Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19.

Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present with different disease severity. Here, we determined 171 microRNAomes from 58 hospitalized COVID-19 patients (Cohort 1) and levels of 25 cytokines and chemokines (CC) in the same samples. Combining microRNA (miRNA) and CC measurements allowed for discrimination of severe cases with greater accuracy than using miRNA or CC levels alone. Severity group-specific associations between miRNAs and COVID-19-associated CC (e.g., IL6, CCL20) or clinical hallmarks of COVID-19 (e.g., neutrophilia, hypoalbuminemia) separated patients with similar CC levels but different disease severity. Analysis of an independent cohort of 108 patients from a different center (Cohort 2) demonstrated feasibility of CC/miRNA profiling in leftover hospital blood samples with similar severe disease CC and miRNA profiles, and revealed CCL20, IL6, IL10, and miR-451a as key correlates of fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin severe COVID-19.

Ventilatory inefficiency adversely affects outcomes and longer-term survival after planned colorectal cancer surgery.

BACKGROUND: Impaired cardiorespiratory reserve is an accepted risk factor for patients having major surgery. Ventilatory inefficiency, defined by an elevated ratio of minute ventilation to carbon dioxide excretion (VE/VCO2), and measured by cardiopulmonary exercise testing (CPET), is a pathophysiological characteristic of patients with cardiorespiratory disease. We set out to evaluate the prevalence of ventilatory inefficiency in a colorectal cancer surgical population, and its influence on surgical outcomes and long-term cancer survival. METHODS: In this retrospective study of 1375 patients who had undergone preoperative CPET followed by colorectal cancer surgery, we used receiver operating characteristic curve analysis to identify an optimal value of VE/VCO2 associated with 90-day mortality. Binary logistic regression was used to evaluate whether this degree of ventilatory inefficiency was independently associated with decreased survival, both after surgery and in the longer term. RESULTS: We identified an optimal VE/VCO2 >39 cut-off for predicting 90-day mortality; 245 patients (17.8%) had VE/VCO2 >39, of which 138 (10% of total cohort) had no known cardiorespiratory risk factors. Ventilatory inefficiency was independently associated with death at 90-days (8.2% mortality vs 1.9%; adjusted odds ratio [OR], 4.04; 95% confidence interval [CI], 2.09-7.84), with death after unplanned critical care admission (OR=4.45; 95% CI, 1.37-14.46) and with decreased survival at 2 yr (OR=2.21; 95%, 1.49-3.28) and 5 yr (OR=2.87; 95% CI, 1.54-5.37) after surgery. CONCLUSIONS: A significant proportion of patients having colorectal cancer surgery have ventilatory inefficiency observed on CPET, the majority of whom have no history of cardiorespiratory risk factors. This group of patients has significantly decreased survival both after surgery and in the long-term, irrespective of cancer stage. Survival might be improved by formal medical evaluation and intervention in this group.

Comparison of esophageal Doppler and plethysmographic variability index to guide intraoperative fluid therapy for low-risk patients undergoing colorectal surgery.

STUDY OBJECTIVE: This study aims to investigate if there is equivalence in volumes of fluid administered when intravenous fluid therapy is guided by Pleth Variability Index (PVI) compared to the established technology of esophageal Doppler in low-risk patients undergoing major colorectal surgery. DESIGN: Randomized controlled trial. SETTING: Operating room. PATIENTS: Forty low-risk patients undergoing elective colorectal surgery. INTERVENTION: Patients were monitored by esophageal Doppler and PVI probes and were randomized to have fluid therapy directed by using one of these technologies, with 250 mL boluses of colloid to maintain a maximal stroke volume, or a PVI of less than 14%. MEASUREMENTS: Absolute volumes of fluid volumes given intraoperatively were measured as were 24 hours fluid volumes. Perioperative measurements of lactate and base excess were recorded as were postoperative complications. MAIN RESULT: There was no significant difference between PVI and esophageal Doppler groups in mean total fluid administered (1286 vs 1520 mL, P=.300) or mean intraoperative fluid balance (+839 v+1145 mL, P=.150). CONCLUSIONS: PVI offers an entirely non-invasive alternative for goal-directed fluid therapy in this group of patients.