Sequential plasma angiogenic factors levels in women with suspected preeclampsia.

BACKGROUND: Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. OBJECTIVE: Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. STUDY DESIGN: We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. RESULTS: During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th to 75th) soluble fms-like tyrosine kinase/placental growth factor ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P < .001). The median (25th to 75th) absolute change per day in soluble fms-like tyrosine kinase levels (pg/mL) was 491.0 pg/mL (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/mL (-177.9, 449.0) among women without adverse outcomes (P = .01). Similarly the absolute change per day for soluble fms-like tyrosine kinase/placental growth factor ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) between the two groups (P = .004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 and 14 (0-39) below a ratio of 85 (P < .001). The positive predictive value for plasma soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 at admission for indicated delivery within 2 weeks was 91% (83-99%). Admission plasma soluble fms-like tyrosine kinase/placental growth factor ratio positively correlated with pre-delivery uterine artery resistive index (r = 0.35; P = .004). CONCLUSION: Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine kinase/placental growth factor ratios delivered sooner than women with low soluble fms-like tyrosine kinase/placental growth factor levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.

Epidemiology, clinical manifestations, and molecular typing of salmonella typhi isolated from patients with typhoid fever in Lebanon.

The objective of this study was to examine the epidemiology and the clinical manifestations of typhoid fever as well as the susceptibility and strain relatedness of Salmonella typhi isolates in Lebanon from 2006 to 2007. A total of 120 patients with typhoid fever were initially identified from various areas of the country based on positive culture results for S. typhi from blood, urine, stools, bone marrow and/or positive serology. Clinical, microbiological and molecular analysis was performed on cases with complete data available. These results indicated that drinking water was an unlikely mode of transmission of the infection. Despite increasing reports of antimicrobial resistance among S. typhi isolates, the vast majority of these isolates were susceptible to various antibiotic agents, including ampicillin, cephalosporins, quinolones, and trimethoprim/sulfamethoxazole. Molecular analysis of the isolates revealed a predominance of one single genotype with no variation in distribution across the geographical regions.

Placental lesions of vascular insufficiency are associated with anti-angiogenic state in women with preeclampsia.

OBJECTIVE: To evaluate if placental histopathological changes of vascular insufficiency correlate with circulating angiogenic factors in patients with preeclampsia. MATERIALS AND METHODS: Subjects were selected from a previous prospective cohort study of preeclampsia based on the availability of plasma anti-angiogenic factor (sFlt1) and pro-angiogenic factor (PlGF) measurements and placental histology specimens. Preeclamptic patients were divided into two groups based on plasma levels of these factors described as a ratio: anti-angiogenic preeclampsia with sFlt1/PlGF ratio ≥85 and normal angiogenic preeclampsia with sFlt1/PlGF < 85. The placental lesions of vascular insufficiency that were studied specifically included atherosis, infarcts, syncytial knots, acute and chronic abruption, hematoma, and fetal thrombosis. The data are shown as median (quartile 1 and quartile 3) or n (%) when appropriate. RESULTS: The anti-angiogenic preeclampsia group (N = 48) presented at an earlier gestational age (weeks) than the normal angiogenic group (N = 28); {32 (28, 34) versus 35 (32, 36), p = 0.002}, had higher systolic blood pressure (mmHg) {154 (147, 168) versus 147 (132, 158), p = 0.02}, delivered early (weeks) {(32 (29, 34) versus 36 (34, 37), p < 0.001} and had lower birth weight (grams) {(1550 (1055, 2060) versus 2655 (2285, 3343), p < 0.001}. Several pathologic lesions were found significantly more often in the anti-angiogenic preeclampsia group; atherosis {27.7% versus 3.6%, p < 0.05}, infarcts {58.3% versus 3.6%, p = 0.002}, and syncytial knots {81.3% versus 39.3%, p < 0.001}. CONCLUSION: Preeclamptic patients with imbalance in circulating angiogenic factors have disproportionally higher rates of placental vascular lesions historically associated with severe disease.