What Are E-Cigarettes?

This JAMA Patient Page describes e-cigarettes and the potential health effects of vaping.

What Is Cirrhosis?

This JAMA Patient Page describes liver cirrhosis, its signs and symptoms, potential complications, and treatment options.

A Quality Improvement Initiative to Increase Completion and Documentation of Advanced Directives in the ICU at a U.S. Community Teaching Hospital.

Advance directives can help guide care in the ICU. As a healthcare quality improvement initiative, we sought to increase the percentage of patients with a healthcare power of attorney and/or practitioner orders for life-sustaining treatment in our ICU and to increase medical resident experience with advance directives through routine screening and documentation of advance directives in the ICU. DESIGN: Prospective analysis. SETTING: Urban U.S. community teaching hospital. PATIENTS: All patients admitted to the ICU from September 2018 to February 2019. INTERVENTIONS: Internal medicine residents in the ICU received a lecture about advance directives and instructions to screen their patients for advance directives. For willing and decisional patients, residents facilitated the creation of a healthcare power of attorney and/or practitioner orders for life-sustaining treatment. Residents were anonymously surveyed at the beginning and end of the ICU rotation about their experience and level of comfort with healthcare power of attorney and practitioner orders for life-sustaining treatment completion. MEASUREMENTS AND MAIN RESULTS: Three-hundred seventy-five patients were admitted to the ICU during the study period. Healthcare power of attorney documents were generated by 34% of all ICU patients without a prior healthcare power of attorney, increased from a baseline rate of 10% (p < 0.001). The number of practitioner orders for life-sustaining treatment documents for patients with code status of "no cardiopulmonary resuscitation" did not increase significantly. The percentage of residents who facilitated completion of a healthcare power of attorney document increased significantly from 56% to 100% (p < 0.001), whereas their practitioner orders for life-sustaining treatment experience did not change significantly by the end of their ICU rotation. On a Likert scale of 0-10, mean resident comfort increased significantly both with healthcare power of attorney documentation, rising from 6.14 to 8.84 (p = 0.005) and with practitioner orders for life-sustaining treatment form completion, increasing from 6.00 to 7.84 (p = 0.008). CONCLUSIONS: Training ICU medical residents to routinely screen for and facilitate completion of advance directives significantly increased the percentage of ICU patients with a healthcare power of attorney and significantly improved medical resident comfort with healthcare power of attorney and practitioner orders for life-sustaining treatment form completion.

How decisions are made to admit patients to medical intensive care units (MICUs): a survey of MICU directors at academic medical centers across the United States.

OBJECTIVE: To determine how medical intensive care unit (MICU) admission decisions are made at U.S. academic MICUs and to learn how these practices compare with the recommendations of the Society of Critical Care Medicine and the American Thoracic Society. DESIGN: A 22-question Web-based survey. SETTING: University health sciences centers. SUBJECTS: MICU directors at academic U.S. medical centers offering fellowship programs in pulmonary/critical care or critical care medicine. INTERVENTIONS: The survey was sent by E-mail to 146 academic MICU directors. MEASUREMENTS AND MAIN RESULTS: Survey response rate was 83% (121/146). MICU attendings were the primary decision-maker for patient admission to the intensive care unit (ICU) in 40% of the MICUs during daytime hours, in 36% on weekends, and in 27% overnight. Critical care fellows and resident house staff were often responsible for making MICU admission decisions, particularly overnight and on weekends. Of the MICUs surveyed, 88% had written admission guidelines, although only 25% used them on a regular basis. Written restriction guidelines were present in only 21% of these ICUs, although 53% of MICU directors believed that MICUs should have standardized criteria for restricting admission to the ICU. Finally, 29% of MICUs surveyed did not authorize MICU attendings to deny ICU admission on a case-by-case basis for futile or inadvisable care, thereby maintaining an open door policy for ICU admission. CONCLUSIONS: Significant practice variability exists across U.S. academic MICUs regarding how decisions are made to admit patients to the ICU. The majority of academic MICUs in the United States do not strictly employ ICU admission and restriction guidelines, as recommended by the Society of Critical Care Medicine and the American Thoracic Society.

Expression of syndecan-1 and expression of epidermal growth factor receptor are associated with survival in patients with nonsmall cell lung carcinoma.

BACKGROUND: Recently, the authors identified molecular signatures and pathways associated with nonsmall cell lung carcinoma histology and lung development. They hypothesized that genetic classifiers of histology would provide insight into lung tumorigenesis and would be associated with clinical outcome when evaluated in a broader set of specimens. METHODS: Associations between patient survival and immunostaining for 11 representative histologic classifiers (epidermal growth factor receptor [EGFR], CDK4, syndecan-1, singed-like, TTF-1, keratin 5, HDAC2, docking protein 1, integrin alpha3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens. RESULTS: Sixty-three tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixty-three percent of tumors were clinical Stage I lesions, and 37% were Stage II-III lesions. In a multivariate analysis that controlled for age, gender, and race, syndecan-1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18-0.87]; P < 0.05). Multivariate analysis also indicated that EGFR expression was associated with a significant reduced risk of death. CONCLUSIONS: The authors demonstrated that expression of either of the nonsmall cell lung carcinoma subtype classifiers syndecan-1 and EGFR was associated with a 30% reduction in the risk of death, with this reduction being independent of histology and other confounders. The results of the current study suggest that loss of expression of these histologic classifiers is associated with biologic aggressiveness in lung tumors and with poor outcome for patients with such tumors. If their significance can be validated prospectively, these biomarkers may be used to guide therapeutic planning for patients with nonsmall cell lung carcinoma.

Extensive stage small cell lung cancer presenting as an acute perforated appendix: case report and review of the literature.

Malignancies of the appendix are uncommon; a small subset of these lesions are actually metastatic cancers. In some rare cases, these lesions can cause obstruction, appendicitis, and perforation. M.K. is a 54-year-old man who presented to our institution with a 1-day history of right lower quadrant pain and a past medical history significant only for a 75-pack-year smoking history. CT scan revealed a perforated appendix, and the patient was taken to the operating room where a gangrenous appendix was removed uneventfully. Two days post-procedure, the patient was found to have acute mental status changes, requiring intubation and transfer to the surgical intensive care unit. As part of a workup, a CT scan of the head revealed multiple lesions compatible with metastatic disease. At that point, the pathology from the appendix came back as small cell lung cancer. Chest CT revealed hilar adenopathy and a hilar mass. The patient received emergent whole-brain irradiation therapy with improvement in his mental status, allowing him to be extubated and discharged from the hospital within 10 days of admission. Surgeons should remember that an underlying oncologic process may be the etiology of appendicitis in a small but important subgroup of patients.

Molecular signatures in biopsy specimens of lung cancer.

Gene expression profiles of resected tumors may predict treatment response and outcome. We hypothesized that profiles derived from lung tumor biopsies would discriminate tumor-specific gene signatures and provide predictive information about outcome. Lung carcinoma specimens were obtained from 23 patients undergoing computed tomography-guided transthoracic biopsy or endobronchial brushing for undiagnosed nodules. Excess tissue was processed for gene profiling. We built class prediction models for lung cancer histology and for cancer outcome. The histology model used an F test to identify 99 genes that were differentially expressed among lung cancer subtypes. The histology validation set class prediction accuracy rate was 86%. The outcome model used the maximum difference subset algorithm to identify 42 genes associated with high risk for cancer death. The outcome training set class prediction accuracy rate was 87%. In conclusion, gene expression profiles of biopsy specimens of lung cancers identify unique tumoral signatures that provide information about tissue morphology and prognosis. The use of specimens acquired from lung biopsy procedures to identify biomarkers of clinical outcome may have application in the management of patients with lung cancer. The procedures are safe and feasible; the efficacy and utility of this strategy will ultimately be determined by prospective clinical trials.

Non-small-cell lung cancer molecular signatures recapitulate lung developmental pathways.

Current paradigms hold that lung carcinomas arise from pleuripotent stem cells capable of differentiation into one or several histological types. These paradigms suggest lung tumor cell ontogeny is determined by consequences of gene expression that recapitulate events important in embryonic lung development. Using oligonucleotide microarrays, we acquired gene profiles from 32 microdissected non-small-cell lung tumors. We determined the 100 top-ranked marker genes for adenocarcinoma, squamous cell, large cell, and carcinoid using nearest neighbor analysis. Results were validated by immunostaining for 11 selected proteins using a tissue microarray representing 80 tumors. Gene expression data of lung development were accessed from a publicly available dataset generated with the murine Mu11k genome microarray. Self-organized mapping identified two temporally distinct clusters of murine orthologues. Supervised clustering of lung development data showed large-cell carcinoma gene orthologues were in a cluster expressed in pseudoglandular and canalicular stages whereas adenocarcinoma homologues were predominantly in a cluster expressed later in the terminal sac and alveolar stages of murine lung development. Representative large-cell genes (E2F3, MYBL2, HDAC2, CDK4, PCNA) are expressed in the nucleus and are associated with cell cycle and proliferation. In contrast, adenocarcinoma genes are associated with lung-specific transcription pathways (SFTPB, TTF-1), cell adhesion, and signal transduction. In sum, non-small-cell lung tumors histology gene profiles suggest mechanisms relevant to ontogeny and clinical course. Adenocarcinoma genes are associated with differentiation and glandular formation whereas large-cell genes are associated with proliferation and differentiation arrest. The identification of developmentally regulated pathways active in tumorigenesis provides insights into lung carcinogenesis and suggests early steps may differ according to the eventual tumor morphology.