Within-hospital and 30-day outcomes in 107,994 patients undergoing invasive coronary angiography with different low-osmolar iodinated contrast media

Comparative clinical outcomes after exposure to alternate low osmolar contrast media (LOCM) during invasive coronary angiography (ICA) and/or percutaneous coronary intervention (PCI) have been incompletely examined. From a retrospective multicenter observational study, we identified 107,994 adults without previous hemodialysis undergoing ICA and/or PCI with iohexol, iopamidol, or ioversol. We created a propensity score for contrast media type using age, gender, coverage status, route of hospitalization, illness severity, physician specialty, co-morbidities, and procedure type. Propensity matching was performed in a 1:1 fashion for iohexol (n = 10,204) and iopamidol (n = 10,204) and in a 1:1 fashion for iohexol (n = 19,482) and ioversol (n = 19,482). Groups were examined for differences in in-hospital mortality or subsequent hemodialysis, length of stay, and 30-day readmission for contrast-induced nephropathy (CIN). Compared to patients exposed to iohexol, no differences were observed for patients exposed to iopamidol or ioversol for in-hospital hemodialysis (0.5% vs 0.4%, p = 0.45; 0.3% vs 0.5%, p = 0.05), in-hospital mortality (0.7% vs 0.6%, p = 0.60; 0.5% vs 0.6%, p = 0.42), or composite hemodialysis or mortality (1.1% vs 1.0%, p = 0.58; 0.8% vs 1.0%, p = 0.06); for hospital length of stay (2.9 ± 2.7 vs 2.9 ± 2.7 days, p = 0.05; 2.8 ± 2.6 vs 2.9 ± 3.1 days, p = 0.35); or for 30-day readmission for CIN (0.1% vs 0.1%, p = 0.82; 0.1% vs 0.1%, p = 0.52). In conclusion, for patients undergoing ICA and/or PCI exposed to alternate LOCM, in-hospital death, need for hemodialysis, or readmission for CIN are uncommon, with no apparent clinical advantage among LOCM agents.     

MDCT to guide transcatheter aortic valve replacement and mitral valve repair

Percutaneous management of valvular heart disease is becoming a reality, with multicenter trials supporting minimally invasive procedures for both aortic and mitral valve disease. Historically, the treatment of choice has been aortic valve replacement with conventional surgery for patients with severe aortic stenosis, as the prognosis of untreated patients is poor, particularly if the patient is symptomatic. Transcatheter aortic valve replacement is now available as a minimally invasive option to treat select high-risk patients with severe aortic stenosis. At present more than 30,000 procedures have been performed worldwide, mostly confined to patients at high surgical risk. The short- and medium-term outcomes have been promising.     

Melatonin enhances thapsigargin-induced apoptosis through reactive oxygen species-mediated upregulation of CCAAT-enhancer-binding protein homologous protein in human renal cancer cells

Melatonin (N-acetyl-5-methoxytryptamine) has differentiated the effects on apoptosis in normal and cancer cells. The mechanisms that account for the opposite effects on these cells are not adequately understood. In this study, we investigated the combined effect of melatonin and thapsigargin (TG) on apoptosis of renal cancer cells. Cotreatment with melatonin (1mm) and TG (50nm) induced approximately 10-fold expression levels of CCAAT-enhancer-binding proteins homologous protein (CHOP) compared with that of TG (50nm) alone. Downregulation of CHOP expression using small interfering RNAs markedly attenuated melatonin plus TG-mediated apoptosis. In addition, cotreatment with TG- and melatonin-induced CHOP upregulation likely relates to melatonin's antioxidant capacity because we proved that this CHOP upregulation is melatonin receptor independent. Our results collectively demonstrate that the upregulation of CHOP contributes to the enhancing effect of melatonin plus TG on apoptosis in cancer cells.     

Phenotypic and genetic characterization of adult T-cell acute lymphoblastic leukemia with del(9)(q34);SET-NUP214 rearrangement

SET-NUP214 rearrangement is a recently recognized recurrent chromosomal translocation mostly observed in T-ALL. In order to characterize this rare entity, we performed phenotypic and genetic characterization of SET-NUP214 rearrangement through an investigation of a series of 40 consecutive samples of adult T-ALL that was selected among 229 adult ALL cases during 4 years in a single institution. Four cases (10%) of SET-NUP214 translocation were identified in our study. In all cases, diagnosis of T-ALL was established according to the World Health Organization (WHO) classification, and clonal TCR rearrangements were found. The immunophenotypic markers were indicative of the precursor nature of T lymphoblasts, and they expressed one or both of the myeloid-associated antigens (CD13, CD33). Conventional cytogenetic analysis revealed complex chromosomal aberrations in all four SET-NUP214 rearranged cases and del(12)(p13)/ETV6 was frequently involved. Array-CGH demonstrated additional genomic imbalances in addition to deletion 9q34. The genomic breakpoint sequencing identified breakpoints at SET intron 7 and NUP214 intron 17, and random nucleotide addition was found in two cases at the site of rearrangement. Our independently derived data set from a single institution confirms previous findings of SET-NUP214 rearrangement, indicates the relatively high incidence of SET-NUP214 rearrangement in adult T-ALLs, and also demonstrates comprehensive clinical, phenotypic, and genetic characteristics of this entity. Also, our report on genomic breakpoints demonstrates the homogeneity in the localization of the genomic breakpoints at 9q34. Concurrent chromosomal aberrations identified in this study should provide further areas of interest in investigation of SET-NUP214-mediated leukemogenesis.     

Circulating IL-17 levels during the peri-transplant period as a predictor for early leukemia relapse after myeloablative allogeneic stem cell transplantation

IL-17 is involved in inducing and mediating pro-inflammatory responses. The association of IL-17 with tumor growth or graft-versus-host disease (GVHD) has become a subject of controversy. We hypothesized that serum IL-17 (sIL-17) levels during the peri-transplant period may affect alloreactive responses after allogeneic stem cell transplantation (SCT). sIL-17 levels of 95 patients with leukemia who had undergone myeloablative allogeneic SCT were measured using ELISA before conditioning and on day?0, +7, and +14 after transplantation. With a median follow-up of 17?months, the overall survival, disease-free survival, non-relapse mortality, and relapse incidence were 70.9%, 66.3%, 10.3%, and 23.4%, respectively. Ten patients relapsed within 180?days (early relapse, 10.5%) post-transplant. The cumulative incidence of acute GVHD over grade II and chronic GVHD was 55.8% and 69.0%, respectively. Analyses using repeated measures of ANOVA and mean values of sIL-17 revealed that patients relapsed within 180?days had higher sIL-17 levels, whereas no association existed between sIL-17 levels and other clinical outcomes, including acute GVHD. Receiver operating characteristic curve analyses also revealed that sIL-17 levels were available for the prediction of early relapse and that patients with higher sIL-17 levels at each time point had a significantly higher early relapse. Multivariate analyses and subgroup analyses with only standard disease status suggest the association of sIL-17 levels with subsequent early relapse independent of disease status at transplantation. This study is the first one demonstrating the early change in sIL-17 during the peri-transplant period and the association with early relapse in humans.     

Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate cells results in decreased secretion of IL-6

AIM: To investigate the mechanism of interleukin (IL)-6 secretion through blocking the IL-17A/IL-17A recepto (IL-17RA) signaling pathway with a short hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro . METHODS: HSCs were derived from the livers of adul male Sprague-Dawley rats. IL-6 expression was evalu ated using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated pro tein kinases (MAPK) and extracellular regulated pro tein kinases (ERK) 1/2 upon induction by IL-17A and suppression by IL-17RA shRNA were examined using Western blotting.RESULTS: IL-6 expression induced by IL-17A was significantly increased compared to control in HSCs (P 0.01 in a dose-dependent manner). Suppression of IL17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL-17A compared to group with only IL-17A treatment (1.44 ± 0.17 vs 4.07 ± 0.43, P 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups without inhibitors preincubation (1.67 ± 0.24, 2.01 ± 0.10 vs 4.08 ± 0.59, P 0.01). Moreover, lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced IL-6 mRNA expression compared to random shRNA in HSCs (1.44 ± 0.17 vs 3.98 ± 0.68, P 0.01). Lentiviral-mediated IL17RA shRNA 1 inhibited phosphorylation of p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure. CONCLUSION: Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of IL-17RA expression may be a strategy to reduce the inflammatory response induced by IL-17A in the liver.