Sunitinib does not impair natural killer cell function in patients with renal cell carcinoma.

Although the available treatment options have expanded, the survival of patients with metastatic renal cell carcinoma (RCC) remains poor. As patients with RCC lack responsiveness to chemotherapy or radiation, therapeutic options predominantly include surgical interventions and immunomodulatory approaches, including the administration of tyrosine kinase inhibitors (TKIs) such as sunitinib. Natural killer (NK) cells have been reported to be key players in TKI-mediated off-target effects on the immune system. However, only limited information is available regarding the possible impact of sunitinib on the function of NK cells of individual patients. The present study reports on the immunomonitoring results of three patients with metastatic RCC who underwent sunitinib treatment. These results were compared with age-matched, healthy controls in terms of the immune status of T, B and NK cells, focusing on functional in vitro analyses of NK cells. In all three patients, NK cell number, subset distribution and function, as measured by cluster of differentiation 107a degranulation, did not exhibit any significant alterations as a result of sunitinib treatment. These results indicate that sunitinib does not negatively affect NK cell function, which supports the pursuit of therapeutic modalities that combine immunomodulation and NK cell-stimulating approaches.

Flow Cytometry-based Assay for the Monitoring of NK Cell Functions.

Natural killer (NK) cells are an important part of the human tumor immune surveillance system. NK cells are able to distinguish between healthy and virus-infected or malignantly transformed cells due to a set of germline encoded inhibitory and activating receptors. Upon virus or tumor cell recognition a variety of different NK cell functions are initiated including cytotoxicity against the target cell as well as cytokine and chemokine production leading to the activation of other immune cells. It has been demonstrated that accurate NK cell functions are crucial for the treatment outcome of different virus infections and malignant diseases. Here a simple and reliable method is described to analyze different NK cell functions using a flow cytometry-based assay. NK cell functions can be evaluated not only for the whole NK cell population, but also for different NK cell subsets. This technique enables scientists to easily study NK cell functions in healthy donors or patients in order to reveal their impact on different malignancies and to further discover new therapeutic strategies.

True First-Line Local-Anesthesia Only Protocol for Transfemoral TAVI.

AIMS: To evaluate the safety and feasibility of transcatheter aortic valve implantation (TAVI) via femoral access under local anesthesia only (without concomitant sedation) as the initial strategy. METHODS AND RESULTS: Patients undergoing planned transfemoral TAVI without routine general anesthesia between May 2005 and December 2013 were identified. Baseline characteristics, procedural outcomes, and a 30-day clinical follow-up were obtained. A total of 215 patients underwent TAVI with local anesthesia only as the initial strategy (LA group). Of these patients, 40 (18.6%) received additional sedation (LAS group) during the procedure due to inadequate pain control or agitation and 7 patients (3.3%) underwent conversion to general anesthesia (GA group). TAVI was successfully performed in 211 cases (98.2%). When 30-day outcomes for patients requiring only local anesthesia were compared with patients requiring additional sedation, there was a significantly longer duration of Intensive Care Unit (ICU) stay in the group with additional sedation (LAS, 5.0 days [range, 3.0-6.0 days] vs LA 3 days [range, 2.0-5.0 days]; P=.02) and general anesthesia (GA 7.0 days [range, 2.5-18.0 days] vs LA 3 days [range, 2.0-5.0]; P=.04). CONCLUSION: Our study suggests that TAVI with LA only as the initial strategy is a feasible alternative to GA, with potential benefit of this strategy over using routine concomitant sedation. LA only may be considered a primary option in many patients.

The impact of live case transmission on patient outcomes during transcatheter aortic valve replacement: results from the VERITAS study.

BACKGROUND: Live case demonstration as an educational tool is widely used to rapidly and effectively disseminate information on surgical and interventional techniques. The risks and benefits of live case transmission for investigational devices, however, are in question. METHODS: Transcatheter Aortic Valve Intervention-Live Transmission (VERITAS) is a case-control study of 60 patients from 5 centers who were treated with transcatheter aortic valve replacement (TAVR) during live- or recorded transmission; of which 42 have matched Control subjects from five sites. Case and Control subjects were matched by valve type, access strategy (Edwards SAPIEN transfemoral, Edwards SAPIEN transapical, CoreValve transfemoral), Society of Thoracic Surgeons (STS) score, date of TAVR procedure, and primary operator. RESULTS: The Case and Control groups' baseline characteristics were similar, with average ages of 84 and 82 years, and STS scores of 6.54±3.22 and 6.46±3.20, respectively. The number of operators, fluoroscopy time, contrast volume and length of hospital stay were also similar between groups. Overall, 91.7% of the cases had TAVR via a transfemoral approach; 72% of these patients received a closure device. The final valve position was adequate in 91.2% of the Case patients and in 97% of the Control patients, with no cases of valve migration or coronary obstruction. The Case patients had longer procedure times (130.2±50.6 versus 100.6±43.7min; p=0.006). The Valve Academic Research Consortium in-hospital complications were similar between groups. Four Case patients and 1 Control patient required additional valve implantation. CONCLUSION: Data support the notion that live transmission of TAVR procedures, when performed by experienced operators, can be done safely with similar outcomes when compared to non-transmitted cases.