NK cell responses to simian immunodeficiency virus vaginal exposure in naive and vaccinated rhesus macaques.

NK cell responses to HIV/SIV infection have been well studied in acute and chronic infected patients/monkeys, but little is known about NK cells during viral transmission, particularly in mucosal tissues. In this article, we report a systematic study of NK cell responses to high-dose vaginal exposure to SIVmac251 in the rhesus macaque female reproductive tract (FRT). Small numbers of NK cells were recruited into the FRT mucosa following vaginal inoculation. The influx of mucosal NK cells preceded local virus replication and peaked at 1 wk and, thus, was in an appropriate time frame to control an expanding population of infected cells at the portal of entry. However, NK cells were greatly outnumbered by recruited target cells that fuel local virus expansion and were spatially dissociated from SIV RNA+ cells at the major site of expansion of infected founder populations in the transition zone and adjoining endocervix. The number of NK cells in the FRT mucosa decreased rapidly in the second week, while the number of SIV RNA+ cells in the FRT reached its peak. Mucosal NK cells produced IFN-γ and MIP-1α/CCL3 but lacked several markers of activation and cytotoxicity, and this was correlated with inoculum-induced upregulation of the inhibitory ligand HLA-E and downregulation of the activating receptor CD122/IL-2Rß. Examination of SIVΔnef-vaccinated monkeys suggested that recruitment of NK cells to the genital mucosa was not involved in vaccine-induced protection from vaginal challenge. In summary, our results suggest that NK cells play, at most, a limited role in defenses in the FRT against vaginal challenge.

Incidence, predictors, and outcomes of device failure of X-sizer thrombectomy: real-world experience of 200 cases in 5 years.

BACKGROUND: Clinical studies have evaluated the safety and efficacy of adjunctive X-sizer (EndiCOR Inc, San Clemente, CA) in percutaneous coronary intervention (PCI). However, patient and lesion subsets were highly selected, and extrapolation of the results to daily practice is problematic. METHODS: X-sizer thrombectomy was performed in 200 procedures from August 2000 to July 2005. The indications for the procedures were primary PCI in 71%. Device failure was defined as the occurrence of 1 or more of the following conditions: (a) failure of the X-sizer to reach the target segment, (b) failure to achieve final thrombolysis in myocardial infarction 3 flow, (c) slow flow or no-reflow, (d) distal embolization, and (e) coronary perforation. RESULTS: Device failure occurred in 48 procedures, giving a device failure rate of 24%. Logistic regression analysis showed that ostial lesion was the only independent predictor of device failure (OR 4.89, 95% CI 1.23-19.51, P = .024). A total of 19 patients had developed 22 adverse events, giving a 30-day adverse event rate of 9.5%. Among these, there were 13 deaths, 4 strokes, 2 reinfarctions, 2 repeat PCIs, and 1 coronary artery bypass grafting. Logistic regression analysis showed that X-sizer device failure was independently associated with 30-day adverse events (OR 3.42, 95% CI 1.04-11.25, P = .043). CONCLUSIONS: The incidence of device failure of X-sizer thrombectomy was 24%. Ostial lesion was an independent predictor of device failure. Notably, X-sizer device failure was independently associated with 30-day adverse event. These highlight the importance of case selection and the problem with its use in ostial lesions.