Lower Airway Dysbiosis Affects Lung Cancer Progression.

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB-IV tumor-node-metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB-IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers. SIGNIFICANCE: Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis.See related commentary by Zitvogel and Kroemer, p. 224.This article is highlighted in the In This Issue feature, p. 211.

Development and Evaluation of a Cognitive Aid Booklet for Use in Rapid Response Scenarios.

INTRODUCTION: Rapid response teams (RRTs) have become ubiquitous among hospitals in North America, despite lack of robust evidence supporting their effectiveness. Many RRTs do not yet use cognitive aids during these high-stakes, low-frequency scenarios, and there are no standardized cognitive aids that are widely available for RRTs on medicine patients. We sought to design an emergency manual to improve resident performance in common RRT calls. METHODS: Residents from the New York University School of Medicine Internal Medicine Residency Program were asked to volunteer for the study. The intervention group was provided with a 2-minute scripted informational session on cognitive aids as well as access to a cognitive aid booklet, which they were allowed to use during the simulation. RESULTS: Resident performance was recorded and scored by a physician who was blinded to the purpose of the study using a predefined scoring card. Residents in the intervention group performed significantly better in the simulated RRT, by overall score (mean score = 7.33/10 and 6.26/10, respectively, P = 0.02), and by performance on the two critical interventions, giving the correct dose of naloxone (89% and 39%, respectively, P < 0.001) and checking the patient's blood glucose level (93% and 52%, respectively, P = 0.001). CONCLUSIONS: In a simulated scenario of opiate overdose, internal medicine residents who used a cognitive aid performed better on critical tasks than those residents who did not have a cognitive aid. The use of an appropriately designed cognitive aid with sufficient education could improve performance in critical scenarios.

The Utility of High-Fidelity Simulation for Training Critical Care Fellows in the Management of Extracorporeal Membrane Oxygenation Emergencies: A Randomized Controlled Trial.

OBJECTIVE: Although extracorporeal membrane oxygenation volume has increased, proficiency in the technology requires extensive training. We compared traditional water-drill-based extracorporeal membrane oxygenation training with simulation-based extracorporeal membrane oxygenation training with the hypothesis that simulation-based training is superior. DESIGN: Randomized controlled trial. SETTING: Academic medical center. SUBJECTS: Pulmonary/critical care fellows. INTERVENTIONS: Participants had a preintervention simulated extracorporeal membrane oxygenation emergency (Sim1-recirculation) then randomized into simulation and traditional groups. Each group participated in three teaching scenarios, via high-fidelity simulation or via water-drills. After 6 weeks and after 1 year, participants returned for two simulated extracorporeal membrane oxygenation emergencies (Sim2-pump failure and Sim3-access insufficiency). Sim2 was a case encountered during teaching, whereas Sim3 was novel. A critical action, necessary for resolution of each scenario, was preidentified for timing. MEASUREMENTS AND MAIN RESULTS: Primary outcome was time required to perform critical actions. Twenty-one fellows participated in the study (simulation, 10; traditional, 11). Groups had similar scenario scores (p = 0.4) and times to critical action (p = 0.8) on Sim1. At 6 weeks, both groups had similar scenario scores on Sim2 (p = 0.5), but the simulation group scored higher on Sim3 (p = 0.03). Times to critical actions were shorter in the simulation group during Sim2 (127 vs 174 s, p = 0.004) and Sim3 (159 vs 300 s; p = 0.04). These findings persisted at 1 year. CONCLUSIONS: In novice critical care fellows, simulation-based extracorporeal membrane oxygenation training is superior to traditional training. Benefits transfer to novel scenarios and are maintained over the long term. Further studies evaluating the utility of simulation in other learner groups and for maintenance of proficiency are required.

Goal-Directed Transthoracic Echocardiography During Advanced Cardiac Life Support: A Pilot Study Using Simulation to Assess Ability.

INTRODUCTION: Goal-directed echocardiography (GDE) is used to answer specific clinical questions that provide invaluable information to physicians managing a hemodynamically unstable patient. We studied perception and ability of house staff previously trained in GDE to accurately diagnose common causes of cardiac arrest during simulated advanced cardiac life support (ACLS); we compared their results with those of expert echocardiographers. METHODS: Eleven pulmonary and critical care medicine fellows, 7 emergency medicine residents, and 5 cardiologists board certified in echocardiography were enrolled. Baseline ability to acquire 4 transthoracic echocardiography views was assessed, and participants were exposed to 6 simulated cardiac arrests and were asked to perform a GDE during ACLS. House staff performance was compared with the performance of 5 expert echocardiographers. RESULTS: Average baseline and scenario views by house staff were of good or excellent quality 89% and 83% of the time, respectively. Expert average baseline and scenario views were always of good or excellent quality. House staff and experts made the correct diagnosis in 68% and 77% of cases, respectively. On average, participants required 1.5 pulse checks to make the correct diagnosis. Of house staff, 94% perceived this study as an accurate assessment of ability. CONCLUSIONS: In an ACLS-compliant manner, house staff are capable of diagnosing management-altering pathologies the majority of the time, and they reach similar diagnostic conclusions in the same amount of time as expert echocardiographers in a simulated cardiac arrest scenario.

The medical emergency team call: a sentinel event that triggers goals of care discussion.

OBJECTIVE: Several studies have questioned the effectiveness of rapid-response systems when measured by outcomes such as decreased overall hospital mortality or cardiac arrest rates. We studied an alternative outcome of rapid-response system implementation, namely, its effect on goals of care and designation of do not resuscitate. DESIGN: Retrospective chart review. SETTING: Veterans Administration Hospital in New York City. SUBJECTS: All patients requiring a medical emergency team call. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: : Monthly hospital census and discharge data, death occurrences, and do-not-resuscitate order placements were collected over an 8-year pre-medical emergency team and 5-year post-medical emergency team period. All medical emergency team calls and subsequent transfers to a critical care unit were reviewed and correlated to the placement and timing of do-not-resuscitate orders. Interrupted time-series analysis was used to evaluate the impact of the medical emergency team implementation on the change in trend of do-not-resuscitate orders and the hospital mortality. A total of 390 medical emergency team calls were associated with 109 do-not-resuscitate orders (28%). Of the 209 medical emergency team calls (54%) resulting in transfer to a critical care unit, 66 were associated with do-not-resuscitate orders, 73% of which were obtained after transfer. The odds of becoming do not resuscitate for a patient going to the ICU after the medical emergency team call were 2.9 (95% CI, 1.6-5.5; p = 0.001) times greater than for patients staying on the floors after the medical emergency team call. The medical emergency team implementation significantly changed the trend of do-not-resuscitate orders (p < 0.001) but had no impact on hospital mortality rate (p = 0.638). CONCLUSION: Implementation of a rapid-response system was associated with an increase in do-not-resuscitate order placement. As a sentinel event, medical emergency team activation and transfer to a critical care unit foster consideration of goals of care and frequently results in a transition to a palliative care strategy.

S-adenosylmethionine as a biomarker for the early detection of lung cancer.

BACKGROUND: S-Adenosylmethionine (AdoMet) is a major methyl donor for transmethylation reactions and propylamine donor for the biosynthesis of polyamines in biological systems, and therefore may play a role in lung cancer development. We hypothesized that AdoMet levels were elevated in patients with lung cancer and may prove useful as a biomarker for early lung cancer. METHODS: High-performance liquid chromatography was used to analyze plasma AdoMet levels in triplicate samples from 68 patients. This included 13 patients with lung cancer, 33 smokers with benign lung disease, and 22 healthy nonsmokers. The three groups of subjects were compared with respect to the distribution of demographic and disease characteristics and AdoMet levels. Distributions were examined using summary statistics and box plots, and nonparametric analysis of variance procedures. RESULTS: Serum AdoMet levels were elevated in patients with lung cancer as compared to smokers with benign lung disorders and healthy nonsmokers. There were no significant correlations between AdoMet levels and tumor cell types, nodule size, or other demographic variables. CONCLUSIONS: Our data demonstrate that plasma levels of AdoMet are significantly elevated in patients with lung cancer. Plasma AdoMet levels may prove to be a useful tool for the diagnosis of early lung cancer, in combination with chest CT. Registered at: clinicaltrials.gov (NCT00301119).

Malignant mesothelioma masquerading as a multinodular bronchioloalveolar cell adenocarcinoma with widespread pulmonary nodules.

A 72-year-old man had a unilateral pleural effusion and multiple bilateral pulmonary nodules. Thoracoscopic biopsy revealed multiple discrete nodules in the pleura and lung. The latter consisted of tall columnar malignant cells arranged on alveolar surfaces in a lepidic growth pattern. Mucin filled the alveolar lumina, both in the nodules and surrounding lung. It stained with Alcian blue but not with periodic acid Schiff, suggesting that it was a glycosaminoglycan, which was confirmed as hyaluronic acid by complete digestion with hyaluronidase. Tumor cells were calretinin, Wilms tumor-1, and high-molecular-weight cytokeratin 5/6 positive, and were negative for thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20. Ultrastructurally, they had very long and abundant, slender microvilli typical of a malignant mesothelioma. This is the first example of a mesothelioma masquerading as a bronchioloalveolar carcinoma.