Differences in Delirium Evaluation and Pharmacologic Management in Children With Developmental Delay: A Retrospective Case-Control Study.

Delirium is associated with increased mortality and cost, decreased neurocognition, and decreased quality of life in the pediatric intensive care unit (PICU) population. The Cornell Assessment for Pediatric Delirium (CAPD) is used in PICUs for delirium screening but lacks specificity in children with developmental delay (DD). Within a cohort of children receiving pharmacologic treatment for intensive care unit (ICU) delirium, we compared delirium scoring and medication management between children with and without DD. We hypothesized that CAPD scores and treatment decisions would differ between DD and neurotypical (NT) patients. In this retrospective case-control study, we queried the medical record of patients admitted to our PICU with respiratory failure from June 2018 to March 2022 who received antipsychotics typically used for ICU delirium. Antipsychotics prescribed for home use were excluded. Nonparametric statistics compared demographics, CAPD scores, medication choice, dosing (mg/kg), and medication continuation after discharge between those with and without DD based on the ICD-10 codes. Twenty-one DD admissions and 59 NT admissions were included. Groups did not significantly differ by demographics, LOS, drug, or initial dosage. DD patients had higher median CAPD scores at admission (17 vs 13; P = .02) and treatment initiation (18 vs 16.5; P = .05). Providers more frequently escalated doses in DD patients (13/21 vs 21/59; P = .04) and discharged them home on new antipsychotics (7/21 vs 5/59; P = .01). DD patients experience delirium screening and management differently than NT counterparts. Providers should be aware of baseline elevated scores in DD patients and carefully attend to indications for dosage escalation. Further work is needed to understand if prolonged duration, even after hospital discharge, benefits patients, or represents potential disparity in care.

G0S2 promotes antiestrogenic and pro-migratory responses in ER+ and ER- breast cancer cells.

G0/G1 switch gene 2 (G0S2) is known to inhibit lipolysis by inhibiting adipose triglyceride lipase (ATGL). In this report, we dissect the role of G0S2 in ER+ versus ER- breast cancer. Overexpression of G0S2 in ER- cells increased cell proliferation, while G0S2 overexpression in ER+ cells decreased cell proliferation. Transcriptome analysis revealed that G0S2 mediated distinct but overlapping transcriptional responses in ER- and ER+ cells. G0S2 reduced genes associated with an epithelial phenotype, especially in ER- cells, including CDH1, ELF3, STEAP4 and TACSTD2, suggesting promotion of the epithelial-mesenchymal transition (EMT). G0S2 also repressed estrogen signaling and estrogen receptor target gene signatures, especially in ER+ cells, including TFF1 and TFF3. In addition, G0S2 overexpression increased cell migration in ER- cells and increased estrogen deprivation sensitivity in ER+ cells. Interestingly, two genes downstream of ATGL in fat utilization and very important in steroid hormone biosynthesis, HMGCS1 and HMGCS2, were downregulated in G0S2 overexpressing ER+ cells. In addition, HSD17B11, a gene that converts estradiol to its less estrogenic derivative, estrone, was highly upregulated in G0S2 overexpressing ER+ cells, suggesting G0S2 overexpression has a negative effect on estradiol production and maintenance. High expression of G0S2 and HSD17B11 was associated with improved relapse-free survival in breast cancer patients while high expression of HMGSC1 was associated with poor survival. Finally, we deleted G0S2 in breast cancer-prone MMTV-PyMT mice. Our data indicates a complex role for G0S2 in breast cancer, dependent on ER status, that may be partially mediated by suppression of the estrogen signaling pathway.