Impact of Diabetes Mellitus on Outcomes after High-Risk Interventional Coronary Procedures.

An increasing number of patients with coronary artery disease are at high operative risk due to advanced age, severe comorbidities, complex coronary anatomy, and reduced ejection fraction. Consequently, these high-risk patients are often offered percutaneous coronary intervention (PCI) as an alternative to coronary artery bypass grafting (CABG). We aimed to investigate the outcome of patients with diabetes mellitus (DM) undergoing high-risk PCI. We analyzed consecutive patients undergoing high-risk PCI (period 01/2016-08/2018). In-hospital major adverse cardiac and cerebrovascular events (MACCEs), defined as in-hospital stroke, myocardial infarction and death, and the one-year incidence of death from any cause were assessed in patients with and without DM. There were 276 patients (age 70 years, 74% male) who underwent high-risk PCI. Eighty-six patients (31%) presented with DM (insulin-dependent DM: n = 24; non-insulin-dependent DM: n = 62). In-hospital MACCEs occurred in 9 patients (3%) with a non-significant higher rate in patients with DM (n = 5/86, 6% vs. n = 4/190 2%; p = 0.24). In patients without DM, the survival rate was insignificantly higher than in patients with DM (93.6% vs. 87.1%; p = 0.07). One-year survival was not significantly different in DM patients with more complex coronary artery disease (SYNTAX I-score ≤ 22: 89.3% vs. > 22: 84.5%; p = 0.51). In selected high-risk patients undergoing high-risk PCI, DM was not associated with an increased incidence of in-hospital MACCEs or a decreased one-year survival rate.

Safety and efficacy of a novel algorithm to guide decision-making in high-risk interventional coronary procedures.

BACKGROUND: Patients with severe coronary artery disease (CAD), comorbidities, or impaired hemodynamics are at risk during percutaneous coronary interventions. The aim of the study was to investigate the safety and efficacy of a novel risk-stratification algorithm for high-risk coronary procedures. METHODS AND RESULTS: We prospectively screened 1189 patients with CAD requiring revascularization (period 07/2017-06/2018). The algorithm was designed to select high-risk procedures. Patients with elevated risk (n = 150) were classified into 3 risk groups (high-risk intervention [HRI] I-III) and procedural management was adjusted according to HRI group. Overall, 55 patients were categorized as HRI I, 52 as HRI II, and 43 as HRI III. With increasing HRI-level, SYNTAX score increased (HRI I:15 ±â€¯5% vs. HRI II:24 ±â€¯8% vs. HRI III:34 ±â€¯7%; p < 0.001), and ejection-fraction decreased (HRI I:48 ±â€¯10% vs. HRI II:49 ±â€¯10% vs. HRI III:40 ±â€¯11%; p < 0.001). The primary endpoint (hemodynamic compromise requiring mechanical circulatory support [MCS] [HRI I/II], unsuccessful weaning from MCS in the catheterization laboratory[HRI III], or periprocedural death[HRI I-III]) occurred in no case. The secondary endpoint of hemodynamic deterioration occurred in 26% (n = 39) but did not result in hemodynamic instability due to the risk-adjusted procedural management. The composite endpoint of in-hospital major adverse cardiac and cerebrovascular events (death, new myocardial infarction, cerebrovascular accident) occurred in 4 patients (3%). CONCLUSIONS: The novel algorithm is a safe team-based stratification method for the identification and management of patients undergoing high-risk coronary interventions.

Access site complications following Impella-supported high-risk percutaneous coronary interventions.

Mechanical circulatory support (MCS) devices are increasingly used to provide hemodynamic stability for patients with severe coronary artery disease, comorbidities, and/or impaired hemodynamics during high-risk percutaneous coronary interventions (PCI). Vascular access site complications, particularly those due to the use of large-bore sheaths, may limit outcomes in these patients. The aim of this study was to investigate the incidence and predictors of vascular complications in protected high-risk PCIs. Therefore, we included patients undergoing high-risk PCI with an Impella device from January 2016 to August 2018. Vascular complications were graded according to 'Valve Academic Research Consortium-2', a definition routinely used in transcatheter valve implantation procedures. In total, 61 patients (mean age 72 ± 11 years, 79% male, SYNTAX score 33 ± 7) were included, and angiographic- and fluoroscopic-guided vascular access was used for Impella implantation in all patients. Major vascular complications occurred in 5 male patients (8%). All major vascular complications were treated conservatively without the need for surgical intervention, and only one patient received a transfusion of three erythrocyte concentrates. Regression analysis revealed that patients with peripheral arterial disease of the lower extremities are at higher risk of major vascular complications. In conclusion, the utilization of Impella using a standardized protocol for angiographic- and fluoroscopic-guided vascular access was associated with a low rate of vascular complications.

Insulin-like growth factor-1 receptor (IGF-1R) inhibition promotes expansion of human NK cells which maintain their potent antitumor activity against Ewing sarcoma cells.

BACKGROUND: Patients with primary metastatic or relapsed Ewing sarcomas (EwS) have a poor prognosis. While inhibitory insulin-like growth factor 1 receptor (IGF-1R)-specific antibodies have shown single agent activity in some patients with refractory disease, effective therapeutic targeting will rely on optimal combinations with conventional or innovative therapies. Specifically, combination of inhibitory IGF-1R antibodies with adoptive transfer of activated natural killer (NK) cells may have therapeutic benefit in EwS without adding toxicity. PROCEDURE: We investigated the in vitro effects of IGF-1R targeting on the immunological profile of EwS cells and on the survival and tumor targeting capacity of K-562-activated NK cells. RESULTS: IGF-1R inhibition reliably reduced EwS cell viability without affecting expression of immune-modulatory and MHC molecules. In NK cells, we observed a significant superior expansion following in vitro activation in the presence of IGF-1R-specific antibodies, while expression of differentiation markers and activating receptors remained unaffected. Activated NK cells coincubated with EwS cells showed potent degranulation responses unaffected by IGF-1R inhibition. These findings were reproducible in a stimulator cell-free NK cell expansion system, suggesting that direct effects of IGF-R1 antibodies on the IGF-R1 pathway in NK cells induce their activation and expansion. CONCLUSIONS: Activated human NK cells respond to IGF-1R inhibition with superior expansion kinetics while maintaining potent antitumor responses against EwS. Combination of adoptive NK cell transfer with IGF-1R targeting may be an efficient means to eliminate minimal residual disease after conventional therapy and thereby rescue patients at the highest risk of relapse.