Individual risk assessment for prenatal counseling in early-onset growth-restricted and small-for-gestational-age fetuses.
- 作者列表："Mendoza M","Hurtado I","Bonacina E","Garcia-Manau P","Serrano B","Tur H","Rodo C","Maiz N","Carreras E
INTRODUCTION:Early-onset fetal growth restriction and small-for-gestational age of fetuses lead to an increased risk of adverse pregnancy outcomes. Doppler abnormalities can predict the occurrence of complications in the short term, but normal fetal Doppler values at the time of diagnosis do not exclude their occurrence in the long term. The objective of this study was to investigate the capacity of a predictive model to assess individual risks for prenatal counseling at the time of diagnosis. MATERIAL AND METHODS:This was a prospective observational study of singleton pregnancies with estimated fetal weight below the 10th centile between 20+0 and 31+6 weeks of gestational age. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) levels, estimated fetal weight centile, uterine artery pulsatility index, fetal Doppler and maternal risk factors for placental disease were assessed at the time of enrollment. The occurrence of adverse perinatal outcomes or the need for elective delivery at <30, <34 or <37 weeks was considered an adverse pregnancy outcomes. Univariable logistic regression analysis was used to examine the association between each predictive variable and the adverse outcomes. A multivariable logistic regression-based model was constructed with the combination of all variables. An additional model without sFlt-1/PlGF was also created. Both models, and the sFlt-1/PlGF alone, were used to develop the different formulas to assess individual risks. Receiver operating characteristic curves were constructed to assess and compare their performance of screening. RESULTS:Forty-nine small-for-gestational-age fetuses and 124 with fetal growth restriction were enrolled at a median gestational age of 23.6 weeks. Elective delivery was needed in 77 (44.5%) women at <37 weeks, 53 (30.6%) women at <34 weeks and 30 (17.3%) at <30 weeks. Adverse perinatal outcomes occurred in 81 (55.9%) pregnancies. When areas under the curve were compared among models, no statistically significant differences were observed between the model with sFlt-1/PlGF and sFlt-1/PlGF alone; however, the model without sFlt-1/PlGF yielded an overall poorer performance. CONCLUSIONS:Individual risk assessment can be made at the time of early-onset fetal growth restriction/small-for-gestational-age diagnosis, which permits accurate counseling of parents with an affected fetus. Two formulas could be used: one combining maternal characteristics and ultrasound findings and the other with a single sFlt-1/PlGF measurement.
引言: 早发性胎儿生长受限和胎儿胎龄过小导致不良妊娠结局的风险增加。多普勒异常可在短期内预测并发症的发生，但诊断时正常的胎儿多普勒值不排除其在长期内的发生。本研究的目的是调查预测模型评估诊断时产前咨询个体风险的能力。 材料和方法: 这是一项前瞻性观察性研究，在胎龄20 + 0至31 + 6周之间，估计胎儿体重低于第10厘泊的单胎妊娠。入组时评估了胎盘生长因子 (PlGF) 和可溶性fms样酪氨酸激酶-1 (sFlt-1) 水平、估计的胎儿体重百分位数、子宫动脉搏动指数、胎儿多普勒和胎盘疾病的母体风险因素。<30、 <34或 <37周时出现不良围产结局或需要择期分娩被认为是不良妊娠结局。单变量logistic回归分析用于检查每个预测变量与不良结局之间的关联。结合所有变量构建了基于多变量逻辑回归的模型。还创建了没有sFlt-1/PlGF的另外的模型。两个模型和单独的sFlt-1/PlGF用于开发不同的公式以评估个体风险。构建受试者操作特征曲线以评估和比较其筛选性能。 结果: 49例小于胎龄儿和124例胎儿生长受限，中位孕龄为23.6周。在 <37周的77名 (44.5%) 女性、 <34周的53名 (30.6%) 女性和 <30周的30名 (17.3%) 女性中需要选择性分娩。81例 (55.9%) 妊娠发生不良围产期结局。当在模型之间比较曲线下面积时，在具有sFlt-1/PlGF和单独的sFlt-1/PlGF的模型之间没有观察到统计学上显著的差异; 然而，没有sFlt-1/PlGF的模型产生总体较差的性能。 结论: 可以在早发性胎儿生长受限/小于胎龄儿诊断时进行个体风险评估，这允许对患有受影响胎儿的父母进行准确的咨询。可以使用两种公式: 一种结合母体特征和超声发现，另一种结合单个sFlt-1/PlGF测量。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.