The structure of the 28 kDa beta-lactamase inhibitor protein-II (BLIP-II) in complex with the TEM-1 beta-lactamase has been determined to 2.3 A resolution. BLIP-II is a secreted protein produced by the soil bacterium Streptomyces exfoliatus SMF19 and is able to bind and inhibit TEM-1 with subnanomolar affinity. BLIP-II is a seven-bladed beta-propeller with a unique blade motif consisting of only three antiparallel beta-strands. The overall fold is highly similar to the core structure of the human regulator of chromosome condensation (RCC1). Although BLIP-II does not share the same fold with BLIP, the first beta-lactamase inhibitor protein for which structural data was available, a comparison of the two complexes reveals a number of similarities and provides further insights into key components of the TEM-1-BLIP and TEM-1-BLIP-II interfaces. Our preliminary results from gene knock-out studies and scanning electron microscopy also reveal a critical role of BLIP-II in sporulation.
Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is a lifesaving tool used in the treatment of cardiogenic shock, acute heart failure, or extracorporeal cardiopulmonary resuscitation (CPR). We report on a single center experience with ECMO and aim to identify the prognostic markers for in-hospital mortality and death at 72 hours after ECMO. Methods Between 2011 and 2019 we evaluated 131 patients, who received ECMO. Collected data was analyzed to identify baseline characteristic, outcomes including clinical variables predictive of poor outcome. Results The mean age was 62.5 years, 67.2% were male patients, with prior CPR in 61.8%. The annual number of VA-ECMO procedures steadily increased, whereas in-hospital mortality is decreasing. Within the total cohort, the indication for VA-ECMO was cardiac arrest in 19.1%, acute coronary syndrome in 41.2%, acute heart failure in 23.7%, and myocarditis in 10.7%. Overall in-hospital mortality was 58.8%. Multivariate logistic regression model revealed presence of malignancy, history of revascularization, duration of cardiac arrest, and low BMI as independent predictors for mortality in 72 hours after ECMO (table). On the other hand, predictors of in-hospital mortality were prior congestive heart failure, male, and history of malignancy. The C-statistic for discriminating mortality in 72 hours after ECMO with the duration of cardiac arrest was 0.67 (figure). Conclusions Although the use of ECMO as a last line in the treatment of critical patients measures constitutes an important improvement in their care; with 41.2% overall survival; patient selection and timing of ECMO initiation remains challenging. The importance of consideration for ECMO use earlier in course of illness rather than later. Funding Acknowledgement Type of funding source: None
Background Clinical benefits of complete revascularization (CR) in acute myocardial infarction (AMI) patients are unclear. Moreover, the benefit of CR is unknown in AMI with Diabetes Mellitus (DM) patient. Objectives We sought to compare prognosis of CR and incomplete revascularization (IR) in patients with AMI and multivessel disease, according to the presence of DM. Methods A total of 2,150 AMI patients with multivessel coronary artery disease were analyzed. CR was defined based on angiographic image. The primary endpoints of this study was patient oriented composite outcome (POCO) defined as a composite of all cause death, any myocardial infarction, and any revascularization within 3 years. Results Overall, 3-year POCO were significantly lower in patients receiving angiographic CR (985 patients, 45.8%) compared with IR (1165 patients, 54.2%). When divided into subgroups according to the presence of DM, CR reduced 3-year clinical outcomes in the non-DM group but not in the DM group (POCO: 11.7% vs. 23.2%, p<0.001, any revascularization: 7.2% vs. 10.8%, p=0.024 in the non-DM group, POCO: 24.3% vs. 27.8%, p=0.295, any revascularization: 13.3% vs. 11.3%, p=0.448 in the DM group, for CR vs. IR). Multivariate analysis showed that CR significantly reduced 3-year POCO (HR 0.52, 95% CI 0.38–0.71) only in the non-DM group. Conclusion In AMI patients with multivessel disease, CR may be ineffective in improving clinical outcomes in patients with DM. Funding Acknowledgement Type of funding source: None
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