Pediatric Surgery from the Roads Less Traveled: Challenges, Communication, and Collaboration from a Community Nonteaching Hospital.

Unique challenges face pediatric surgeons at community-based nonteaching hospitals. Communication and collaboration among and between healthcare providers, hospital administrators, and quaternary referral programs is crucial for the success of these smaller hospitals as they care for children.

Enhanced ER-associated degradation of HMG CoA reductase causes embryonic lethality associated with Ubiad1 deficiency.

UbiA prenyltransferase domain-containing protein-1 (UBIAD1) synthesizes the vitamin K subtype menaquinone-4 (MK-4). Previous studies in cultured cells (Schumacher et al., 2015) revealed that UBIAD1 also inhibits endoplasmic reticulum (ER)-associated degradation (ERAD) of ubiquitinated HMG CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway that produces cholesterol and essential nonsterol isoprenoids. Gene knockout studies were previously attempted to explore the function of UBIAD1 in mice; however, homozygous germ-line elimination of the Ubiad1 gene caused embryonic lethality. We now report that homozygous deletion of Ubiad1 is produced in knockin mice expressing ubiquitination/ERAD-resistant HMGCR. Thus, embryonic lethality of Ubiad1 deficiency results from depletion of mevalonate-derived products owing to enhanced ERAD of HMGCR rather than from reduced synthesis of MK-4. These findings provide genetic evidence for the significance of UBIAD1 in regulation of cholesterol synthesis and offer the opportunity in future studies for the discovery of new physiological roles of MK-4.

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida.

PURPOSE: Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. MATERIALS AND METHODS: In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. RESULTS: An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. CONCLUSIONS: The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements.

Port-site complications after pediatric urologic robotic surgery.

The incidence of port-site hernia development after adult laparoscopic surgery is reported to be between 0.1% and 3.0%. There are no published reports concerning hernia incidence or related factors after pediatric urologic laparoscopic interventions. We present our experience with port-site complications following pediatric urologic robotic surgery (PURS). From July 2005 to June 2009 we prospectively followed the first 200 PURS cases performed at Children's Hospital of Philadelphia. All cases had follow-up available for at least 2 months postoperatively. The data collected allowed for evaluation of the outcomes for each port site separately and compared its size, location, and fascial closure status. Median age was 3.2 years (0.4-18.8 years). All 200 patients had follow-up with median of 11 months (0.2-83.4 months). There were 600 port sites analyzed in the 200 cases. Of the 600 port sites, 200 were umbilical. The other 400 port sites were lateral to the rectus muscle, either subcostal or at the level of the anterior superior iliac spine. There was no wound irrigation prior to closure on any sites. All the patients received perioperative antibiotics. One umbilical port had a hernia diagnosed 2 weeks postoperatively. Four of the 600 ports (0.6%) developed skin dehiscence secondary to superficial wound infection within 1 week postoperatively. At our institution, the overall incidence of port-site complications after PURS was 0.83%. This is slightly lower than the published incidence in adults undergoing conventional laparoscopy. Due to the low incidence of complications it is difficult to draw conclusions on contributing factors.

Robotic ureterocalicostomy in the pediatric population.

PURPOSE: Ureterocalicostomy is a potential option in patients with ureteropelvic junction obstruction and significant lower pole calicectasis. It is often reserved for patients with a failed pyeloplasty and a minimal pelvis, or patients with an exaggerated intrarenal pelvis. We present our technique of robotic ureterocalicostomy in the pediatric population as a primary modality for an exaggerated intrarenal collecting system not amenable to standard dismembered pyeloplasty, and for secondary ureteropelvic junction obstruction. MATERIALS AND METHODS: Nine patients 3 to 15 years old (mean age 6.5) underwent transperitoneal robotic ureterocalicostomy for ureteropelvic junction obstruction. Six of the patients had recurrent ureteropelvic junction obstruction after primary pyeloplasty performed elsewhere. The remaining 3 patients had an exaggerated intrarenal collecting system with minimal or no appreciable renal pelvis for reconstruction. Outcome measures included operative time, length of hospital stay and postoperative ultrasound at 3 months, as well as resolution of obstruction by diuretic radionuclide imaging at 6 and 12 months of followup. RESULTS: Mean operative time was 168 minutes (range 102 to 204) for the ureterocalicostomy portion. Two patients underwent concomitant pyelolithotomy, with 14 and 21 minutes added to the operative time. Mean hospital stay was 21 hours (range 17 to 26). Diuretic radionuclide imaging, which was performed in all patients at 6 and 12 months postoperatively, revealed no evidence of obstruction in any patient. CONCLUSIONS: Robotic ureterocalicostomy is a viable and technically feasible treatment option for patients with recurrent ureteropelvic junction obstruction, or patients with difficult intrarenal ureteropelvic junctions.

Use of a replication-defective vector to track cells initially infected by SIV in vivo: infected mononuclear cells rapidly appear in the draining lymph node after intradermal inoculation of rhesus monkeys.

A better understanding of the mechanisms of HIV dissemination, a key step in pathogenesis, would be possible if the cellular pathways of viral dissemination could be followed in simian immunodeficiency virus (SIV)- inoculated monkeys or HIV-infected people. In an initial attempt to follow this process using a traceable virus infection, we inoculated rhesus monkeys intradermally (ID) or directly into lymph nodes with a replication-defective SIV-based vector expressing the enhanced jellyfish green fluorescent protein (EGFP), V1EGFP. EGFP expression was detected in mononuclear cells isolated from the sites of inoculation (skin and lymph node) at 5 and 16 hr after inoculation and then cultured in vitro for 6 days to allow maximum EGFP expression. Similarly, EGFP-expressing, SIV-infected cells could be detected at 16 hr postinfection in the lymph nodes that drained the sites of ID inoculation. Since V1EGFP is a replication-defective vector, the EGFP-expressing cells are the initial target cells infected by the virions in the original inoculum. The results of flow cytometric analysis were confirmed by a nested PCR assay to detect SIV DNA and hence infection of cells and reverse transcription. These experiments indicate that 16 hr after ID inoculation newly infected cells either remain in the skin at the site of inoculation or have migrated to the draining lymph node. The results in this SIV vector model probably reflect the short time (less than 16 hr) required for HIV to move from a site of epithelial penetration to the lymphoid tissues via lymphatic vessels.