Protecting Lyophilized Escherichia coli Adenylate Kinase.

Drying protein-based drugs, usually via lyophilization, can facilitate storage at ambient temperature and improve accessibility but many proteins cannot withstand drying and must be formulated with protective additives called excipients. However, mechanisms of protection are poorly understood, precluding rational formulation design. To better understand dry proteins and their protection, we examine Escherichia coli adenylate kinase (AdK) lyophilized alone and with the additives trehalose, maltose, bovine serum albumin, cytosolic abundant heat soluble protein D, histidine, and arginine. We apply liquid-observed vapor exchange NMR to interrogate the residue-level structure in the presence and absence of additives. We pair these observations with differential scanning calorimetry data of lyophilized samples and AdK activity assays with and without heating. We show that the amino acids do not preserve the native structure as well as sugars or proteins and that after heating the most stable additives protect activity best.

Durable mechanical circulatory support device use in the United States by geographic region and minority status.

BACKGROUND: Durable mechanical circulatory support device (MCSD) therapy has experienced rapid dissemination in the United States. Few studies have evaluated geographic patterns of its dissemination based upon patient characteristics that could identify potential variation in its application. METHODS: A combined Interagency Registry for Mechanically Assisted Circulatory Support and Medicare dataset identified durable MCSD implants from 2008 through 2014. MCSD implant rates were estimated using yearly US Census population data, estimated from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database and stratified by age, race, and United Network for Organ Sharing (UNOS) region. RESULTS: Overall, 16,331 patients received an MCSD implant from 232 unique centers. Annual MCSD implant rate (per 1 million population) significantly increased in each UNOS region (absolute range of increase, 5.3-16.4) with UNOS Region 7 demonstrating the highest overall absolute rate (20.9) in 2014 and UNOS Region 11 demonstrating the greatest relative increase in rate (430.5%). Geographical differences in the rate of MCSD implants were observed among whites and minorities with higher rates of MCSD implants observed for minorities for nearly all UNOS regions across all years. Significantly greater relative increases in MCSD implants for minorities compared with whites were observed within UNOS Regions 2, 3, 6, 7, 8, 9, and 11 (P < .001). CONCLUSIONS: Geographical differences exist in rates of MCSD implantation among whites and minorities. The reasons for these differences are unknown, but may reflect underlying differences in disease burden or disparities in access to heart transplantation and warrant further study.

Risk and Safety Perceptions Contribute to Transfusion Decisions in Coronary Artery Bypass Grafting.

Variability persists in intraoperative red blood cell (RBC) transfusion rates, despite evidence supporting associated adverse sequelae. We evaluated whether beliefs concerning transfusion risk and safety are independently associated with the inclination to transfuse. We surveyed intraoperative transfusion decision-makers from 33 cardiac surgery programs in Michigan. The primary outcome was a provider's reported inclination to transfuse (via a six-point Likert Scale) averaged across 10 clinical vignettes based on Class IIA or IIB blood management guideline recommendations. Survey questions assessed hematocrit threshold for transfusion ("hematocrit trigger"), demographic and practice characteristics, years and case-volume of practice, knowledge of transfusion guidelines, and provider attitude regarding perceived risk and safety of blood transfusions. Linear regression models were used to estimate the effect of these variables on transfusion inclination. Mixed effect models were used to quantify the variation attributed to provider specialties and hematocrit triggers. The mean inclination to transfuse was 3.2 (might NOT transfuse) on the survey Likert scale (SD: .86) across vignettes among 202/413 (48.9%) returned surveys. Hematocrit triggers ranged from 15% to 30% (average: 20.4%; SE: .18%). The inclination to transfuse in situations with weak-to-moderate evidence for supporting transfusion was associated with a provider's hematocrit trigger (p < .01) and specialty. Providers believing in the safety of transfusions were significantly more likely to transfuse. Provider specialty and belief in transfusion safety were significantly associated with a provider's hematocrit trigger and likelihood for transfusion. Our findings suggest that blood management interventions should target these previously unaccounted for blood transfusion determinants.