A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children

IntroductionPrenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).ObjectivesOur aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.MethodsA total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).ResultsAssociations of maternal DEHP exposure (median 4.54$\mu g/kg\_bw/day$) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) $\mu g/kg\_bw/day$for an integrated CBCL score.ConclusionsThe current TDI (RfD) of 50 (20) $\mu g/kg\_bw/day$ for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.     

Sildenafil Monotherapy to Treat Portopulmonary Hypertension Before Liver Transplant

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Patients with severe PPHTN are contraindicated for liver transplant because of the associated risk of intraoperative acute right heart failure during reperfusion phase or massive volume infusion. Therefore, it has been recommended that patients with moderate to severe PPHTN undergo medical treatment to lower the pulmonary artery pressure before undergoing transplant. Herein, we report 3 patients with severe PPHTN who underwent sildenafil monotherapy before living donor liver transplant. None of the patients experienced associated adverse effects during sildenafil treatment, and the pulmonary artery pressure was effectively reduced before transplant. The first patient was diagnosed during anesthesia prior to transplant, and the mean pulmonary artery pressure was reduced by 34% after treatment. The second and third patients were followed-up with echography, and the estimated pulmonary artery systolic pressure were reduced by 34% and 47%, respectively. Pretransplant right heart catheterization also confirmed the reduction of the mean pulmonary artery pressure. Intraoperative hemodynamic parameters were stable, and the 3 patients were discharged uneventfully. After transplant, sildenafil was discontinued, and all patients remained in a stable clinical and functional status during follow-up.     

Does Hemophilia Increase Risk of Adverse Outcomes Following Total Hip and Knee Arthroplasty? A Propensity Score–Matched Analysis of a Nationwide,Population-Based Study

BackgroundEnd-stage hemophilic arthropathy is the result of recurrent joint hemarthrosis. Although total hip arthroplasty (THA) and total knee arthroplasty (TKA) can reduce severe joint pain and improve functional activity, controversy remains regarding outcomes after THA and TKA among patients with hemophilia. This study evaluated the risk of adverse outcomes of hemophilia patients who underwent THA and TKA.MethodsThis retrospective cohort study was conducted using data from the National Health Insurance Research Database. Patients who had hemophilia and underwent THA and TKA between 2000 and 2015 were identified. A total of 121 patients with hemophilia and 194,026 patients without hemophilia were included. Through propensity score matching, patients with hemophilia were matched at a 1:4 ratio to patients without hemophilia. Multivariable regression analysis was used to control for confounding variables and compare the risk of postoperative complications and mortality, differences in length of stay, and cost of care for the hospital.ResultsAfter propensity score matching and multivariate regression analysis, the adjusted hazard ratio of postoperative transfusion for hemophilia patients was 5.262 (95% confidence interval [CI] = 3.044-26.565, P < .001) in THA group and 6.279 (95% CI = 3.246-28.903, P < .001) in TKA group, when compared with the control group. Patients with hemophilia had longer length of hospital stay (THA group: 95% CI, 1.541-2.669, P < .001; TKA group: 95% CI, 1.568-2.786; P < .001) and higher total hospital charges (THA group: 95% CI, 3.518-8.293, P < .001; TKA group: 95% CI, 3.584-8.842; P < .001) compared to patients without hemophilia. Hemophiliacs had a higher yet nonsignificant 1-year infection rate (8.11% vs 3.38%, P = .206) in the THA group. There were no differences between the rates of 30-day and 90-day complications, 1-year infection, reoperation and mortality between the hemophilia and nonhemophilia groups.ConclusionHemophilia patients have higher rates of postoperative transfusion, hospital costs, and increased length of stay. There is an appreciable clinical difference in 1-year infection rates following THA but our analysis was limited by the small sample size. Other postoperative complications and mortality rates were comparable. Patients with hemophilia should be counseled that infection rate maybe as high as 8% following THA. Further investigation is needed to develop prophylactic and effective methods to decrease the rates of transfusions and associated adverse outcomes in hemophilia patients undergoing THA and TKA.     

Is the anchor matter? A short-term follow-up of the effect of mini-invasive mid urethra sling without anchor for urinary incontinence women

ObjectiveStress urinary incontinence (SUI) is a common disease in aged women, and some of them need surgical correction. Recently, the mid-urethral sling is an accepted surgical approach for SUI. However, complication may occur in this surgery, and some of them are needle-related. Therefore, the needleless system may diminish this-type complication.Materials and methodsWe conducted a retrospective study to evaluate the feasibility of women with SUI undergoing needleless sling surgery in 2017. Assessments were performed by two independent special urogynecologists before, during and post operation periods. We used a category-time-site-pain code following the International Continence Society and International Urogynecological Association (ICS/IUGA) Complication Classification Code (CCC) guidelines.ResultsThirty-eight women were analyzed. The characteristics of the patients were 66.3 ± 12.8 years old (mean ± standard deviation) of age, 2.8 ± 1.2 of parity, and 25.6 ± 4.2 kg/m² of body mass index. All had history of vaginal delivery for term. The objective cure rate at 2- and 4-week follow-up was 97.4% (n = 37) and 94.7% (n = 36), respectively. The subjective cure rate at 2- and 4-week follow-up was both 89.5% (n = 34). Both objective and subjective cure rates remained constant and similar to the end of 4 weeks. There were 6 patients (15.8%) who had complications according to ICS/IUGA CCC guidelines.ConclusionThis needleless mid-urethral sling procedure seemed to be feasible in the management of women with SUI in this small series and short-term follow-up study, suggesting that a further prospective, randomized, comparative study with other tension-free procedures and mini-sling systems can be conducted.