Risk Factors for Peri-intubation Cardiac Arrest in a Pediatric Emergency Department.

OBJECTIVES: Cardiac arrest is a significant complication of emergent endotracheal intubation (ETI) within the pediatric population. No studies have evaluated risk factors for peri-intubation cardiac arrest (PICA) in a pediatric emergency department (ED) setting. This study identified risk factors for PICA among patients undergoing emergent ETI in a pediatric ED. METHODS: We performed a nested case-control study within the cohort of children who underwent emergent ETI in our pediatric ED during a 9-year period. Cases were children with PICA within 20 minutes of ETI. Controls (4 per case) were randomly selected children without PICA after ETI. We analyzed potential risk factors based on published data and physiologic plausibility and created a simple risk model using univariate results, model fit statistics, and clinical judgment. RESULTS: In the cohort of patients undergoing ETI, PICA occurred in 21 of 543 subjects (3.9%; 95% confidence interval [CI], 2.2-5.9%), with return of spontaneous circulation in 16 of 21 (76.2%; 95% CI, 52.8-91.8%) and survival to discharge in 12 of 21 (57.1%; 95% CI, 34.0-78.2%). On univariate analysis, cases were more likely to be younger, have delayed capillary refill time, systolic or diastolic hypotension, hypoxia, greater than one intubation attempt, no sedative or paralytic used, and pulmonary disease compared with controls. Our 4-category risk model for PICA combined preintubation hypoxia (or an unobtainable pulse oximetry value) and younger than 1 year. The area under the receiver operating characteristic curve for this model was 0.87 (95% CI, 0.77-0.97). CONCLUSIONS: Hypoxia (or an unobtainable pulse oximetry value) was the strongest predictor for PICA among children after emergent ETI in our sample. A simple risk model combining pre-ETI hypoxia and younger than 1 year showed excellent discrimination in this sample. Our results require independent validation.

Heat Waves and Emergency Department Visits Among the Homeless, San Diego, 2012-2019.

Objectives. To determine the effect of heat waves on emergency department (ED) visits for individuals experiencing homelessness and explore vulnerability factors. Methods. We used a unique highly detailed data set on sociodemographics of ED visits in San Diego, California, 2012 to 2019. We applied a time-stratified case-crossover design to study the association between various heat wave definitions and ED visits. We compared associations with a similar population not experiencing homelessness using coarsened exact matching. Results. Of the 24 688 individuals identified as experiencing homelessness who visited an ED, most were younger than 65 years (94%) and of non-Hispanic ethnicity (84%), and 14% indicated the need for a psychiatric consultation. Results indicated a positive association, with the strongest risk of ED visits during daytime (e.g., 99th percentile, 2 days) heat waves (odds ratio = 1.29; 95% confidence interval = 1.02, 1.64). Patients experiencing homelessness who were younger or elderly and who required a psychiatric consultation were particularly vulnerable to heat waves. Odds of ED visits were higher for individuals experiencing homelessness after matching to nonhomeless individuals based on age, gender, and race/ethnicity. Conclusions. It is important to prioritize individuals experiencing homelessness in heat action plans and consider vulnerability factors to reduce their burden. (Am J Public Health. 2022;112(1):98-106. https://doi.org/10.2105/AJPH.2021.306557).

Notch suppresses angiogenesis and progression of hepatic metastases.

The Notch pathway plays multiple key roles in tumorigenesis, and its signaling components have therefore aroused great interest as targets for emerging therapies. Here, we show that inhibition of Notch, using a soluble receptor Notch1 decoy, unexpectedly caused a remarkable increase in liver metastases from neuroblastoma and breast cancer cells. Increased liver metastases were also seen after treatment with the γ-secretase inhibitor PF-03084014. Transgenic mice with heterozygous loss of Notch1 demonstrated a marked increase in hepatic metastases, indicating that Notch1 signaling acts as metastatic suppressor in the liver microenvironment. Inhibition of DLL1/4 with ligand-specific Notch1 decoys increased sprouting of sinusoidal endothelial cells into micrometastases, thereby supporting early metastatic angiogenic growth. Inhibition of tumor-derived JAG1 signaling activated hepatic stellate cells, increasing their recruitment to vasculature of micrometastases, thereby supporting progression to macrometastases. These results demonstrate that inhibition of Notch causes pathologic activation of liver stromal cells, promoting angiogenesis and growth of hepatic metastases. Our findings have potentially serious implications for Notch inhibition therapy.