It's actually a lot like what the title sounds like. You play as a crewmate among the Skeld and try to eject imposters and not die to them as they roam around.

Background

Patients with ST-elevation myocardial infarction (STEMI) complicated by an out-of-hospital-cardiac-arrest (OHCA) may vary widely in their probability of dying. Large variation in mortality may have implications for current national efforts to benchmark operator and hospital mortality rates for coronary angiography. We aimed to build a risk-adjustment model of in-hospital mortality among OHCA survivors with concurrent STEMI.

Methods

Within the Cardiac Arrest Registry to Enhance Survival (CARES), we included adults with OHCA and STEMI who underwent emergent angiography within 2 hours of hospital arrival between January 2013 and December 2019. Using multivariable logistic regression to adjust for patient and cardiac arrest factors, we developed a risk-adjustment model for in-hospital mortality and examined variation in patients' predicted mortality.

Results

Of 2,999 patients (mean age 61.2 ± 12.0, 23.1% female, 64.6% white), 996 (33.2%) died during their hospitalization. The final risk-adjustment model included higher age (OR per 10-year increase, 1.50 [95% CI: 1.39-1.63]), unwitnessed OHCA (OR, 2.51 [1.99-3.16]), initial non-shockable rhythm [OR, 5.66 [4.52-7.13]), lack of sustained pulse for > 20 minutes (OR, 2.52 [1.88-3.36]), and longer resuscitation time (increased with each 10-minute interval) (c-statistic = 0.804 with excellent calibration). There was large variability in predicted mortality: median, 25.2%, inter-quartile-range: 14.0% to 47.8%, 10th-90th percentile: 8.2 % to 74.1%.

Conclusions

In a large national registry, we identified 5 key predictors for mortality in patients with STEMI and OHCA and found wide variability in mortality risk. Our findings suggest that current national benchmarking efforts for coronary angiography, which simply adjusts for the presence of OHCA, may not adequately capture patient case-mix severity.

Background

Health status outcomes are increasingly being promoted as measures of health care quality, given their importance to patients. In heart failure (HF), an American College of Cardiology/American Heart Association Task Force proposed using the proportion of patients with preserved health status as a quality measure but not as a performance measure because risk adjustment methods were not available.

Methods

We built risk adjustment models for alive with preserved health status and for preserved health status alone in a prospective registry of outpatients with HF with reduced ejection fraction across 146 US centers between December 2015 and October 2017. Preserved health status was defined as not having a ≥5-point decrease in the Kansas City Cardiomyopathy Questionnaire Overall Summary score at 1 year. Using only patient-level characteristics, hierarchical multivariable logistic regression models were developed for 1-year outcomes and validated using data from 1 to 2 years. We examined model calibration, discrimination, and variability in sites' unadjusted and adjusted rates.

Results

Among 3932 participants (median age [interquartile range] 68 years [59-75], 29.7% female, 75.4% White), 2703 (68.7%) were alive with preserved health status, 902 (22.9%) were alive without preserved health status, and 327 (8.3%) had died by 1 year. The final risk adjustment model for alive with preserved health status included baseline Kansas City Cardiomyopathy Questionnaire Overall Summary, age, race, employment status, annual income, body mass index, depression, atrial fibrillation, renal function, number of hospitalizations in the past 1 year, and duration of HF (optimism-corrected C statistic=0.62 with excellent calibration). Similar results were observed when deaths were ignored. The risk standardized proportion of patients alive with preserved health status across the 146 sites ranged from 62% at the 10th percentile to 75% at the 90th percentile. Variability across sites was modest and changed minimally with risk adjustment.

Conclusions

Through leveraging data from a large, outpatient, observational registry, we identified key factors to risk adjust sites' proportions of patients with preserved health status. These data lay the foundation for building quality measures that quantify treatment outcomes from patients' perspectives.

Abstract Background It is well established that vaccination of humans and transgenic animals against fibrillar Aβ prevents amyloid accumulation in plaques and preserves cognitive function in transgenic mouse models. However, autoimmune side effects have halted the development of vaccines based on full length human Aβ. Further development of an effective vaccine depends on overcoming these side effects while maintaining an effective immune response. Results We have previously reported that the immune response to amyloid oligomers is largely directed against generic epitopes that are common to amyloid oligomers of many different proteins and independent of a specific amino acid sequence. Here we have examined whether we can exploit this generic immune response to develop a vaccine that targets amyloid oligomers using a non-human random sequence amyloid oligomer. In order to study the effect of vaccination against generic oligomer epitopes, a random sequence oligomer (3A) was selected as it forms oligomers that react with the oligomer specific A11 antibody. Oligomer mimics from 3A peptide, Aβ, islet amyloid polypeptide (IAPP), and Aβ fibrils were used to vaccinate Tg2576 mice, which develop a progressive accumulation of plaques and cognitive impairment. Vaccination with the 3A random sequence antigen was just as effective as vaccination with the other antigens in improving cognitive function and reducing total plaque load (Aβ burden) in the Tg2576 mouse brains, but was associated with a much lower incidence of micro hemorrhage than Aβ antigens. Conclusion These results shows that the amyloid Aβ sequence is not necessary to produce a protective immune response that specifically targets generic amyloid oligomers. Using a non-human, random sequence antigen may facilitate the development of a vaccine that avoids autoimmune side effects.

Background

Platelets play a pivotal role in hemostasis, wound healing, and inflammation, and are thus implicated in a variety of diseases, including cancer. Platelet function is associated with release of granule content, cellular shape change, and upregulation of receptors that promote establishment of a thrombus and maintenance of hemostasis.

Objectives

The role of heat shock proteins (Hsps) in modulating platelet function has been studied for a number of years, but comparative roles of individual Hsps have not been thoroughly examined.

Methods

We utilized a panel of specific inhibitors of Hsp40, Hsp70, Hsp90, and Grp94 (the endoplasmic reticulum homolog of Hsp90) to assess their impact on several aspects of platelet function.

Results

Inhibition of each of the aforementioned Hsps reduced alpha granule release. In contrast, there was some selectivity in impacts on dense granule release. Thromboxane synthesis was impaired after exposure to inhibitors of Hsp40, Hsp90, and Grp94, but not after inhibition of Hsp70. Both expression of active glycoprotein IIb/IIIa (GPIIb/IIIa) and fibrinogen-induced platelet shape change were diminished by our inhibitors. In contrast, aggregation was selectively abrogated after inhibition of Hsp40 or Hsp90. Lastly, activated platelet-cancer cell interactions were reduced by inhibition of both Hsp70 and Grp94.

Conclusions

These data suggest the importance of Hsp networks in regulating platelet activity.