Serum Total Cholinesterase Activity on Admission Is Associated with Disease Severity and Outcome in Patients with Traumatic Brain Injury

<div><p>Background</p><p>Traumatic brain injury (TBI) is one of the leading causes of neurological disability. In this retrospective study, serum total cholinesterase (ChE) activities were analyzed in 188 patients for diagnostic as well as predictive values for mortality.</p><p>Methods and Findings</p><p>Within 72 hours after injury, serum ChE activities including both acetylcholinesterase and butyrylcholinesterase were measured. Disease severity was evaluated with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow Coma Score, length of coma, post-traumatic amnesia and injury feature. Neurocognitive and functional scores were assessed using clinical records. Of 188 patients, 146 (77.7%) survived and 42 (22.3%) died within 90 days. Lower ChE activities were noted in the non-survivors <i>vs</i>. survivors (5.94±2.19 <i>vs</i>. 7.04±2.16 kU/L, p=0.023), in septic <i>vs</i>. non-infected patients (5.93±1.89 <i>vs</i>. 7.31±2.45 kU/L, p=0.0005) and in patients with extremely severe injury <i>vs</i>. mild injury (6.3±1.98 vs. 7.57±2.48 kU/L, p=0.049). The trajectories of serum ChE levels were also different between non-survivors and survivors, septic and non-infected patients, mild and severely injured patients, respectively. Admission ChE activities were closely correlated with blood cell counts, neurocognitive and functional scores both on admission and at discharge. Receiver operating characteristic analysis showed that the area under the curve for ChE was inferior to that for either APACHE II or white blood cell (WBC) count. However, at the optimal cutoff value of 5 kU/L, the sensitivity of ChE for correct prediction of 90-day mortality was 65.5% and the specificity was 86.4%. Kaplan-Meier analysis showed that lower ChE activity (<5 kU/L) was more closely correlated with poor survival than higher ChE activity (>5 kU/L) (p=0.04). After adjusting for other variables, ChE was identified as a borderline independent predictor for mortality as analyzed by Binary logistic regression (P=0.078).</p><p>Conclusions</p><p>Lowered ChE activity measured on admission appears to be associated with disease severity and outcome for TBI patients.</p></div

Scatterplot of the correlation of admission ChE activity with blood cell counts, neurocognitive scores, APACHE II score and hospital length of stay (LOS) in total population or in patients dichotomized by outcome.

<p>Scatterplot of the correlation of admission ChE activity with blood cell counts, neurocognitive scores, APACHE II score and hospital length of stay (LOS) in total population or in patients dichotomized by outcome.</p

Kinetics of serum ChE activities in TBI patients categorized by disease severity (A), infected status (B), and outcome (C).

<p>Kinetics of serum ChE activities in TBI patients categorized by disease severity (A), infected status (B), and outcome (C).</p

Kaplan-Meier analysis comparing the cumulative percentages of patients who survived according to their serum ChE activities measured 72 hours after TBI.

<p>Patients with serum ChE levels >5 kU/L showed a significantly higher chance to survive than patients with lower levels (log-rank test, p = 0.04).</p

Admission ChE activity and blood cell counts in TBI patients as classified according to the severity (A), infected status (B), and the outcome (C).

<p>Boxes represented lower, median (line) and upper quartiles; whiskers showed the range of the data excluding outliers (。). *P<0.05, **P<0.01, ***P<0.001, compared with corresponding mild (A), non-infection (B) and survived (C) patients as analyzed by nonparametric test of several independent samples test (The Kruskal-Wallis H test).</p

Association of admission ChE activity with neurocognitive (GCS, MMSE) and functional scores examined both on admission (in) and at discharge (out) in TBI patients (Spearman’s correlation).

<p>It was revealed the positive correlations of ChE activity with neurocognitive scores (GCS, MMSE) and neurofunctional score (QLI, FIM, GOS), but negatively with impairment scores (MRS, RDS, DRS-F).</p><p>Association of admission ChE activity with neurocognitive (GCS, MMSE) and functional scores examined both on admission (in) and at discharge (out) in TBI patients (Spearman’s correlation).</p

The correlation of serum ChE activity on admission with blood cell counts, neurocognitive scores, APACHE II score and hospital length of stay (LOS) in total or in patients with different outcome (Spearman’s correlation).

<p>There were significant correlations between serum ChE activity and the above parameters in all population, but not always so significant in subgroups dichotomized by outcome.</p><p>The correlation of serum ChE activity on admission with blood cell counts, neurocognitive scores, APACHE II score and hospital length of stay (LOS) in total or in patients with different outcome (Spearman’s correlation).</p

Table1_Impact of early heparin therapy on mortality in critically ill patients with sepsis associated acute kidney injury: a retrospective study from the MIMIC-IV database.DOCX

Background: Inflammatory-coagulation dysfunction plays an increasingly important role in sepsis associated acute kidney injury (SAKI). This study aimed to investigate whether early heparin therapy improves survival in patients with SAKI.Methods: Patients with SAKI were identified from the Medical Information Mart for Intensive Care-IV database. The patients were divided into two groups: those who received heparin subcutaneously within 48 h after intensive care unit (ICU) admission and the control group, who received no heparin. The primary endpoint was ICU mortality, the secondary outcomes were 7-day, 14-day, 28-day, and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), and E-value analyses were performed.Results: The study included 5623 individuals with SAKI, 2410 of whom received heparin and 3213 of whom did not. There were significant effects on ICU and 28-day mortality in the overall population with PSM. MSCM further reinforces the efficacy of heparin administration reduces ICU mortality in the general population. Stratification analysis with MSCM showed that heparin administration was associated with decreased ICU mortality at various AKI stages. Heparin use was also associated with reduced 28-day mortality in patients with only female, age >60 years, and AKI stage 3, with HRs of 0.79, 0.77, and 0.60, respectively (p Conclusion: Early heparin therapy for patients with SAKI decreased ICU mortality. Further analysis demonstrated that heparin therapy was associated with reduced 28-day mortality rate in patients only among female, age > 60 years and AKI stage 3.</p