BackgroundAge, reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. We previously detected bovine leukemia virus (BLV), a common oncogenic virus of cattle, in the breast epithelium of humans. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer.MethodsThis was a case-control study of archival formalin fixed paraffin embedded breast tissues from 239 donors, received 2002–2008 from the Cooperative Human Tissue Network. Case definition as breast cancer versus normal (women with no history of breast cancer) was established through medical records and examination of tissues by an anatomical pathologist. Breast exposure to BLV was determined by in situ-PCR detection of a biomarker, BLV DNA, localized within mammary epithelium.ResultsThe frequency of BLV DNA in mammary epithelium from women with breast cancer (59%) was significantly higher than in normal controls (29%) (multiply- adjusted odds ratio = 3.07, confidence interval = 1.66–5.69, p = .0004, attributable risk = 37%). In women with premalignant breast changes the frequency of BLV DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001).ConclusionsAmong the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer. The odds ratio magnitude was comparable to those of well-established breast cancer risk factors related to reproductive history, hormones, and lifestyle and was exceeded only by risk factors related to genetics (familial breast cancer), high dose ionizing radiation, and age. These findings have the potential for primary and secondary prevention of breast cancer.

SUMMARY Lipid droplets (LDs) are the major fat storage organelles in eukaryotic cells, but how their size is regulated is unknown. Using genetic screens in C. elegans for LD morphology defects in intestinal cells, we found that mutations in atlastin, a GTPase required for homotypic fusion of endoplasmic reticulum (ER) membranes, cause not only ER morphology defects, but also a reduction in LD size. Similar results were obtained after depletion of atlastin or expression of a dominant-negative mutant, whereas overexpression of atlastin had the opposite effect. Atlastin depletion in Drosophila fat bodies also reduced LD size and decreased triglycerides in whole animals, sensitizing them to starvation. In mammalian cells, co-overexpression of atlastin-1 and REEP1, a paralog of the ER tubule-shaping protein DP1/REEP5, generates large LDs. The effect of atlastin-1 on LD size correlates with its activity to promote membrane fusion in vitro. Our results indicate that atlastin-mediated fusion of ER membranes is important for LD size regulation.

OBJECT Even with improved prenatal and neonatal care, intraventricular hemorrhage (IVH) occurs in approximately 25%–30% of preterm infants, with a subset of these patients developing hydrocephalus. This study was undertaken to describe current trends in hospitalization of preterm infants with posthemorrhagic hydrocephalus (PHH) using the Nationwide Inpatient Sample (NIS) and the Kids’ Inpatient Database (KID). METHODS The KID and NIS were combined to generate data for the years 2000–2010. All neonatal discharges with ICD-9-CM codes for preterm birth with IVH alone or with IVH and hydrocephalus were included. RESULTS There were 147,823 preterm neonates with IVH, and 9% of this group developed hydrocephalus during the same admission. Of patients with Grade 3 and 4 IVH, 25% and 28%, respectively, developed hydrocephalus in comparison with 1% and 4% of patients with Grade 1 and 2 IVH, respectively. Thirty-eight percent of patients with PHH had permanent ventricular shunts inserted. Mortality rates were 4%, 10%, 18%, and 40%, respectively, for Grade 1, 2, 3, and 4 IVH during initial hospitalization. Length of stay has been trending upward for both groups of IVH (49 days in 2000, 56 days in 2010) and PHH (59 days in 2000, 70 days in 2010). The average hospital cost per patient (adjusted for inflation) has also increased, from $201,578 to $353,554 (for IVH) and $260,077 to $495,697 (for PHH) over 11 years. CONCLUSIONS The number of neonates admitted with IVH has increased despite a decrease in the number of preterm births. Rates of hydrocephalus and mortality correlated closely with IVH grade. The incidence of hydrocephalus in preterm infants with IVH remained stable between 8% and 10%. Over an 11-year period, there was a progressive increase in hospital cost and length of stay for preterm neonates with IVH and PHH that may be explained by a concurrent increase in the proportion of patients with congenital cardiac anomalies.

OBJECT Cushing's disease (CD) is a potentially lethal neuroendocrinopathy that often requires specialized multidisciplinary treatment to achieve optimized outcomes. The authors analyzed data pertaining to patient, hospital, and admission characteristics as they relate to outcomes following transsphenoidal surgery (TSS) in more than 5500 patients treated for CD. METHODS The Nationwide Inpatient Sample (NIS) database was used to identify all patients admitted with CD between 2002 and 2010. A variety of patient demographic data (e.g., age, sex, race, payer status), hospital variables (e.g., bed size, TSS volume, teaching status), and admission subtypes (e.g., elective, emergency) were tested for association with postoperative endocrine and nonendocrine complications, mortality, nonroutine discharge, length of stay, and total hospital charges. All tests were performed using univariate analysis followed by multivariate analysis, with 4 models tested via an additive methodology. Statistical significance was defined as a p value < 0.05 for all analyses. RESULTS From 2002 to 2010, 5527 individuals who were admitted for TSS (54 biopsies, 4254 partial resections, and 1271 total resections; 5579 total TSS procedures) were identified as patients with CD. There were 25 deaths following TSS, resulting in a mortality incidence rate of 0.45%. Nonendocrine and endocrine complications were reported in 22.4% and 11.1% of patients, respectively. The most common nonendocrine complications were postoperative neurological complications (6.98%) and mechanical ventilation (1.71%). Diabetes insipidus was reported in 14.79% of patients. In a multivariate analysis, patients with Medicare were at increased risk of nonendocrine complications (relative risk [RR] 2.24, 95% CI 1.15–4.38; p = 0.02). Patients with Medicare had increased risk of higher charges (RR 1.89, 95% CI 1.04–3.45; p = 0.04), as did those with Medicaid (RR 1.93, 95% CI 1.10–3.41; p = 0.02). Additionally, as compared with white patients, Hispanic patients had an increased rate of higher charges (RR 1.86, 95% CI 1.12–3.10; p = 0.02). Patients whose age was less than 40 years had a higher risk of developing diabetes insipidus (RR 1.39, 95% CI 1.0–1.93; p = 0.05). When compared with those in northeast hospitals, patients in western hospitals were more likely to experience nonendocrine complications (RR 1.85, 95% CI 0.99–3.46; p = 0.05) and endocrine complications (RR 1.98, 95% CI 1.28–3.07; p < 0.01). Patients treated in teaching hospitals were at significantly lower risk of incurring higher hospital charges (RR 0.49, 95% CI 0.28–0.85; p = 0.01). Patients with emergency admissions had a risk of higher hospital charges (RR 3.06, 95% CI 1.26–7.46; p = 0.01) and nonendocrine complications (RR 3.18, 95% CI 1.22–8.28; p = 0.02). CONCLUSIONS This review of NIS data in more than 5500 patients treated surgically for CD pointed to major outcome disparities predicted primarily by payer status, admission type, and hospital region. Identification and targeting of such barriers to quality health care in patients with CD may help optimize patient outcomes on a national level and present an opportunity to improve access of high-risk patient subgroups to specialty centers of excellence.

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