Faculty Bibliography

OBJECTIVE: Aging decreases the strength of association between established coronary heart disease (CHD) and its risk factors. Carotid intima media thickness (IMT) is a widely used surrogate for coronary artery disease, which we hypothesized has a similar diminishing age-mediated strength of association with CHD occurrence and prevalence of its risk factors. METHODS AND RESULTS: Data from the Atherosclerosis Risk in Communities (ARIC) cohort of 14,562 individuals aged 45 to 64 (mean follow up nine years) was stratified into two age groups, 45-54 and 55-64 years, within each of ARIC's four examination visits (n = 14,562; 13,622; 7869; 6628 for visits 1 to 4, respectively). Cross-sectional and longitudinal analyses with multiple linear and logistic regression modeling were used to compare the relationships between carotid IMT (the mean of six far wall sites from the right and left carotid bifurcation, common and internal carotid arteries with imputation of missing data) and the risk factors of smoking, hypertension, hypercholesterolemia, diabetes, and obesity with age. The strength of the associations between carotid IMT and most risk factors were qualitatively stronger across successive visits and within each visit, these associations were stronger in the older, as compared to the younger, age group. CONCLUSIONS: In a large cohort followed for nearly one decade, our hypothesis that age attenuates the association of CHD risk factors and carotid IMT was not supported by ARIC data. Rather, we found that associations between carotid IMT and CHD risk factors remained stable with advancing age, contrary to the relationship between risk factors and CHD outcomes with age. These findings suggest that there is efficacy to continued risk factor management in the elderly.

BACKGROUND: One of the most controversial aspects of New York City's highly effective TB control program is the use of public health law and court-ordered detention to treat persistently recalcitrant patients with active TB. We now report on characteristics and outcomes of patients undergoing detention for completion of TB treatment due to nonadherence in New York City from 2002 through 2009. METHODS: A retrospective cohort study was designed to compare patients undergoing court-ordered detention (n = 79) and time-matched control subjects undergoing TB treatment in outpatient directly observed therapy (DOT) at Bellevue Hospital in New York City. RESULTS: From January 1, 2002, through December 31, 2009, 79 patients underwent court-ordered detention for TB treatment. Compared with patients completing treatment in DOT, univariate analysis found that detainees were younger; more likely to be of minority race/ethnicity; to have a history of substance abuse, tobacco use, homelessness, incarceration, HIV infection; and to be born in the United States. Multivariate analysis adjusting for other variables found smear positivity (OR = 3.93; 95% CI, 1.05-14.75; P = .04), mental illness (OR = 5.80; 95% CI, 1.18-28.51; P = .03), and substance abuse (OR = 9.25; 95% CI, 2.81-30.39; P < .01) to be the strongest independent predictors of likelihood of detention. Of those initially detained, 46 (58%) completed treatment during inpatient detention, 29(37%) completed treatment under outpatient court-ordered DOT, and four died during their hospitalization. CONCLUSIONS: The majority of patients undergoing court-ordered detention for TB treatment (95%) successfully completed therapy. Likelihood of detention was most strongly associated with factors expected to be associated with poor adherence, including mental illness and substance abuse.

BACKGROUND: Contemporary studies have shown that spontaneous but not procedural myocardial infarction (MI) are related to subsequent mortality. Whether PCI reduces spontaneous (non-procedural) MI is unknown. METHODS AND RESULTS: PUBMED, EMBASE, and CENTRAL were searched for randomized clinical trials (RCTs), until October 2012, comparing PCI with OMT, for stable ischemic heart disease, and reporting MI outcomes - spontaneous non-procedural MI, procedural MI and all MI including procedure related MI. Given the varying length of follow-up between trials, a mixed-effect poisson regression meta-analysis was employed. From 12 RCTs with 37548 patient-years of follow-up, PCI, when compared with OMT alone, was associated with significant lower incident rate ratio (IRR) for spontaneous non-procedural MI (IRR=0.76, 95% CI 0.58-0.99) at the risk of higher procedural MI (IRR=4.11, 95% CI 2.53-6.88) without any difference in all MI (IRR=0.96, 95% CI 0.74-1.21). The point estimate for PCI vs. OMT for all-cause mortality (IRR=0.88, 95% CI 0.75-1.03) and cardiovascular mortality (IRR=0.70, 95% CI 0.44-1.09) paralleled that of spontaneous non-procedural MI (but not procedural or all nonfatal MI) although these were not statistically significant. CONCLUSIONS: PCI compared to OMT reduced spontaneous MI at the risk of procedural MI without any difference in all MI. Consistent with prior studies showing that spontaneous MI but not procedural MI are related to subsequent mortality, in the present report the point estimate for reduced mortality with PCI compared to OMT paralleled the prevention of spontaneous MI with PCI. Further studies are needed to determine whether these associations are causal.

BACKGROUND: The role of percutaneous coronary intervention (PCI) in the management of stable coronary artery disease remains controversial. Given advancements in medical therapies and stent technology over the last decade, we sought to evaluate whether PCI, when added to medical therapy, improves outcomes when compared with medical therapy alone. METHODS AND RESULTS: We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and CENTRAL databases, until January 2012, for randomized clinical trials comparing revascularization with PCI to optimal medical therapy (OMT) in patients with stable coronary artery disease. The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular death, nonfatal myocardial infarction, subsequent revascularization, and freedom from angina. Primary analyses were based on longest available follow-up with secondary analyses stratified by trial duration, with short-term (/=5 years) time points. We identified 12 randomized clinical trials enrolling 7182 participants who fulfilled our inclusion criteria. For the primary analyses, when compared with OMT, PCI was associated with no significant improvement in mortality (risk ratio [RR], 0.85; 95% CI, 0.71-1.01), cardiac death (RR, 0.71; 95% CI, 0.47-1.06), nonfatal myocardial infarction (RR, 0.93; 95% CI, 0.70-1.24), or repeat revascularization (RR, 0.93; 95% CI, 0.76-1.14), with consistent results over all follow-up time points. Sensitivity analysis restricted to studies in which there was >50% stent use showed attenuation in the effect size for all-cause mortality (RR, 0.93; 95% CI, 0.78-1.11) with PCI. However, for freedom from angina, there was a significant improved outcome with PCI, as compared with the OMT group (RR, 1.20; 95% CI, 1.06-1.37), evident at all of the follow-up time points. CONCLUSIONS: In this most rigorous and comprehensive analysis in patients with stable coronary artery disease, PCI, as compared with OMT, did not reduce the risk of mortality, cardiovascular death, nonfatal myocardial infarction, or revascularization. PCI, however, provided a greater angina relief compared with OMT alone, larger studies with sufficient power are required to prove this conclusively.

Campylobacter jejuni, a gram-negative, invasive organism, is a common cause of food-borne bacterial diarrheal disease. However, the relationship between C. jejuni and the innate immune system is not well described. To better characterize host defense against C. jejuni, we investigated the ability of nitric oxide/reactive nitrogen species to kill two strains of C. jejuni. C. jejuni viability was measured after exposure to reactive nitrogen species produced biochemically as acidified nitrite and by bone marrow-derived macrophages. We report that acidified nitrite caused a 3-log-increased kill of C. jejuni (P < 0.05) at doses that did not affect the viability of Salmonella enterica serovar Typhimurium. Expression of NOS2, the gene responsible for the production of inducible nitric oxide, was increased >100-fold in murine macrophages after incubation with C. jejuni (P < 0.001). These macrophages effected a 2-log-increased kill of C. jejuni over 24 h compared to that by NOS2-/- macrophages unable to produce nitric oxide (P < 0.05). These findings suggest that the mammalian host upregulates the production of nitric oxide in response to exposure to C. jejuni and that nitric oxide and reactive nitrogen species comprise part of the innate defense mechanisms that contribute to the resolution of C. jejuni infection

Persistent interstitial pulmonary emphysema (PIPE) is a syndrome characterized by air-leakage in the perivascular tissues of the lung, primarily affecting mechanically ventilated neonates. Reports in the literature of infants developing PIPE with no history of respiratory distress syndrome (RDS) or mechanical ventilation are scarce. Here, we present a case of a 3-month-old former full term male infant with no history of RDS or mechanical ventilation who presented with focal cystic lung disease associated with spontaneous tension pneumothorax. He was ultimately found to have PIPE based on pathologic evaluation of the resected cystic region. We believe that focal PIPE should be included in the differential diagnosis of cystic lung disease in a full term, unventilated infant, even when spontaneous pneumothorax is the presenting entity

The ability to biopsy indeterminate pulmonary lesions in children has evolved with advances in minimal access surgery. Recent advances in preoperative localization including image-guided dye injection or wire implantation have expanded the types of lesions that are accessible via minimal access surgery. We present a case of a 13-year-old boy who underwent preoperative localization using both methylene blue dye and microcoil labeling, and a subsequent thoracoscopic pulmonary wedge resection under the same anesthesia. The combined use of both dye and microcoil localization provides the advantage of superior intraoperative visualization of the lesion and the ability to use fluoroscopy to confirm the presence of the nodule in the surgical specimen. We recommend this technique for the biopsy of indeterminate pulmonary lesions that would not otherwise be accessible via a minimally invasive approach