Factors and outcomes associated with under- and overdiagnosis of sepsis in the first hour of emergency department care.

Background: Sepsis remains the leading cause of in-hospital death and one of the costliest inpatient conditions in the United States, while treatment delays worsen outcomes. We sought to determine factors and outcomes associated with a missed emergency physician (EP) diagnosis of sepsis.

Methods: We conducted a secondary analysis of a prospective single-center observational cohort of undifferentiated, critically ill medical patients (September 2020-May 2022).

Antiprogestins suppress basal and activin-stimulated follicle-stimulating hormone secretion in an estrogen-dependent manner.

Previous studies from our laboratory, demonstrating that suppression of serum FSH by RU486 requires a high estrogen (E) background, suggested that E-inducible progesterone receptors play a role in the regulation of FSH secretion. We demonstrated further that the type II antiprogestin RU486 and the type I antiprogestin ZK98299 both suppressed the elevated serum FSH and FSHbeta messenger RNA levels similarly on the evening of proestrus, but had divergent effects on the morning of estrus, when only RU486, but not ZK98299, lowered the elevated serum FSH level (secondary FSH surge). In the present work we used primary anterior pituitary cell culture to examine whether RU486 caused direct, E-dependent suppression of basal and recombinant human activin A (activin)-induced FSH secretion in the gonadotrope and to compare this direct effect, if any, with that of ZK98299.

The antiprogestins RU486 and ZK98299 affect follicle-stimulating hormone secretion differentially on estrus, but not on proestrus.

Previous in vivo studies from our laboratory indicated that administration of the antiprogestin RU486 on proestrus suppresses both the preovulatory gonadotropin surges and the secondary FSH surge, suggesting a role for the progesterone receptor (PR) in the generation of these surges. The present study was designed to test the effects of another antiprogestin, ZK98299, which has been reported to block the PR through a mechanism different from that of RU486, on gonadotropin secretion in vivo. RU486 and ZK98299 (2 and 6 mg/kg) were administered s.

Corticosterone selectively increases follicle-stimulating hormone beta-subunit messenger ribonucleic acid in primary anterior pituitary cell culture without affecting its half-life.

We demonstrated previously that glucocorticoids differentially affect the levels of the two pituitary gonadotropins, LH and FSH, both in vivo and in vitro. In vivo, the effect of glucocorticoids is GnRH independent, indicating a direct action on the gonadotrope, and it leads to selective up-regulation of the pituitary content of FSH and FSH beta-subunit messenger RNA (mRNA). The objective of the present study was to confirm the direct action of corticosterone (B) on FSH beta-subunit mRNA in primary anterior pituitary cell culture and to assess whether the selective B-induced rise in FSH beta mRNA is mediated through altered stability of the FSH beta transcript.

RU486 on an estrogen background blocks the rise in serum follicle-stimulating hormone induced by antiserum to inhibin or ovariectomy.

We used passive immunization with an antiserum to the alpha-subunit of inhibin (anti-I) or acute ovariectomy to investigate the relationship between serum inhibin levels and FSH secretion in the presence of the progesterone/glucocorticoid antagonist RU486. We demonstrated previously that 1) anti-I administered at 1700 h causes serum FSH to rise on the morning of estrus, even in the presence of a GnRH antagonist, when the two treatments are delivered on proestrus; and that 2) RU486 given on proestrus (1230 h), a time when serum estradiol levels are high, not only blocks the natural secondary FSH surge, but also suppresses the anti-I-induced rise in serum FSH on the morning of estrus. We have now extended our studies of the relationship between inhibin and RU486 to investigate treatment with RU486 and anti-I on a different day of the cycle, estrus, when serum estradiol levels are low.