Citations

Abstract The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13]. Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.

ABSTRACT Human adenoviruses (HAdVs) are ubiquitous double-stranded DNA viruses that cause a wide array of diseases in humans including pharyngitis, pneumonia, gastroenteritis, hemorrhagic cystitis, and keratoconjunctivitis. They also cause life-threatening opportunistic infections in immunocompromised individuals and are responsible for outbreaks in certain populations. Diagnosis is traditionally by cell culture or antigen detection methods. However, some HAdVs can take up to 4 weeks to isolate, and diarrheagenic types 40 and 41 will not grow in routine cell culture. Therefore, the goal of this study was to design a rapid, real-time PCR assay to detect all known 57 HAdV types from multiple different specimen sources. Primers and fluorescence resonance energy transfer hybridization probes were designed to target a 185-bp region of the penton base gene of HAdV. The analytical sensitivity was determined to be 10 copies/μl for HAdV types showing exact primer/probe homology in specimen matrix. Using whole-virus strains, the analytical sensitivity for representative HAdV types ranged from 10 −1 to 10 3 50% tissue culture infective dose (TCID 50 )/ml. The assay demonstrated 100% sensitivity and 99% specificity. This real-time PCR assay provides a rapid method for the detection of all 57 known HAdV types from respiratory specimens, blood, stool, urine, and ocular swabs.

Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation.

Diabetic ketoacidosis (DKA) during pregnancy carries significant risk of intrauterine fetal demise, but little is known about its postnatal sequelae in surviving neonates. We report here the case of an infant who was born to a mother with White's class C diabetes mellitus during an episode of DKA. Throughout pregnancy her glucose control was suboptimal, as evidenced by a predelivery glycosylated hemoglobin level of 8.1%. At 33 weeks' gestation, the mother presented with nausea and vomiting, a serum glucose concentration of 575 mg/dL, and other metabolic derangements consistent with DKA. Despite rehydration and insulin therapy, fetal distress necessitated cesarean delivery. At birth the infant required intubation, but her clinical status quickly improved and she was extubated within the first day of life. However, on day-of-life 4 she exhibited seizure-like activity, and subsequent brain MRI revealed bilateral basal ganglia infarctions. Previous research has revealed that the keto acid β-hydroxybutyrate (β-OHB) can cross the placenta into the fetal circulation and thereafter accumulate in the fetal brain, which leads to severe metabolic derangements. Furthermore, β-OHB accumulates rapidly in the basal ganglia of older children during episodes of DKA, wherein its presence is associated with neuronal injury. We suspect that transplacental transfer of maternal β-OHB led to an acquired ketoacidosis in the fetus and that accumulation of β-OHB contributed to neuronal injury and subsequent infarction of the basal ganglia. Further research is necessary to better characterize neonatal complications of maternal DKA, as well as the possible inclusion of β-OHB levels in the goal-directed treatment of this disease.

With improved treatments and increasingly life expectancy, the burden of metastatic disease in the spine is expected to rise. The role of conventional surgery for spinal metastases is well established but often involves procedures of large magnitude. We describe minimally invasive techniques for spinal stabilization and decompression in patients with symptomatic metastatic disease of the spine.