重度子痫前期合并大量胸腔积液12例临床分析

目的探讨重度子痫前期合并大量胸腔积液患者的临床特点及母儿预后。方法回顾性分析比较重度子痫前期合并大量胸腔积液患者12例（胸腔积液组）及未合并胸腔积液患者69例（非胸腔积液组）的临床特点、发病情况、诊治情况、孕妇严重并发症及围生儿结局。结果两组年龄、孕次、分娩孕周、住院天数、入院后最高收缩压和舒张压比较差异无统计学意义（P〉0.05）,胸腔积液组血浆白蛋白明显低于非胸腔积液组,24h尿蛋白定量以及子痫、心力衰竭发生率、围产儿死亡率明显高于对照组。结论合并大量胸腔积液是重度子痫前期的少见、严重并发症,易出现子痫、心力衰竭,增加围产儿死亡。出现大量胸腔积液应及时终止妊娠。终止妊娠后胸腔积液在2周内自然消失,不必特殊治疗。     

Pre-eclampsia is associated with elevated CXCL12 levels in placental syncytiotrophoblasts and maternal blood

Objectives

Placental derived vasculogenic/angiogenic substances in maternal blood are dysregulated in pre-eclampsia. We hypothesized that CXCL12, a chemokine with vasculogenic actions, is amongst such molecules.

Study design

CXCL12, CXCL16, CXCR4, and CXCR6 immunolocalization in placental tissue was analyzed in pre-eclampsia (n = 8) in comparison to controls (n = 8). CXCL12, measured by ELISA in blood, in women diagnosed with pre-eclampsia (n = 14) and prior to the development of pre-eclampsia (at 20 weeks’ gestation, n = 20) was compared with CXCL12 concentrations in gestation-matched, healthy control subjects (n = 34).

Results

In placental tissue, syncytiotrophoblast staining for CXCL12 was increased in pre-eclampsia. Maternal serum CXCL12 was increased in pre-eclampsia [2000 (SD 402) vs 1484 (SD 261) pg/ml, P = 0.01] but not in plasma obtained at 20 weeks of gestation prior to the onset of pre-eclampsia [1183 (SD 336) vs 1036 (SD 144) pg/ml, P = 0.09].

Conclusion

Our data suggest that the syncytiotrophoblast contributes to a pre-eclampsia-associated increase in CXCL12 levels in maternal blood. These findings support the hypothesis that an imbalance of angiogenic factors contributes to the pathogenesis of pre-eclampsia.     

Pre-eclampsia: associated with increased syncytial apoptosis when the infant is small-for-gestational-age

The present investigation was undertaken to study the association between placental apoptosis and pre-eclampsia, discriminating between pre-eclamptic pregnancies with appropriate-, and small-for-gestational-age (SGA), infants. Twenty pregnancies with pre-eclampsia and SGA (birth weight at or below -2 standard deviations) infants were selected in a retrospective study. Subsequently, corresponding numbers of gestational age-matched pre-eclampsia cases with appropriate-gestational-age (AGA) (birth weight at or above the 50% centile) infants and AGA controls without pre-eclampsia were selected. Formalin-fixed placental tissue was obtained from all groups. Apoptosis was assessed by a monoclonal antibody (M30), detecting a neoepitope of cytokeratin that is generated early in the apoptotic cascade. M30-positive cells were counted in villous and decidual/ basal plate tissue fields, and results were given as numbers of M30-positive cells per field. The study was performed blinded. Increased apoptosis was found in the syncytiotrophoblast layer in pre-eclampsia with SGA infants (0.14 apototic incidents per field of villous tissue, with 0.04-0.23 as the corresponding 25-75% inter quartile range (IQR) (P=0.05)). Syncytial apoptosis in the syncytial layer in the pre-eclampsia group with AGA infants was lower (0.09, IQR 0.03-0.15) and corresponded to the level detected among controls (0.06, IQR 0.03-0.17). Apoptosis in other placental cellular compartments did not differ between groups. The increased syncytial apoptosis found in placentas from pregnancies with SGA infants may either be due to specific mechanisms associated with pre-eclampsia complicated with growth restriction, or may simply reflect the presence of syncytiotrophoblast layer damage, regardless of underlying pathological condition.     

Severe pre-eclampsia is associated with abnormal trace elements concentrations in maternal and fetal blood

Objective: The study was aimed to compare trace elements concentrations in women with and without severe pre-eclampsia (PE). Methods: A prospective case-control study was conducted comparing 43 parturients with severe PE (who received magnesium sulfate [MgSO4]) and 80 healthy parturients and their newborns, matched for gestational age and mode of delivery. Inductively coupled plasma mass spectrometry (ICPMS) was used for the determination of zinc (Zn), copper (Cu), selenium (Se) and magnesium (Mg) levels in maternal as well as arterial and venous umbilical cord serum. Results: Zn levels (µg/L) were significantly higher in fetal arterial and venous blood of the PE group (947.3?±?42.5 vs. 543.1?±?226, 911.1?±?220.2 vs. 422.4?±?145, p?<?0.001; respectively). Se levels (µg/L) were significantly lower in maternal and fetal arterial and venous cord blood of the PE group (98.6?±?24.2, 110.7?±?19.4, 82?±?17.8 vs. 111.6?±?17.6, 82.1?±?17.4 vs. 107.1?±?25.7, p?<?0.001; respectively). Cu levels (µg/L) were significantly lower in fetal arterial and venous cord blood (581.6?±?367.4 vs. 949?±?788.8, p?=?0.022, 608.3?±?418.1 vs. 866.9?±?812.6, p?=?0.001 respectively) but higher in maternal blood (2264.6?±?751.7 vs. 1048?±?851.1, p?<?0.001). These differences remained significant while controlling for the mode of delivery. Mg levels were significantly higher in the PE group as compared with the control group. Conclusions: Severe PE is associated with abnormal concentrations of Zn, Cu and Se. Therefore, trace elements may have a crucial role in the pathogenesis of severe PE.     

Severe hyponatremia associated with pre-eclampsia

Abstract

Background: Pre-eclampsia associated hyponatraemia is a very rare condition that can potentially lead to serious maternal and fetal complications and that constitute a diagnostic and therapeutic challenge even for an experienced physician.

Case report: A 25-year old female presented to the clinic at 25.3 weeks of gestation with mild physical signs of edema along with hypertension, proteinuria, and a severe hyponatremia (113?mEq/L). Hyponatremia was classified as hypervolemic and resolved 72 hours after the delivery with water restriction.

Conclusions: The pathogenesis of pre-eclampsia associated hyponatremia is relatively unknown. A non-osmotic stimulation of vasopresin release in the setting of a hypervolemic state with low effective circulating plasma volume is thought to be the main mechanism. Advanced maternal age and nephrotic range proteinuria have been postulated as risk factors, but their causal role remains unclear. Fluid restriction is a reasonable treatment, and maternal outcomes are favourable. This condition is a rare indication for urgent delivery, but neonatal outcomes are variable.     

Low potassium level during the first half of pregnancy is associated with lower risk for the development of gestational diabetes mellitus and severe pre-eclampsia

Objective.?To examine the association between potassium level during the first half of pregnancy and the development of gestational diabetes mellitus (GDM) and hypertensive disorders in the second half of the pregnancy.

Methods.?The study population included all registered births between the years 2001–2007. The potassium levels during the first half of pregnancy were sorted by the following groups: K?<?3.5 mEq/l; K?=?3.5–3.99?mEq/l; and K?≥?4?mEq/l. The linear by linear χ²-test was used to determine the association between potassium level during the beginning of pregnancy and pregnancy complications.

Results.?The study population included 8114 deliveries. A significant linear association was documented between potassium level in the first half of the pregnancy and the prevalence of GDM in the second half of the pregnancy: 6.3% in the K?<?3.5?mEq/l group, 6.6% in the K?=?3.5–3.99?mEq/l group and 8.2% in the K?>?4?mEq/l group; (p?=?0.008). A statistically significant for lower rates of severe pre-eclampsia was noted between the groups: 0.4% in the K?<?3.5?mEq/l group, 0.9% in the K?=?3.5–3.99?mEq/l group, 1.3% in the K?=?4.0–4.99?mEq/l group and 1.5% in the K?≥?5?mEq/l group, (p?=?0.027). Indeed, K?>?5?mEq/l was noted as a significant risk factor for both, severe pre-eclampsia and for GDM. Using two multiple logistic regression models controlling for maternal age, potassium level was noted as an independent risk factor for both GDM and severe pre-eclampsia.

Conclusions.?High potassium levels during the first half of pregnancy are associated with higher risk for the development of GDM and severe pre-eclampsia.     

Abnormal expression of estrogen receptor is associated with thin endometrium

Abstract

This study was conducted to investigate the association of estrogen receptor (ER) and progesterone receptor (PR) expressions with thin endometrium. Patients with endometrial thickness of less than 7?mm were classified as the study group, while the control group was comprised of patients with endometrial thickness of 7 to 14?mm. The expressions of ER and PR were detected with semi-quantitative immunohistochemical analysis, and the differences were compared between the two groups. The expression of ER was significantly decreased (p?<?.05) in the stromal cells of thin endometrium during both proliferative and secretory phases as compared to those of normal endometrium. Likewise, ER expression was found to be lower in the glandular cells of thin endometrium than those of normal endometrium during proliferative phase. However, no significant differences were observed for the expression of PR in both glandular and stromal cells between the two groups. Thin endometrium was associated with reduced expression of ER in stromal cells both during proliferative and secretory phase, but in glandular epithelial cells only during proliferative phase.     

Morbidity and mortality associated with pre-eclampsia at two tertiary care hospitals in Sri Lanka

AIM: To report the occurrence of morbidity and mortality associated with carefully phenotyped pre-eclampsia in a sample of nulliparous Sinhalese women with strictly defined disease. METHODS: A phenotyping database of 180 nulliparous women with pre-eclampsia and 180 nulliparous normotensive pregnant women who were recruited for a study into genetics of pre-eclampsia was analyzed. RESULTS: Women who developed pre-eclampsia had significantly higher systolic blood pressure (SBP; P = 0.002) and diastolic blood pressure (DBP; P = 0.002) at booking (at approximately 13 weeks of gestation). 38.3%, 28.3% and 33.3% of women delivered at <34 weeks, at 34-36 weeks, and at term, respectively. 78% required a cesarean section. Complications included SBP > or = 160 mmHg (75.5%); DBP > or = 110 mmHg (83.8%); proteinuria > or =3 + (150 mg/dL) in the urine protein heat coagulation test (87%); renal failure requiring dialysis (2%); platelet counts <100 x 10(9)/L (13%); > or =70 U/L in aspartate and/or alanine aminotransaminase (15%); placental abruption (4%); eclampsia (9%); and one maternal death. Maternal complications indicative of severe disease, apart from the incidence of SBP > or = 160 mmHg and DBP > or = 110 mmHg, were not significantly different in early and late-onset pre-eclampsia; fetal outcome was better with late-onset disease. 48% of babies were small for gestational age. Only 80 of 135 babies of women with pre-eclampsia whose condition could be confirmed at 6 weeks post-partum were alive. CONCLUSIONS: Pre-eclampsia in Sinhalese women is associated with severe maternal morbidity and fetal morbidity and mortality, suggesting that modification of the Western diagnostic criteria and/or guidelines for medical care may be necessary. There is an urgent need to improve neonatal intensive care services in Sri Lanka.     

Fetal endothelium dysfunction is associated with circulating maternal levels of sE-selectin,sVCAM1, and sFlt-1 during pre-eclampsia

Objectives.?To evaluate the association between endothelial activation markers in the maternal circulation with nitric oxide (NO) synthesis in human umbilical endothelial cells.

Study design.?This is a case-control study of normal and pre-eclamptic pregnancies. The levels of sE-selectin, soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble fms-like tyrosine kinase 1 (sFlt-1) were measured by enzyme-linked immunosorbent assay, and histamine-induced NO synthesis was detected by fluorometric examination of the human umbilical vein endothelial cells (HUVECs) isolated from normal and pathological pregnancies.

Results.?Mothers with severe pre-eclamptic pregnancies have premature and smaller babies than mothers with normal pregnancies (P?<?0.05); they also have high maternal plasma levels of sVCAM-1 (～2-fold), sFlt-1 (～2.5-fold), and lower (～70%) histamine-stimulated NO synthesis in HUVECs. A positive relationship between systolic blood pressure (SBP) and plasma levels of sE-selectin, sVCAM-1, and sFlt-1 was demonstrated. Moreover, levels of sE-selectin, sVCAM-1, and sFlt-1 were negatively associated with newborn weight (NBW), gestational age at delivery, and NO synthesis. Women with high E-selectin (>63?ng/ml), VCAM-1 (>752?ng/ml), and sFlt-1 (>15204 pg/ml) showed high risk (～2-fold) for preterm delivery and very preterm delivery, or fetal weight <1500?g (～1.5-fold) compared with women with low levels.

Conclusions.?High circulating levels of maternal endothelial dysfunction markers present in pre-eclampsia are associated with decreased NO synthesis in fetal endothelium.     

Oligohydramnios is an independent risk factor for perinatal morbidity among women with pre-eclampsia who delivered preterm

Purpose: The purpose of this study is to determine the relationship between oligohydramnios and adverse maternal and neonatal outcomes in a unique cohort of preterm pre-eclamptic patients.

Materials and methods: A retrospective matched case–control study comparing 81 preterm parturients (28 0/7 and 36 6/7 weeks) with pre-eclampsia and oligohydramnios to 81 preterm pre-eclamptic patients with a normal amniotic fluid index (AFI).

Results: About 4.8 percent of all our preterm pre-eclamptic patients had oligohydramnios. Patients in the study group showed a trend toward being older than 35 years (18.5%% versus 27.2%) and were more likely more likely to be primi-parous, and have previously delivered a small for gestational age (SGA) or a dead fetus (p?=?.012, .039, and .032). Severity of pre-eclampsia, including HELLP and eclampsia as well as gestational age at delivery did not differ statistically between the study groups (p?=?.47, .516). Growth restricted fetuses were more common in the study group (p?p?=?.046). Post-partum complications, pre-eclampsia during the puerperium, admission to intensive care units, and MgSO₄ treatment were more common in the control group (p?=?.028, .012, .008). But study group patients had more cesarean sections (p?=?.011). Neonates of study group parturients had lower fetal weight, were more likely to be SGA, and experience fetal distress during labor (p?=?.001, .001, and .03). Following delivery, they were more likely to have anemia and stay longer in neonatal intensive care unit (NICU) (p?=?.017, .017). A multivariate logistic regression analysis showed that oligohydramnios, but not the severity of pre-eclampsia, significantly affected Composite Neonatal Outcome {Apgar scores at 1 &; 5?min (<5 and <7, respectively), neonatal death, umbilical cord pH <7.1, fetal distress (category III fetal heart rate tracing), fetal anemia, fetal hypoglycemia}.

Conclusions: Oligohydramnios is an independent risk factor for early neonatal morbidity in preterm pre-eclamptic patients. AFI <5?cm can be used as one component in the educated decision for delivery of these patients.

Brief rationale

The significance of oligohydramnios in pregnancies complicated by preterm delivery, preeclampsia or both is controversial. By comparing two relatively large, almost similar, cohorts of preterm preeclamptic parturient with and without oligohydramnios we demonstrated that Amniotic Fluid Index <5 cm is associated with a significant neonatal morbidity. This question was not previously addressed in proper manner aside one, much smaller, study that was under powered to address this topic. We innovate by illustrating the significance of oligohydramnios and its association with subsequent neonatal morbidity. Thus, we conclude that the presence of oligohydramnios in women with preterm preeclampsia can be a factor in the decision for or against conservative management of these patients.     

Targeted sequencing analysis of ACVR2A gene identifies novel risk variants associated with preeclampsia

Background: Preeclampsia (PE) is the most common complication of pregnancy that remains to be a major cause of maternal and fetal mortality. Prediction and early diagnosis of PE would allow for timely initiation of preventive therapy. According to recent studies of ACVR2A gene polymorphism is associated with PE, but it is still unclear whether these findings reflect specific pathogenetic mechanisms of this disease.

Methods: We performed targeted next-generation sequencing (NGS) sequencing of ACVR2A gene by means of Ion Torrent Personal Genome machine (PGM) Sequencer. A genetic analysis of patients with PE and control group was performed. Bioinformatics analysis using Polyphen2 (Boston, MA), SIFT (La Jolla, CA), and SnpSift software were used. To select genetic markers in PE patients two additive models and score analysis were applied.

Results: Based on the score analysis, we detected two substitutions (rs145399059 and rs17692648) and one insertion insAA at position 148642724 that were associated with PE in our cohorts. We also detected a variant rs17742573 that can be considered as protective against preeclampsia.

Conclusions: Our data suggest that some variants in ACVR2A gene are associated with PE. But more studies are required to reveal the role of ACVR2A gene in the pathogenesis of this disease during pregnancy.     

Smoking during pregnancy is associated with alterations in markers of endothelial function

OBJECTIVE: Alterations in endothelial function may explain the reduced risk of preeclampsia that is associated with smoking. We hypothesized that markers of endothelial function increase over pregnancy but decrease with smoking. STUDY DESIGN: Plasma samples were obtained throughout pregnancy from 63 primiparous women with normal pregnancies. The samples were assayed for cellular fibronectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1. Smoking status was determined by urinary cotinine concentrations. RESULTS: Mean cellular fibronectin concentrations were different by time (P<.001) and smoking status (P=.01); the lowest concentrations were found in smokers. In contrast, intracellular adhesion molecule-1 was different by smoking status (P=.046); the highest concentrations were found in smokers. Vascular cell adhesion molecule-1 was different over time (P<.001), but not by smoking status. CONCLUSION: Smoking during pregnancy is associated with reduced cellular fibronectin and increased intracellular adhesion molecule-1. These differences may be the result of different aspects of endothelial function or the source of the marker. The explanation for reduced preeclampsia in smokers remains elusive.     

Venous thromboembolism during primary treatment of ovarian clear cell carcinoma is associated with decreased survival

Objectives

To determine the impact of venous thromboembolism (VTE) during primary treatment of ovarian clear cell carcinoma (OCCC) on survival.

Methods

After Institutional Review Board approval, 74 cases of OCCC were retrieved from our pathology files. Clinical and pathological data were obtained by medical record and pathology review. Standard statistical analyses were performed.

Results

Among 74 patients with OCCC, VTE was diagnosed in 11 (15%) during primary treatment and 7 (9%) at time of cancer recurrence. 56 (76%) patients never developed VTE. Patients with VTE during OCCC primary treatment had shorter progression-free survival (PFS) and overall survival (OS) than OCCC patients without VTE (median PFS 11 vs. 76 months, p = 0.01, median OS 19 vs. 90 months, p = 0.001). Patients with VTE during OCCC primary treatment had a 3.9-fold increase in risk of recurrence (p = 0.007) and a 6.3-fold increase in risk of death (p < 0.001). After controlling for cancer stage, VTE during OCCC primary treatment remained an independent prognostic factor for death (HR = 3.6, p = 0.005). No patient died of VTE.

Conclusions

VTE during OCCC primary treatment is associated with a significantly higher risk of cancer recurrence and death. This increased risk is not attributable to VTE-related mortality and raises the possibility that a paracrine circuit involving thrombosis might contribute to a more aggressive tumor biology.     

Ovarian carcinoma associated with endometriosis

Objectives

Previous studies have suggested an association between endometriosis and development of ovarian cancer. A study was performed to evaluate the cases of ovarian carcinoma associated with endometriosis.

Study design

The study includes patients with ovarian carcinoma associated with endometriosis diagnosed between 2000 and 2010 at Hacettepe University Hospital, Ankara, Turkey. A total of 1086 patients who underwent surgical staging for ovarian carcinoma were analyzed retrospectively for the presence of histologically documented endometriosis. The clinical and pathological characteristics of 45 ovarian carcinoma patients associated with endometriosis were evaluated including histologic subtype, stage and grade.

Results

Ovarian carcinoma was found to be associated with endometriosis in 4.1% (45/1086) of the cases. Of them, 17 patients (37.8%) had clear cell, 15 (33.3%) had endometrioid, 6 (13.3%) had serous papillary, 4 (8.9%) had mucinous and the remaining 3 patients had an undifferentiated subtype of ovarian carcinoma. Twenty-three (51.1%) patients had stage I, 4 (8.9%) had stage II and 18 (40.0%) had stage III disease. The frequency of coexistence of endometriosis was 20.4% (17/83) for clear cell carcinoma and 9.3% (15/161) for endometrioid cell carcinoma.

Conclusions

Only a small proportion of ovarian cancer cases were found to be associated with endometriosis. Endometriosis was most frequently associated with clear cell and endometrioid types of ovarian carcinoma. Ovarian carcinoma associated with endometriosis seems to represent a distinct disease entity with different histological subtypes, early presentation and a relatively favorable outcome.     

Fetal "nonreassuring status" is associated with elevation of nucleated red blood cell counts and interleukin-6

OBJECTIVE: Previous studies have established the association between fetal hypoxia and elevated nucleated red blood cells (NRBCs). Animal studies have demonstrated that a rise in plasma erythropoietin (EPO) is not detectable until 4 to 6 hours after the initiation of hypoxia. In contrast, interleukin-6 (IL-6) has the capacity to directly induce erythroid maturation. Therefore, we set forth to evaluate the role of EPO and IL-6 as potential mediators of elevated fetal NRBCs in response to acute hypoxia. STUDY DESIGN: Low-risk pregnancies with a normal fetal heart rate at admission to labor and delivery were eligible for participation. Deliveries for "nonreassuring fetal status" comprised the study group. All other deliveries served as controls. Umbilical cord blood was prospectively collected for blood gas analysis, NRBC counts, EPO, and IL-6. RESULTS: One hundred women participated in the study. Nonparametric univariate analysis demonstrated a significant association between elevated NRBC counts and Apgar scores, arterial cord blood pH, base excess, EPO, and IL-6 levels (all P values <.01). Stepwise regression analysis identified only pH, IL-6, and EPO as independent variables associated with elevated NRBC counts at birth (all P values <.0001 with R2 of 0.27, 0.42, and 0.46, respectively). A significant increase in NRBC counts was noted in study patients. IL-6 was significantly increased in study patients, whereas there was no difference in EPO between groups. CONCLUSION: The fact that NRBC counts were elevated in fetuses who were delivered for "nonreassuring fetal status" with EPO being normal and IL-6 being elevated implies that IL-6 may have a unique, short-term role in elevating fetal NRBC counts.     

Adjuvant radiation in early stage,unfavorable histology endometrial carcinoma is associated with improved local control and survival

Objective

Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer.

Methods

We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival.

Results

The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local–regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local–regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p = 0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p = 0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value = 0.018) was associated with a significant increase in local relapse free survival.

Conclusions

Adjuvant radiation therapy was significantly associated with an improvement in local–regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer.