Prenatal aneuploidy screening and its impact on stillbirth etiology evaluation.

BACKGROUND: Stillbirth impacts 1% of all pregnancies in the USA with the underlying cause often remaining unknown. The objective of this study was to identify if prenatal aneuploidy screening impacted patient agreement to stillbirth evaluation. METHODS: We performed a retrospective cohort study of patients with a singleton stillbirth after 20 weeks of gestation between October 2017 and December 2021. Demographics and stillbirth evaluation were collected for all patients. Multivariable logistic regression was performed adjusting for variables that were significant in univariate analysis. RESULTS: A total of 81 persons experienced stillbirth during the study period. Approximately 59.3% of patients had prenatal aneuploidy screening: 39.5% integrated screening, 37.5% non-invasive prenatal testing (NIPT), and 22.9% quad screen. Prenatal genetic screening did not significantly impact patient agreement to placental pathology, serum laboratory evaluation, or fetal autopsy. Patients with NIPT were less likely to have genetic testing sent at the time of stillbirth compared to those with another aneuploidy screening (aOR 0.27, 95% CI 0.07-0.99). CONCLUSIONS: Prenatal aneuploidy screening was not associated with patient acceptance of stillbirth evaluation. However, patients with NIPT were less likely to pursue further genetic testing during stillbirth evaluation, so further education regarding the benefit of karyotype and microarray should be included in patient counseling.

Expression of the Androgen Receptor Governs Radiation Resistance in a Subset of Glioblastomas Vulnerable to Antiandrogen Therapy.

New approaches are needed to overcome intrinsic therapy resistance in glioblastoma (GBM). Because GBMs exhibit sexual dimorphism and are reported to express steroid hormone receptors, we reasoned that signaling through the androgen receptor (AR) could mediate therapy resistance in GBM, much as it does in AR-positive prostate and breast cancers. We found that nearly half of GBM cell lines, patient-derived xenografts (PDX), and human tumors expressed AR at the transcript and protein level-with expression levels overlapping those of primary prostate cancer. Analysis of gene expression datasets also revealed that AR expression is higher in GBM patient samples than normal brain tissue. Multiple clinical-grade antiandrogens slowed the growth of and radiosensitized AR-positive GBM cell lines and PDXs in vitro and in vivo Antiandrogens blocked the ability of AR-positive GBM PDXs to engage adaptive transcriptional programs following radiation and slowed the repair of radiation-induced DNA damage. These results suggest that combining blood-brain barrier permeable antiandrogens with radiation may have promise for patients with AR-positive GBMs.