Outcomes after extended azithromycin administration in preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes accounts for approximately one-quarter of all preterm deliveries and occurs in 2% to 3% of all pregnancies. With subclinical infection being a suspected cause of preterm premature rupture of membranes, the administration of prophylactic antibiotics is an accepted standard of care to extend the latency period. Historically, erythromycin was used in the antibiotic regimen recommended for women with preterm premature rupture of membranes during expectant management; however, azithromycin has recently been shown to be a suitable alternative. OBJECTIVE: This study aimed to evaluate whether extended azithromycin administration affects the latency time in preterm premature rupture of membranes. STUDY DESIGN: This was a retrospective multi-institutional cohort study in Washington, District of Columbia, of patients admitted from January 2012 to December 2019 with preterm premature rupture of membranes of singleton pregnancies between 23 0/7 and 33 6/7 weeks of gestation. Patients were excluded if they had multiple pregnancies, had an allergy to penicillin or macrolides, were in labor, had suspected placental abruptions, had overt chorioamnionitis, or had nonreassuring fetal status on presentation indicating the need for prompt delivery. Patients that received limited azithromycin administration (<2 days) and patients that received extended azithromycin administration (7 days) were compared. All patients otherwise received the institutional standard of 2 days of intravenous ampicillin followed by 5 days of oral amoxicillin. The primary outcome was length of gestational latency, defined as the time from membrane rupture to delivery. The selective secondary outcomes that were evaluated were rates of chorioamnionitis and adverse neonatal outcomes, including sepsis, respiratory distress, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal death. RESULTS: During the study period, 416 cases of preterm premature rupture of membranes were identified. Of the 287 patients who met the inclusion criteria, 165 (57.5%) received limited azithromycin administration, and 122 (42.5%) received extended azithromycin administration. Adjusted median gestational latency was significantly longer for patients who received extended azithromycin administration, extended by >3 days (2.6 days [interquartile range, 2.2-3.1] for limited azithromycin administration vs 5.8 days [interquartile range, 4.8-6.9] for extended azithromycin administration; P<.001). Neonatal secondary outcome evaluation was performed on 216 cases (76%). There was no difference in chorioamnionitis or adverse neonatal outcomes between the 2 groups. CONCLUSION: Among patients with preterm premature rupture of membranes, extended azithromycin administration was associated with increased latency, without any effect on other maternal or neonatal outcomes.

IgG3 regulates tissue-like memory B cells in HIV-infected individuals.

Immunoglobulin G3 (IgG3) has an uncertain role in the response to infection with and vaccination against human immunodeficiency virus (HIV). Here we describe a regulatory role for IgG3 in dampening the immune system-activating effects of chronic HIV viremia on B cells. Secreted IgG3 was bound to IgM-expressing B cells in vivo in HIV-infected chronically viremic individuals but not in early-viremic or aviremic individuals. Tissue-like memory (TLM) B cells, a population expanded by persistent HIV viremia, bound large amounts of IgG3. IgG3 induced clustering of B cell antigen receptors (BCRs) on the IgM+ B cells, which was mediated by direct interactions between soluble IgG3 and membrane IgM of the BCR (IgM-BCR). The inhibitory IgG receptor CD32b (FcγRIIb), complement component C1q and inflammatory biomarker CRP contributed to the binding of secreted IgG3 onto IgM-expressing B cells of HIV-infected individuals. Notably, IgG3-bound TLM B cells were refractory to IgM-BCR stimulation, thus demonstrating that IgG3 can regulate B cells during chronic activation of the immune system.

Lipid-dependent regulation of exocytosis in S. cerevisiae by OSBP homolog (Osh) 4.

Polarized exocytosis is an essential process in many organisms and cell types for correct cell division or functional specialization. Previous studies established that homologs of the oxysterol-binding protein (OSBP) in S. cerevisiae, which comprise the Osh protein family, are necessary for efficient polarized exocytosis by supporting a late post-Golgi step. We define this step as the docking of a specific sub-population of exocytic vesicles with the plasma membrane. In the absence of other Osh proteins, yeast Osh4p can support this process in a manner dependent upon two lipid ligands, PI4P and sterol. Osh6p, which binds PI4P and phosphatidylserine, is also sufficient to support polarized exocytosis, again in a lipid-dependent manner. These data suggest that Osh-mediated exocytosis depends upon lipid binding and exchange without a strict requirement for sterol. We propose a two-step mechanism for Osh protein-mediated regulation of polarized exocytosis by using Osh4p as a model. We describe a specific in vivo role for lipid binding by an OSBP-related protein (ORP) in the process of polarized exocytosis, guiding our understanding of where and how OSBP and ORPs may function in more complex organisms.