Cassandra N. Spracklen

The role of imaging in the management of progressive glioblastoma: A systematic review and evidence-based clinical practice guideline

QuestionWhich imaging techniques most accurately differentiate true tumor progression from pseudo-progression or treatment related changes in patients with previously diagnosed glioblastoma?Target populationThese recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process.RecommendationsLevel IIMagnetic resonance imaging with and without gadolinium enhancement is recommended as the imaging surveillance method to detect the progression of previously diagnosed glioblastoma.Level IIMagnetic resonance spectroscopy is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma.Level IIIThe routine use of positron emission tomography to identify progression of glioblastoma is not recommended.Level IIISingle-photon emission computed tomography imaging is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma.

Maternal lipid levels during pregnancy and gestational diabetes: a systematic review and meta-analysis.

Lipid levels during pregnancy in women with gestational diabetes mellitus (GDM) have been extensively studied; however, it remains unclear whether dyslipidaemia is a potential marker of preexisting insulin resistance.

Maternal Hyperlipidemia and the Risk of Preeclampsia: a Meta-Analysis

Published reports examining lipid levels during pregnancy and preeclampsia have been inconsistent. The objective of this meta-analysis was to test the association between preeclampsia and maternal total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and triglyceride levels measured during pregnancy. We conducted a systematic search for studies published between the index date until July 2013 reporting maternal lipid levels in women with preeclampsia and normotensive pregnant women. Seventy-four studies met all eligibility criteria and were included in the meta-analysis. Weighted mean differences in lipid levels were calculated using a random-effects model. Statistical heterogeneity was investigated using the I(2) statistic. Meta-regression was used to identify sources of heterogeneity. Preeclampsia was associated with elevated total cholesterol, non-HDL-C, and triglyceride levels, regardless of gestational age at the time of blood sampling, and with lower levels of HDL-C in the third trimester. A marginal association was found with LDL-C levels. Statistical heterogeneity was detected in all analyses. Meta-regression analyses suggested that differences in body mass index (weight (kg)/height (m)(2)) across studies may be partially responsible for the heterogeneity in the triglyceride and LDL-C analyses. This systematic review and meta-analysis demonstrates that women who develop preeclampsia have elevated levels of total cholesterol, non-HDL-C, and triglycerides during all trimesters of pregnancy, as well as lower levels of HDL-C during the third trimester.

Intimate partner violence during pregnancy and the risk for adverse infant outcomes: a systematic review and meta‐analysis

Intimate partner violence (IPV) is of particular concern during pregnancy when not one, but two lives are at risk. Previous meta‐analyses have suggested an association between IPV and adverse birth outcomes; however, many large studies have since been published, illustrating the need for updated pooled effect estimates.

Cervical surgery for cervical intraepithelial neoplasia and prolonged time to conception of a live birth: a case-control study

To determine whether women with a history of surgery for cervical intraepithelial neoplasia (CIN) are at an increased risk of subfertility, measured as a time to pregnancy of more than 12 months.

Birth weight and subsequent risk of cancer

BACKGROUND We aimed to determine the association between self-reported birth weight and incident cancer in the Womens Health Initiative Observational Study cohort, a large multiethnic cohort of postmenopausal women. METHODS 65,850 women reported their birth weight by category (<6 lbs, 6-7 lbs 15 oz, 8-9 lbs 15 oz, and ≥10 lbs). All self-reported, incident cancers were adjudicated by study staff. We used Cox proportional hazards regression to estimate crude and adjusted hazard ratios (aHR) for associations between birth weight and: (1) all cancer sites combined, (2) gynecologic cancers, and (3) several site-specific cancer sites. RESULTS After adjustments, birth weight was positively associated with the risk of lung cancer (p=0.01), and colon cancer (p=0.04). An inverse trend was observed between birth weight and risk for leukemia (p=0.04). A significant trend was not observed with breast cancer risk (p=0.67); however, women born weighing ≥10 lbs were less likely to develop breast cancer compared to women born between 6 lbs-7 lbs 15 oz (aHR 0.77, 95% CI 0.63, 0.94). CONCLUSION Birth weight category appears to be significantly associated with the risk of any postmenopausal incident cancer, though the direction of the association varies by cancer type.

Exome chip meta-analysis identifies novel loci and East Asian–specific coding variants that contribute to lipid levels and coronary artery disease

Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian–specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

Maternal factors and complications of preterm birth associated with neonatal thyroid stimulating hormone

Abstract Thyroid hormones are important regulators of fetal neurodevelopment. Among preterm infants, thyroid stimulating hormone (TSH) is highly variable. Understanding this variability will further improvements in screening for thyroid disorders in preterm infants. We examined 61 maternal and infant clinical and demographic factors for associations with neonatal TSH levels in 698 preterm neonates. TSH was measured as part of routine State-mandated newborn screening in Iowa. Of the maternal characteristics, nulliparous women (p=8×10–4), women with preeclampsia (p=2×10–3), and those with induced labor (p=3×10–3) had infants with higher TSH levels. TSH levels at the time of newborn screening were associated with respiratory distress syndrome (RDS) (p<0.0001) and sepsis (p=3×10–3). We replicated findings between parity and preeclampsia previously observed in primarily term infants. We also observed strong relationships between neonatal TSH and complications of prematurity including RDS and sepsis, which have implications for future studies examining this relationship both prenatally and longitudinally after birth.

Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis

Tight regulation of actin remodeling is essential for development, and misregulation results in disease. Cytoskeletal dynamics are regulated by prostaglandins (PGs)—lipid signals. PGs temporally regulate actin remodeling during Drosophila oogenesis, at least in part, by modulating the activity of the actin elongation factor Enabled.

Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia

BACKGROUND Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia. METHODS Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. RESULTS The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04). CONCLUSIONS Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia.