Association between out-of-hospital emergency department transfer and poor hospital outcome in critically ill stroke patients.

INTRODUCTION: Transfer of critically ill patients from outside emergency department has the potential for delaying the admission to the intensive care unit. We sought to determine the effect of outside emergency department transfer on hospital outcomes in critically ill patients with stroke. METHODS: We designed a retrospective cohort analysis using a prospectively compiled and maintained registry (Cerner Project IMPACT). Patients with acute ischemic stroke and intracerebral hemorrhage admitted to our intensive care unit from our emergency department and transfers from outside emergency department within 24 hours of stroke between January 1, 2003, and December 31, 2008, were selected for the analysis. Data collected included demographics, admission physiologic variables, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II score, and total intensive care unit and hospital length of stay. Primary (poor) outcome was a composite of death or fully dependent status at hospital discharge, and secondary outcomes were intensive care unit and hospital length of stay. To assess for the impact of outside emergency department transfer on primary and secondary outcomes, demographic and admission clinical variables were used to construct logistic regression models using the outcome measure as a dependent variable. RESULTS: A total of 448 patients were selected for analysis. The mean age was 65 ± 14 years, of which 214 (48%) were male and 282 (65%) white, 152 (34%) were patients with acute ischemic stroke, and 296 (66%) were patients with intracerebral hemorrhage. The median hospital length of stay was 7 days (interquartile range, 4-11 days) and median intensive care unit length of stay was 2 days (interquartile range, 1-3 days). Overall hospital mortality was 30%, and outside emergency department transfer increased the odds of poor outcome by 2-fold (65% vs 34%; P = .05). Multivariate regression analysis showed that age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01-1.1), Acute Physiology and Chronic Health Evaluation II score >14 (OR, 1.9; 95% CI, 1.3-2.7), Glasgow Coma Scale <12 (OR, 2.0; 95% CI, 1.4-2.8), do-not-resuscitate status (OR, 3.5; 95% CI, 2.2-5.9), and outside emergency department transfers (OR, 1.4; 95% CI, 1.02-1.8) were independently associated with poor outcome. Outside emergency department transfer was not significantly associated with secondary outcomes. CONCLUSION: These data suggest that in critically ill patients with stroke, transfer from outside emergency department is independently associated with poor outcome at hospital discharge. Further research is needed as to identify the potential causes for this effect.

Escape from suppression: tumor-specific effector cells outcompete regulatory T cells following stem-cell transplantation.

Immune reconstitution of autologous hematopoietic stem-cell transplant recipients with the progeny of mature T cells in the graft leads to profound changes in the emerging functional T-cell repertoire. In the steady state, the host is frequently tolerant to tumor antigens, reflecting dominant suppression of naive and effector T cells by regulatory T cells (T(regs)). We examined the relative frequency and function of these 3 components within the tumor-specific T-cell compartment during immune reconstitution. Grafts from tumor-bearing donors exerted a significant antitumor effect in irradiated, syngeneic tumor-bearing recipients. This was associated with dramatic clonal expansion and interferon-gamma (IFNgamma) production by previously tolerant tumor-specific T cells. While donor-derived T(regs) expanded in recipients, they did not inhibit the antigen-driven expansion of effector T cells in the early posttransplantation period. Indeed, the repopulation of tumor-specific effector T cells significantly exceeded that of T(regs), the expansion of which was limited by IL-2 availability. Although the intrinsic suppressive capacity of T(regs) remained intact, their diminished frequency was insufficient to suppress effector cell function. These findings provide an explanation for the reversal of tolerance leading to tumor rejection in transplant recipients and likely contribute to the efficacy of adoptive T-cell therapies in lymphopenic hosts.