Cervical pessary for preventing preterm birth in singletons and twin pregnancies: an update systematic review and meta-analysis.

OBJECTIVES: To evaluate the effectiveness of cervical pessary in preventing preterm birth (PTB) and improving perinatal outcomes among singleton and twin pregnancies. METHODS: Electronic databases were systematically searched from their inception until 14 March 2019. Randomized clinical trials comparing the effectiveness of cervical pessary placement with expectant management were included. The primary outcome was the incidence of PTB <34 weeks. RESULTS: Thirteen studies were included, involving eight studies about singleton and six studies about twin pregnancies. For singleton pregnancies with short cervical length, cervical pessary, comparing with expectant treatment, seemed have no effectiveness in preventing PTB <34 weeks (relative risk, 95% confidence interval, 0.73, 0.42-1.28), <37 weeks (0.69, 0.43-1.09), and <28 weeks (0.79, 0.42-1.48); while for twin pregnancies with short cervical length, cervical pessary also did not reduce the risk of PTB <34 weeks (0.81, 0.49-1.35), <37 weeks (0.93, 0.83-1.05), and <28 weeks (0.72, 0.38-1.38). However, cervical pessary seemed have the effectiveness of reducing the risk of spontaneous PTB <28 weeks (0.50, 0.25-0.99) and low birth weight (<1500 g) (0.68, 0.50-0.94) among twin pregnancies with short cervical length. In addition, cervical pessary increased the rate of vaginal discharge and did not improve perinatal outcomes among both singleton and twin pregnancies. CONCLUSIONS: Comparing with the expectant treatment, the effectiveness of cervical pessary for reducing the risk of PTB remains uncertain. Additional trials are warranted to further evaluate the effectiveness of cervical pessary.

Effects of Motherwort Injection Versus Intramuscular Oxytocin for Preventing Postpartum Hemorrhage Among Women Who Underwent Cesarean Section.

Objectives: Subject to ethical constraints, real-world data are an important resource for evaluating treatment effects of medication use during pregnancy and the postpartum period. This study investigated whether motherwort injection, a traditional Chinese medicine preparation, was more effective than intramuscular (IM) oxytocin for preventing postpartum hemorrhage (PPH) in a real-world setting when intravenous (IV) oxytocin is administered. Methods: We conducted an active-controlled, propensity-score matched cohort study using an established pregnancy registry database. Women who underwent cesarean section and received IV oxytocin at the third stage of labor were included. We used an active-comparator design to minimize indication bias, in which we compared IM motherwort injection in the uterus versus IM oxytocin, both on top of IV oxytocin use. We applied 1:1 propensity-score matching (PSM) to balance patient baseline characteristics and used a logistic regression model to estimate treatment effect (i.e., risk difference (RD) and odds ratio (OR)) by using the counterfactual framework. The outcomes of interest were blood loss over 500 ml within 2 h after delivery (PPH, primary) and blood loss over 1,000 ml (severe PPH, secondary). We conducted four sensitivity analyses to examine the robustness of the results. Results: A total of 22,519 pregnant women underwent cesarean sections, among which 4,081 (18.12%) PPH and 480 (2.13%) severe PPH occurred. Among included women, 586 (2.60%) were administrated with IM motherwort injection, and 21,933 (97.40%) used IM oxytocin. After PSM, patient baseline characteristics were well balanced. Compared with IM oxytocin, the use of IM motherwort injection was associated with significantly lower risk of PPH (RD -25.26%, 95% CI -30.04% to -20.47%, p < 0.001; OR 0.25, 95% CI 0.18 to 0.32, p < 0.001) and severe PPH (RD -3.58%, 95% CI -5.87% to -1.30%, p < 0.001; OR 0.39, 95% CI 0.20 to 0.71, p < 0.002). Sensitivity analyses showed that the results were similar. Conclusion: With the use of data from a real-world setting, the findings consistently showed that among women undergoing cesarean section who had received IV oxytocin, the additional use of IM motherwort injection could achieve a lower risk of PPH as compared to the additional use of IM oxytocin. Our study suggested a paradigm for investigating the treatment effect of Chinese herbal medicine in the real-world practice setting.

Creating rat hepatocyte organoid as an in vitro model for drug testing.

BACKGROUND: Liver organoids have recently been applied as models for liver disease and drug screening, especially when combined with liver-on-a-chip technologies. Compared to hepatocyte-like cells, primary hepatocytes have high functionality but cannot maintain their function when cultured in vitro. Mesenchymal stem cells (MSCs) enhance hepatocyte function and maintain hepatocyte metabolism when co-cultured with hepatocytes. MSCs can help induced pluripotent stem cells to generate an organoid structure via the MSC-based traction force triggered by extracellular matrix (ECM) proteins. In this study, primary hepatocytes were co-cultured with MSCs on a liver-derived ECM to generate liver organoids within a short duration. AIM: To create hepatocyte organoids by co-culturing primary hepatocytes with MSCs on a porcine liver extracellular matrix (PLECM) gel. METHODS: Perfusion and enzymatic hydrolysis were used to form the PLECM gel. Rat hepatocytes and human MSCs were mixed and plated on pre-solidified PLECM gel in a 48-well plate for 48 h to generate organoids. Generated organoids were evaluated through hematoxylin and eosin, periodic acid-Schiff, immuno-histological, and immunofluorescence staining, and quantitative PCR for alb, CYP450 gene markers, and urea cycle genes. Culture medium was collected to detect albumin (ALB) and urea production on days 2, 4, 6, 8, 14, and 20. RESULTS: The whole porcine liver was perfused and enzymatically hydrolyzed to form a PLECM gel. The structural components and basement membrane composition of the ECM, such as collagen type I, collagen type IV, fibronectin, and laminin, were demonstrated to be retained. Through interaction of human MSCs with the liver-derived ECM, primary hepatocytes and human MSCs assembled together into a 3D construction and generated primary hepatocyte organoids for 48 h. The mRNAs of the gene alb, the CYP450 gene markers cyp1a1, cyp1a2, and cyp3a2 as well as urea cycle genes arg-1, asl, ass-1, cps-1, nags were highly expressed in hepatocyte organoids. Long-term survival of the primary hepatocyte organoids, as well as stable functionality, was demonstrated via ALB and urea production in vitro. CONCLUSION: Our new method of creating primary hepatocyte organoids by co-culturing hepatocytes with MSCs on liver-derived ECM hydrogels could be used to develop models for liver disease and for drug screening.

Association between prepregnancy subnormal body weight and obstetrical outcomes after autologous in vitro fertilization cycles: systematic review and meta-analysis.

OBJECTIVE: To study the association between prepregnancy subnormal body weight and obstetrical outcomes after autologous in vitro fertilization (IVF) cycles. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women with prepregnancy subnormal body weight (body mass index <18.5 kg/m2) and normal body weight (body mass index 18.5-25 kg/m2) after assisted reproductive treatment. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate. CPR and LBR were calculated at per-woman and per-cycle levels. RESULT(S): A total of 38 cohort studies with low risk of bias were included. Meta-analyses showed that, compared with normal-weight women, those underweight before pregnancy had a lower CPR at per-woman and per-cycle levels. Compared with normal weight, underweight before pregnancy had little impact on LBR at both per-woman and per-cycle levels, nor on miscarriage rate. CONCLUSION(S): Compared with women of normal weight, women who were underweight before pregnancy had modest association with a lower CPR, but underweight did not seem to affect LBR or miscarriage after IVF.

Bioartificial liver support systems for acute liver failure: A systematic review and meta-analysis of the clinical and preclinical literature.

BACKGROUND: Acute liver failure (ALF) has a high mortality varying from 80% to 85% with rapid progress in multi-organ system failure. Bioartificial liver (BAL) support systems have the potential to provide temporary support to bridge patients with ALF to liver transplantation or spontaneous recovery. In the past decades, several BAL support systems have been conducted in clinical trials. More recently, concerns have been raised on the renovation of high-quality cell sources and configuration of BAL support systems to provide more benefits to ALF models in preclinical experiments. AIM: To investigate the characteristics of studies about BAL support systems for ALF, and to evaluate their effects on mortality. METHODS: Eligible clinical trials and preclinical experiments on large animals were identified on Cochrane Library, PubMed, and EMbase up to March 6, 2019. Two reviewers independently extracted the necessary information, including key BAL indicators, survival and indicating outcomes, and adverse events during treatment. Descriptive analysis was used to identify the characteristics of the included studies, and a meta-analysis including only randomized controlled trial (RCT) studies was done to calculate the overall effect of BAL on mortality among humans and large animals, respectively. RESULTS: Of the 30 selected studies, 18 were clinical trials and 12 were preclinical experiments. The meta-analysis result suggested that BAL might reduce mortality in ALF in large animals, probably due to the recent improvement of BAL, including the type, cell source, cell mass, and bioreactor, but seemed ineffective for humans [BAL vs control: relative risk (95% confidence interval), 0.27 (0.12-0.62) for animals and 0.72 (0.48-1.08) for humans]. Liver and renal functions, hematologic and coagulative parameters, encephalopathy index, and neurological indicators seemed to improve after BAL, with neither meaningful adverse events nor porcine endogenous retrovirus infection. CONCLUSION: BAL may reduce the mortality of ALF by bridging the gap between preclinical experiments and clinical trials. Clinical trials using improved BAL must be designed scientifically and conducted in the future to provide evidence for transformation.

Perioperative outcomes in geriatric patients undergoing hip fracture surgery with different anesthesia techniques: A systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses assessing anesthetic techniques in adult patients undergoing hip fractures surgery are available. However, whether the anesthetic technique is associated with risk of mortality and complications in geriatric patients with hip fractures remains unclear. This study was conducted to assess postoperative outcomes of anesthesia technique in geriatric patients undergoing hip fracture surgery. METHODS: Cochrane Library, PubMed, EMBASE, MEDLINE, CNKI, and CBM were searched from inception up to May 25, 2018. Observational studies and randomized controlled trials (RCTs) that assessed the perioperative outcomes of technique of anesthesia (general or regional [epidural/spinal/neuraxial]) in geriatric patients (≥60 years old) undergoing hip fracture surgery were included. Two investigators independently screened studies for inclusion and performed data extraction. Heterogeneity was assessed by the I and Chi-square tests. The odds ratio (OR) of the dichotomous data, mean difference (MD) of continuous data, and 95% confidence intervals (CI) were calculated to assess the pooled data. RESULTS: Eleven retrospective and 2 RCTs were included. There was no difference in 30-day mortality (OR = 0.96; 95% CI 0.86-1.08; P = .51) between the general and regional anesthesia groups. In-hospital mortality (OR = 1.26; 95% CI 1.17-1.36; P < .001), acute respiratory failure (OR = 2.66; 95% CI 2.34-3.02; P < .001), length of hospital stay (MD = 0.33; 95% CI 0.24-0.42; P < .001), and readmission (OR = 1.09; 95% CI 1.01-1.18; P = .03) were significantly reduced in the regional anesthesia group. Pneumonia (OR = 0.99; 95% CI 0.91-1.07; P = .79), heart failure (OR = 0.97; 95% CI 0.86-1.09; P = .62), acute myocardial infraction (OR = 1.07; 95% CI 0.99-1.16; P = .10), acute renal failure (OR = 1.32; 95% CI 0.97-1.79; P = .07), cerebrovascular accident (OR = 1.08; 95% CI 0.82-1.42; P = .58), postoperative delirium (OR = 1.51; 95% CI 0.16-13.97; P = .72), and deep vein thrombosis/pulmonary embolism (OR = 1.42; 95% CI 0.84-2.38; P = .19) were similar between the two anesthetic techniques. CONCLUSION: General anesthesia is associated with increased risk of in-hospital mortality, acute respiratory failure, longer hospital stays, and higher readmission. There is evidence to suggest that regional anesthesia is associated with improved perioperative outcomes. Large RCTs are needed to explore the most optimal anesthetic techniques for geriatric patients with hip fractures before drawing final conclusions. PROSPERO REGISTRATION NUMBER: CRD42018093582.

The mediation effect of multiple gestations on the association between in vitro fertilisation and severe maternal morbidities: a retrospective cohort study.

OBJECTIVE: To investigate whether the association between in vitro fertilisation (IVF) and severe maternal morbidity (SMM) was mediated by multiple gestations. DESIGN: A retrospective cohort study. SETTING: The study was conducted at six hospitals in China. PARTICIPANTS: Pregnant women at 20 gestational weeks or longer. OUTCOME MEASURE: The outcome was SMM, which was a composite of potential life-threatening conditions, the use of critical medical interventions, or the status of maternal near-miss that occurred during pregnancy, childbirth or within 42 days of pregnancy termination, as defined by WHO. RESULTS: In total, 22 368 eligible pregnant women were included, among whom 497 (2.2%) received IVF, and 776 developed SMM (incidence 34.7/1000 live births, 95% CI 32.3/1000 to 37.1/1000). Four multivariable logistic regression models were constructed. Model 1, without including the variable of multiple gestations, showed that IVF was associated with higher risk of SMM (adjusted OR (aOR) 1.54, 95% CI 1.03 to 2.29). Model 2, assessing the association between IVF and multiple gestations, showed that IVF was strongly associated with multiple gestations (aOR 14.75, 95% CI 11.38 to 19.10). Model 3, by adding the variable of multiple gestations to model 1, showed that IVF was not statistically associated with SMM (aOR 0.89, 95% CI 0.58 to 1.36), but multiple gestations were associated with higher risk of SMM (aOR 5.92, 95% CI 4.88 to 7.83). Model 4, investigating the association between IVF and SMM among singleton pregnancies, showed no statistically significant association (aOR 0.70, 95% CI 0.37 to 1.32). An additional analysis by adding the interaction term of IVF by multiple gestations to model 3 showed no statistical significance of the interaction term (aOR 1.15, 95% CI 0.36 to 3.68), confirming the absence of exposure-mediator interaction. CONCLUSIONS: Using the established rule for judging mediation effect, the results suggested that multiple gestations might mediate the association between the use of IVF and higher risk of SMM. Further prospective studies are warranted to test our finding.

Association between Maternal Weight Indicators and Iron Deficiency Anemia during Pregnancy: A Cohort Study.

BACKGROUND: The effect of maternal weights on the risk of iron deficiency anemia (IDA) during pregnancy remains unclear. The study aimed to investigate the association between maternal weight indicators and IDA during pregnancy. METHODS: We conducted a cohort study to examine the association between maternal weight indicators, including prepregnancy body mass index and the rate of gestational weight gain (GWG), and the risk of IDA among Chinese pregnant women. Data about new-onset IDA at different trimesters from a national cross-sectional survey were collected; information regarding baseline variables and rate of GWG from women participating in the survey were retrospectively collected. Tested IDA and reported IDA were documented. Multilevel logistic regression to examine the association between maternal weight indicators and the risk of IDA after adjusting for potential confounders was conducted. RESULTS: This study enrolled 11,782 pregnant women from 24 hospitals from September 19, 2016, to November 20, 2016. Among those, 1515 (12.9%) IDA events were diagnosed through test (test IDA); 3915 (33.3%) were identified through test and patient reporting (composite IDA). After adjusting for confounders and cluster effect of hospitals, underweight pregnant women, compared with normal women, were associated with higher risk of test IDA (adjusted odds ratio [aOR]: 1.35, 95% confidence interval [CI]: 1.17-1.57 and composite IDA (aOR: 1.35, 95% CI: 1.21-1.51); on the contrary, overweight and obese women had lower risk of test IDA (aOR: 0.68, 95% CI: 0.54-0.86 overweight; aOR: 0.30, 95% CI: 0.13-0.69 obese) and composite IDA (aOR: 0.77, 95% CI: 0.67-0.90 overweight; aOR: 0.34, 95% CI: 0.21-0.55 obese). The higher rate of GWG was associated with higher risk of IDA (test aOR: 1.86 95% CI: 1.26-2.76; composite aOR: 1.54, 95% CI: 1.16-2.03). CONCLUSIONS: Pregnant women who are underweight before pregnancy and who have faster GWG are more likely to develop IDA. Enforced weight control during pregnancy and use of iron supplements, particularly among underweight women, may be warranted.

Genetic and dietary determinants of insulin-like growth factor (IGF)-1 and IGF binding protein (BP)-3 levels among Chinese women.

BACKGROUND: Higher insulin-like growth factor (IGF)-1 and lower IGF binding protein (BP)-3 levels have been associated with higher commoncancer risk, including breast cancer. Dietary factors, genetic polymorphisms, and the combination of both may influence circulating IGF-1 and IGFBP-3 serum concentrations. METHODS: From September 2011 to July 2012, we collected demographic, reproductive and dietary data on 143 women (≥ 40 years). We genotyped IGF-1 rs1520220 and IGFBP-3 rs2854744 and measured circulating IGF-1 and IGFBP-3 levels in serum. Covariance analyses were used to estimate the associations of serum levels of IGF-1 and IGFBP-3, and the molar ratio of IGF-1 to IGFBP-3 with IGF-1 rs1520220 and IGFBP-3 rs2854744 genotypes. We subsequently assessed the combined influence of genetics and diet (daily intake of protein, fat and soy isoflavones) on IGF-1 and IGFBP-3 levels. RESULTS: Among women aged less than 50 years, circulating IGF-1 serum levels were significantly lower for those with CC genotype for IGF-1 rs1520220 than levels for those with the GC or GG genotypes (in recessive model: P = 0.007).In gene-diet analyses among these women, we found carrying CC genotype for IGF-1 rs1520220 and high soy isoflavone intake tend to be associated with lower circulating IGF-1 levels synthetically (P = 0.002). Women with GG or GC genotypes for IGF-1 rs1520220 and with low intake of soy isoflavones had the highest levels of circulating IGF-1 (geometric mean [95% CI]: 195 [37, 1021] µg/L). Comparatively, women with both the CC genotype and high soy intake had the lowest levels of circulating IGF-1 (geometric mean [95% CI]: 120 [38,378] µg/L). CONCLUSIONS: IGF-1 serum levels are significantly lower among women with the CC genotype for IGF-1-rs1520220. High soy isoflavone intake may interact with carrying CC genotype for IGF-1-rs1520220 to lower women's serum IGF-1 levels more.