Pediatric Tracheostomy-Related Complications: A Cross-sectional Analysis.

OBJECTIVE: To determine the rate of tracheostomy-related complications in pediatric patients from nationally representative databases. STUDY DESIGN: Cross-sectional analysis. SETTING: 2016 Kids' Inpatient Database and 2016 Nationwide Readmission Database. METHODS: All pediatric tracheostomy procedures were included. Complication type, admission outcomes, and readmission rates were recorded with a logistic regression analysis to determine patient characteristics associated with complications. RESULTS: An estimated 5309 tracheostomies were performed among pediatric patients in 2016, 8% (n = 432) of whom developed tracheostomy-related complications. This group was younger (4.7 vs 8.7 years, P < .001) and required longer hospital admissions (68.7 vs 33.2 days, P < .001) than children without tracheostomy-related complications. Mean costs ($459,324 vs $397,937, P < .001) and mean total charges ($1,573,964 vs $1,099,347, P < .001) were increased if a tracheostomy-related complication occurred. These events occurred more often in those with bronchopulmonary dysplasia (24% vs 12%, P < .001), heart disease (24% vs 12%, P = .001), gastroesophageal reflux disease (31% vs 19%, P < .001), short gestational age (24% vs 14%, P < .001), and subglottic stenosis (9.9% vs 5.4%, P = .001). The estimated 30-day readmission rate was 24% (SE, 1.7%) but did not increase after tracheostomy complications (27% vs 15%, P = .04). Tracheostomy-related complications were predicted by gastroesophageal reflux disease (odds ratio [OR], 1.50; 95% CI, 1.14-1.97; P = .004), younger age (OR, 1.12; 95% CI, 1.04-1.22; P = .002), and lengthier hospitalization (OR, 1.00; 95% CI, 1.00-1.01; P < .001) on multiple logistic regression analysis. CONCLUSION: Tracheostomy-related complications occur in approximately 8% of pediatric patients and are higher in younger children or those with longer admission lengths. These data have implications for benchmarking standards of posttracheostomy complications across institutions.

Reactivation of silenced α-N-catenin induces retinoic acid sensitivity in neuroblastoma cells.

BACKGROUND: High-risk neuroblastoma remains the most difficult pediatric solid tumor to treat and is associated with chemotherapy and radiation resistance that may be secondary to epigenetic modifications. We have previously found that α-N-catenin, a cell-adhesion protein encoded by the gene CTNNA2, plays a tumor suppressor role in neuroblastoma by inhibiting the NF-κB signaling pathway. A subset of neuroblastoma tumors that lack α-N-catenin are resistant to all-trans retinoic acid. However, the mechanism of CTNNA2 silencing in neuroblastoma remains unknown. Herein, we sought to determine the mechanism of α-N-catenin silencing in neuroblastoma. METHODS: Two human neuroblastoma cell lines, SK-N-AS and BE(2)-C, were stably transfected with a plasmid expressing CTNNA2. Both cell lines were treated with the histone deacetylase inhibitor Trichostatin A alone and in combination with retinoic acid. Cell survival and colony formation were measured. Cellular differentiation and expression of cell survival signaling pathways were analyzed. Immunoblotting and reverse transcription quantitative polymerase chain reaction were used to examine protein and messenger RNA expression. RESULTS: Retinoic acid treatment induced cellular differentiation and inhibited cellular proliferation in BE(2)-C cells but did not induce differentiation in SK-N-AS cells. Re-expression of α-N-catenin enhanced the sensitivity to retinoic acid-induced cell growth arrest and downregulated key cell survival pathways in both cell lines. Trichostatin A treatment induced CTNNA2 expression in SK-N-AS cells, and combination treatment with Trichostatin A induced retinoic acid sensitivity in retinoic acid-resistant cells. CONCLUSION: Re-expression of α-N-catenin in retinoic acid-resistant cells induced sensitivity to retinoic acid treatment and is controlled epigenetically via histone deacetylase. α-N-catenin is a potential biomarker for retinoic acid sensitivity and combination treatment with Trichostatin A and retinoic acid may improve survival among children with high-risk, retinoic acid-resistant neuroblastoma.

Development and Pilot Testing of a Context-Relevant Safe Anesthesia Checklist for Cesarean Delivery in East Africa.

BACKGROUND: Maternal mortality rate in developing countries is 20 times higher than in developed countries. Detailed reports surrounding maternal deaths have noted an association between substandard management during emergency events and death. In parallel with these findings, there is increasing evidence for cognitive aids as a means to prevent errors during perioperative crises. However, previously published findings are not directly applicable to cesarean delivery in low-income settings. Our hypothesis was that the use of obstetric anesthesia checklists in the management of high-fidelity simulated obstetrical emergency scenarios would improve adherence to best practice guidelines in low- and middle-income countries. METHODS: Accordingly, with input from East African health care professionals, we created a context-relevant obstetric anesthesia checklist for cesarean delivery. Second, clinical observations were performed to assess in a real-world setting. Third, a pilot testing of the cognitive aid was undertaken. RESULTS: Clinical observation data highlighted significant deficiencies in the management of obstetric emergencies. The use of the cesarean delivery checklist during simulations of peripartum hemorrhage and preeclampsia showed significant improvement in the percentage of completed actions (pretraining 23% ± 6% for preeclampsia and 22% ± 13% for peripartum hemorrhage, posttraining 75% ± 9% for preeclampsia, and 69% ± 9% for peripartum hemorrhage [P < .0001, both scenarios; data as mean ± standard deviation]). CONCLUSIONS: We developed, evaluated, and begun implementation of a context-relevant checklist for the management of obstetric crisis in low- and middle-income countries. We demonstrated not only the need for this tool in a real-world setting but also confirmed its potential efficacy through a pilot simulation study.

Application of vinylogous carbamates and vinylogous aminonitriles to the regiospecific synthesis of uniquely functionalized pyrroles and quinolones.

Pyrroles and quinolones represent core structures, which are routinely found in both natural and synthetic bioactive substances. Consequently, the development of efficient and regiospecific methods for the preparation of such heterocycles with unique functionality is of some importance. We describe herein the regiospecific synthesis of 1,2,3,4-tetrasubstituted pyrroles containing polar substituents and such products are prepared from vinylogous carbamates and vinylogous aminonitriles. We also describe the regiospecific synthesis of 3-aryl containing 1,3,6trisubstituted quinolones from vinylogous carbamates. The use of an amine exchange reaction to prepare precursors for the pyrrole and quinolone forming cyclizations represents a key factor in the strategy.