Search

BACKGROUND Acute variceal bleeding is a major complication of portal hypertension and is a leading cause of death in patients with cirrhosis. There is limited data on the outcomes of patients with esophageal variceal bleeding in teaching versus nonteaching hospitals. Because esophageal variceal bleeding requires complex management, it may be hypothesized that teaching hospitals have lower mortality. AIM To assess the differences in mortality, hospital length of stay (LOS) and cost of admission for patients admitted for variceal bleed in teaching versus nonteaching hospitals across the US. METHODS The National Inpatient Sample is the largest all-payer inpatient database consisting of approximately 20% of all inpatient admissions to nonfederal hospitals in the United States. We collected data from the years 2008 to 2014. Cases of variceal bleeding were identified using the International Classification of Diseases, Ninth Edition, Clinical Modification codes. Differences in mortality, LOS and cost were evaluated for patients with esophageal variceal bleed between teaching and nonteaching hospitals and adjusted for patient characteristics and comorbidities. RESULTS Between 2008 and 2014, there were 58362 cases of esophageal variceal bleeding identified. Compared with teaching hospitals, mortality was lower in non-teaching hospitals (8.0% vs 5.3%, P < 0.001). Median LOS was shorter in nonteaching hospitals as compared to teaching hospitals (4 d vs 5 d, P < 0.001). A higher proportion of non-white patients were managed in teaching hospitals. As far as procedures in nonteaching vs teaching hospitals, portosystemic shunt insertion (3.1% vs 6.9%, P < 0.001) and balloon tamponade (0.6% vs 1.2%) were done more often in teaching hospitals while blood transfusions (64.2% vs 59.9%, P = 0.001) were given more in nonteaching hospitals. Using binary logistic regression models and adjusting for baseline patient demographics and comorbid conditions the mortality, LOS and cost in teaching hospitals remained higher. CONCLUSION In patients admitted for esophageal variceal bleeding, mortality, length of stay and cost were higher in teaching hospitals versus nonteaching hospitals when controlling for other confounding factors.

Summary The lack of persistence of infused T cells is a principal limitation of adoptive immunotherapy in man. Interleukin (IL)-15 can sustain memory T cell expansion when presented in complex with IL-15Rα (15Rα/15). We developed a novel in-vitro system for generation of stable 15Rα/15 complexes. Immunologically quantifiable amounts of IL-15 were obtained when both IL-15Rα and IL-15 genes were co-transduced in NIH 3T3 fibroblast-based artificial antigen-presenting cells expressing human leucocyte antigen (HLA) A:0201, β2 microglobulin, CD80, CD58 and CD54 [A2-artificial antigen presenting cell (AAPC)] and a murine pro-B cell line (Baf-3) (A2-AAPC15Rα/15and Baf-315Rα/15). Transduction of cells with IL-15 alone resulted in only transient expression of IL-15, with minimal amounts of immunologically detectable IL-15. In comparison, cells transduced with IL-15Rα alone (A2-AAPCRα) demonstrated stable expression of IL-15Rα; however, when loaded with soluble IL-15 (sIL-15), these cells sequestered 15Rα/15 intracellularly and also demonstrated minimal amounts of IL-15. Human T cells stimulated in vitro against a viral antigen (CMVpp65) in the presence of 15Rα/15 generated superior yields of high-avidity CMVpp65 epitope-specific T cells [cytomegalovirus-cytotoxic T lymphocytes (CMV-CTLs)] responding to ≤ 10− 13 M peptide concentrations, and lysing targets cells at lower effector : target ratios (1 : 10 and 1 : 100), where sIL-15, sIL-2 or sIL-7 CMV-CTLs demonstrated minimal or no activity. Both soluble and surface presented 15Rα/15, but not sIL-15, sustained in-vitro expansion of CD62L+ and CCR7+ central memory phenotype CMV-CTLs (TCM). 15Rα/15 complexes represent a potent adjuvant for augmenting the efficacy of adoptive immunotherapy. Such cell-bound or soluble 15Rα/15 complexes could be developed for use in combination immunotherapy approaches.