International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality

Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach

Low-severity Musculoskeletal Complaints Evaluated in the Emergency Department

Patients with musculoskeletal disorders represent a considerable percentage of emergency department volume. Although patients with acute or high-severity conditions are encouraged to seek care in the emergency department, patients with nonacute, low-severity conditions may be better served elsewhere. This study prospectively assessed patients presenting to the emergency department with nonacute, low-severity musculoskeletal conditions to test the hypothesis that these patients have access to care outside the emergency department. One thousand ten adult patients with a musculoskeletal complaint were identified, and a detailed questionnaire was completed by 862 (85.3%) during their emergency department stay. Three hundred fifty (40.6%) patients presented with nonacute, low-severity conditions. Patients with nonacute, low-severity problems were less likely to have a primary care physician (62.5% versus 72.3%) or to have medical insurance (82.5% versus 87.7%), but a majority had both (59.3%). Only 14.3% had neither. Forty-four percent of all patients with primary care physicians believed their primary care physician was incapable of managing musculoskeletal problems. Appropriate use of the emergency department by patients with musculoskeletal disorders may require not only increased access to insurance and primary care, but also improved public understanding of the scope of care offered by primary care physicians and the conflicting demands placed on emergency department providers

Pairwise detection of site-specific receptor phosphorylations using single-molecule blotting

Post-translational modifications (PTMs) of receptor tyrosine kinases (RTKs) at the plasma membrane (PM) determine the signal transduction efficacy alone and in combination. However, current approaches to identify PTMs provide ensemble results, inherently overlooking combinatorial PTMs in a single polypeptide molecule. Here, we describe a single-molecule blotting (SiMBlot) assay that combines biotinylation of cell surface receptors with single-molecule fluorescence microscopy. This method enables quantitative measurement of the phosphorylation status of individual membrane receptor molecules and colocalization analysis of multiple immunofluorescence signals to directly visualize pairwise site-specific phosphorylation patterns at the single-molecule level. Strikingly, application of SiMBlot to study ligand-dependent epidermal growth factor receptor (EGFR) phosphorylation, which is widely thought to be multi-phosphorylated, reveals that EGFR on cell membranes is hardly multi-phosphorylated, unlike in vitro autophosphorylated EGFR. Therefore, we expect SiMBlot to aid understanding of vast combinatorial PTM patterns, which are concealed in ensemble methods, and to broaden knowledge of RTK signaling.ope