A government mandated consent safely reduces opioid utilization for major pediatric genitourinary surgeries.

INTRODUCTION: We describe the effect of a state mandated opioid consent on opioid utilization and multimodal pain use for major pediatric genitourinary surgeries. METHODS: All patients who underwent an inpatient pediatric genitourinary surgery at the Children's Hospital of Pittsburgh between August 2015 and February 2020 were identified. Inpatient and outpatient multimodal pain control utilization were assessed. Delayed prescriptions or emergency department visits within 30 days were identified and when applicable referenced against National Surgical Quality Improvement Program data. RESULTS: After accounting for a 6-month transition period following policy implementation, 462 major pediatric genitourinary procedures were identified. The frequency of discharge opiate prescriptions decreased from 68.4% prior to the transition period to 10.7% afterward(p<0.001). Morphine milligram equivalents per prescription decreased from 75(IQR 45-150) to 45(IQR 22.5-75)(p<0.001). The rate of delayed non-opioid analgesic prescriptions (6.6% vs 7.4%), delayed opioid prescriptions (1.5% vs 0.3%), or emergency department visits (11.8% vs 12.6%)(p = 0.809) remained unchanged. Data agreed with National Surgical Quality Improvement Program data in 98.5% of cases. After excluding one surgeon who departed after the transition period, regional block utilization did not change from 61/115(53%) to 147/320(45.9%)(p = 0.425). CONCLUSIONS: A state mandated opioid consent safely reduced opioid utilization for most major pediatric genitourinary surgeries. LEVEL OF EVIDENCE: Level III.

Point-of-care ultrasound is an accurate, time-saving, and cost-effective modality for post-operative imaging after pyeloplasty.

BACKGROUND: Dismembered pyeloplasty is considered the gold standard treatment for ureteropelvic junction obstruction (UPJO). Although the frequency and timing of follow up imaging after pyeloplasty is variable, renal ultrasound (RUS) is commonly utilized. With minimal training, point-of-care ultrasound (POCUS) can be easily performed by a urologist during a post-operative visit. OBJECTIVE: Our hypothesis is that POCUS is an accurate, time-saving, and cost-effective alternative to a complete retroperitoneal ultrasound (CRUS) performed by the Radiology Department after pyeloplasty. STUDY DESIGN: The clinical records of all children who underwent pyeloplasty (by any method) over a 12 month period at our institution were retrospectively reviewed. The exact timing and method (POCUS vs. CRUS) of follow up imaging was surgeon-dependent. Statistical analysis was performed to compare the time and cost of POCUS vs. CRUS. The clinical course of each patient who had each type of imaging was assessed. RESULTS: A total 45 patients were included in this analysis. Over a mean follow up period of 29 months, a total of 73 CRUS and 67 POCUS were performed. Each CRUS on average added 2 h to each patient's healthcare encounter. Had the 73 CRUS been performed as POCUS instead, this would have corresponded to $83,751 less charges to payers. There was no difference in the rate of the detection of worsening, stable, or improved hydronephrosis (HN) between either modality (p > 0.05). The recommended follow up time for observed HN was no different between CRUS and POCUS (p > 0.05). Children with worsening HN on POCUS underwent functional studies without confirmatory CRUS. Interestingly, two patients had metachronous, contralateral UPJO discovered during post-operative imaging. These were both discovered by POCUS. Nineteen (42%) patients who had attended at least one post-operative visit were eventually loss to follow-up. This occurred exclusively in those who did not have worsening ultrasound (p < 0.01). There was no difference in the loss to follow-up after POCUS (8) or CRUS (12) (p > 0.05). CONCLUSIONS: POCUS performed by a urologist is an accurate assessment of HN after pyeloplasty with time and cost savings to compared to a CRUS performed by a radiologist. POCUS is not associated with any difference in rate of detection of worsening HN or rate of loss to follow up.

Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36.

UNLABELLED: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of three human malignancies. KSHV ORF36 encodes a serine/threonine viral protein kinase, which is conserved throughout all herpesviruses. Although several studies have identified the viral and cellular substrates of conserved herpesvirus protein kinases (CHPKs), the precise functions of KSHV ORF36 during lytic replication remain elusive. Here, we report that ORF36 interacts with another lytic protein, ORF45, in a manner dependent on ORF36 kinase activity. We mapped the regions of ORF36 and ORF45 involved in the binding. Their association appears to be mediated by electrostatic interactions, since deletion of either the highly basic N terminus of ORF36 or an acidic patch of ORF45 abolished the binding. In addition, the dephosphorylation of ORF45 protein dramatically reduced its association with ORF36. Importantly, ORF45 enhances both the stability and kinase activity of ORF36. Consistent with previous studies of CHPK homologs, we detected ORF36 protein in extracellular virions. To investigate the roles of ORF36 in the context of KSHV lytic replication, we used bacterial artificial chromosome mutagenesis to engineer both ORF36-null and kinase-dead mutants. We found that ORF36-null/mutant virions are moderately defective in viral particle production and are further deficient in primary infection. In summary, our results uncover a functionally important interaction between ORF36 and ORF45 and indicate a significant role of ORF36 in the production of infectious progeny virions. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumor virus with a significant public health burden. KSHV ORF36 encodes a serine/threonine viral protein kinase, whose functions throughout the viral life cycle have not been elucidated. Here, we report that ORF36 interacts with another KSHV protein, ORF45. We mapped the regions of ORF36 and ORF45 involved in their association and further characterized the consequences of this interaction. We engineered ORF36 mutant viruses in order to investigate the functional roles of ORF36 in the context of KSHV lytic replication, and we confirmed that ORF36 is a component of KSHV virions. Moreover, we found that ORF36 mutants are defective in virion production and primary infection. In summary, we discovered and characterized a functionally important interaction between KSHV ORF36 and ORF45, and our results suggest a significant role of ORF36 in the production of infectious progeny virions, a process critical for KSHV pathogenesis.