Faculty Bibliography

BACKGROUND: Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24-50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant. METHODS: We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128). RESULTS: The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas. CONCLUSIONS: NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases.

BACKGROUND: Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways. METHODS: We performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts. RESULTS: Statistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer. CONCLUSION: A pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers

INTRODUCTION: Traditionally, Mycobacterium abscessus pulmonary disease has poor long term response to current antibiotic regimens. The data regarding the clinical efficacy of linezolid and aerosolized amikacin in M. abscessus pulmonary disease is limited. CASE PRESENTATION: A 52 year-old Caucasian female presented in 2004 with scant hemoptysis and intermittent night sweats. Her past medical history was unremarkable. She denied history of pneumonias. She did not smoke tobacco. She worked as a middle school secretary. Computed tomographic (CT) evaluation of the chest showed significant bronchiectasis in the right middle lobe with irregular opacities throughout the right upper lobe and right lower lobe. She was treated empirically with levofloxacin for recurrent episodes of infection with a presumed response. In 2007, she had more severe hemoptysis with several teaspoons of bright red blood that woke her up from sleep at night. M. chelonae and M. abscessus were identified in her sputum and she was started on clarithromycin combined with ciprofloxacin. In 2008, pulmonary function tests showed evidence of decreasing diffusing capacity. Chest CT showed interval increase in the nodular densities primarily in the right middle lobe and many were cavitating. She required hospitalization in 2009 for increasing hemoptysis and underwent IR embolization of branches of the right bronchial artery and right internal mammary artery. Nebulized amikacin 250 mg daily was started along with linezolid 600 mg daily. After 6 months of moxifloxacin, clarithromycin, nebulized amikacin, and linezolid, chest CT in late 2009 showed improvement and there was no further hemoptysis. DISCUSSIONS: Intermittent courses of parenteral therapy combined with and followed by an oral macrolide, aerosolized amikacin, and linezolid may be used to suppress infection and control disease progression of M. abscessus pulmonary disease. (1) Cost and side effects may limit the feasibility of prolonged treatment with parenteral antibiotic therapy. Aminoglycosides exhibit significant concentration-dependent bactericidal activity against nontuberculous mycobacteria. Extended parenteral therapy with aminoglycosides has been avoided due to the substantial risks of nephrotoxicity, ototoxicity, and vestibular toxicity. Aerosolized antibiotic delivery offers the potential advantage of achieving high drug concentrations in the lung with low systemic absorption and diminished risk of systemic toxicities. Aerosolized antibiotics have been used with notable success in the treatment of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis. In an observational case series, six HIV-negative patients with Mycobacterium avium intracellulare pulmonary infections who had failed standard therapy were administered aerosolized amikacin at 15 mg/kg daily in addition to standard multi-drug macrolide-based oral therapy. Five responded to therapy and achieved symptomatic improvement. Four were sputum culture negative after 6 months of therapy. (2) Approximately 50% of M. abscessus isolates are susceptible or exhibit intermediate susceptibility in vitro to the oxazolidinone linezolid. A small number of patients with M. abscessus lung disease have been treated with linezolid and a companion drug, usually a macrolide, with varied results. Impediments to long-term use of linezolid include the cost and potential side effects of chronic therapy which include peripheral neuropathy and anemia. Once daily dosing of linezolid 600mg instead of the traditional twice daily dosing is currently used by some to treat mycobacterial disease with seemingly fewer side effects and retained antimycobacterial activity. CONCLUSION: Preliminary case series suggest that nonparenteral agents including oral macrolides, aerosolized amikacin, and linezolid may be effective for the treatment of M. abscessus pulmonary disease

RATIONALE: Numerous accrediting organizations are calling for competency-based medical education that would help define specific specialties and serve as a foundation for ongoing assessment throughout a practitioner's career. Pulmonary Medicine and Critical Care Medicine are two distinct subspecialties, yet many individual physicians have expertise in both because of overlapping content. Establishing specific competencies for these subspecialties identifies educational goals for trainees and guides practitioners through their lifelong learning. OBJECTIVES: To define specific competencies for graduates of fellowships in Pulmonary Medicine and Internal Medicine-based Critical Care. METHODS: A Task Force composed of representatives from key stakeholder societies convened to identify and define specific competencies for both disciplines. Beginning with a detailed list of existing competencies from diverse sources, the Task Force categorized each item into one of six core competency headings. Each individual item was reviewed by committee members individually, in group meetings, and conference calls. Nominal group methods were used for most items to retain the views and opinions of the minority perspective. Controversial items underwent additional whole group discussions with iterative modified-Delphi techniques. Consensus was ultimately determined by a simple majority vote. MEASUREMENTS AND MAIN RESULTS: The Task Force identified and defined 327 specific competencies for Internal Medicine-based Critical Care and 276 for Pulmonary Medicine, each with a designation as either: (1) relevant, but competency is not essential or (2) competency essential to the specialty. CONCLUSIONS: Specific competencies in Pulmonary and Critical Care Medicine can be identified and defined using a multisociety collaborative approach. These recommendations serve as a starting point and set the stage for future modification to facilitate maximum quality of care as the specialties evolve

BACKGROUND: Recommendations for optimizing continuing medical education (CME) effectiveness in improving physician application of knowledge and psychomotor skills are needed to guide the development of processes that effect physician change and improve patient care. METHODS: The guideline panel reviewed evidence tables and a comprehensive review of the effectiveness of CME developed by The Johns Hopkins Evidence-based Practice Center for the Agency for Healthcare Research and Quality (AHRQ Evidence Report). The panel considered studies relevant to the effect of CME on physician knowledge application and psychomotor skill development. From the 136 studies identified in the systematic review, 15 articles, 12 addressing physician application of knowledge and 3 addressing psychomotor skills, were identified and reviewed. Recommendations for optimizing CME were developed using the American College of Chest Physicians guideline grading system. RESULTS: The preponderance of evidence demonstrated improvement in physician application of knowledge with CME. The quality of evidence did not allow specific recommendations regarding optimal media or educational techniques or the effectiveness of CME in improving psychomotor skills. CONCLUSIONS: CME is effective in improving physician application of knowledge. Multiple exposures and longer durations of CME are recommended to optimize educational outcomes

The immune-reconstitution syndrome is a paradoxical inflammatory response to a preexisting or a coexisting disease, after the initiation of highly active antiretroviral therapy for the human immunodeficiency virus. Infrequently described, the radiographic and computed tomographic findings of the immune-reconstitution syndrome, which is related to the Mycobacterium avium-intracellulare infection and to highly active antiretroviral therapy, are presented in 2 patients. Homogeneous mediastinal and hilar lymphadenopathy were present in both individuals, with one having a large mass accompanied by small nodules