Search

Background Prenatal diagnosis of congenital heart disease has been associated with early‐term delivery and cesarean delivery (CD). We implemented a multi‐institutional standardized clinical assessment and management plan (SCAMP) through the University of California Fetal‐Maternal Consortium. Our objective was to decrease early‐term (37–39 weeks) delivery and CD in pregnancies complicated by fetal congenital heart disease using a SCAMP methodology to improve practice in a high‐risk and clinically complex setting. Methods and Results University of California Fetal‐Maternal Consortium site‐specific management decisions were queried following SCAMP implementation. This contemporary intervention group was compared with a University of California Fetal‐Maternal Consortium historical cohort. Primary outcomes were early‐term delivery and CD. A total of 496 maternal–fetal dyads with prenatally diagnosed congenital heart disease were identified, 185 and 311 in the historical and intervention cohorts, respectively. Recommendation for later delivery resulted in a later gestational age at delivery (38.9 versus 38.1 weeks, P =0.01). After adjusting for maternal age and site, historical controls were more likely to have a CD (odds ratio [OR],1.8; 95% CI, 2.1–2.8; P =0.004) and more likely (OR, 2.1; 95% CI, 1.4–3.3) to have an early‐term delivery than the intervention group. Vaginal delivery was recommended in 77% of the cohort, resulting in 61% vaginal deliveries versus 50% in the control cohort ( P =0.03). Among pregnancies with major cardiac lesions (n=373), vaginal birth increased from 51% to 64% ( P =0.008) and deliveries ≥39 weeks increased from 33% to 48% ( P =0.004). Conclusions Implementation of a SCAMP decreased the rate of early‐term deliveries and CD for prenatal congenital heart disease. Development of clinical pathways may help standardize care, decrease maternal risk secondary to CD, improve neonatal outcomes, and reduce healthcare costs.

OBJECTIVES: To perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis. STUDY DESIGN: This study included neonates with gastroschisis within sites in the University of California Fetal Consortium (UCFC). The study’s primary outcome was growth failure at hospital discharge, defined as a weight or length z-score decrease > 0.8 from birth. Regression analysis was performed to assess changes in z-scores over time. RESULTS: Among 125 infants with gastroschisis, the median gestational age was 37 weeks (IQR 35–37). Length of stay was 32 days (23–60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z-scores at 14 d, 30 d, and discharge were less than birth (p

Objective: Seven public and private California cardiac centers have joined to form the first statewide consortium created to improve the quality and value of congenital cardiac care. The overall goals of the consortium are: 1) to understand variation in modifiable perioperative processes of care among participating hospitals, and 2) to determine whether standardization of those process measures will reduce adverse events and cost. In this pilot study, preoperative management of neonates undergoing arterial switch operation (ASO) within one center was analyzed for variation and these process measures were then associated with increased inpatient costs and length of stay. Methods: Through retrospective analysis of neonates undergoing ASO for Transposition of the Great Arteries with Intact Ventricular Septum (TGA/IVS) (n=34) at one center between 2004-2014, variation within the following preoperative process measures was described: feeding protocols, ventilation management, use of balloon atrial septostomy (BAS) and prostaglandin, and timing of surgery. Independent review by echocardiologists (SS, SP, AMG) confirmed preoperative and discharge diagnoses. Risk factors for increased total hospital length of stay (TLOS), postoperative length of stay (PLOS) and inpatient hospital costs were analyzed by univariable linear regression. Results: The population (N=34) was predominantly male (80%, 27/34) with low overall prenatal diagnosis rate (27%, 9/34). Birth weight was 3295±521 grams and gestational age (GA) was 39.1±1.4 weeks. Variation was found in duration of preoperative hospital stay (7.1±3.7 days), proportion of preoperative stay spent in the Cardiac ICU (0.58±0.35), use of BAS (53%, 18/34), preoperative enteral feeding (50%, 17/34) and preoperative extubation (24%, 8/34). Increased birth weight was negatively associated with costs (p=0.01), TLOS (p=0.14) and PLOS (p=0.02). Delayed timing of surgery was positively associated with TLOS (p=0.0004) and total costs (p=0.01) but not PLOS (p=0.93). Preoperative Cardiac ICU management trended towards negative association with total costs (p=0.20) but not TLOS (p=0.35) or PLOS (p=0.99) when compared with preoperative Neonatal ICU management. Lower GA, preoperative BAS, preoperative enteral feeding and preoperative extubation were not significantly associated with increased costs, TLOS, and PLOS. Conclusions: Variations in preoperative management of neonates undergoing ASO for TGA/IVS are significantly associated with total healthcare costs and hospital LOS. Concatenated data from the remaining consortium members will be critical to validate these findings and to power morbidity and mortality analysis. Integrated findings will allow the consortium to develop and implement consensus based recommendations regarding standardization of those process measures that will reduce major complications and cost.

Objective: There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80% of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract. Methods: Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined. Results: HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels. Conclusions: The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.

Transfection with synthetic mRNA is a safe and efficient method of delivering antigens to dendritic cells for immunotherapy. Targeting antigens to the lysosome can sometimes enhance the CD4+ T-cell response. We transfected antigen-presenting cells (APCs) with mRNA encoding Gag-p24 and cytoplasmic, lysosomal, and secreted forms of Nef. Antigen-specific cytotoxic T cells were able to lyse the majority of transfected targets, indicating that transfection was efficient. Transfection of APCs with a Nef construct bearing lysosomal targeting signals produced rapid and prolonged antigen presentation to CD4+ and CD8+ T cells. Polyclonal CD4+ and CD8+ T-cell lines recognizing multiple distinct epitopes were expanded by coculture of transfected dendritic cells with peripheral blood mononuclear cells from viremic and aviremic HIV-infected subjects. Importantly, lysosome-targeted antigen drove a significantly greater expansion of Nef-specific CD4+ T cells than cytoplasmic antigen. The frequency of recognition of CD8 but not CD4 epitopes by mRNA-expanded T cells was inversely proportional to sequence entropy and was similar to ex vivo responses from a large chronic cohort. Thus human dendritic cells transfected with mRNA encoding lysosome-targeted HIV antigen can expand a broad, polyclonal repertoire of antiviral T cells, offering a promising approach to HIV immunotherapy.

Although an important quality metric, current technical performance scores may not be generalizable and may omit operative factors that influence outcomes. We examined factors not included in current technical performance scores that may contribute to increased postoperative length of stay, major complications, and cost after primary repair of tetralogy of Fallot.This is a retrospective single site study of patients younger than age 2 years with tetralogy of Fallot undergoing complete repair between 2007 and 2015. Medical record data and discharge echocardiograms were reviewed to ascertain component and composite technical performance scores. Primary outcomes included postoperative length of stay, major complications, and total hospital costs. Multivariable logistic and linear regression identified determinants of each outcome.Patient population (n = 115) had a median postoperative length of stay of 8 days (interquartile range, 6-10 days), and a median total cost of $71,147. Major complications occurred in 33 patients (29%) with 1 death. Technical performance scores assigned were optimum in 28 patients (25%), adequate in 59 patients (52%), and inadequate in 26 patients (23%). Neither technical performance score components nor composite scores were associated with increased postoperative length of stay. Optimum or adequate repairs versus inadequate had equal risk of a complication (P = .79), and equivalent mean total cost ($100,000 vs $187,000; P = .25). Longer cardiopulmonary bypass time per 1-minute increase (P .01) was associated with longer postoperative length of stay and reintervention (P = .02). The need to return to bypass also increased total cost (P .01).Current tetralogy of Fallot technical performance scores were not associated with selected outcomes in our postoperative population. Although returning to bypass and bypass length are not included as components in the current score, these are important factors influencing complications and resource use in our population. Revisions anticipated from a prospective trial should consider including these variables.

Deficient retro-aortic rim has been identified as a potential risk factor for aortic erosion, following device closure of atrial septal defects (ASD). However, the prevalence of deficient retro-aortic has not been well defined. The purpose of this study was to report the prevalence of retro-aortic

Background: Bacterial vaginosis (BV) has been associated with increased HIV cervicovaginal shedding. We hypothesized that this might relate to BV-associated increases in mucosal activated CD4 + T cells, which could enhance local HIV replication. Methods: Vaginal flora, cytokine/chemokine levels, and mucosal immune cell populations collected by cervical cytobrush were analyzed in 15 HIV-infected Kenyan female sex workers, before and after BV therapy with oral metronidazole. Results: Therapy reduced the Nugent score in all but 1 participant, and BV elimination was associated with reduced genital levels of interleukin 1β(IL1β), interleukin 8 (IL-8), and Regulated Upon Activation Normal T-cell Expressed and Secreted (RANTES). In addition, BV elimination reduced the total number of cervical CD4 + T cells, including those expressing the HIV coreceptor CCR5 and the activation marker CD69. Conclusions: BV induces significant and reversible alterations in cervical immune cell populations and local inflammatory cytokines that would be expected to enhance local HIV replication.

Background. Chroniccoinfectionwithherpessimplexvirustype2(HSV-2)andhumanimmunodeficiencyvirus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2‐associated alterations in host immunity. Methods. Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA. HIV-specific CD8 T cell epitopes were mapped, and proliferation of HIV-specific cells was also assessed. Systemic inflammatory and regulatory T cell populations were assayed by flow cytometry. Results. The breadth of both the HIV-specific CD8 T cell interferon- and proliferative responses was reduced inparticipantscoinfectedwithHIVandHSV-2,independentoftheHIVplasmaviralloadandCD4Tcellcount,and the magnitude of the responses was also reduced. HSV-2 infection in this group was associated with increased T cell CD38 expression but not with differences in the proportion of CD4 FoxP3 regulatory T cells. However, in women not infected with HIV, acquisition of HSV-2 was associated with an increase in the proportion of regulatory T cells. Conclusions. HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation.TheimmuneeffectsofHSV-2mayunderliethenegativeimpactthatthiscoinfectionhasontheclinicalcourse of HIV infection. Infection with herpes simplex virus type 2 (HSV-2) has been shown to affect the acquisition and subsequent course of HIV-1 (hereafter, “HIV”) in several ways. Chronic HSV-2 infection increases HIV acquisition ratesapproximately3-foldforbothmenandwomen[1] and up to 6-fold for high-risk female sex workers [2]. In sub-Saharan Africa, where the HIV pandemic has hit hardest, 60% of the general population may be infected by HSV-2 [3]. At this prevalence, it has been estimated that as many as half of the incident cases of HIV infection can be directly attributed to infection with HSV-2 [4].