Association between Maternal Obesity Class, Adherence to Labor Guidelines, and Perinatal Outcomes.

Background Data are limited concerning rates of perinatal complications in women with a body mass index (BMI) ≥40 kg/m2 compared to women with other BMI classes when guidelines for the safe prevention of the primary cesarean delivery are applied. Objective The aim of the study is to evaluate labor guideline adherence by BMI class and to compare perinatal outcomes across BMI classes with guideline adherent management. Study Design This retrospective study included low-risk women admitted for delivery between April 2014 and April 2017 after the labor guidelines were implemented. BMI closest to delivery was used for analysis. Women with cesarean for nonreassuring fetal status were excluded. Results Guideline adherence decreased with increasing BMI, with 93% adherence among women of normal weight compared to 81% for class III obese women ( p < 0.0001). Among women who had guideline-adherent management, there was increased rates of cesarean among class III versus other obesity classes; however, there were no differences in rates of infectious morbidity ( p = 0.98) or hemorrhage ( p = 0.93). Although newborns of women with class III obesity had higher rates of meconium at birth, neonatal outcomes were not different with increasing maternal BMI ( p = 0.65). Conclusion There were no differences in adverse perinatal outcomes with increasing BMI.

Pregnancy-related mortality in the United States, 2003-2016: age, race, and place of death.

BACKGROUND: Pregnancy-related deaths in the United States are increasing. Medical, social, economic, and cultural issues have all been implicated in this trend, but few data exist to differentiate the relative contributions of these various factors. OBJECTIVE: The objective of the study was to examine trends in US pregnancy-related mortality by place of death and maternal race and age. We hypothesized that such an analysis may allow some distinction between deaths related to medical performance and those more closely related to social, cultural, or environmental issues. STUDY DESIGN: We conducted a retrospective, cross-sectional study for the years 2003-2016 using multiple cause-of-death mortality data provided by the Centers for Disease Control and Natality Data provided by National Vital Statistics System of the National Center for Health Statistics. Temporal trends analyses for the place of death, race/ethnicity, and age at the time of death were performed using joinpoint regression over the study period. RESULTS: Approximately one third of pregnancy-related deaths occurred outside a medical facility. The fraction of maternal deaths occurring in inpatient facilities fell by 20% over the study period, from 53% to 44% of all maternal deaths (P < .0001). Maternal deaths in an outpatient facility or emergency room demonstrated a similar decline (24%) in relative frequency (P < .0001). In contrast, there was a significant increase in the relative frequency of maternal mortality in other settings, particularly within the descendant's home, with a doubling over this time period. However, overall pregnancy-related deaths continued to increase in all settings. These increases were particularly striking in non-Hispanic black and white women and among women in the youngest and oldest age groups. CONCLUSION: Against a background of rising US pregnancy-related mortality, stratification of such deaths by place of death and maternal age and race highlights both the need for ongoing improvements in the quality of medical care and the potential contribution of events occurring outside a medical facility to the overall morality ratio. Current trends in pregnancy-related mortality in the United States are, in part, driven by social, cultural, and financial issues beyond the direct control of the medical community.

Opportunities for hospitals, hospital systems and leadership to improve VTE prophylaxis.

A sustained increase in the maternal death rate in the U.S. remains one of the most challenging issues of the twenty-first century. Ten years ago, we investigated the major conditions contributing to the maternal death rate between the years 2000 and 2006. The leading causes of death in the U.S. at that time were complications of preeclampsia, pulmonary thromboembolism, amniotic fluid embolism, obstetric hemorrhage and cardiac disease. Venous thromboembolism accounted for 9% of all maternal death, and an overall pregnancy-related mortality risk of 0.9 maternal deaths per 100,000 live births. VTE was the most common preventable cause of maternal death noted during that time period. In this paper, we will review and summarize changes in obstetric health care over the last ten years implemented to prevent VTE and its related morbidity. We will then examine opportunities for hospitals and hospital systems to improve VTE prophylaxis.

Characterization of Placental Microvasculature Using Superb Microvascular Imaging.

Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA) uses clutter suppression to extract flow signals at rapid frame rates, which provides high-resolution vessel-branching details without the need for contrast agents. The potential diagnostic benefits of SMI, as described in other areas of medicine, requires further exploration during pregnancy. In this pictorial essay, we demonstrate the complementary use of SMI compared to conventional Doppler ultrasound and how it may improve our ability to characterize placental microvascular patterns without the need for ultrasound contrast agents.

Risk Factors for Intrapartum Fever in Term Gestations and Associated Maternal and Neonatal Sequelae.

AIM: To determine factors associated with intrapartum fever and to examine associated maternal and neonatal outcomes. METHODS: Retrospective study of patients between 360/7 and 420/7 gestational weeks who entered spontaneous or induced active labor and developed temperature ≥38°C; a similar group that did not develop fever were controls. Univariate and multivariate analyses were performed with p < 0.05 as significant. RESULTS: Fifty-four febrile patients and 306 nonfebrile controls met inclusion criteria. Nulligravidity (45.8 vs. 77.8%, p < 0.001), length of first stage ≥720 min (OR 3.59, 95% CI 1.97-6.55, p < 0.001), length of second stage ≥120 min (OR 4.76, 95% CI 2.29-9.89, p < 0.001), membrane rupture ≥240 min (46.4 vs. 79.6%, p < 0.001), increasing number of vaginal exams (4 vs. 6, p < 0.001), oxytocin (44.8 vs. 63.0%, p = 0.014), and meperidine (14.7 vs. 35.2%, p < 0.001) were all associated with intrapartum fever. Associated morbidity included cesarean delivery (22.5 vs. 44.4%, p = 0.001), Apgar score <7 at 5 min (0.7 vs. 5.6%, p = 0.011), and neonatal intensive care unit admission (9.5 vs. 51.9%, p < 0.001). CONCLUSION: We have identified several noninfectious factors that are associated with intrapartum fever. Modification of risk factors may improve both maternal and neonatal outcomes.

Determination of antepartum and intrapartum risk factors associated with neonatal intensive care unit admission.

OBJECTIVE: To determine antepartum and intrapartum factors that are associated with admission to neonatal intensive care unit (NICU) among infants delivered between 36.0 and 42.0 weeks at our institution. METHODS: The retrospective cohort study included 73 consecutive NICU admissions and 375 consecutive non-NICU admissions. Data on demographic, antepartum, intrapartum and neonatal factors were collected. The primary endpoint defined was admission to NICU. Univariate analyses using the Student's t-test, Mann-Whitney U-test, χ2 Fisher's exact test was performed along with multivariate analysis of significant non-redundant variables. RESULTS: Those with a significantly higher risk of NICU admission underwent induction of labor with prostaglandin analogs (12.5% vs. 24.7%, P=0.007). Length of first stage ≥720 min (33.5% vs. 51.9%, P=0.011), length of second stage of labor ≥240 min (10.6% vs. 31.6%, P<0.001) and prolonged rupture of membranes ≥120 min (54.0% vs. 80.0%, P=0.001) were all associated with an increased chance of NICU admission. Intrapartum factors predictive of NICU admission included administration of meperidine (11.7% vs. 27.4%, P<0.001), presence of preeclampsia (5.5% vs. 0.8%, P=0.015), use of intrapartum IV antihypertensives (1.1% vs. 13.7%, P<0.001), maternal fever (5.3% vs. 31.5%, P<0.001), fetal tachycardia (1.9% vs. 12.3%, P<0.001), and presence of meconium (30% vs. 8%, P<0.001). CONCLUSION: Identification of modifiable risk factors may reduce neonatal morbidity and mortality. Results from this study can be used to develop and validate a risk model based on combined antepartum and intrapartum risk factors.

Unannounced standardized patients: a promising method of assessing patient-centered care in your health care system.

BACKGROUND: While unannounced standardized patients (USPs) have been used to assess physicians' clinical skills in the ambulatory setting, they can also provide valuable information on patients' experience of the health care setting beyond the physician encounter. This paper explores the use of USPs as a methodology for evaluating patient-centered care in the health care system. METHODS: USPs were trained to complete a behaviorally-anchored assessment of core dimensions of patient-centered care delivered within the clinical microsystem, including: 1) Medical assistants' safe practices, quality of care, and responsiveness to patients; 2) ease of clinic navigation; and 3) the patient-centeredness of care provided by the physician. Descriptive data is provided on these three levels of patient-centeredness within the targeted clinical microsystem. Chi-square analyses were used to signal whether variations by teams within the clinical microsystem were likely to be due to chance or might reflect true differences in patient-centeredness of specific teams. RESULTS: Sixty USP visits to 11 Primary Care teams were performed over an eight-month period (mean 5 visits/team; range 2-8). No medical assistants reported detecting an USP during the study period. USPs found the clinic easy to navigate and that teams were functioning well in 60% of visits. In 30% to 47% of visits, the physicians could have been more patient-centered. Medical assistants' patient safety measures were poor: patient identity was confirmed in only 5% of visits and no USPs observed medical assistants wash their hands. Quality of care was relatively high for vital signs (e.g. blood pressure, weight and height), but low for depression screening, occurring in only 15% of visits. In most visits, medical assistants greeted the patient in a timely fashion but took time to fully explain matters in less than half of the visits and rarely introduced themselves. Physicians tried to help patients navigate the system in 62% of visits. CONCLUSIONS: USP assessment captured actionable, critical, behaviorally-specific information on team and system performance in an urban community clinic. This methodology provides unique insight into the patient-centeredness and quality of care in medical settings.

Heme oxygenase (HO-1) rescue of adipocyte dysfunction in HO-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin.

BACKGROUND/AIMS: HO-1 and EETs are functionally linked and their interactions influence body weight, insulin sensitivity, and serum levels of inflammatory cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is essential for regulating physiological levels of ROS. Recent studies have suggested a potential role of EET in modifying adipocyte differentiation through up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo. METHODS: Four-month-old HO-2 null (HO-2(-/-)) and B6/129SF2/J (WT) mice were divided into three groups (four mice/group): WT, HO-2(-/-), and HO-2(-/-) +CoPP. Adipogenesis was performed on purified MSC-derived adipocytes cultured in adipogenic differentiation media and an EET-agonist was added every 3 days. RESULTS: HO-2 depletion of MSC adipocytes resulted in increased adipogenesis (p<0.01) and increased levels of inflammatory cytokines including (TNF)-alpha (p<0.05), (MCP)-1 (p<0.05), and (IL-1)-beta (p<0.05). These results were accompanied by decreases in HO-1 (p<0.05) and subsequently EET and HO activity (p<0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte differentiation, decreased production of TNF-alpha and MCP-1 and increased levels of adiponectin (p<0.05). Cyp2J5 (p<0.05), HO-1 (p<0.05), and adiponectin mRNA levels (p<0.05) were also decreased in visceral adipose tissue isolated from HO-2 null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from HO-2 null mice yielded similar results. CONCLUSION: Increased levels of EET and HO-1 are essential for protection against the adverse effects of adipocyte hypertrophy and the ensuing metabolic syndrome. These results offer a portal into therapeutic approaches for the prevention of the metabolic syndrome.

Epoxyeicosatrienoic acids and heme oxygenase-1 interaction attenuates diabetes and metabolic syndrome complications.

MSCs are considered to be the natural precursors to adipocyte development through the process of adipogenesis. A link has been established between decreased protective effects of EETs or HO-1 and their interaction in metabolic syndrome. Decreases in HO-1 or EET were associated with an increase in adipocyte stem cell differentiation and increased levels of inflammatory cytokines. EET agonist (AKR-I-27-28) inhibited MSC-derived adipocytes and decreased the levels of inflammatory cytokines. We further describe the role of CYP-epoxygenase expression, HO expression, and circulating cytokine levels in an obese mouse, ob/ob(-/-) mouse model. Ex vivo measurements of EET expression within MSCs derived from ob/ob(-/-) showed decreased levels of EETs that were increased by HO induction. This review demonstrates that suppression of HO and EET systems exist in MSCs prior to the development of adipocyte dysfunction. Further, adipocyte dysfunction can be ameliorated by induction of HO-1 and CYP-epoxygenase, i.e. EET.

Crosstalk between EET and HO-1 downregulates Bach1 and adipogenic marker expression in mesenchymal stem cell derived adipocytes.

Epoxygenase activity and synthesis of epoxyeicosatrienoic acids (EETs) have emerged as important modulators of obesity and diabetes. We examined the effect of the EET-agonist 12-(3-hexylureido)dodec-8(2) enoic acid on mesenchymal stem cell (MSC) derived adipocytes proliferation and differentiation. MSCs expressed substantial levels of EETs and inhibition of soluble epoxide hydrolase (sEH) increased the level of EETs and decreased adipogenesis. EET agonist treatment increased HO-1 expression by inhibiting a negative regulator of HO-1 expression, Bach-1. EET treatment also increased ßcatenin and pACC levels while decreasing PPARγ C/EBPα and fatty acid synthase levels. These changes were manifested by a decrease in the number of large inflammatory adipocytes, TNFα, IFNγ and IL-1α, but an increase in small adipocytes and in adiponectin levels. In summary, EET agonist treatment inhibits adipogenesis and decreases the levels of inflammatory cytokines suggesting the potential action of EETs as intracellular lipid signaling modulators of adipogenesis and adiponectin.

A pilot study on using eye tracking to understand assessment of surgical outcomes from clinical photography.

Appearance changes resulting from breast cancer treatment impact the quality of life of breast cancer survivors, but current approaches to evaluating breast characteristics are very limited. It is challenging, even for experienced plastic surgeons, to describe how different aspects of breast morphology impact overall assessment of esthetics. Moreover, it is difficult to describe what they are looking for in a manner that facilitates quantification. The goal of this study is to assess the potential of using eye-tracking technology to understand how plastic surgeons assess breast morphology by recording their gaze path while they rate physical characteristics of the breasts, e.g., symmetry, based on clinical photographs. In this study, dwell time, transition frequency, dwell sequence conditional probabilities, and dwell sequence joint probabilities were analyzed across photographic poses and three observers. Dwell-time analysis showed that all three surgeons spent the majority of their time on the anterior-posterior (AP) views. Similarly, transition frequency analysis between regions showed that there were substantially more transitions between the breast regions in the AP view, relative to the number of transitions between other views. The results of both the conditional and joint probability analyses between the breast regions showed that the highest probabilities of transitions were observed between the breast regions in the AP view (APRB, APLB) followed by the oblique views and the lateral views to complete evaluation of breast surgical outcomes.

Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice.

Increases in visceral fat are associated with increased inflammation, dyslipidemia, insulin resistance, glucose intolerance, and vascular dysfunction. We examined the effect of the potent heme oxygenase (HO)-1 inducer, cobalt protoporphyrin (CoPP), on regulation of adiposity and glucose levels in both female and male obese mice. Both lean and obese mice were administered CoPP intraperitoneally (3 mg/kg once per week) for 6 weeks. Serum levels of adiponectin, tumor necrosis factor α (TNFa), interleukin (IL)-1ß and IL-6, and HO-1, PPARγ, pAKT, and pAMPK protein expression in adipocytes and vascular tissue were measured. While female obese mice continued to gain weight at a rate similar to controls, induction of HO-1 slowed the rate of weight gain in male obese mice. HO-1 induction led to lowered blood pressure levels in obese male and female mice similar to that of lean male and female mice. HO-1 induction also produced a significant decrease in the plasma levels of IL-6, TNFα, IL-1ß, and fasting glucose of obese females compared to untreated female obese mice. HO-1 induction increased the number and decreased the size of adipocytes of obese animals. HO-1 induction increased adiponectin, pAKT, pAMPK, and PPARγ levels in adipocyte of obese animals. Induction of HO-1 in adipocytes was associated with an increase in adiponectin and a reduction in inflammatory cytokines. These findings offer the possibility of treating not only hypertension, but also other detrimental metabolic consequences of obesity including insulin resistance and dyslipidemia in obese populations by induction of HO-1 in adipocytes.

Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARγ.

Human mesenchymal stem cells (MSCs) expressed substantial levels of CYP2J2, a major CYP450 involved in epoxyeicosatrienoic acid (EET) formation. MSCs synthesized significant levels of EETs (65.8 ± 5.8 pg/mg protein) and dihydroxyeicosatrienoic acids (DHETs) (15.83 ± 1.62 pg/mg protein), suggesting the presence of soluble epoxide hydrolase (sEH). The addition of an sEH inhibitor to MSC culture decreased adipogenesis. EETs decreased MSC-derived adipocytes in a concentration-dependent manner, 8,9- and 14,15-EET having the maximum reductive effect on adipogenesis. We examined the effect of 12-(3-hexylureido)dodec-8(Z)-enoic acid, an EET agonist, on MSC-derived adipocytes and demonstrated an increased number of healthy small adipocytes, attenuated fatty acid synthase (FAS) levels (P < 0.01), and reduced PPARγ, C/EBPα, FAS, and lipid accumulation (P < 0.05). These effects were accompanied by increased levels of heme oxygenase (HO)-1 and adiponectin (P < 0.05), and increased glucose uptake (P < 0.05). Inhibition of HO activity or AKT by tin mesoporphyrin (SnMP) and LY2940002, respectively, reversed EET-induced inhibition of adipogenesis, suggesting that activation of the HO-1-adiponectin axis underlies EET effect in MSCs. These findings indicate that EETs decrease MSC-derived adipocyte stem cell differentiation by upregulation of HO-1-adiponectin-AKT signaling and play essential roles in the regulation of adipocyte differentiation by inhibiting PPARγ, C/EBPα, and FAS and in stem cell development. These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome.

Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 in Zucker rats and reduce adipogenesis in human mesenchymal stem cells.

Adiponectin, an abundant adipocyte-derived plasma protein that modulates vascular function in type 2 diabetes, has been shown to provide cytoprotection to both pancreatic and vascular systems in diabetes. Therefore, we examined whether up-regulation of heme oxygenase (HO)-1 ameliorates the levels of inflammatory cytokines and influences serum adiponectin in Zucker fat (ZF) rats. ZF rats displayed a decrease in both HO activity and HO-1 and HO-2 protein levels and an increase in tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 compared with Zucker lean (ZL) rats. Treatment of ZF animals with 2 mg/kg cobalt protoporphyrin IX (CoPP) increased protein levels of HO-1 and HO activity, but HO-2 was unaffected. The increase in HO-1 was associated with a decrease in superoxide levels (p < 0.05) and an increase in plasma adiponectin (p < 0.005), compared with untreated ZF rats. CoPP treatment decreased visceral and s.c. fat content, and it reduced weight gain (p < 0.01). In addition, the inflammatory cytokines TNF-alpha and IL-6 were decreased (p < 0.04 and p < 0.008, respectively). Treatment of human bone marrow-derived adipocytes cultured with CoPP resulted in an increase in HO-1 and a decrease in superoxide levels. Up-regulation of HO-1 caused adipose remodeling, smaller adipocytes, and increased adiponectin secretion in the culture medium of human bone marrow-derived adipocytes. In summary, this study demonstrates that the antiobesity effect of HO-1 induction results in an increase in adiponectin secretion, in vivo and in vitro, a decrease in TNF-alpha and IL-6, and a reduction in weight gain. These findings highlight the pivotal role and symbiotic relationship of HO-1 and adiponectin in the modulation of the metabolic syndrome phenotype.

Social and Environmental Risk Factors for Hypertension in African Americans.

This study tests the hypothesis that disparities of hypertension risk in African Americans is related to lead exposure, perceptions of racism, and stress, among urban (Roxbury, MA) and rural (Gadsden, FL) communities. Analysis of preliminary data from Phase I reveal 60% in Gadsden and 39% in Roxbury respondents self-reported having hypertension. In Gadsden 80% people did not know if their residence contained lead paint, compared to 45% in Roxbury. In Gadsden County, 58% of respondents reported experiencing racial discrimination in different settings compared with 72% in Roxbury. In regression analyses high cholesterol emerged as a significant predictors of hypertension in Gadsden County (OR=8.29, CI=1.4-49.3), whereas monthly household income (OR=0.15, CI=0.04-0.7) and diabetes (OR=6.06, CI=1.4-26.17) were significant predictors of hypertension in Roxbury after adjusting for other covariates. These preliminary findings set the stage for initiating Phase II (Phase I continues recruitment), that entail biological marker measurements to rigorously test main hypothesis.

Enhanced transduction of dendritic cells by FcgammaRI-targeted adenovirus vectors.

BACKGROUND: The high affinity Fcgamma receptor I (FcgammaRI; aka CD64) is expressed by dendritic cells (DC) and antigens targeted to this receptor elicit enhanced immune responses. This study was designed to test the hypothesis that targeting an adenoviral (Ad) vector to FcgammaRI would lead to enhanced transduction of DC and an improved immune response to vector-encoded antigens. METHODS: A bispecific adaptor molecule consisting of a trimeric adenovirus fiber-binding moiety fused to a single-chain antibody specific for human FcgammaRI was generated. Transduction of cultured cells, including human DC, by the FcgammaRI-targeted Ad was then evaluated using reporter genes (GFP, luciferase). Immunophenotypic and functional characteristics of vector-transduced DC were also measured by flow cytometry, cytokine ELISA and mixed lymphocyte reaction (MLR); antigen-specific stimulation of autologous CD8(+) T cells was evaluated using vectors encoding cytomegalovirus (CMV) pp65. RESULTS: FcgammaRI-targeted Ad transduced primary DC with 10-15-fold greater efficiency than unmodified Ad or Ad vectors complexed to an adaptor protein that targeted an irrelevant receptor. However, FcgammaRI-targeting had no effect of Ad-induced activation of DC, as measured by cytokine release or expression of cell surface activation markers. Finally, FcgammaRI-targeting of vectors encoding CMV pp65 resulted in an increase in the activation of antigen-specific autologous human CD8(+) T cells. CONCLUSIONS: FcgammaRI-targeting significantly enhances the efficiency of Ad vector-mediated gene transfer in primary human DC, and results in an improved immune response to a vector-encoded antigen.