Faculty Bibliography

There continues to remain uncertainty regarding the effect of percutaneous coronary intervention (PCI) vs medical therapy in patients with stable angina. We therefore performed a systematic review and study-level meta-analysis of randomized controlled trials of patients with stable angina comparing PCI vs medical therapy for each of the following individual outcomes: all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), and angina relief. We used 8 strategies to identify eligible trials including bibliographic database searches of MEDLINE, PubMed, EMBASE, and the Cochrane Controlled Trials Registry until November 2011. Two independent reviewers undertook decisions about study eligibility and data abstraction. Data were pooled using a random effects model. Ten prospective randomized controlled trials fulfilled our eligibility criteria and they included a total of 6752 patients. We did not detect differences between PCI vs medical therapy for all-cause mortality (663 events; relative risk [RR], 0.97 [confidence interval (CI), 0.84-1.12]; I(2) = 0%), CV mortality (214 events; RR, 0.91 [CI, 0.70-1.17]; I(2) = 0%), MI (472 events; RR, 1.09 [CI, 0.92-1.29]; I(2) = 0%), or angina relief at the end of follow-up (2016 events; RR, 1.10 [CI, 0.97-1.26]; I(2)=85%). PCI was not associated with reductions in all-cause or CV mortality, MI, or angina relief. Considering the cost implication and the lack of clear clinical benefit, these findings continue to support existing clinical practice guidelines that medical therapy be considered the most appropriate initial clinical management for patients with stable angina.

Mastocytosis is characterized by the proliferation and accumulation of mast cells within organs and most commonly the skin; localization accounting for the frequent presentation of skin lesions in affected individuals. The authors detail a case report involving a patient with telangiectasia macularis eruptive perstans, a rare cutaneous form of mastocytosis, accompanied by an unusual clinical finding of island sparing.

PURPOSE: To evaluate the dose to the left anterior descending artery in patients receiving left-sided tangential breast radiation. METHODS AND MATERIALS: The study cohort consisted of 50 left-sided breast cancer patients who were sequentially simulated at our institution. The heart and left anterior descending (LAD) artery were contoured from its origin on the left main coronary artery down to the last visible segment of the vessel. Detailed dosimetry of the heart and LAD artery were obtained and analyzed. RESULTS: Excellent correlation between the dose to the heart and LAD artery was discovered. The mean LAD dose was 17.98 Gy. The mean dose to the proximal LAD was 2.46 Gy. The median V25 was 2.91% and the mean heart dose 3.10 Gy. For every 100 cGy increase in mean heart dose, mean LAD dose increased by 4.82 Gy. For every percent increase in the heart V10 and V25, there was a 2.23 Gy and 2.77 Gy increase in mean LAD dose, respectively. For every percent increase of heart V25, a 5.6% increase in the LAD V20 was demonstrated. CONCLUSIONS: The LAD artery dose correlates very closely with all of the commonly measured heart dose constraints, and does not need to be contoured separately when standard tangential borders are used. Incidental LAD artery doses remain with supine breast tangential radiation therapy.

Several prominent bacterial pathogens secrete nuclease (Nuc) enzymes that have an important role in combating the host immune response. Early studies of Staphylococcus aureus Nuc attributed its regulation to the agr quorum-sensing system. However, recent microarray data have indicated that nuc is under the control of the SaeRS two-component system, which is a major regulator of S. aureus virulence determinants. Here we report that the nuc gene is directly controlled by the SaeRS two-component system through reporter fusion, immunoblotting, Nuc activity measurements, promoter mapping, and binding studies, and additionally, we were unable identify a notable regulatory link to the agr system. The observed SaeRS-dependent regulation was conserved across a wide spectrum of representative S. aureus isolates. Moreover, with community-associated methicillin-resistant S. aureus (CA MRSA) in a mouse model of peritonitis, we observed in vivo expression of Nuc activity in an SaeRS-dependent manner and determined that Nuc is a virulence factor that is important for in vivo survival, confirming the enzyme's role as a contributor to invasive disease. Finally, natural polymorphisms were identified in the SaeRS proteins, one of which was linked to Nuc regulation in a CA MRSA USA300 endocarditis isolate. Altogether, our findings demonstrate that Nuc is an important S. aureus virulence factor and part of the SaeRS regulon.

Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent pathogens. However, little is known about their emergence in patients with hematologic malignancies. We identified 18 patients with hematologic malignancies over 3.5 years who developed bloodstream infections (BSIs) caused by CRE. Fourteen BSIs were caused by Klebsiella pneumoniae, three by Enterobacter cloacae, and one was polymicrobial. Initial empirical antimicrobial therapy was active in two patients (11%), and a median of 55 h elapsed between culture collection and receipt of an active agent. Ten patients (56%) died, including nine (69%) of 13 neutropenic patients, with a median of 4 days from culture collection until death. CRE isolates were analyzed for carbapenemase production, beta-lactamase genes and outer membrane porin deletions and characterized by multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). Carbapenem resistance mechanisms included Klebsiella pneumoniae carbapenemase production and CTX-M-15 production with an absent outer membrane porin protein. No isolate had >/=95% homology on PFGE, indicating a heterogeneous, non-outbreak population of isolates. CRE BSIs are emerging in patients with hematologic malignancies and are associated with ineffective initial empirical therapy, long delays in administration of active antimicrobials and high mortality rates. New diagnostic, therapeutic and preventive strategies for CRE infections in this vulnerable population are needed.

BACKGROUND: Obesity is associated with poor asthma outcomes; weight loss improves such outcomes. Inaccurate recognition of obesity may impede weight control. PURPOSE: We examined perception of weight by early adolescents with uncontrolled asthma and their caregivers, and tested the relationship between medical visit frequency and accuracy of perceived weight status. METHODS: A total of 373 adolescents and their caregivers reported the adolescent's height/weight and weight perception; caregivers reported healthcare utilization. We measured height/weight. Logistic regression modeled accuracy of weight perception. RESULTS: A total of 43.7 % of the overweight/obese adolescents and caregivers accurately perceived weight status. BMI percentile [odds ratio (OR) = 1.19, confidence interval (CI) = 1.10-1.28] and total medical visits (OR = 1.18, CI = 1.05-1.33) were associated with higher accuracy in caregivers. Total medical visits (OR = 0.84, CI = 0.74-0.96) was associated with lower accuracy in adolescents. CONCLUSIONS: Accurate perception of weight status was poor for overweight adolescents with uncontrolled asthma and their caregivers. Frequent medical visits were associated with improved caregivers' but not adolescents' perceptions.

Background. We and others have shown that primary hepatitis C (HCV) infection in men infected with human immunodeficiency virus (HIV) causes early-onset liver fibrosis; however, little is known about the long-term natural history of the liver disease in these HIV-infected men. Methods. We followed a cohort of HIV-infected men with primary HCV infection in New York City. Results. Four men who were not cured after their primary HCV infection developed decompensated cirrhosis within 17 months to 6 years after primary HCV infection. Three died within 8 years of primary HCV infection, and 1 survived after liver transplant done 2 years after primary HCV infection. Three of the 4 men had AIDS at the time of primary HCV infection, and the most rapid progression occurred in the 2 men with the lowest CD4 counts at the time of HCV infection. Liver histopathology was most consistent with HCV-induced damage even though some had exposures to other potential hepatotoxins. Conclusions. Primary HCV infection resulted in decompensated cirrhosis and death within 2-8 years in 4 HIV-infected men. The rapid onset of fibrosis due to primary HCV infection in HIV-infected men cannot therefore be considered benign. The rate of continued progression to liver failure may be proportional to the degree of underlying immunocompromise caused by HIV infection. More research is needed to better define the mechanisms behind accelerated liver damage.