Increased pediatric sub-specialization is associated with decreased surgical complication rates for inpatient pediatric urology procedures.

INTRODUCTION: Increased case volumes and training are associated with better surgical outcomes. However, the impact of pediatric urology sub-specialization on perioperative complication rates is unknown. OBJECTIVES: To determine the presence and magnitude of difference in rates of common postoperative complications for elective pediatric urology procedures between specialization levels of urologic surgeons. The Nationwide Inpatient Sample (NIS), a nationally representative administrative database, was used. STUDY DESIGN: The NIS (1998-2009) was retrospectively reviewed for pediatric (≤18 years) admissions, using ICD-9-CM codes to identify urologic surgeries and National Surgical Quality Improvement Program (NSQIP) inpatient postoperative complications. Degree of pediatric sub-specialization was calculated using a Pediatric Proportion Index (PPI), defined as the ratio of children to total patients operated on by each provider. The providers were grouped into PPI quartiles: Q1, 0-25% specialization; Q2, 25-50%; Q3, 50-75%; Q4, 75-100%. Weighted multivariate analysis was performed to test for associations between PPI and surgical complications. RESULTS: A total of 71,479 weighted inpatient admissions were identified. Patient age decreased with increasing specialization: Q1, 7.9 vs Q2, 4.8 vs Q3, 4.8 vs Q4, 4.6 years, P < 0.01). Specialization was not associated with race (P > 0.20), gender (P > 0.50), or comorbidity scores (P = 0.10). Mortality (1.5% vs 0.2% vs 0.3% vs 0.4%, P < 0.01) and complication rates (15.5% vs 11.7% vs 9.6% vs 10.9%, P < 0.0001) both decreased with increasing specialization. Patients treated by more highly specialized surgeons incurred slightly higher costs (Q2, +4%; Q3, +1%; Q4 + 2%) but experienced shorter length of hospital stay (Q2, -5%; Q3, -10%; Q4, -3%) compared with the least specialized providers. A greater proportion of patients treated by Q1 and Q3 specialized urologists had CCS ≥2 than those seen by Q2 or Q4 urologists (12.5% and 12.2%, respectively vs 8.4% and 10.9%, respectively, P = 0.04). Adjusting for confounding effects, increased pediatric specialization was associated with decreased postoperative complications: Q2 OR 0.78, CI 0.58-1.05; Q3 OR 0.60, CI 0.44-0.84; Q4 OR 0.70, CI 0.58-0.84; P < 0.01. DISCUSSION: Providers with proportionally higher volumes of pediatric patients achieved better postoperative outcomes than their less sub-specialized counterparts. This may have arisen from increased exposure to pediatric anatomy and physiology, and greater familiarity with pediatric techniques. LIMITATION: The NIS admission-based retrospective design did not enable assessment of long-term outcomes, repeated admissions, or to track a particular patient across time. The study was similarly limited in evaluating the effect of pre-surgical referral patterns on patient distributions. CONCLUSIONS: Increased pediatric sub-specialization among urologists was associated with a decreased risk of mortality and surgical complications in children undergoing inpatient urologic procedures.

Study of phase behavior of poly(ethylene glycol)-polysorbate 80 and poly(ethylene glycol)-polysorbate 80-water mixtures.

Mixtures of poly(ethylene glycols) (PEGs) with polysorbate 80 are often used to dissolve poorly water-soluble drugs in dosage forms, where polysorbate 80 helps either in enhancing dispersion or in inhibiting precipitation of drugs once the solution is mixed with water. Binary phase diagrams of polysorbate 80 with several low molecular weight PEGs and a ternary phase diagram of polysorbate 80 with PEG 400 and water are presented. Two phases were observed in the binary mixtures when the concentration of PEG 200, PEG 300, PEG 400, or PEG 600 was >55%(w/w). The miscibility of the binary mixtures increases with an increase in temperature; the upper consolute temperatures of PEG 200-polysorbate 80, PEG 300-polysorbate 80, PEG 400-polysorbate 80, and PEG 600-polysorbate 80 mixtures were 100, 85, 75, and 40 degrees C, respectively. The upper consolute temperature of PEG 1000-polysorbate 80 could not be determined because the melting temperature of the mixtures is approximately 40 degrees C and the consolute temperature appeared to be less than this temperature. The decrease in upper consolute temperature with an increase in PEG molecular weight indicated a greater miscibility of the two components. In the ternary system, phase separation of polysorbate 80 was observed when the concentration of PEG 400 was >50-60 % (w/w), possibly because of the high exclusion volume of PEG 400.

Hybridization analysis of RNA transported from rat liver nuclei in response to 35 kDa normal and 60 kDa messenger RNA transport factors.

The transport of messenger RNA (mRNA) in response to normal adult (35 kDa) and oncofetal (60 kDa) transport factors has been studied in a reconstituted cell-free system. Poly(A)+ mRNA sequences transported by the 35 kDa and 60 kDa transport factors were compared by cDNA:RNA hybridization kinetics. Heterologous hybridization reactions indicated that a proportion of messengers transported in response to the 35 kDa factor were absent or at a markedly reduced abundance in the mRNA released by the 60 kDa factor. Recombinant DNA probes containing cDNA inserts were used to quantitate transport of rat-liver-specific alpha 2 mu-globulin and albumin mRNA from isolated nuclei in presence of the normal and tumor-specific transport factors. More alpha 2 mu-globulin and albumin messenger sequences were transported in response to the 35 kDa transport factor as compared to the 60 kDa factor. These results indicate that the 35 kDa transport protein isolated from rat liver cytosol and the 60 kDa transport protein isolated from hepatoma cytosol, differ significantly in specificity for the classes of RNA sequences released from nuclei. Monoclonal antibodies against the 60 kDa factor do not cross-react with the 35 kDa factor or other proteins as determined by the immunobioassay and by the Western blot technique.

Analysis of nuclear RNA processing and transport by temperature perturbation of a cell-free system from mammalian cells.

The similarity of the Arrhenius plots relating temperature to messenger RNA (mRNA) transport from intact and membrane-denuded rat liver nuclei demonstrates that the ATP and cytosol-dependent transport is independent of the lipid phase of the nuclear membrane. This temperature dependence of RNA release was confirmed for alpha 2u-globulin mRNA by use of a recombinant DNA probe. Ribosomal RNA (rRNA) release showed a similar temperature dependence, suggesting that both mRNA and rRNA share a common temperature-sensitive step. The kinetics of RNA release at different temperatures suggest that RNA transport from mammalian cell nuclei is a rate-controlled rather than a graded unlocking phenomenon. The processing of mRNA precursors also exhibits a temperature dependence as shown by the linear increase in the ratio of total alpha 2u-globulin RNA to alpha 2u-globulin precursor as a function of time at 30 degrees C but not at 14 degrees C in spite of residual transport at the lower temperature. This temperature dependence of mRNA processing was confirmed by Northern blot analysis of the nuclear RNA following a 45 min incubation. Thus, both the processing and transport of RNA show temperature-sensitive steps when analyzed in cell-free systems derived from mammalian cells.

Benzo[a]pyrene diol epoxide DNA adduct formation in transformable and non-transformable human foreskin fibroblast cells in vitro.

The uptake of benzo[a]pyrene (BP) by low passage (LP) and high passage (HP) human skin fibroblast cells is followed by its transport into the nucleus as the parent compound. When the LP and HP cells were treated with BP for 24 h and the DNA was isolated and enzymatically digested, several DNA adducts were detected. In both the LP and HP cells a small amount of the radiolabel was associated with the 7 beta-BPDE-I-dG, 7 alpha-BPDE-I-dG and BPDE-II-dG adducts. Although there were no major qualitative differences in the adducts formed in the LP and HP cells, a higher proportion of the radiolabel was associated with the 7 beta-BPDE-I-dG adduct in the LP cells. When LP or HP cells were treated with BPDE-I, the ultimate carcinogenic form of BP, similar levels of DNA modification were observed in the two cell types and the h.p.l.c. profiles of these adducts were essentially identical. BPDE-I induced a carcinogenic event in the LP but not the HP cells as measured by anchorage independent growth in soft agar and cellular invasiveness of the chick embryonic skin organ cultures.

Characteristics of benzo[a]pyrene and A-ring reduced 7,12-dimethyl benz[a]anthracene induced neoplastic transformation of human cells in vitro.

The polynuclear aromatic hydrocarbons (PAH) benzo[a]pyrene (BP) and the A-ring reduced analogue of 7,12-dimethylbenz[a]anthracene (DMBA), 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene (TH-DMBA) are carcinogenic to human cells. The unsaturated PAH, DMBA exhibits no carcinogenic activity on human cells as measured by growth in soft agar. The TH-DMBA and BP treated cells exhibit a colony frequency in soft agar of 84 and 86, respectively. These anchorage independent cells, when seeded on the chick embryonic skin (CES) organ cultures, are invasive and form a fibrosarcoma. It is highly unlikely that TH-DMBA, which does not contain an aromatic A-ring, can undergo metabolism in human cells in culture to form a bay region 3,4-dihydrodiol-1,2-epoxide. These results suggest that an alternate mechanism for the induction of carcinogenesis is appropriate to explain the absence of bay region diol-epoxide metabolite as the ultimate form of the carcinogen in TH-DMBA induced carcinogenesis in human diploid cells.

Analysis of intracellular distribution and binding of benzo[alpha]pyrene in human diploid fibroblasts.

Previous work with low passage synchronized human foreskin fibroblast cell populations has indicated that benzo[alpha]pyrene (BP) can induce a carcinogenic event [3]. BP additionally has shown to damage DNA in log-arithmically growing low passage cultures [9]. High passage cells, on the other hand, seem to be refractory to transformation by BP, even though this agent can induce DNA damage, similar to that seen in low passage cells. When low passage cells were treated with BP, the initial binding of the hydrocarbon was primarily to a cytoplasmic protein complex of molecular weight 12,500 while in high passage cells, a major portion of BP was bound to protein complex of molecular weight 200,000. High-pressure liquid chromatography (HPLC) profiles of ethyl acetate extractable fractions from the BP-cytoplasmic protein complexes of low and high passage cells demonstrated that the majority of the BP remained unmetabolized. When nuclei were isolated from low and high passage cells prior to the HPLC analysis, the major component (90%) was again unmetabolized BP. The results suggest selective attachment of BP to different cytoplasmic protein complexes of logarithmically growing human diploid fibroblast cells dependent on the passage level of the cells.