Early changes in the circulating T cells are associated with clinical outcomes after PD-L1 blockade by durvalumab in advanced NSCLC patients.

Immune checkpoint inhibitors (ICI) are designed to activate exhausted tumor-reactive T cells thereby leading to tumor regression. Durvalumab, an ICI that binds to the programmed death ligand-1 (PD-L1) molecule, is approved as a consolidation therapy for treatment of patients with stage III, unresectable, non-small cell lung cancer (NSCLC). Immunophenotypic analysis of circulating immune cells revealed increases in circulating proliferating CD4 + and CD8 + T cells earlier after durvalumab treatment. To examine durvalumab's mechanism of action and identify potential predictive biomarkers, we assessed the circulating T cells phenotypes and TCR genes of 71 NSCLC patients receiving durvalumab enrolled in a Phase I trial (NCT01693562, September 14, 2012). Next-generation sequencing of TCR repertoire was performed on these NSCLC patients' peripheral blood samples at baseline and day 15. Though patients' TCR repertoire diversity showed mixed responses to the treatment, patients exhibiting increased diversity on day 15 attained significantly longer overall survival (OS) (median OS was not reached vs 17.2 months for those with decreased diversity, p = 0.015). We applied network analysis to assess convergent T cell clonotypes indicative of an antigen-driven immune response. Patients with larger TCR clusters had improved OS (median OS was not reached vs 13.1 months for patients with smaller TCR clusters, p = 0.013). Early TCR repertoire diversification after durvalumab therapy for NSCLC may be predictive of increased survival and provides a mechanistic basis for durvalumab pharmacodynamic activity.

The Diagnostic Yield of Noninvasive Microbiologic Sputum Sampling in a Cohort of Patients with Clinically Diagnosed Hospital-Acquired Pneumonia.

The clinical predictors of positive sputum culture have not been previously reported in hospital-acquired pneumonia (HAP), and data on yield of sputum culture in this setting are scant. Current Infectious Disease Society of America guidelines for HAP recommend noninvasive sputum sampling, though the data for this practice are limited. We assessed the yield of sputum culture in HAP cases at an academic medical center from January 2007 to July 2013. HAP cases were identifi ed by International Classifi cation of Diseases, Ninth Revision-Clinical Modifi cation codes for bacterial pneumonia and all cases were validated by chart review. Our cohort had 1172 hospitalizations with a HAP diagnosis. At least 1 sputum specimen was collected noninvasively and sent for bacterial culture after hospital day 2 and within 7 days of HAP diagnosis in 344 of these hospitalizations (29.4%), with a total of 478 sputum specimens, yielding 63 (13.2%) positive, 109 (22.8%) negative, and 306 (64.0%) contaminated cultures (>10 epithelial cells per high power fi eld). Signifi cant predictors of a positive sputum culture were chronic lung disease (relative risk [RR] = 2.0; 95% confi dence interval [CI], 1.2-3.4) and steroid use (RR = 1.8; 95% CI, 1.1-3.2). The most commonly identifi ed organisms were Gram-negative rods not further speciated (25.9%), Staphylococcus aureus (21.0%), and Pseudomonas aeruginosa (14.8%). Because of the ease of obtaining a sputum sample combined with the prevalence of commonly drug-resistant organisms, we suggest that sputum culture in HAP is a potentially useful noninvasive diagnostic technique.

Antipsychotics and the Risk of Aspiration Pneumonia in Individuals Hospitalized for Nonpsychiatric Conditions: A Cohort Study.

BACKGROUND/OBJECTIVES: Off-label use of antipsychotics is common in hospitals, most often for delirium management. Antipsychotics have been associated with aspiration pneumonia in community and nursing home settings, but the association in hospitalized individuals is unexplored. We aimed to investigate the association between antipsychotic exposure and aspiration pneumonia during hospitalization. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PARTICIPANTS: All adult hospitalizations between January 2007 and July 2013. We excluded outside hospital transfers, hospitalizations shorter than 48 hours, and psychiatric hospitalizations. MEASUREMENTS: Antipsychotic use defined as any pharmacy charge for an antipsychotic medication. Aspiration pneumonia was defined according to a discharge diagnosis code for aspiration pneumonia not present on admission and validated using chart review. A generalized estimating equation was used to control for 43 potential confounders. RESULTS: Our cohort included 146,552 hospitalizations (median age 56; 39% male). Antipsychotics were used in 10,377 (7.1%) hospitalizations (80% atypical, 35% typical, 15% both). Aspiration pneumonia occurred in 557 (0.4%) hospitalizations. The incidence of aspiration pneumonia was 0.3% in unexposed individuals and 1.2% in those with antipsychotic exposure (odds ratio (OR) = 3.9, 95% confidence interval (CI) = 3.2-4.8). After adjustment, antipsychotic exposure was significantly associated with aspiration pneumonia (adjusted OR = (aOR) = 1.5, 95% CI = 1.2-1.9). Similar results were demonstrated in a propensity-matched analysis and in an analysis restricted to those with delirium or dementia. The magnitude of the association was similar for typical (aOR = 1.4, 95% CI = 0.94-2.2) and atypical (aOR = 1.5, 95% CI = 1.1-2.0) antipsychotics. CONCLUSION: Antipsychotics were associated with greater odds of aspiration pneumonia after extensive adjustment for participant characteristics. This risk should be considered when prescribing antipsychotics in the hospital.

Cesium-associated hypokalemia successfully treated with amiloride.

Self-treatment of cancer with cesium chloride, despite proven lack of efficacy, continues to produce serious adverse effects. Among these is hypokalemia predisposing to life-threatening arrhythmia. The mechanism of cesium-associated hypokalemia (CAH) has not been described. We report urinary potassium wasting responsive to amiloride therapy in a cancer patient with CAH, and discuss possible mechanisms.