Maternal mortality due to cardiovascular disease in the Netherlands:a 21-year experience

Objective Cardiovascular disorders are the leading cause of indirect maternal mortality in Europe. The aim of this study is to present an extensive overview concerning the specific cardiovascular causes of maternal death and to identify avoidable contributing care factors related to these deaths. Methods We assessed all cases of maternal death due to cardiovascular disorders collected by a systematic national confidential enquiry of maternal deaths published by the Dutch Maternal Mortality and Morbidity Committee on behalf of the Netherlands Society of Obstetrics and Gynaecology over a 21-year period (1993-2013) in the Netherlands. Results There were 96 maternal cardiovascular deaths (maternal mortality rate due to cardiovascular diseases 2.4/100,000 liveborn children). Causes were aortic dissection (n & x202f;= 20, 21%), ischaemic heart disease (n & x202f;= 17, 18%), cardiomyopathies (including peripartum cardiomyopathy and myocarditis, n & x202f;= 20, 21%) and (unexplained) sudden death (n & x202f;= 27, 28%). Fifty-five percent of the deaths occurred postpartum (n & x202f;= 55, 55%). Care factors that may have contributed to the adverse outcome were identified in 27 cases (28%). These factors were patient-related in 40% (pregnancy against medical advice, underestimation of symptoms) and healthcare-provider-related in 60% (symptoms not recognised, delay in diagnosis, delay in referral). Conclusion The maternal cardiovascular mortality ratio is low in the Netherlands and the main causes of maternal cardiovascular mortality are in line with other European reports. In a minority of cases, care factors that were possibly preventable were identified. Women with cardiovascular disease should be properly counselled about the risks of pregnancy and the symptoms of complications. Education of care providers regarding the incidence, presentation and diagnosis of cardiovascular disease during pregnancy is recommended

Host hindrance to HIV-1 replication in monocytes and macrophages

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types

The concordance of the limiting antigen and the Bio-Rad avidity assays in persons from Estonia infected mainly with HIV-1 CRF06_cpx

BACKGROUND: Serological assays to determine HIV incidence have contributed to estimates of HIV incidence, monitoring of HIV spread, and evaluation of prevention strategies. Two frequently used incidence assays are the Sedia HIV-1 LAg-Avidity EIA (LAg) and the Bio-Rad avidity incidence (BRAI) assays with a mean duration of recent infection (MDRI) of 130 and 240 days for subtype B infections, respectively. Little is known about how these assays perform with recombinant HIV-1 strains. We evaluated the concordance of these assays in a population infected mainly with HIV-1 CRF06_cpx. MATERIAL/METHODS: Remnant serum samples (n = 288) collected from confirmed, newly-diagnosed HIV-positive persons from Estonia in 2013 were tested. Demographic and clinical data were extracted from clinical databases. LAg was performed according to the manufacturer’s protocol and BRAI testing was done using a validated protocol. Samples with LAg-pending or BRAI-invalid results were reclassified as recent if they were from persons with viral loads <1000 copies/mL or were reclassified as long-term if presenting with AIDS. RESULTS: In total 325 new HIV infections were diagnosed in 2013 in Estonia. Of those 276 persons were tested with both LAg and BRAI. Using assay results only, the recency rate was 44% and 70% by LAg and BRAI, respectively. The majority of samples (92%) recent by LAg were recent by BRAI. Similarly, 89% of samples long-term by BRAI were long-term by LAg. After clinical information was included in the analysis, the recency rate was 44% and 62% for LAg and BRAI, respectively. The majority of samples (86%) recent by LAg were recent by BRAI and 91% of long-term infections by BRAI were long-term by LAg. CONCLUSIONS: Comparison of LAg and BRAI results in this mostly CRF06_cpx-infected population showed good concordance for incidence classification. Our finding of a higher recency rate with BRAI in this population is likely related to the longer MDRI for this assay

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study

Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. Conclusion: The definition persistent postpartum haemo

Substandard care in maternal mortality due to hypertensive disease in pregnancy in the Netherlands

Objective To review the standard of care in cases of maternal mortality due to hypertensive diseases in pregnancy and to make recommendations for its improvement. Design Care given to women with hypertensive disease in pregnancy was audited and substandard care factors identified. Setting Confidential enquiry by the Dutch Maternal Mortality Committee (MMC) from the Netherlands Society of Obstetrics and Gynaecology. Population All maternal deaths reported to the MMC due to hypertensive disease in pregnancy in the Netherlands during the years 2000-04. Methods Assessment for substandard care factors using a checklist based on the Dutch guideline of 'Hypertensive Disorders in Pregnancy'. Main outcome measures Substandard care in cases of maternal mortality due to hypertensive diseases in pregnancy. Results A total of 27 cases of maternal death due to hypertensive disease in pregnancy were reported to the committee in the study period. In 26 cases (96%), substandard care factors were present, of which in 17 cases (63%), these were for more than five different items. In community midwifery care, the most frequent substandard care factor was no testing for proteinuria when clearly indicated (41%). In hospital care, the most frequent substandard care was related to insufficient diagnostic testing when indicated (41%), insufficient management of hypertension by obstetricians (85%), no use or inadequate use of magnesium sulphate (67%), inadequate stabilisation before transport to tertiary care centres and/or delivery (52%) and failure to consider timely delivery (44%). Conclusions Education of pregnant women concerning danger signs of hypertensive disease should be improved. Training of midwives and obstetricians should be improved in the following areas: performing basic diagnostic tests, adequate management of hypertension and eclampsia, with more attention to treatment of systolic blood pressure. This training should be guided by clear local protocols. Delivery should not be delayed in serious cases of hypertensive disease in pregnancy, not only after 32-34 weeks but also in early-onset pre-eclampsia as maternal risks often outweigh possible fetal benefits of temporising management

Differential Transmission of Human Immunodeficiency Virus Type 1 by Distinct Subsets of Effector Dendritic Cells

Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4(+) Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission