Association between Peripartum Mean Arterial Pressure and Postpartum Readmission for Preeclampsia with Severe Features.

OBJECTIVE: This study aimed to evaluate the relationship between peripartum mean arterial pressure (MAP) and postpartum readmission for preeclampsia with severe features. STUDY DESIGN: This is a retrospective case-control study comparing adult parturients readmitted for preeclampsia with severe features to matched nonreadmitted controls. Our primary objective was to evaluate the association between MAP at three time points during the index hospitalization (admission, 24-hour postpartum, and discharge) and readmission risk. We also evaluated readmission risk by age, race, body mass index, and comorbidities. Our secondary aim was to establish MAP thresholds to identify the population at highest risk of readmission. Multivariate logistic regression and chi-squared tests were used to determine the adjusted odds of readmission based on MAP. Receiver operating characteristic analyses were performed to evaluate risk of readmission relative to MAP; optimal MAP thresholds were established to identify those at highest risk of readmission. Pairwise comparisons were made between subgroups after stratifying for history of hypertension, with a focus on readmitted patients with new-onset postpartum preeclampsia. RESULTS: A total of 348 subjects met inclusion criteria, including 174 controls and 174 cases. We found that elevated MAP at both admission (adjusted odds ratio [OR]: 1.37 per 10 mm Hg, p < 0.0001) and 24-hour postpartum (adjusted OR: 1.61 per 10 mm Hg, p = 0.0018) were associated with increased risk of readmission. African American race and hypertensive disorder of pregnancy were independently associated with increased risk of readmission. Subjects with MAP > 99.5 mm Hg at admission or >91.5 mm Hg at 24-hour postpartum had a risk of at least 46% of requiring postpartum readmission for preeclampsia with severe features. CONCLUSION: Admission and 24-hour postpartum MAP correlate with risk of postpartum readmission for preeclampsia with severe features. Evaluating MAP at these time points may be useful for identifying women at higher risk for postpartum readmission. These women may otherwise be missed based on standard clinical approaches and may benefit from heightened surveillance. KEY POINTS: · Existing literature focuses on management of antenatal hypertensive disorders of pregnancy.. · Elevated peripartum MAP is associated with increased odds of readmission for preeclampsia.. · Peripartum MAP may predict readmission risk for de novo postpartum preeclampsia..

Bariatric surgery normalizes diabetes risk index by one month post-operation.

AIM: The Diabetes risk index (DRI) is a composite of NMR-measured lipoproteins and branched chain amino acids predictive of diabetes mellitus development. Bariatric surgery is indicated in patients with severe obesity, many of whom are at high-risk for developing diabetes. Substantial weight loss occurs following bariatric surgery and sustained weight loss likely contributes to reductions in the development of diabetes and cardiovascular disease. However, some evidence suggests that bariatric surgical procedures themselves may contribute to reducing risk of these conditions independent of weight loss. We aimed to investigate DRI and its association with reductions in body weight and adiposity over one year following bariatric surgery. METHODS: We examined 51 severely obese premenopausal women without diabetes. DRI, BMI, body weight and waist measurements were made before and at 1, 6 and 12 months after Roux-en-Y Gastric Bypass (RYGB) or Sleeve Gastrectomy. Values were compared to healthy women with normal BMI (18.5-24.9 kg/m2; n = 15). RESULTS: Non-diabetic women with severe obesity (BMI 44.7 ± 6.2 kg/m2) exhibited significantly elevated DRI scores prior to surgery versus controls (35 [26, 39] vs 12 [1, 20]; p < 0.0001). At 1 month after surgery, BMI decreased 5.1 ± 1.1 kg/m2, but DRI decreased so that it no longer differed from that of normal BMI controls (1.9 [1, 17] vs control 12 [1, 20]; p = 0.35). Subjects continued to lose weight, whereas DRI remained similar, throughout follow-up with DRI 1.0 [1, 7] at 12 months. Changes in DRI did not correlate with changes in BMI, body weight or waist circumference at any time during follow-up. There was no difference in change in DRI between surgical procedures or pre-operative metabolic syndrome status. CONCLUSIONS: Our analysis of DRI scores supports the capacity of bariatric surgery to reduce risk of developing diabetes in severely obese individuals. Our findings suggest that bariatric surgical techniques may have inherent effects that improve cardiometabolic risk independent of reductions in body weight or adiposity.

Cucurbitacin B exhibits antitumor effects on CD133+ HepG2 liver cancer stem cells by inhibiting JAK2/STAT3 signaling pathway.

Cancer stem cells (CSCs), a crucial cancer cell subpopulation, possess stemness phenotypic characteristics. Cucurbitacin B (CuB), a tetracyclic triterpenoid isolated from Cucurbitaceae, exerts widely pharmacological activities in many diseases. The aim of this study was to enrich, identify liver CSCs and investigate antitumor effects of CuB as well as explore the underlying molecular mechanisms in these liver CSCs. HepG2 cell lines were used for the enrichment of liver CSCs by serum-free medium culture and magnetic-activated cell sorting. The CSC characteristics were analyzed by immunofluorescent staining, sphere-forming, western blot and xenograft tumorigenicity assay. CuB' antitumor effects and underlying molecular mechanism were measured by cell counting kit-8, colony formation, sphere-forming, cell cycle, xenograft and western blot assay. Our results showed that we could enrich 97.29% CD133+ HepG2 cells, which possessed CSC characteristics including re-renewal capacity, proliferative ability, sorafenib resistance, overexpressed stemness-related molecules and enhanced tumorigenic potential. Furthermore, we also found that CuB inhibited cell viability, sphere formation, colony formation and arrested cell cycle at G2/M phase as well as sensitized CD133+ HepG2 cells to sorafenib in vitro and in vivo. Western blot assay indicated that CuB inhibited expression levels of cyclin B1, CDK1, CD133, p-JAK2 and p-STAT3. In conclusion, our findings indicated that CuB could exhibit antitumor effects on CD133+ HepG2 CSCs by inhibiting the Janus kinase 2/signal transducers and activators of transcription-3 signaling pathway, expanding basic and preclinical investigations on liver CSCs.

Lipoprotein insulin resistance score in nondiabetic patients with obesity after bariatric surgery.

BACKGROUND: Lipoprotein insulin resistance (LPIR) score is a composite biomarker representative of atherogenic dyslipidemia characteristic of early insulin resistance. It is elevated in obesity and may provide information not captured in glycosylated hemoglobin and homeostatic model assessment for insulin resistance. While bariatric surgery reduces diabetes incidence and resolves metabolic syndrome, the effect of bariatric surgery on LPIR is untested. OBJECTIVES: We sought to assess the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on LPIR in nondiabetic women with obesity. SETTING: Nonsmoking, nondiabetic, premenopausal Hispanic women, age ≥18 years, undergoing Roux-en-Y gastric bypass or sleeve gastrectomy at Bellevue Hospital were recruited for a prospective observational study. METHODS: Anthropometric measures and blood sampling were performed preoperatively and at 6 and 12 months postoperatively. LPIR was measured by nuclear magnetic resonance spectroscopy. RESULTS: Among 53 women (Roux-en-Y gastric bypass, n = 22; sleeve gastrectomy, n = 31), mean age was 32 ± 7 years and body mass index 44.1 ± 6.4 kg/m2. LPIR was reduced by 35 ± 4% and 46 ± 4% at 6 and 12 months after surgery, respectively, with no difference by procedure. Twenty-seven of 53 patients met International Diabetes Federation criteria for metabolic syndrome preoperatively and had concomitant higher homeostatic model assessment for insulin resistance, glycosylated hemoglobin, nonhigh-density lipoprotein-cholesterol and LPIR. Twenty-five of 27 patients experienced resolution of metabolic syndrome postoperatively. Concordantly, the preoperative differences in homeostatic model assessment for insulin resistance, glycosylated hemoglobin, and nonhigh-density lipoprotein-cholesterol between those with and without metabolic syndrome resolved at 6 and 12 months. In contrast, patients with metabolic syndrome preoperatively exhibited greater LPIR scores at 6 and 12 months postoperatively. CONCLUSION: This is the first study to demonstrate improvement in insulin resistance, as measured by LPIR, after bariatric surgery with no difference by procedure. This measure, but not traditional markers, was persistently higher in patients with a preoperative metabolic syndrome diagnosis, despite resolution of the condition.

Elevated GlycA in severe obesity is normalized by bariatric surgery.

Chronic inflammation drives many obesity-associated conditions including atherosclerosis. GlycA, a marker of systemic inflammation with lower intra-individual variability than high sensitivity C-reactive protein, is independently associated with incident cardiovascular events and mortality. Although GlycA is elevated in obesity, correlations with anthropometric measures are modest and the effect of body weight loss on GlycA is untested. Obese (body mass index [BMI] 44.6 ± 6.6 kg/m2 ), non-diabetic women (33.7 ± 8.2 years) undergoing Roux-en-Y gastric bypass (n = 23) or sleeve gastrectomy (n = 31) were prospectively studied at baseline, 6 and 12 months postprocedure. Women with normal BMI (n = 14) served as controls. Bariatric surgery significantly reduced GlycA by 6 months (451 ± 47 µmol/L vs. 383 ± 50 µmol/L; P < 0.001) with further reduction at 12 months (348 ± 41 µmol/L; P < 0.001) and no difference between procedures. At 12 months, despite 41% of surgical subjects maintaining BMI >30 kg/m2 , GlycA levels did not differ between surgical and control subjects (P = 0.13). Increased high density lipoprotein particle size was strongly associated with reduced GlycA (r = -0.49; P < 0.001) and was found to mediate up to 43% of its body weight-loss-associated fall. This is the first study to demonstrate that surgical body weight loss markedly reduces levels of GlycA.

Changes in High-Density Lipoprotein Cholesterol Efflux Capacity After Bariatric Surgery Are Procedure Dependent.

OBJECTIVE: High-density lipoprotein cholesterol efflux capacity (CEC) is inversely associated with incident cardiovascular events, independent of high-density lipoprotein cholesterol. Obesity is often characterized by impaired high-density lipoprotein function. However, the effects of different bariatric surgical techniques on CEC have not been compared. This study sought to determine the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on CEC. APPROACH AND RESULTS: We prospectively studied severely obese, nondiabetic, premenopausal Hispanic women not using lipid medications undergoing RYGB (n=31) or SG (n=36). Subjects were examined before and at 6 and 12 months after surgery. There were no differences in baseline characteristics between surgical groups. Preoperative CEC correlated most strongly with Apo A1 (apolipoprotein A1) concentration but did not correlate with body mass index, waist:hip, high-sensitivity C-reactive protein, or measures of insulin resistance. After 6 months, SG produced superior response in high-density lipoprotein cholesterol and Apo A1 quantity, as well as global and non-ABCA1 (ATP-binding cassette transporter A1)-mediated CEC (P=0.048, P=0.018, respectively) versus RYGB. In multivariable regression models, only procedure type was predictive of changes in CEC (P=0.05). At 12 months after SG, CEC was equivalent to that of normal body mass index control subjects, whereas it remained impaired after RYGB. CONCLUSIONS: SG and RYGB produce similar weight loss, but contrasting effects on CEC. These findings may be relevant in discussions about the type of procedure that is most appropriate for a particular obese patient. Further study of the mechanisms underlying these changes may lead to improved understanding of the factors governing CEC and potential therapeutic interventions to maximally reduce cardiovascular disease risk in both obese and nonobese patients.