Characterization of the Inflammatory Response to Severe COVID-19 Illness.

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1ß, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1ß, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1ß, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

A Prospective Study of the Timing and Accuracy of Neutrophil Gelatinase-Associated Lipocalin Levels in Predicting Acute Kidney Injury in High-Risk Cardiac Surgery Patients.

OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker in the effort to predict acute kidney injury (AKI) after cardiac surgery. The authors aimed to identify the specific time point in the perioperative period at which measurement of either urinary or serum concentrations of NGAL would have the highest predictive power for AKI. The authors also investigated whether change in NGAL from baseline was a better predictor of AKI than absolute NGAL values. DESIGN: A prospective, investigator-blinded observational study. SETTING: The cardiac surgical unit of a university teaching hospital. PARTICIPANTS: The study consisted of 50 patients undergoing cardiac surgery who were classified preoperatively as high risk for developing postoperative AKI. INTERVENTIONS: No changes to standard practice were required. MEASUREMENTS AND MAIN RESULTS: The authors performed serial measurements of urinary and serum NGAL concentrations at 18 time points throughout the first 48 postoperative hours and assessed the variables required to diagnose AKI with standard criteria. Statistical analysis of predictive ability was performed using the area under receiver operator curves (AUROC) calculated for each time point. It was demonstrated that urinary NGAL performed marginally better than serum NGAL in predicting AKI. Urinary sampling at 4 and 24 hours after initiation of cardiopulmonary bypass provided the greatest diagnostic ability (AUROC, 0.702 and 0.712, respectively). Absolute NGAL values performed better than changes in NGAL values in predicting AKI. CONCLUSIONS: Urinary NGAL performed better than serum NGAL in predicting AKI and was most accurate when measured at 24 hours after initiation of cardiopulmonary bypass; however, NGAL appeared to be at best only a fair predictor of cardiac surgery-associated AKI.

Tracheostomy insertion in COVID-19: insertion practice and factors leading to unplanned tube exchange.

Background: Tracheostomy insertion in patients with coronavirus disease 2019 (COVID-19) presents unique challenges. Patients frequently have high ventilatory requirements, and as an aerosol generating procedure, tracheostomy insertion creates the potential for staff transmission. Problems with tracheostomies contribute to morbidity and mortality, and tracheostomy changes may increase risks of staff transmission. We sought to quantify the incidence of clinically necessitated tracheostomy changes, establish the indications for change and investigate the incidence of staff transmission. Methods: We conducted a single institution, retrospective, observational cohort study of all intensive care unit (ICU) patients with COVID-19 who had a tracheostomy between March 2020 and April 2021. The institution is a large tertiary referral centre in Ireland. Results: Forty-three patients had a tracheostomy during the study period. All were a Shiley™ Flexible Adult Taperguard or Shiley™ XLT Tracheostomy. 14 patients (33%) required a tracheostomy change, with the majority (57%) involving a change from a standard size to an extended length tracheostomy. Persistent leak was the most common indication for change (71.6%). Other indications included patient-ventilator dyssynchrony, persistent cough and accidental decannulation. No staff transmission of COVID-19 occurred during this study. Conclusions: The incidence of tracheostomy change was 33%, highlighting the importance of selecting the right tracheostomy for each patient. We discuss how key characteristics of tracheostomies such as type, size, length and inner diameter may impact flow, resistance and work of breathing, leading to unplanned tracheostomy change. No staff transmission occurred arising from tracheostomy insertion, adding to increasing evidence that tracheostomy insertion in COVID-19 appears safe with adherence to guidelines describing the correct use of personal protective equipment.

The catabolic triad: case report of fasting, major cardiac surgery and sodium-glucose co-transporter 2 inhibitors leading to perioperative euglycaemic ketoacidosis.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are novel oral hypoglycaemic agents. For patients with diabetes mellitus, without a prior history of myocardial infarction or atherosclerotic disease, SGLT2i have been shown to reduce incident heart failure and worsening renal function. SGLT2i therapy is increasing among patients presenting for cardiac surgery. However, the perioperative use of SGLT2i carries a significant risk of euglycaemic diabetic ketoacidosis, due to their catabolic mechanism of action. This case report demonstrates euglycaemic ketoacidosis post-coronary artery bypass grafting secondary to SGLT2i, highlighting the multiple risk factors and consequences of this iatrogenic complication.