Disparities in high risk prenatal care adherence along racial and ethnic lines.

The term "high-risk pregnancy" describes a pregnancy at increased risk for complications due to various maternal or fetal medical, surgical, and/or anatomic issues. In order to best protect the pregnant patient and the fetus, frequent prenatal visits and monitoring are often recommended. Unfortunately, some patients are unable to attend these appointments for various reasons. Moreover, it has been documented that patients from ethnically and racially diverse backgrounds are more likely to miss medical appointments than are Caucasian patients. For instance, a case-control study retrospectively identified the race/ethnicity of patients who no-showed for mammography visits in 2018. Women who no-showed were more likely to be African American than patients who kept their appointments, with an odds ratio of 2.64 (4). Several other studies from several other primary care and specialty disciplines have shown similar results. However, the current research on high-risk obstetric no-shows has focused primarily on why patients miss their appointments rather than which patients are missing appointments. This is an area of opportunity for further research. Given disparities in health outcomes among underrepresented racial/ethnic groups and the importance of prenatal care, especially in high-risk populations, targeted attempts to increase patient participation in prenatal care may improve maternal and infant morbidity/mortality in these populations.

"Small" Intestinal Immunopathology Plays a "Big" Role in Lethal Cytokine Release Syndrome, and Its Modulation by Interferon-γ, IL-17A, and a Janus Kinase Inhibitor.

Chimeric antigen receptor T cell (CART) therapy, administration of certain T cell-agonistic antibodies, immune check point inhibitors, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and Toxic shock syndrome (TSS) caused by streptococcal as well as staphylococcal superantigens share one common complication, that is T cell-driven cytokine release syndrome (CRS) accompanied by multiple organ dysfunction (MOD). It is not understood whether the failure of a particular organ contributes more significantly to the severity of CRS. Also not known is whether a specific cytokine or signaling pathway plays a more pathogenic role in precipitating MOD compared to others. As a result, there is no specific treatment available to date for CRS, and it is managed only symptomatically to support the deteriorating organ functions and maintain the blood pressure. Therefore, we used the superantigen-induced CRS model in HLA-DR3 transgenic mice, that closely mimics human CRS, to delineate the immunopathogenesis of CRS as well as to validate a novel treatment for CRS. Using this model, we demonstrate that (i) CRS is characterized by a rapid rise in systemic levels of several Th1/Th2/Th17/Th22 type cytokines within a few hours, followed by a quick decline. (ii) Even though multiple organs are affected, small intestinal immunopathology is the major contributor to mortality in CRS. (iii) IFN-γ deficiency significantly protected from lethal CRS by attenuating small bowel pathology, whereas IL-17A deficiency significantly increased mortality by augmenting small bowel pathology. (iv) RNA sequencing of small intestinal tissues indicated that IFN-γ-STAT1-driven inflammatory pathways combined with enhanced expression of pro-apoptotic molecules as well as extracellular matrix degradation contributed to small bowel pathology in CRS. These pathways were further enhanced by IL-17A deficiency and significantly down-regulated in mice lacking IFN-γ. (v) Ruxolitinib, a selective JAK-1/2 inhibitor, attenuated SAg-induced T cell activation, cytokine production, and small bowel pathology, thereby completely protecting from lethal CRS in both WT and IL-17A deficient HLA-DR3 mice. Overall, IFN-γ-JAK-STAT-driven pathways contribute to lethal small intestinal immunopathology in T cell-driven CRS.