Placental lesions associated with acute atherosis

Objective: Acute atherosis is a lesion of the spiral arteries characterized by fibrinoid necrosis of the vessel wall, an accumulation of fat-containing macrophages, and a mononuclear perivascular infiltrate, which can be found in patients with preeclampsia, fetal death, small-for-gestational age, spontaneous preterm labor/premature prelabor rupture of membrane, and spontaneous mid-trimester abortion. This lesion is thought to decrease blood flow to the intervillous space which may lead to other vascular lesions of the placenta. The objective of this study was to test whether there is an association between acute atherosis and placental lesions that are consistent with maternal vascular underperfusion (MVU), amniotic fluid infection (AFI), fetal vascular thrombo-occlusive disease (FVTOD) or chronic inflammation.

Material and methods: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women’s Hospital/Detroit Medical Center was conducted examine 16?457 placentas. The frequency of placenta lesions (diagnosed using the criteria of the Perinatal Section of the Society for Pediatric Pathology) was compared between pregnancies with and without acute atherosis.

Results: Among 16?457 women who were enrolled, 10.2% (1671/16?457) were excluded, leaving 14?786 women who contributed data for analysis. Among them, the prevalence of acute atherosis was 2.2% (326/14?786). Women with acute atherosis were more than six times as likely as those without to have placental lesions consistent with maternal underperfusion (adjusted odds ratio – aOR: 6.7; 95% CI 5.2–8.6). To a lesser degree, acute atherosis was also associated with greater risks of having either lesions consistent with FVTOD (aOR 1.7; 95% CI 1.2–2.3) or chronic chorioamnionitis (aOR 1.9; 95% CI 1.3–3), but not with other chronic inflammatory lesions, after adjusting for gestational age at delivery. In contrast, women with acute atherosis were 60% less likely to have lesions consistent with AFI, adjusting for gestational age at delivery (aOR 0.4; 95% CI 0.3–0.5).

Conclusions: Acute atherosis is associated with increased risks of having placental lesions consistent with MVU, and to a lesser extent, chronic chorioamnionitis and those consistent with FVTOD.     

National Trends and Outcomes in Dialysis-Requiring Acute Kidney Injury in Heart Failure: 2002–2013

Background

Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.

A novel patient stratification strategy to enhance the therapeutic efficacy of dasatinib in glioblastoma

BackgroundGlioblastoma is the most common primary malignancy of the central nervous system with a dismal prognosis. Genomic signatures classify isocitrate dehydrogenase 1 (IDH)-wildtype glioblastoma into three subtypes: proneural, mesenchymal, and classical. Dasatinib, an inhibitor of proto-oncogene kinase Src (SRC), is one of many therapeutics which, despite promising preclinical results, have failed to improve overall survival in glioblastoma patients in clinical trials. We examined whether glioblastoma subtypes differ in their response to dasatinib and could hence be evaluated for patient enrichment strategies in clinical trials.MethodsWe carried out in silico analyses on glioblastoma gene expression (TCGA) and single-cell RNA-Seq data. In addition, in vitro experiments using glioblastoma stem-like cells (GSCs) derived from primary patient tumors were performed, with complementary gene expression profiling and immunohistochemistry analysis of tumor samples.ResultsPatients with the mesenchymal subtype of glioblastoma showed higher SRC pathway activation based on gene expression profiling. Accordingly, mesenchymal GSCs were more sensitive to SRC inhibition by dasatinib compared to proneural and classical GSCs. Notably, SRC phosphorylation status did not predict response to dasatinib treatment. Furthermore, serpin peptidase inhibitor clade H member 1 (SERPINH1), a collagen-related heat-shock protein associated with cancer progression, was shown to correlate with dasatinib response and with the mesenchymal subtype.ConclusionThis work highlights further molecular-based patient selection strategies in clinical trials and suggests the mesenchymal subtype as well as SERPINH1 to be associated with response to dasatinib. Our findings indicate that stratification based on gene expression subtyping should be considered in future dasatinib trials.     

Diaphragmatic and crural FDG uptake in hyperventilating patients: a rare pattern important to recognize

The authors describe various patterns of F-18 fluorodeoxyglucose (FDG) accumulation in the diaphragm and crura. They present 6 patients in whom incidental diaphragmatic and crural uptake of FDG was observed during positron emission tomography (PET). Hyperventilation is thought to be the potential underlying mechanism of this condition.     

The spatial-temporal distribution of drought, wetting, and human cases of St. Louis encephalitis in southcentral Florida

Using a dynamic hydrology model, we simulated land surface wetness conditions at 42 sites in 28 counties in southcentral Florida from 1990 to 1998 and compared these simulations with the incidence of human cases of St. Louis encephalitis (SLE) within these counties. Within counties, drought four months prior and wetting one-half month prior were significantly associated with human cases of SLE. Simulated land surface wetness conditions resolved transmission loci in both space and time, and May drought was significantly associated with the subsequent occurrence of human SLE cases. These findings are consistent with previous results associating simulated land surface wetness conditions with the transmission of SLE virus as measured in sentinel chickens, and support our working hypothesis that springtime drought facilitates SLE virus amplification in mosquito and wild bird populations.     

Advanced hepatic fibrosis and cirrhosis due to nonalcoholic fatty liver disease in Sri Lankan children: a preliminary report

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and may progress to advanced hepatic fibrosis and cirrhosis in some patients. Cirrhosis due to NAFLD is considered extremely rare in children in the Asia–Pacific region. We report the characteristics of 5 children with advanced hepatic fibrosis and cirrhosis due to NAFLD. Four of them were obese, and all of them had high alanine transaminase levels and ultrasonographic evidence of fatty liver. None had diabetes mellitus or hyperlipidemia. The calculated HOMA-IR was more than two in all five cases. Liver biopsy showed stage III fibrosis in 2 patients and stage IV fibrosis (cirrhosis) in 3.