D4-Chip Reveals Impaired T Cell Function in Sepsis: Insights from Plasma Microenvironment Analysis and Mitochondrial Targeted Therapy.

BACKGROUND: Sepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear. METHODS: We developed a novel method using the D4-Chip to assess sepsis T cell migration function. This microfluidic platform enabled precise analysis of migration function under controlled conditions. Additionally, We explored the impact of the plasma microenvironment on T cell behavior, along with the redox environment in sepsis, and assessed the potential efficacy of Mitoquinone mesylate (MitoQ), a mitochondrial-targeted drug. RESULTS: Our findings revealed impaired migration function in sepsis T cells compared to healthy controls. Interestingly, sepsis plasma enhanced the migration of healthy T cells, yet incubation with healthy plasma did not fully restore migration impairments in sepsis T cells. Subsequent investigations uncovered a significant increase in NADH/NAD+ levels in sepsis T cells, with healthy T cells exposed to various sepsis plasma conditions also showing elevated NADH/NAD+ levels. Importantly, MitoQ normalized abnormal intracellular NADH/NAD+ levels and enhanced the migration ability of T cells. CONCLUSIONS: Short-term incubation with sepsis plasma does not directly inhibit T cell migration but instead affects T cell function by disrupting the intracellular redox environment. Improving the intracellular redox environment of sepsis patients contributes to restoring impaired migration and proliferation, with MitoQ demonstrating therapeutic potential.

Assessment of Nutritional Risk Scores (the Nutritional Risk Screening 2002 and Modified Nutrition Risk in Critically Ill Scores) as Predictors of Mortality in Critically Ill Patients on Extracorporeal Membrane Oxygenation.

Nutritional risk is associated with intensive care unit (ICU) stay and mortality, the Nutritional Risk Screening 2002 (NRS 2002) and the modified Nutritional Risk in the Critically Ill (mNUTRIC) score are assessment instruments and useful in predicting the risk regarding mortality in ICU patients. Our aim was to assess the effects of mNUTRIC and NRS 2002 on mortality in patients on extracorporeal membrane oxygenation (ECMO). A retrospective cohort study was performed and 78 patients were included for final analysis. In the current study, the NRS 2002 and the mNUTRIC score within 24 hours before starting ECMO were applied to assess patients' nutritional status on ECMO and explore the relationship between nutritional status and patient outcomes. This study suggests that both mNUTRIC and NRS 2002 scores were found to be significant independent risk and prognostic factors for in-hospital and 90 day morality among ECMO patients based on multivariable logistic regression analysis ( p < 0.05), with those in the high-risk group having higher in-hospital and 90 day mortality rates than those identified as being at low risk ( p < 0.001). In comparison to the NRS 2002 score, the mNUTRIC score demonstrated a superior prognostic ability in ECMO patients.

Intensivist-Led Transportation of Patients on Extracorporeal Membrane Oxygenation: A Single Center Experience.

This study evaluated the suitability, feasibility, safety, and outcomes of transport of the ECMO-dependent patient (EDP) by EDP transport team (EDPTT) in China. Eighty-two EDPs (forty-one cases on VV ECMO and forty-one cases on VA ECMO) received transport between June 2018 and June 2021 and were retrospectively analyzed. ECMO circulation was performed by the outlying hospital, mainly using percutaneous ECMO cannulation. The EDPTT consists of three intensive therapists, one of whom serves as a team leader, and one intensive care unit nurse. Of these, 81 (98.8%) patients were transferred by ambulance, no deaths occurred during transport, the EDP-related complications were 19% (n = 16); bleeding at the cannula site (n = 7, 8.5%) was the most prominent; equipment-related problems accounted for 14.6% of the problems requiring urgent intervention, with hand cranking being the most common (9.7%). The survival rate during transport was 100%, with 36 (43.9%) patients surviving to discharge. The ECMO weaning rate was 61% for VV ECMO and 63.7% for VA ECMO. The results demonstrated the suitability, feasibility, and safety of transporting EDP in a team led by an intensivist, with few complications and no deaths during transport. This may be the recommended staffing model for EDP transport in developing countries.

Exploration of a nomogram prediction model of 30-day survival in adult ECMO patients.

Objective: To investigate the factors of 30-day survival in ECMO patients, establish a nomogram model, and evaluate the predictive value of the model. Methods: A total of 105 patients with extracorporeal membrane oxygenation (ECMO) were admitted to the Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, from January 2018 to March 2021. Cox regression analysis screened out the risk factors. Based on the results of multivariate analysis, the nomogram model was established by using R software, and the discrimination of the model was verified by bootstrap and calibration. Results: The results showed that sex, acute physiology and chronic health evaluation (APACHE) II score, disseminated intravascular coagulation (DIC) score before ECMO initiation and average daily dose of norepinephrine were independent risk factors for prognosis. Verify that the nomogram model is verified by bootstrap internally, and the corrected C-index is C-index: 0.886, showing a good degree of discrimination. The calibration curve (calibration) showed that the nomogram model had good agreement. The decision curve analysis(DCA) curve shows good clinical validity above the two extreme curves. Kaplan-Meier curves were drawn for patients in the tertile and compared with the first and second groups. The third group predicted the worst 30-day prognosis for ECMO patients. Conclusion: The nomogram prediction model constructed based on the sex, APACHE II and DIC score, average daily dose of norepinephrine can effectively screen out the factors affecting the prognosis and provide a reference for individualized treatment of ECMO patients.

The importance of serum LMAN2 level in septic shock and prognosis prediction in sepsis patients.

Objectives: To study the importance of LMAN2 in septic shock and prognosis prediction in sepsis patients. Methods: Serum LMAN2 was measured by ELISA in 109 sepsis patients within 24 h after their admission to ICU. We also collected clinical and laboratory variables. Results: Compared with sepsis group (1.21 (1.05) ng/ml), serum LMAN2 level was significantly higher in patients with septic shock (1.75 (2.04) ng/ml) on the day of admission to the ICU (P < 0.001), and serum LMAN2 level were significantly higher in the sepsis non-survival group (1.91 (1.66) ng/ml) than in the survival group (1.15 (1.17) ng/ml). COX regression analysis showed that high serum LMAN2 level (>1.28 ng/ml) was a predictor of 28-day mortality in sepsis patients. Conclusions: This study shows that high serum LMAN2 level may indicate septic shock and is associated with an unfavorable prognosis for sepsis patients.

Veno-venous extracorporeal membrane oxygenation for septic shock patients with pulmonary infection: A propensity score matching-based retrospective study.

OBJECTIVE: To evaluate whether septic shock patients with pulmonary infection and life-threatening hypoxemia can benefit from V-V ECMO. METHODS: Retrospective clinical data analysis on patients who suffered septic shock with pulmonary infection, categorized into V-V ECMO and control groups. The propensity score matching (PSM) method was used to screen patients matched for age, gender, and disease severity. The primary outcome was 30- and 90-day mortality after diagnosis of septic shock. RESULTS: After PSM, 31 pairs of patients were enrolled in this study, and there were no significant differences between the two groups in terms of gender, age, chronic disease, acute physiological and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. Within 28 days after the diagnosis of septic shock, the median time of renal replacement therapy-free days was longer in the V-V ECMO group than in the control group (27 days vs. 9 days; p = 0.044). Kaplan-Meier analysis showed that 30-day mortality was lower in the V-V ECMO group than in the control group (38.7% vs. 61.3%; HR 0.488; 95% CI 0.240-0.992; p = 0.043, by log-rank test); 90-day mortality was not significantly different between the two groups (51.6% vs. 67.7%, p = 0.097). CONCLUSION: Patients receiving V-V ECMO support had lower 30-day mortality and faster recovery of renal function within 28 days compared with those receiving conventional therapy. However, V-V ECMO did not improve 90-day survival in septic shock patients with pulmonary infection.

Evaluation of the revised ISTH overt DIC score (2018) for predicting 90-day mortality in critically ill adult patients undergoing extracorporeal membrane oxygenation.

BACKGROUND AND OBJECTIVE: Coagulopathy is a common and serious problem in patients who received extracorporeal membrane oxygenation (ECMO), and this study evaluated whether the 2018 diffuse intravascular coagulation (DIC) score established by the International Society on Thrombosis and Hemostasis (ISTH) is associated with 90-day mortality in adult ECMO patients. METHODS: A retrospective study analyzed data from adult patients receiving ECMO in our hospital from September 2018 to April 2021. Pre-ECMO DIC score and other variables were assessed and compared to predict 90-day mortality. RESULTS: Among 103 eligible patients, 55.3% received V-V ECMO and 44.7% received V-A ECMO. The overall 90-day mortality for study patients was 54.4%, including 45.6% in the V-V group and 65.2% in the V-A group. Multiple logistic regression analysis showed that after adjusting for sex, sepsis, and APACHE II score, pre-ECMO DIC scores in the total and V-V group predicted 90-day mortality (odds ratio(OR): 1.419, 95% confidence interval (CI): 1.101-1.828; OR: 2.562; 95% CI: 1.452-4.520). Receiver operating characteristic (ROC) curves displayed that pre-ECMO DIC score of 4 in the total and V-V group was a good predictor of 90-day mortality (area under the curve [AUC] = 0.706, 95% CI: 0.606-0.806; AUC = 0.737, 95% CI: 0.604-0.870). Kaplan-Meier curves demonstrated the 90-day mortality of patients with pre-ECMO DIC score ≥ 4 in the total and V-V group was higher than that of patients with DIC score < 4 (hazard ratio [HR]: 2.821, 95% CI: 1.632-4.879; HR: 3.864, 95% CI: 1.660-8.992). CONCLUSION: The pre-ECMO ISTH DIC score was associated with 90-day mortality in adult patients undergoing ECMO, particularly in the V-V ECMO group.