To evaluate correlations between rucaparib exposure and selected efficacy and safety endpoints in patients with recurrent ovarian carcinoma using pooled data from Study 10 and ARIEL2.

Efficacy analyses were limited to patients with carcinomas harboring a deleterious BRCA1 or BRCA2 mutation who had received ≥2 prior lines of chemotherapy. Safety was evaluated in all patients who received ≥1 rucaparib dose. Steady-state daily area under the concentration-time curve (AUC

) and maximum concentration (C

) for rucaparib were calculated for each patient and averaged by actual dose received over time (AUC

and C

) using a previously developed population pharmacokinetic model.

Rucaparib exposure was dose-proportional and not associated with baseline patient weight. In the exposure-efficacy analyses (n=121), AUC

was positively associated with independent radiology review-assessed RECIST response in the subgroup of patients with platinum-sensitive recurrent disease (n=75, p=0.017). In the exposure-safety analyses (n=393, 40mg once daily to 840mg twice daily [BID] starting doses), most patients received a 600mg BID rucaparib starting dose, with 27% and 21% receiving 1 or≥2 dose reductions, respectively. C

was significantly correlated with grade≥2 serum creatinine increase, grade≥3 alanine transaminase/aspartate transaminase increase, platelet decrease, fatigue/asthenia, and maximal hemoglobin decrease (p<0.05).

The exposure-response analyses provide support for the approved starting dose of rucaparib 600mg BID for maximum clinical benefit with subsequent dose modification only following the occurrence of a treatment-emergent adverse event in patients with BRCA-mutated recurrent ovarian carcinoma.

The exposure-response analyses provide support for the approved starting dose of rucaparib 600 mg BID for maximum clinical benefit with subsequent dose modification only following the occurrence of a treatment-emergent adverse event in patients with BRCA-mutated recurrent ovarian carcinoma.Purpose While central venous port placement is common, there remains variation in placement technique and rates of technical complications. The aim of this study was to assess variability in techniques and identify predictors of complications for children undergoing port placement. Methods We retrospectively reviewed all 331 patients who underwent venous port placement at a single tertiary children’s hospital from May 2018 to June 2020. The primary outcome was early revision or replacement (R/R) for complications occurring within 30 days. Secondary outcomes included radiation exposure and rate of intraoperative conversion to a secondary site. Results The median age was 7 years (Interquartile Range 3-13 years) and the most common diagnoses were leukemia (30.2%), solid tumors (27.8%), and brain tumors (16.9%). Initial approach for port placement was ultrasound-guided internal jugular (IJV) in 255 (147 by surgery and 108 by interventional radiology [IR]) and landmark subclavian vein (SCV) in 76 (all by surgery).eferences.

Perforated appendicitis is a well-documented child health disparity. Geographic patterns in perforated appendicitis exist in several United States regions, but such patterns have not been described in California. We aimed to analyze spatial-temporal patterns of pediatric perforated appendicitis and identify population characteristics contributing to these cluster patterns.

We geocoded risk-adjusted perforated appendicitis rates per 1000 appendicitis cases in patients 1-17 years from 2005-2015 in California. We performed a space-time cube analysis to identify hot spot trends. We performed logistic regression to estimate rural classification associated with spatial-temporal hot spots and multivariate analysis to assess effects of socioeconomic factors.

In 2005-2015, 43,888 cases of pediatric perforated appendicitis occurred in California. Median risk-adjusted perforated appendicitis rate was 312 per 1000 appendicitis cases. We identified 11 spatial-temporal hot spots of perforated appendicitis. Temsirolimus Rural micropolitan counties had 14 times higher odds of being classified as a hot spot (p<0.05, 95% CI 1-185). Poverty was a significant predictor of high perforated appendicitis median risk-adjusted rate (p<0.004).

We identified 11 California hot spots of perforated appendicitis that persisted across a ten-year time span. Incorporating geography alongside our understanding of socioeconomic factors is a critical step in addressing this important child health disparity.

We identified 11 California hot spots of perforated appendicitis that persisted across a ten-year time span. Incorporating geography alongside our understanding of socioeconomic factors is a critical step in addressing this important child health disparity.Ventriculoperitoneal (VP) shunts in pediatric patients are an important aspect of management for patients with hydrocephalus and are fraught with complications. Surgical revision rates for VP shunts in the pediatric population are currently high, which necessitates innovation in operative techniques for placing VP shunts in attempt to decrease complication risks. Here we describe a novel approach for placement of VP shunts that we hypothesize can reduce potential morbidity among pediatric patients. By utilizing the falciform ligament of the liver and the suprahepatic recess to suspend and maintain the shunt, outcomes may portend fewer iatrogenic intra-abdominal injuries, enhanced ease of shunt removal, provide a large surface area for absorption of drained cerebrospinal fluid, and result in fewer adhesions secondary to device placement. We are referring to the operative technique as the “SupraHepatic IntraFalciform Tubing” (SHIFT) technique. In summary, the SHIFT shunt is fashioned by creating a window through the falciform ligament, inserting the shunt, and placing tubing in the suprahepatic recess.

Patients with anorectal malformations (ARM) commonly have associated urologic anomalies. Few large studies exist to accurately characterize the incidence or associations between severity of malformation and urologic diagnosis. The purpose of our study was to determine the incidence of urologic diagnoses in a large cohort of children with ARM and evaluate for any correlation between severity of ARM and the incidence and number of associated urologic diagnoses.

A retrospective review was performed of patients with ARM treated at our pediatric colorectal center. All patients underwent protocolized urologic screening. ARM subtypes were ordered with increasing severity as follows in males perineal, bulbar, prostatic and bladder neck fistulae. Females were similarly categorized as perineal, vestibular and vaginal fistulae followed by cloaca with <3cm common channel and cloaca with >3cm common channel. The following urologic diagnoses were assessed to determine whether a correlation existed with the severity of the ARM subtype hydronephrosis, vesicoureteral reflux (VUR), solitary kidney, renal ascent anomalies (ectopic or pelvic), renal fusion anomalies (horseshoe or cross fused kidney), duplex kidney, hypospadias and undescended testicle.