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Our data indicate that GrA+ Th cells represent a distinct Th subset and are critical mediators of aGVHD.Interstitial cells of Cajal (ICCs) are pacemaker cells in the intestine, and their function can be compromised by loss of C-KIT expression. Macrophage activation has been identified in intestine affected by Hirschsprung disease-associated enterocolitis (HAEC). In this study, we examined proinflammatory macrophage activation and explored the mechanisms by which it downregulates C-KIT expression in ICCs in colon affected by HAEC. We found that macrophage activation and TNF-α production were dramatically increased in the proximal dilated colon of HAEC patients and 3-week-old Ednrb-/- mice. Moreover, ICCs lost their C-KIT+ phenotype in the dilated colon, resulting in damaged pacemaker function and intestinal dysmotility. However, macrophage depletion or TNF-α neutralization led to recovery of ICC phenotype and restored their pacemaker function. In isolated ICCs, TNF-α-mediated phosphorylation of p65 induced overexpression of microRNA-221 (miR-221), resulting in suppression of C-KIT expression and pacemaker currents. We also identified a TNF-α/NF-κB/miR-221 pathway that downregulated C-KIT expression in ICCs in the colon affected by HAEC. These findings suggest the important roles of proinflammatory macrophage activation in a phenotypic switch of ICCs, representing a promising therapeutic target for HAEC.BACKGROUNDPatients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK/STAT signaling pathways, which can be disabled by small molecules.METHODSWe treated a group of patients (n = 20) with baricitinib according to an off-label use of the drug. The study was designed as an observational, longitudinal trial and approved by the local ethics committee. The patients were treated with 4 mg baricitinib twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of phosphorylated STAT3 (p-STAT3) in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies against severe acute respiratory syndrome-coronavirus 2 (anti-SARS-CoV-2). In a single treated patient, we also evaluated the alteration of myeloid cell functional activity.RESULTSWe provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1β, and TNF-α, a rapid recovery of circulating T and B cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein, all of which were clinically associated with a reduction in the need for oxygen therapy and a progressive increase in the P/F (PaO2, oxygen partial pressure/FiO2, fraction of inspired oxygen) ratio.CONCLUSIONThese data suggest that baricitinib prevented the progression to a severe, extreme form of the viral disease by modulating the patients' immune landscape and that these changes were associated with a safer, more favorable clinical outcome for patients with COVID-19 pneumonia.TRIAL REGISTRATIONClinicalTrials.gov NCT04438629.FUNDINGThis work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM.Objectives We describe a standardized, scalable outpatient surveillance model for pregnant women with COVID-19 with several objectives (1) to identify and track known, presumed, and suspected COVID-positive pregnant patients both during their acute illness and after recovery, (2) to regularly assess patient symptoms and escalate care for those with worsening disease while reducing unnecessary hospital exposure for others, (3) to educate affected patients on warning symptoms, hygiene, and quarantine recommendations, and (4) to cohort patient care, isolating stable infected patients at home and later within the same physical clinic area upon their return to prenatal care. Methods Pregnant women in an urban public hospital system with presumed or confirmed COVID-19 were added to a list in our electronic medical record as they came to the attention of providers. They received a series of phone calls based on their illness severity and were periodically assessed until deemed stable. Results A total of 83 patients were followed between March 19 and May 31, 2020. Seven (8%) were asymptomatic, 62 (75%) had mild disease, 11 (13%) had severe disease, and three (4%) had critical illness. Conclusions We encourage others to develop and utilize outpatient surveillance systems to facilitate appropriate care and to optimize maternal and fetal well-being.

Current literature evaluating the role of induction of labor (IOL) following successful external cephalic version (ECV) attempt as compared to expectant management is limited. We aim to assess the risk of cesarean delivery in those undergoing immediate IOL following successful ECV as compared to those who were expectantly managed.

A retrospective cohort study of successful external cephalic versions. The study group included 57 women that were induced after procedure in the lack of maternal or fetal indications for induction of labor. These women were compared to 341 expectantly managed women. Maternal and fetal characteristics and outcomes were compared.

Gestation age at delivery was higher among the expectant management group (401/7 vs. 384/7, median, p=0.002) as compared to the induction group. Cesarean delivery rates were similar between both groups (28 [8.2%] vs. Ac-FLTD-CMK 3 [5.3%], p=0.44). In a multivariate logistic regression analysis, only nulliparity was significantly associated with cesarean delivery (adjusted odds ratio 3.42, confidence interval 1.61-7.24, p=0.001). No correlation was found between the version-to-delivery interval and the risk for cesarean delivery.

Induction of labor after successful ECV was not shown to influence cesarean delivery rates. As immediate IOL may result in higher rate of early-term deliveries, and in light of the lack of clinical benefit, we advocate against elective IOL following successful ECV.

Induction of labor after successful ECV was not shown to influence cesarean delivery rates. As immediate IOL may result in higher rate of early-term deliveries, and in light of the lack of clinical benefit, we advocate against elective IOL following successful ECV.

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