Targeted Phage Display-based Pulmonary Vaccination in Mice and Non-human Primates.

BACKGROUND: The extensive alveolar capillary network of the lungs is an attractive route for administration of several agents. One key functional attribute is the rapid onset of systemic action due to the absence of first-pass metabolism. METHODS: Here we applied a combinatorial approach for ligand-directed pulmonary delivery as a unique route for systemic targeting in vaccination. FINDINGS: We screened a phage display random peptide library in vivo to select, identify, and validate a ligand (CAKSMGDIVC) that specifically targets and is internalized through its receptor, α3ß1 integrin, on the surface of cells lining the lung airways and alveoli and mediates CAKSMGDIVC-displaying phage binding and systemic delivery without compromising lung homeostasis. As a proof-of-concept, we show that the pulmonary delivery of targeted CAKSMGDIVC-displaying phage particles in mice and non-human primates elicit a systemic and specific humoral response. CONCLUSIONS: This broad methodology blueprint represents a robust and versatile platform tool enabling new ligand-receptor discovery with many potential translational applications. FUNDING: Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center (CA016672), University of New Mexico Comprehensive Cancer Center (CA118100), Rutgers Cancer Institute of New Jersey (CA072720), research awards from the Gillson Longenbaugh Foundation, and National Institutes of Health (NIH) grant no. 1R01CA226537.

Linezolid-induced photoreceptor dysfunction masquerading as autoimmune retinopathy.

PURPOSE: To report a case of linezolid-induced reversible retinopathy. METHODS: Case report with literature review. RESULTS: Clinical examination and imaging are presented over a 7-month interval, from initial presentation to subsequent follow-up (6 months after discontinuation of linezolid). The subject was found to have not only an optic neuropathy but also severe reversible photoreceptor dysfunction as demonstrated by electrophysiologic testing. Upon discontinuation of linezolid, not only did the patient's visual acuity, visual fields, and visual evoked potential significantly improve, but the electroretinogram did as well. CONCLUSIONS: Linezolid has previously been reported to cause a toxic optic neuropathy. Reversible photoreceptor dysfunction on full-field electroretinography has never been reported in conjunction with linezolid toxicity. This novel case suggests that linezolid toxicity should be considered in cases of photoreceptor dysfunction.

Forced oscillation technique in veterans with preserved spirometry and chronic respiratory symptoms.

PURPOSE: To evaluate the utility of the forced oscillation technique (FOT) among military veterans with preserved spirometry and chronic unexplained respiratory symptoms. METHODS: 178 veterans referred for evaluation of unexplained respiratory symptoms completed pulmonary function testing and FOT. Preserved spirometry was defined as FEV1/FVC, FEV1 and FVC ≥ 5th percentile. Frequency dependence of resistance (R4-R20) and reactance area (AX) were assessed via FOT, and R4-R20 ≥ 20% and AX ≥ 95th percentile were considered abnormal. RESULTS: Spirometry was preserved in 71.3%, of whom 124 had acceptable FOT data. 93 of 124 (75.0%) veterans with preserved spirometry had one or more abnormal findings on FOT. Veterans with abnormal R4-R20 and/or AX had reduced FVC, FEV1, FEF25-75, and diffusing capacity (% predicted) in comparison to those with Normal FOT (p = 0.030 to p < 0.001). CONCLUSIONS: In our referral sample, distal airway dysfunction in the presence of preserved spirometry appears common and may represent an at-risk group requiring closer surveillance.

A Man in His 20s With Diffuse Lung Opacities and Acute Respiratory Failure After Hookah Smoking.

A man in his 20s with no medical history presented with 2 days of progressively worsening shortness of breath accompanied by subjective fevers, chills, body aches, decreased appetite, night sweats, and cough producing nonbloody sputum. He denied childhood lung diseases, allergies, or a family history of lung disease. He did not smoke cigarettes but had smoked hookah in Saudi Arabia before moving to the United States 1 month before presentation and had restarted 2 days before the start of symptoms. He denied travel outside of the northeastern United States. He did not take medications, use illicit drugs, or engage in high-risk behavior.

Palliative and end-of-life educational practices in US pulmonary and critical care training programs.

PURPOSE: To describe educational features in palliative and end-of-life care (PEOLC) in pulmonary/critical care fellowships and identify the features associated with perceptions of trainee competence in PEOLC. METHODS: A survey of educational features in 102 training programs and the perceived skill and comfort level of trainees in 6 PEOLC domains: communication, symptom control, ethical/legal, community/institutional resources, specific syndromes, and ventilator withdrawal. We evaluated associations between perceived trainee competence/comfort in PEOLC and training program features, using regression analyses. RESULTS: Fifty-five percent of program directors (PDs) reported faculty with training in PEOLC; 30% had a written PEOLC curriculum. Neither feature was associated with trainee competence/comfort. Program directors and trainees rated bedside PEOLC teaching highly. Only 20% offered PEOLC rotations; most trainees judged these valuable. Most PDs and trainees reported that didactic teaching was insufficient in communication, although sufficient teaching of this was associated with perceived trainee competence in communication. Perceived trainee competence in managing institutional resources was rated poorly. Program directors reporting significant barriers to PEOLC education also judged trainees less competent in PEOLC. Time constraint was the greatest barrier. CONCLUSION: This survey of PEOLC education in US pulmonary/critical care fellowships identified associations between certain program features and perceived trainee skill in PEOLC. These results generate hypotheses for further study.

Influenza immunization among resident physicians in an urban teaching hospital.

We surveyed resident physicians (RPs) at an academic medical center to determine the rate of influenza vaccination and reasons for nonvaccination. The overall self-reported immunization rate of RPs in 2013-2014 was 76.7%, and the most common reason for not being vaccinated was lack of time to get immunized (38.6%). Making flu vaccination available in training hospitals and at convenient locations and times that take into account varying work schedules may increase compliance.

Complications in operationalizing lifelong fatigue as an exclusionary criterion.

The case definitions for chronic fatigue syndrome (CFS) and chronic fatigue syndrome/Myalgic Encephalomyelitis (ME) stipulate that the experience of lifelong fatigue is an exclusionary criterion (Carruthers et al., 2003 ; Fukuda et al., 1994 ). This article examines the lifelong fatigue construct and identifies potential validity and reliability issues in using lifelong fatigue as an exclusionary condition. Participants in the current study completed the DePaul Symptom Questionnaire (Jason et al., 2010 ), and responses were examined to determine if they had experienced lifelong fatigue. This article discusses the extensive process that was needed to confidently discern which participants had or did not have lifelong fatigue. Using the most rigorous standards, few individuals were classified as having lifelong fatigue. In addition, those with and without lifelong fatigue had few significant differences in symptoms and functional areas. This article concludes with a recommendation that lifelong fatigue should no longer be used as an exclusionary criterion for CFS or ME/CFS.

Association of patient-provider communication domains with lung cancer treatment.

BACKGROUND: Patient-physician communication is critical for helping patients understand and complete the complex steps needed to diagnose stage and treat lung cancer. We assessed which domains of patient-physician communication about lung cancer and its treatment are associated with receipt of disease-directed, stage-appropriate treatment. METHODS: Patients with recently diagnosed lung cancer were recruited from four medical centers in New York City from 2008 to 2011. Participants were surveyed about discussions with physicians regarding treatment, symptoms, and needs. Multiple regression analysis and structural equation modeling were used to assess which communication factors were associated with disease treatment. RESULTS: Of the 352 participants, 191 (54%) received disease-directed, stage-appropriate treatment. Unadjusted associations between communication items and treatment found that participants who felt that their physicians explained the risks and disadvantages of lung cancer treatment (p < 0.01), discussed their chances of cure (p = 0.02), discussed goals of treatment (p < 0.01), or who were warm and friendly (p = 0.04) were more likely to undergo treatment. Three communication domains were identified: treatment information, physician support, and patient symptoms/needs. After adjusting for known determinants of lung cancer treatment, increased treatment information was associated with higher probability of cancer-directed treatment (p = 0.003). Other communication domains (physician support or patient symptoms/needs) were not independent predictors of treatment (p > 0.05 for both comparisons). CONCLUSION: These data suggest that treatment information is particularly important for increasing the probability of cancer-directed therapy among lung cancer patients. Clinicians should ensure that they clearly discuss treatment goals and options with patients while maintaining empathy, supporting patient needs, and addressing symptoms.

Impact of critical care medicine training programs' palliative care education and bedside tools on ICU use at the end of life.

BACKGROUND: Intensive care unit (ICU) use at the end of life is rising. Little research has focused on associations among critical care fellows' training, institutional support, and bedside tools with ICU use at the end of life. OBJECTIVE: We evaluated whether hospital and critical care medicine program interventions were associated with ICU use in the last 6 months of life for patients with chronic illness. METHODS: Our observational, retrospective study explored associations between results from a survey of critical care program directors and hospital-level Medicare data on ICU use in the last 6 months of life. Program directors evaluated quality of palliative care education in their critical care fellowships and reported on the number of bedside tools and the presence or absence of an inpatient palliative care consultation service. RESULTS: For the 89 hospitals and 71 affiliated training programs analyzed, there were statistically significant relationships between 2 of the explanatory variables-the quality of palliative care education and the number of bedside tools-in ICU use. Each level of increased educational quality (1-5 Likert scale) was associated with a 0.57-day decrease in ICU days, whereas, for each additional, evidence-based bedside tool, there was a 0.31-day decrease. The presence of an inpatient palliative care program was not a significant predictor of ICU use. CONCLUSIONS: We found that the quality of palliative care training in critical care medicine programs and the use of bedside tools were independently associated with reduced ICU use at the end of life.

Fiber-optic bronchoscopy and volume-cycled mouthpiece ventilation for a patient with multiple sclerosis and ventilatory failure.

Fiber-optic bronchoscopy supported by continuous or bilevel positive airway pressure has helped patients with hypoxemic or hypercapnic respiratory failure avoid respiratory complications. The authors describe a case of a 57-yr-old man with multiple sclerosis with a vital capacity of 250 ml (5% of predicted normal) who was using continuous noninvasive intermittent positive pressure ventilatory support when he underwent bronchoscopy while receiving continuous noninvasive intermittent positive pressure ventilatory support via a 15-mm angled mouthpiece interface. He was switched from a nasal to a 15-mm angled mouthpiece interface for continuous noninvasive intermittent positive pressure ventilatory support for the procedure. Simple mouthpieces may be useful alternatives to other facial interfaces for ventilatory support during bronchoscopy because of patient comfort and operator convenience.

Cultural factors associated with racial disparities in lung cancer care.

RATIONALE: Minority patients with lung cancer are less likely to receive stage-appropriate treatment. Along with access to care and provider-related factors, cultural factors such as patients' lung cancer beliefs, fatalism, and medical mistrust may help explain this disparity. OBJECTIVES: To determine cultural factors associated with disparities in lung cancer treatment. METHODS: Patients with newly diagnosed lung cancer were recruited from four medical centers in New York City from 2008 to 2011. Using validated tools, we surveyed participants about their beliefs regarding lung cancer, fatalism, and medical mistrust. We compared rates of stage-appropriate treatment among blacks, Hispanics, and nonminority patients. Multiple regression analyses and structural equation modeling were used to assess whether cultural factors are associated with and/or mediate disparities in care. MEASUREMENTS AND MAIN RESULTS: Of the 352 patients with lung cancer in the study, 21% were black and 20% were Hispanic. Blacks were less likely to receive stage-appropriate treatment (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.27-0.93) compared with whites, even after adjusting for age, sex, marital status, insurance, income, comorbidities, and performance status. No differences in treatment rates were observed among Hispanics (OR, 1.05; 95% CI, 0.53-2.07). Structural equation modeling showed that cultural factors (negative surgical beliefs, fatalism, and medical mistrust) partially mediated the relationship between black race and lower rates of stage-appropriate treatment (total effect: -0.43, indirect effect: -0.13; 30% of total effect explained by cultural factors). CONCLUSIONS: Negative surgical beliefs, fatalism, and mistrust are more prevalent among minorities and appear to explain almost one-third of the observed disparities in lung cancer treatment among black patients. Interventions targeting cultural factors may help reduce undertreatment of minorities.

Chest radiograph findings and time to culture conversion in patients with multidrug-resistant tuberculosis and HIV in Tugela Ferry, South Africa.

BACKGROUND: The majority of patients with multidrug-resistant tuberculosis (MDR-TB) in South Africa are co-infected with HIV, but the radiographic features of MDR-TB and their relationship with time to sputum culture conversion in the antiretroviral therapy era have not been described. METHODS: We reviewed baseline chest radiographs for 56 patients with MDR-TB from a rural area of South Africa. We analyzed the association of cavities, consolidation, pleural effusion and hilar lymphadenopathy with time to sputum culture conversion, adjusting for HIV status, baseline sputum smear and CD4 count. RESULTS: Of the 56 subjects, 49 (88%) were HIV-positive, with a median CD4 count of 136 cells/mm(3) (IQR 65-249). Thirty-two (57%) patients were sputum smear positive. Twenty-two (39%) patients had a cavity and 37 (66%) patients had consolidations. Cavitary disease and consolidations were each associated with longer time to culture conversion on bivariate analysis but not after adjusting for sputum smear status (aORs 1.79 [0.94-3.42] and 1.09 [0.67-1.78], respectively). Positive baseline sputum smear remained independently associated with longer time to conversion (aOR 3.45 [1.39-8.59]). We found no association between pleural effusion or hilar lymphadenopathy and time to conversion. Seventy-nine percent of patients were cured at the end of treatment. CONCLUSIONS: Despite high rates of HIV co-infection and advanced immunodeficiency, the majority of patients had severe pathology on baseline chest radiograph. Nevertheless, culture conversion rates were high and treatment outcomes were favorable. Cavitation and consolidation do not appear to have an independent association with time to culture conversion beyond that of baseline sputum smear status.

Evaluating beliefs associated with late-stage lung cancer presentation in minorities.

INTRODUCTION: Minority patients in the United States present with later stages of lung cancer and have poorer outcomes. Cultural factors, such as beliefs regarding lung cancer and discrimination experiences, may underlie this disparity. METHODS: Patients with a new diagnosis of lung cancer were recruited from four medical centers in New York City. A survey, using validated items, was conducted on the minority (black and Hispanic) and nonminority patients about their beliefs regarding lung cancer, fatalism, and medical mistrust. Univariate and logistic regression analyses were used to compare beliefs among minorities and nonminorities and to assess the association of these factors with late-stage (III and IV) presentation. RESULTS: Of the 357 lung cancer patients, 40% were black or Hispanic. Minorities were more likely to be diagnosed with advanced-stage lung cancer (53% versus 38%, p = 0.01). Although beliefs about lung cancer etiology, symptoms, and treatment were similar between groups (p > 0.05), fatalistic views and medical mistrust were more common among minorities and among late-stage lung cancer patients (p < 0.05, for all comparisons). Adjusting for age, sex, education, and insurance, minorities had increased odds of advanced-stage lung cancer (odds ratio: 1.79; 95% confidence interval, 1.04-3.08). After controlling for fatalism and medical mistrust, the association between minority status and advanced stage at diagnosis was attenuated and no longer statistically significant (odds ratio: 1.56; 95% confidence interval, 0.84-2.87). CONCLUSIONS: Fatalism and medical mistrust are more common among minorities and may partially explain the disparities in cancer stage at diagnosis. Addressing these factors may contribute to reducing disparities in lung cancer diagnosis and outcomes.

Racial and ethnic differences in beliefs about lung cancer care.

BACKGROUND: Disparities in lung cancer treatment and palliative care are well documented. However,the mechanisms underlying these disparities are not fully understood. In this study, we evaluated racial and ethnic differences in beliefs and attitudes about lung cancer treatment and palliative care among patients receiving a new diagnosis of lung cancer. METHODS: Patients were recruited from four medical centers in New York City and surveyed about their beliefs regarding lung cancer care, including disease-directed treatments, palliative and end-of-life care, and fatalistic and spiritual beliefs. We used univariate and multiple regression analyses to compare the distribution of beliefs among minority (black and Hispanic) and nonminority patients. RESULTS: Of the 335 patients, 21% were black, 20% were Hispanic, and 59% were nonminority. Beliefs about chemotherapy and radiotherapy were similar across the three groups ( P > .05),whereas black patients were more likely to believe that surgery might cause lung cancer to spread( P =.008). Fatalistic beliefs potentially affecting cancer treatment were more common among both minority groups ( P ≤ .02). No signifi cant differences were found in attitudes toward clinician communication about cancer prognosis ( P > .05). However, both blacks and Hispanics were more likely to have misconceptions about advance directives and hospice care ( P ≤ .02). CONCLUSIONS: Similarities and differences in beliefs about disease-directed treatment were observed between minority and nonminority patients with lung cancer. Minority patients hold more fatalistic views about the disease and misperceptions about advance care planning and hospice care. Further research is needed to assess the impact of these beliefs on decisions about lung cancer care and patient outcomes.

Management of patients with end-stage chronic obstructive pulmonary disease.

Patients with end-stage chronic obstructive pulmonary disease (COPD) have poor quality of life, with limited activity, breathlessness, dependence on others, and recurrent needs for medical evaluation and treatment. Such patients demonstrate significant and progressive impairments in physical, mental, and social functioning. Because the rate of decline is variable, however, it is difficult to predict prognosis of survival. Currently available treatments only partially relieve symptoms, and patients become increasingly more disabled. This article reviews quality of life issues, proposed prognostic indicators, and pharmacologic and nonpharmacologic treatments in advanced COPD. Palliative measures to address breathlessness and unmet needs among patients with end-stage COPD are discussed.

Patients rate physician communication about lung cancer.

BACKGROUND: High-quality lung cancer care includes physician-patient communication about the disease and treatment, patient needs/preferences, and care goals. In this study, the authors evaluated communication with patients at all stages across multiple topics. METHODS: A standardized questionnaire asked patients with lung cancer to rate (on 5-point, verbal descriptor scale) the extent of communication with physicians on symptoms, spiritual concerns, practical needs, proxy appointment, living will preparation, prognosis, care goals, potential complications of therapy, life support preferences, and hospice. Communication was defined as inadequate if the patient reported discussing ≥5 of 11 questionnaire topics "not at all" or "a little bit." Multivariate logistic regression was used to evaluate the factors associated with inadequate communication. RESULTS: In total, 276 of 348 (79%) eligible patients were enrolled (mean age [±standard deviation], 65 ± 10 years; 55% white, 21% black, and 19% Hispanic; all disease stages). For most topics, the majority of respondents reported that physicians communicated "not at all" or "a little bit." Low ratings were frequent for discussion of emotional symptoms (56%; 95% confidence interval [CI], 49%-62%), practical needs (71%; 95% CI, 65%-76%), spiritual concerns (80%; 95% CI, 75%-85%), proxy appointment (63%; 95% CI, 57%-69%), living will preparation (90%; 95% CI, 85%-93%), life support preferences (80%; 95% CI, 75%-84%), and hospice (88%; 95% CI, 86%-94%). Communication was inadequate for patients of different ages, stages, and races, although Hispanics were less likely than non-Hispanic whites and blacks to report inadequate communication (odds ratio, 0.31; 95% CI, 0.15-0.65). CONCLUSIONS: Across all stages, patients with lung cancer reported low rates of physician-patient communication on key topics, which may increase patient distress, impair decision-making, and compromise clinical outcomes and use patterns.

Thoracic splenosis: A diagnosis by history and imaging.

Thoracic splenosis (TS) is autoimplantation of ectopic splenic tissue in the thoracic cavity that occurs following splenic injury. The majority of cases of TS are asymptomatic and are diagnosed in the course of an evaluation of incidentally discovered pulmonary lesions. Some cases may be difficult to diagnose, especially if features suggesting TS are not recognized. This may lead to an extensive work-up and unnecessary invasive diagnostic procedures including thoracotomy. This case report describes a 40-year-old man, who was diagnosed incidentally with TS, several years after the initial injury. Multiple, asymptomatic, left-sided pleural based lesions associated with a history of thoracoabdominal injury and splenectomy are the key points that should alert suspicion of TS, which can then simply be confirmed by a Tc-99m sulphur colloid radionuclide scan. Most patients are treated conservatively unless they are symptomatic. Physicians must recognize the key features suggesting a diagnosis of TS, order appropriate imaging studies and avoid unnecessary invasive diagnostic procedures.