Citations

Background— There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. Methods and Results— We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; P =0.59). Compared with ETT, index testing costs were higher for exercise MPI ( P <0.001), whereas downstream procedural costs were slightly lower ( P =0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI ( P <0.001). Conclusions— In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00282711.

Abstract Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240–9. ©2011 AACR.

Transurethral needle ablation (TUNA) is an accepted and effective therapy for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). ProstivaTM(Medtronic, Shoreview, MN) is the newest-generation device, which includes a new needle design and radio frequency (RF) generator. This device creates temperatures of 120°C and necrotic lesions in less than 2.5 min. Using previously described techniques, we analyzed dynamic, gadolinium-enhanced MRIs to characterize the ablative properties of the new ProstivaTMRF device.Ten men with LUTS due to BPH were treated with the standard ProstivaTMmanufacturer–recommended protocol. The bladder neck and lateral lobes received treatment based on prostate volume and prostatic urethral length. Gadolinium-enhanced MRI sequences were obtained prior to and 1 week post-treatment. Analyze® software (Mayo Clinic Biomedical Imaging Resource, Rochester, MN) was used to evaluate MRIs. New gadolinium defects were seen in all patients following ProstivaTMtreatments. All lesions coalesced within the prostate. No defects were seen beyond the prostate, and the urethra was spared in all patients. The mean volume of necrosis was 7.56 cc, representing a mean of 11.28% of total prostate volume.Dynamic, gadolinium-enhanced MRIs demonstrate new vascular defects representing necrosis caused by ProstivaTMRF therapy of the prostate. The standard ProstivaTMRF protocol produces lesions that coalesce to create larger lesions in the bladder neck and lateral lobes. Compared to the TUNA® Precision PlusTMdevice, the ablative lesions appear comparable while produced with a shorter burn time.

Background— Approximately 10% of sudden infant death syndrome (SIDS) may stem from cardiac channelopathies. The KCNJ8 -encoded Kir6.1 (K ATP ) channel critically regulates vascular tone and cardiac adaptive response to systemic metabolic stressors, including sepsis. KCNJ8 -deficient mice are prone to premature sudden death, particularly with infection. We determined the spectrum, prevalence, and function of KCNJ8 mutations in a large SIDS cohort. Methods and Results— Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, comprehensive open reading frame/splice-site mutational analysis of KCNJ8 was performed on genomic DNA isolated from necropsy tissue on 292 unrelated SIDS cases (178 males, 204 white; age, 2.9±1.9 months). KCNJ8 mutations were coexpressed heterologously with SUR2A in COS-1 cells and characterized using whole-cell patch-clamp. Two novel KCNJ8 mutations were identified. A 5-month-old white male had an in-frame deletion (E332del) and a 2-month-old black female had a missense mutation (V346I). Both mutations localized to Kir6.1's C-terminus, involved conserved residues and were absent in 400 and 200 ethnic-matched reference alleles respectively. Both cases were negative for mutations in established channelopathic genes. Compared with WT, the pinacidil-activated K ATP current was decreased 45% to 68% for Kir6.1-E332del and 40% to 57% for V346I between −20 mV and 40 mV. Conclusions— Molecular and functional evidence implicated loss-of-function KCNJ8 mutations as a novel pathogenic mechanism in SIDS, possibly by predisposition of a maladaptive cardiac response to systemic metabolic stressors akin to the mouse models of KCNJ8 deficiency.

Background and Purpose— Intracranial hemorrhage (ICH) is a rare and devastating complication of carotid revascularization. We sought to determine the prevalence of, type of, and risk factors associated with ICH among recipients of carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAS) within the National Inpatient Sample (NIS). Methods— Postoperative cases of ICH after CEA (International Classification of Disease 9 th edition [ICD-9]: 38.12) or CAS (ICD-9: 00.63) were retrieved from the 2001 to 2008 NIS. Clinical presentation (asymptomatic versus symptomatic), discharge status, in-hospital mortality, demographics, and hospital characteristics were extracted from NIS data. Charlson indices of comorbidity were determined based on ICD-9 and clinical classification software codes. Multivariate regression was used to determine the impact of revascularization procedure type and symptom status on adverse outcomes, including ICH, in-hospital mortality, and unfavorable discharge status. Results— Among 57 663 486 NIS hospital admissions, 215 012 CEA and 13 884 CAS procedures were performed. Symptomatic presentations represented the minority of CEA (N=10 049; 5%) and CAS cases (N=1251; 10%). ICH occurred significantly more frequently after CAS than CEA in both symptomatic (4.4% versus 0.8%; P <0.0001) and asymptomatic presentations (0.5% versus 0.06%; P <0.0001). Multivariate regression suggested that symptomatic presentations (versus asymptomatic) and CAS procedures (versus CEA) were both independently predictive of 6-fold to 7-fold increases in the frequency of postoperative ICH. ICH was independently predictive in a 30-fold increased risk of mortality before discharge. Conclusions— CAS procedures are associated with elevated adverse outcomes, including ICH, in-hospital death, and unfavorable discharges, especially among symptomatic presentations.