation from January 1984 to March 2008 and performed univariate subgroup analysis in those with posterior urethral valves. We evaluated the ureteroneocystotomy method, immunosuppression and valve treatment. In patients with posterior urethral valves we regarded nocturnal and/or daytime incontinence, severe urgency and the need for intermittent catheterization or double voiding for increased post-void residual urine as signs of bladder dysfunction. RESULTS: The initial renal transplant was received by 418 children at a mean age of 5.6 years. The 59 boys with posterior urethral valves received a total of 69 kidneys. By 8-year followup the kidney had failed in 24 of 59 boys with and 143 of 359 without posterior urethral valves (OR 0.9665, 95% CI 0.5462-1.692, p = 0.9105). Immunosuppression was consistent in the 2 groups. Outcomes were similar across all ureteroneocystotomy techniques. Initial management for posterior urethral valves was valve ablation alone in 12 boys, vesicostomy in 7 and supravesical diversion in 11. There was no difference in transplant survival or bladder dysfunction based on valve intervention. In 18 boys (55%) we noted overlapping signs of bladder dysfunction, of whom 11 performed intermittent catheterization or had increased post-void residual urine, 4 had severe urgency, 4 had daytime incontinence and 7 had nocturnal incontinence. Bladder dysfunction did not predict increased graft loss (OR 3.306, 95% CI 0.7615-16.27, p = 0.1134). CONCLUSIONS: Of children who undergo renal transplantation boys with posterior urethral valves do not have a higher graft failure rate. Treatment for posterior urethral valves did not significantly impact transplant survival or bladder dysfunction.

Diagnosis and Management of Opioid Use Disorder in Hospitalized Patients.

The diagnosis of opioid use disorder (OUD) is often overlooked or inadequately managed during the inpatient admission. When recognized, a common strategy is opioid detoxification, an approach that is often ineffective and can be potentially dangerous because of loss of tolerance and subsequent risk for overdose. Medication for addiction treatment (MAT), including methadone and buprenorphine, is effective and can be dispensed in the hospital for both opioid withdrawal and initiation of maintenance treatment. Hospitalists should be knowledgeable about diagnosing and managing patients with OUD, including how to manage acute pain or MAT during the perioperative setting.

PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent Mechanism.

Insulin stimulates the conversion of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) to phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3), which mediates downstream cellular responses. PI(4,5)P2 is produced by phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) and by phosphatidylinositol-5-phosphate 4-kinases (PIP4Ks). Here, we show that the loss of PIP4Ks (PIP4K2A, PIP4K2B, and PIP4K2C) in vitro results in a paradoxical increase in PI(4,5)P2 and a concomitant increase in insulin-stimulated production of PI(3,4,5)P3. The reintroduction of either wild-type or kinase-dead mutants of the PIP4Ks restored cellular PI(4,5)P2 levels and insulin stimulation of the PI3K pathway, suggesting a catalytic-independent role of PIP4Ks in regulating PI(4,5)P2 levels. These effects are explained by an increase in PIP5K activity upon the deletion of PIP4Ks, which normally suppresses PIP5K activity through a direct binding interaction mediated by the N-terminal motif VMLΦPDD of PIP4K. Our work uncovers an allosteric function of PIP4Ks in suppressing PIP5K-mediated PI(4,5)P2 synthesis and insulin-dependent conversion to PI(3,4,5)P3 and suggests that the pharmacological depletion of PIP4K enzymes could represent a strategy for enhancing insulin signaling.