Objective To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia.Design Systematic review and meta-analysis of cohort studies.Data sources PubMed and Embase databases, 2000-15.Eligibility criteria for selecting studies Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation.Data extraction Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors.Results There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors.Conclusions There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

Chronic HIV infection results in a loss of HIV-specific CD8؉ T cell effector function, termed "exhaustion," which is mediated, in part, by the membrane coinhibitory receptor T cell immunoglobulin mucin domain-3 (Tim-3). Like many other receptors, a soluble form of this protein has been described in human blood plasma. However, soluble Tim-3 (sTim-3) is poorly characterized, and its role in HIV disease is unknown. Here, we show that Tim-3 is shed from the surface of responding CD8 ؉ T cells by the matrix metalloproteinase ADAM10, producing a soluble form of the coinhibitory receptor. Despite previous reports in the mouse model, no alternatively spliced, soluble form of Tim-3 was observed in humans. Shed sTim-3 was found in human plasma and was significantly elevated during early and chronic untreated HIV infection, but it was not found differentially modulated in highly active antiretroviral therapy (HAART)-treated HIV-infected subjects or in elite controllers compared to HIV-uninfected subjects. Plasma sTim-3 levels were positively correlated with HIV load and negatively correlated with CD4 counts. Thus, plasma sTim-3 shedding correlated with HIV disease progression. Despite these correlations, we found that shedding Tim-3 did not improve the function of CD8 ؉ T cells in terms of gamma interferon production or prevent their apoptosis through galectin-9. Further characterization studies of sTim-3 function are needed to understand the contribution of sTim-3 in HIV disease pathogenesis, with implications for novel therapeutic interventions. IMPORTANCEDespite the overall success of HAART in slowing the progression to AIDS in HIV-infected subjects, chronic immune activation and T cell exhaustion contribute to the eventual deterioration of the immune system. Understanding these processes will aid in the development of interventions and therapeutics to be used in combination with HAART to slow or reverse this deterioration. Here, we show that a soluble form of T cell exhaustion associated coinhibitory molecule 3, sTim-3, is shed from the surface of T cells. Furthermore, sTim-3 is elevated in the plasma of treatment-naive subjects with acute or chronic HIV infection and is associated with markers of disease progression. This is the first study to characterize sTim-3 in human plasma, its source, and mechanism of production. While it is still unclear whether sTim-3 contributes to HIV pathogenesis, sTim-3 may represent a new correlate of HIV disease progression. D espite significant advances in the development of highly active antiretroviral therapy (HAART) to reduce viral replication in subjects chronically infected with human immunodeficiency virus type 1 (HIV), the immune system is incapable of completely eliminating the virus. The resulting persistent antigen levels drive a process called "T cell exhaustion," whereby responding T cells undergo hierarchical loss of their effector functions, including their ability to proliferate, their cytotoxic potential, and their ability to produce cytokines (1). Coinhibitor...

(BMJ. 2016;353:i1753) Earlier studies have reported the effectiveness of aspirin in preventing preeclampsia in women considered to be at moderate to high risk of developing this disorder. This current study was a meta-analysis of cohort studies examining risk factors for preeclampsia with the goal of estimating early in pregnancy (≤16 wk gestation) a woman’s risk of developing preeclampsia based on the presence of absence of various risk factors. Three practical estimates were generated: the absolute risk of developing preeclampsia in the presence or absence of a given risk factor; the relative risk in the presence or absence of a given risk factor, and the population attributable fraction (PAF) for preeclampsia in relation to each risk factor. On the basis of their analysis, the authors aimed to provide a list of risk factors that could be used to identify those women at high risk for developing preeclampsia.

Women from Africa and the Caribbean and, in particular, Ghana and Jamaica, are at higher risk of admission to ICU around the time of delivery, as are their newborns.

Chronic Human Immunodeficiency Virus Type-1 (HIV) infection results in a loss of HIV-specific CD8+ T cell effector function, termed “exhaustion”, which is mediated, in-part, by the co-inhibitory receptor T-cell immunoglobulin mucin domain-containing protein 3 (Tim-3). Like many other receptors, a soluble form of this protein has been described in human blood plasma. However, this soluble Tim-3 (sTim-3) is poorly characterized and it’s unclear whether it plays a role in HIV pathogenesis. Using a Tim-3 ELISA, we found that levels of sTim-3 were significantly elevated in HIV+ antiretroviral treatment naïve patient plasma compared to healthy controls or HIV+ antiretroviral treated patients, and significantly correlated positively with viral load but not with CD4+ T cell counts. To characterize this construct, we immunoprecipitated the protein from HIV+ patient plasma; western blotting analysis revealed that plasma sTim-3 is the approximate size of the Tim-3 ectodomain. Following detection of sTim-3 from activated PBMCs in culture, no alternatively spliced Tim-3 constructs were observed, however, levels of sTim-3 were abrogated with the inclusion of a matrix metalloproteinase, ADAM10, inhibitor. Further, we showed that this sTim-3 was produced from activated T cells treated with an ADAM10 agonist and was the approximate size of plasma sTim-3. Our results suggest that increasing levels of viral antigen result in increased Tim-3 shedding from the T cell surface during HIV infection.