Trevor M. Stantliff

Background: Critical illness in coronavirus disease 2019 may require extracorporeal membrane oxygenation support. We quantified immunothrombotic markers in patients with COVID-19 receiving ECMO and evaluated their predictive capacity for death. Methods: We performed a retrospective analysis of 74 consecutive patients with COVID-19 on ECMO at a single academic medical center between March 2020 and February 2021. Severe acute respiratory syndrome coronavirus-2 nucleocapsid RNA and 16 immunothrombotic biomarkers were longitudinally quantified and their trajectories were used to predict death and decannulation across multiple models. Results: Male sex, smoking, serum bilirubin levels, and low partial arterial oxygen pressure–fraction of inspired oxygen ratio were associated with increased risk of death. Plasma levels of 10 immunothrombotic markers were significantly elevated in fatal cases and some were associated with an increased hazard of death (eg, interleukin 8, von Willebrand factor) or decreased hazard for decannulation (eg, angiopoietin 2, interleukin 1β) when adjusting for sex, smoking status, and time to cannulation. Predictive models incorporating biomarkers were superior to demographics alone and equivalent to models including clinical information. Conclusions: We found that male sex, smoking, and select clinical variables and immunothrombotic markers were risk factors for death in patients with COVID-19 on ECMO informing pathogenesis and prognostication of severe COVID-19.

Background: Sepsis is a leading cause of death worldwide. Identifying novel host-directed therapeutic targets may improve sepsis outcomes. Methods: Six nonhuman primates were infected with Klebsiella pneumoniae to induce septic shock and provided supportive care for up to 72 hours. Flow cytometry was used to characterize whole-blood neutrophils (WBNs) and low-density neutrophils (LDNs) at time 0 (T0), T6, T24, and T48 hours postinfection, and postmortem examination (ie, necropsy). Dimensional reduction with clustering via FlowSOM and traditional gating strategies were used to compare WBNs to LDNs and delineate spleen tyrosine kinase (SYK) expression across neutrophils subsets. We measured soluble biomarkers of end-organ dysfunction and neutrophil activation, and quantified SYK and myeloperoxidase in tissue. Results: At T6, we identified populations of active immature WBNs and a population of LDNs not detected at baseline. At T24, neutrophil heterogeneity increased across WBNs and LDNs with differential expression of myeloperoxidase (MPO). Compared to WBNs, LDNs were more activated with increased MPO expression. At T6, SYK expression surged in WBNs and LDNs and SYK+ WBNs and LDNs expressed higher levels of MPO and lactoferrin compared to SYK− neutrophils. Circulating levels of SYK+ LDNs significantly correlated with serum creatinine levels, indicative of acute kidney injury; prolonged prothrombin time and decreased fibrinogen, indicative of consumptive coagulopathy; and SYK expression in tissues. Conclusions: Bacterial sepsis leads to heterogenous populations of circulating neutrophils, including LDNs. Elevated SYK expression in WBNs and LDNs correlates with end-organ dysfunction, highlighting SYK as a potential therapeutic target in bacterial sepsis.

Tuberculosis infection (TBI) has been associated with increased cardiovascular risks. We aimed to characterize abnormal blood pressure (BP) readings in individuals with TBI. We conducted a retrospective study of adults with TBI presenting for their initial medical visit at a large midwestern U.S. public health clinic between 2019 and 2020. Abnormal BP was defined as having a systolic BP ≥ 130 mmHg and/or a diastolic BP ≥ 80 mmHg. Of 310 individuals with TBI, median age was 36 years (interquartile range 27–48), 34% were male, 64% non-US-born; 58 (18.7%) were previously diagnosed with hypertension. The prevalence of any hypertension (i.e., had a history of hypertension and/or an abnormal BP reading) was 64.2% (95% confidence interval 58.7–69.4). Any hypertension was independently associated with older age, male sex, higher body mass index, and individuals of Black race. In conclusion, any hypertension was present in over half of the adults evaluated for TBI in our clinic. Established hypertension risk factors were also common among this group, suggesting that individuals with TBI could benefit from clinical and public health interventions aiming to reduce the risk of future cardiovascular events.

Summary: Tuberculosis infection (LTBI) has been associated with increased cardiovascular risks. We aimed to characterize abnormal blood pressure (BP) readings in individuals with LTBI. We conducted a retrospective study of adults with LTBI presenting for their initial medical visit at a large midwestern US public health clinic between 2019-2020. Abnormal BP was defined as having a systolic BP≥ 130mmHg and/or a diastolic BP≥ 80mmHg. Of 310 individuals with LTBI, median age was 36 years (interquartile range 27 – 48), 34% were male, 64% non-US-born; 58 (18.7%) were previously diagnosed with hypertension. The prevalence of any hypertension (i.e., had a history of hypertension and/or an abnormal BP reading) was 64.2% (95% confidence interval 58.7 – 69.4). Any hypertension was independently associated with older age, male sex, higher body mass index, and Black race. In conclusion, any hypertension was present in over half of adults evaluated for LTBI in our clinic. Established hypertension risk factors were also common among this group, suggesting that individuals with LTBI could benefit from clinical and public health interventions aiming to reduce the risk of future cardiovascular events.