Infiltrating T-cell markers in cervical carcinogenesis: a systematic review and meta-analysis.

BACKGROUND: The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis. METHODS: A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis. RESULTS: There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels. CONCLUSIONS: Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies.

Obstetrical and neonatal outcomes in patients with surgically repaired heart disease.

BACKGROUND: Congenital and acquired heart disease complicate 1% to 4% of pregnancies in the United States. Beyond the risks of the underlying maternal congenital heart disease, cardiac surgery and its sequelae, such as surgical scarring resulting in higher rates of arrhythmias and implanted valves altering anticoagulation status, have potential implications that could affect gestation and delivery. OBJECTIVE: This study aimed to investigate whether history of maternal cardiac surgery is associated with adverse obstetrical or neonatal outcomes compared with patients without a history of cardiac disease or surgery, considered "healthy controls." STUDY DESIGN: This is a secondary analysis of retrospective cohort studies performed at a tertiary care facility in the United States comparing obstetrical outcomes in patients with a history of open cardiac surgery who delivered from January 2007 to December 2018 with healthy controls, who delivered from April 2020 to July 2020. There were 74 pregnancies in 61 patients with a history of open cardiac surgery that were compared with pregnancies in healthy controls. Of the 74 pregnancies, 65 were successfully matched based on gestational age to controls at a 1:3 (case-to-control) ratio. The remainder of cases were matched at a 1:2 or 1:1 ratio; therefore, a total of 219 control pregnancies were included in the analysis. Our primary outcome was the incidence of hypertensive disorders of pregnancy, as well as cesarean delivery, in patients with a history of open cardiac surgery compared with healthy controls. Our secondary outcome was the incidence of low-birthweight neonates in patients with a history of open cardiac surgery compared with healthy controls. RESULTS: Patients with a history of cardiac surgery were not more likely to have any hypertensive disorder diagnosed than healthy controls. Patients with a history of cardiac surgery were more likely to have an operative delivery (P<.0001) but equally likely to have a cesarean delivery (P=.528) compared with healthy controls. Birthweight was not statistically different of 2655±808 g in neonates born to patients with a history of cardiac surgery vs 2844±830 g born to healthy controls (P=.092). CONCLUSION: Patients with a history of cardiac surgery may not be at higher risk of hypertensive disorder diagnosis during pregnancy. Similarly, most patients with a history of cardiac surgery are also likely not at higher risk of cesarean delivery or low-birthweight neonates.

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.