LASSO-Based Machine Learning Algorithm for Prediction of PICS Associated with Sepsis.

Introduction: This study aims to establish a comprehensive, multi-level approach for tackling tropical diseases by proactively anticipating and managing Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) within the initial 14 days of Intensive Care Unit (ICU) admission. The primary objective is to amalgamate a diverse array of indicators and pathogenic microbial data to pinpoint pivotal predictive variables, enabling effective intervention specifically tailored to the context of tropical diseases. Methods: A focused analysis was conducted on 1733 patients admitted to the ICU between December 2016 and July 2019. Utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression, disease severity and laboratory indices were scrutinized. The identified variables served as the foundation for constructing a predictive model designed to forecast the occurrence of PICS. Results: Among the subjects, 13.79% met the diagnostic criteria for PICS, correlating with a mortality rate of 38.08%. Key variables, including red-cell distribution width coefficient of variation (RDW-CV), hemofiltration (HF), mechanical ventilation (MV), Norepinephrine (NE), lactic acidosis, and multiple-drug resistant bacteria (MDR) infection, were identified through LASSO regression. The resulting predictive model exhibited a robust performance with an Area Under the Curve (AUC) of 0.828, an accuracy of 0.862, and a specificity of 0.977. Subsequent validation in an independent cohort yielded an AUC of 0.848. Discussion: The acquisition of RDW-CV, HF requirement, MV requirement, NE requirement, lactic acidosis, and MDR upon ICU admission emerges as a pivotal factor for prognosticating PICS onset in the context of tropical diseases. This study highlights the potential for significant improvements in clinical outcomes through the implementation of timely and targeted interventions tailored specifically to the challenges posed by tropical diseases.

LASSO-Based Identification of Risk Factors and Development of a Prediction Model for Sepsis Patients.

Objective: The objective of this study was to utilize LASSO regression (Least Absolute Shrinkage and Selection Operator Regression) to identify key variables in septic patients and develop a predictive model for intensive care unit (ICU) mortality. Methods: We conducted a cohort consisting of septic patients admitted to the ICU between December 2016 and July 2019. The disease severity and laboratory index were analyzed using LASSO regression. The selected variables were then used to develop a model for predicting ICU mortality. AUCs of ROCs were applied to assess the prediction model, and the accuracy, sensitivity and specificity were calculated. Calibration were also used to assess the actual and predicted values of the predictive model. Results: A total of 1733 septic patients were included, among of whom 382 (22%) died during ICU stay. Ten variables, namely mechanical ventilation (MV) requirement, hemofiltration (HF) requirement, norepinephrine (NE) requirement, septicemia, multiple drug-resistance infection (MDR), thrombocytopenia, hematocrit, red-cell deviation width coefficient of variation (RDW-CV), C-reactive protein (CRP), and antithrombin (AT) III, showed the strongest association with sepsis-related mortality according to LASSO regression. When these variables were combined into a predictive model, the area under the curve (AUC) was found to be 0.801. The AUC of the validation group was 0.791. The specificity of the model was as high as 0.953. Within the probability range of 0.25 to 0.90, the predictive performance of the model surpassed that of individual predictors within the cohort. Conclusion: Our findings suggest that a predictive model incorporating the variables of MV requirement, HF requirement, NE requirement, septicemia, MDR, thrombocytopenia, HCT, RDW-CV, CRP, and AT III exhibiting an 80% likelihood of predicting ICU mortality in sepsis and demonstrates high accuracy.

Co-expression module analysis reveals high expression homogeneity for both coding and non-coding genes in sepsis.

Sepsis is a life-threatening condition characterized by a harmful host response to infection with organ dysfunction. Annually about 20 million people are dead owing to sepsis and its mortality rates is as high as 20%. However, no studies have been carried out to investigate sepsis from the system biology point of view, as previous research predominantly focused on individual genes without considering their interactions and associations. Here, we conducted a comprehensive exploration of genome-wide expression alterations in both mRNAs and long non-coding RNAs (lncRNAs) in sepsis, using six microarray datasets. Co-expression networks were conducted to identify mRNA and lncRNA modules, respectively. Comparing these sepsis modules with normal modules, we observed a homogeneous expression pattern within the mRNA/lncRNA members, with the majority of them displaying consistent expression direction. Moreover, we identified consistent modules across diverse datasets, consisting of 20 common mRNA members and two lncRNAs, namely CHRM3-AS2 and PRKCQ-AS1, which are potential regulators of sepsis. Our results reveal that the up-regulated common mRNAs are mainly involved in the processes of neutrophil mediated immunity, while the down-regulated mRNAs and lncRNAs are significantly overrepresented in T-cell mediated immunity functions. This study sheds light on the co-expression patterns of mRNAs and lncRNAs in sepsis, providing a novel perspective and insight into the sepsis transcriptome, which may facilitate the exploration of candidate therapeutic targets and molecular biomarkers for sepsis.

Inferior vena cava thrombosis during extracorporeal membrane oxygenation: a case report and review of the literature.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an effective cardiopulmonary support therapy, which can provide temporary cardiopulmonary support for critically ill patients whose condition cannot be reversed by conventional therapy. However, there are many complications in the use of ECMO, such as bleeding, thrombosis, and so on. Among them, inferior vena cava (IVC) thrombosis which can cause pulmonary embolism is a rare complication, which may be life-threatening. CASE PRESENTATION: A 75-year-old female patient (Han Chinese ethnicity) with acute heart failure due to acute myocardial infarction in our department was retrospectively analyzed. After regular treatment was unsuccessful, she was treated with venoarterial ECMO (VA-ECMO). After her condition improved, she was withdrawn from ECMO and experienced a complication of IVC thrombosis. Enoxaparin was given immediately for 1 mg/kg every 12 hours hypodermic injection. The thrombus disappeared after anticoagulant therapy. She was discharged on the 60th day. Her level of consciousness returned to normal without residual central nervous system-related complications. CONCLUSIONS: IVC thrombosis is one of the possible serious complications in the process of ECMO therapy. Prevention of thrombosis and optimization of the anticoagulant regimen are the main preventive measures. Anticoagulant therapy is still the main treatment of IVC thrombosis in the process of ECMO therapy. Other interventional strategies need to accumulate clinical experience.

Knockdown of lncRNA MALAT1 Alleviates LPS-Induced Acute Lung Injury via Inhibiting Apoptosis Through the miR-194-5p/FOXP2 Axis.

PURPOSE: We aimed to identify and verify the key genes and lncRNAs associated with acute lung injury (ALI) and explore the pathogenesis of ALI. Research showed that lower expression of the lncRNA metastasis-associated lung carcinoma transcript 1 (MALAT1) alleviates lung injury induced by lipopolysaccharide (LPS). Nevertheless, the mechanisms of MALAT1 on cellular apoptosis remain unclear in LPS-stimulated ALI. We investigated the mechanism of MALAT1 in modulating the apoptosis of LPS-induced human pulmonary alveolar epithelial cells (HPAEpiC). METHODS: Differentially expressed lncRNAs between the ALI samples and normal controls were identified using gene expression profiles. ALI-related genes were determined by the overlap of differentially expressed genes (DEGs), genes correlated with lung, genes correlated with key lncRNAs, and genes sharing significantly high proportions of microRNA targets with MALAT1. Quantitative real-time PCR (qPCR) was applied to detect the expression of MALAT1, microRNA (miR)-194-5p, and forkhead box P2 (FOXP2) mRNA in 1 µg/ml LPS-treated HPAEpiC. MALAT1 knockdown vectors, miR-194-5p inhibitors, and ov-FOXP2 were constructed and used to transfect HPAEpiC. The influence of MALAT1 knockdown on LPS-induced HPAEpiC proliferation and apoptosis via the miR-194-5p/FOXP2 axis was determined using Cell counting kit-8 (CCK-8) assay, flow cytometry, and Western blotting analysis, respectively. The interactions between MALAT1, miR-194-5p, and FOXP2 were verified using dual-luciferase reporter gene assay. RESULTS: We identified a key lncRNA (MALAT1) and three key genes (EYA1, WNT5A, and FOXP2) that are closely correlated with the pathogenesis of ALI. LPS stimulation promoted MALAT1 expression and apoptosis and also inhibited HPAEpiC viability. MALAT1 knockdown significantly improved viability and suppressed the apoptosis of LPS-stimulated HPAEpiC. Moreover, MALAT1 directly targeted miR-194-5p, a downregulated miRNA in LPS-stimulated HPAEpiC, when FOXP2 was overexpressed. MALAT1 knockdown led to the overexpression of miR-194-5p and restrained FOXP2 expression. Furthermore, inhibition of miR-194-5p exerted a rescue effect on MALAT1 knockdown of FOXP2, whereas the overexpression of FOXP2 reversed the effect of MALAT1 knockdown on viability and apoptosis of LPS-stimulated HPAEpiC. CONCLUSION: Our results demonstrated that MALAT1 knockdown alleviated HPAEpiC apoptosis by competitively binding to miR-194-5p and then elevating the inhibitory effect on its target FOXP2. These data provide a novel insight into the role of MALAT1 in the progression of ALI and potential diagnostic and therapeutic strategies for ALI patients.

Whole blood transcriptomic investigation identifies long non-coding RNAs as regulators in sepsis.

BACKGROUND: Sepsis is a fatal disease referring to the presence of a known or strongly suspected infection coupled with systemic and uncontrolled immune activation causing multiple organ failure. However, current knowledge of the role of lncRNAs in sepsis is still extremely limited. METHODS: We performed an in silico investigation of the gene coexpression pattern for the patients response to all-cause sepsis in consecutive intensive care unit (ICU) admissions. Sepsis coexpression gene modules were identified using WGCNA and enrichment analysis. lncRNAs were determined as sepsis biomarkers based on the interactions among lncRNAs and the identified modules. RESULTS: Twenty-three sepsis modules, including both differentially expressed modules and prognostic modules, were identified from the whole blood RNA expression profiling of sepsis patients. Five lncRNAs, FENDRR, MALAT1, TUG1, CRNDE, and ANCR, were detected as sepsis regulators based on the interactions among lncRNAs and the identified coexpression modules. Furthermore, we found that CRNDE and MALAT1 may act as miRNA sponges of sepsis related miRNAs to regulate the expression of sepsis modules. Ultimately, FENDRR, MALAT1, TUG1, and CRNDE were reannotated using three independent lncRNA expression datasets and validated as differentially expressed lncRNAs. CONCLUSION: The procedure facilitates the identification of prognostic biomarkers and novel therapeutic strategies of sepsis. Our findings highlight the importance of transcriptome modularity and regulatory lncRNAs in the progress of sepsis.

Attenuation of hyperoxic acute lung injury by Lycium barbarum polysaccharide via inhibiting NLRP3 inflammasome.

Lycium barbarum polysaccharide (LBP), an active component from Goji berry which is a traditional Chinese medicine, has anti-inflammatory and antioxidant features. The aim of our study was to investigate whether LBP has any role in hyperoxia-induced acute lung injury (ALI). Using a murine model of hyperoxia-induced ALI, we investigate the effect of LBP on pulmonary pathological changes as well as Sirtuin 1 (SIRT1) and the nucleotide binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome. Exposure to 100% oxygen for 72 h in male C57BL/6 mice resulted in increased protein levels of tumor necrosis factor-α and interleukin-1ß in lung tissues, and aggravated lung histological alterations. These hyperoxia-induced changes and mortality were improved by LBP. LBP markedly suppressed the activation of NLRP3 inflammasome both in vivo and in vitro. Moreover, LBP upregulated SIRT1 expression compared with vehicle-treated group. Importantly, knockdown of SIRT1 reversed the inhibitory effect of LBP on NLRP3 inflammasome activation in vitro. LBP meliorated hyperoxia-induced ALI in mice by SIRT1-dependent inhibition of NLRP3 inflammasome activation.

Differential Expression Pattern of Exosome Long Non-Coding RNAs (lncRNAs) and MicroRNAs (miRNAs) in Vascular Endothelial Cells Under Heat Stroke.

BACKGROUND Heat stroke is a life-threatening disease which is characterized by a high body temperature and multiple organ dysfunction syndrome. Vascular endothelial cell injury is a main feature of heat stroke. Little is known about the long noncoding RNA (lncRNA) and microRNA (miRNA) expression alternation in endothelial cell exosomes related to heat stroke. The aim of this study was to explore the changes of lncRNAs and miRNAs expression pattern in exosomes derived from vascular endothelial cells under heat stroke temperature conditions. MATERIAL AND METHODS Cultured medium exosomes from HUVECs (human vascular endothelial cells) either under normal temperature or heat stroke temperature conditions were harvested; then RNA was extracted and the lncRNAs and miRNAs were analyzed by high throughput sequencing. RESULTS Ten significantly upregulated and 10 downregulated lncRNAs were identified in exosomes derived from heat stroke temperature treated cells. Furthermore, GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were used to evaluate the signaling pathway of differential expressions in lncRNAs. Finally, the interaction network of lncRNAs-miRNAs-mRNA was uncovered using ceRNA (competing endogenous RNA) principle via prediction software. CONCLUSIONS These results indicate that the identified lncRNAs and miRNAs in endothelial cell exosomes might serve as non-invasive biomarkers for heat stroke.

Omega-3 Fish Oil Reduces Mortality Due to Severe Sepsis with Acute Gastrointestinal Injury Grade III.

BACKGROUND: Sepsis plays an important role in acute gastrointestinal injury (AGI). Our research was designed to determine the effects of omega-3 fish oil (FO) in patients suffering from severe sepsis combined with AGI III, and the ability of FO to modulate immune function. METHODS: Seventy-eight patients diagnosed with severe sepsis with AGI III and a need for mechanical ventilation were randomized to two groups. In the FO group, 50 g of long chain fatty acid soybean oil (n = 6) and 10 g of FO (n = 3) were administered as total parenteral nutrition (TPN). The control group was treated with 50 g of long chain fatty acid soybean oil without addition of FO to TPN. RESULTS: At baseline, there were no significant differences between the two groups. The 60-day mortality was lower in the FO group. Multiple factor logistic regression analysis revealed that intra-abdominal pressure (IAP) and abdominal infection were correlated with the FO intervention. The patients with abdominal infection demonstrated a lower mortality rate, fewer CD3 T lymphocytes, and fewer helper/inducer T lymphocytes in the FO group compared with the control group. After 7 days, the Marshall Score was lower in the FO group than in the control group. CONCLUSION: FO has positive effects in terms of improving the long-term prognosis of patients with severe sepsis with AGI III. Patients with a high IAP and abdominal infection might experience greater benefit from FO. This effect might be due, in part, to immunomodulation. SUMMARY: Fish oil (FO) has positive effects in terms of improving the long-term prognosis of patients with severe sepsis with acute gastrointestinal injury Grade IIIPatients with a high intra-abdominal pressure and abdominal infection might experience greater benefit from FOThis effect might be due, in part, to immunomodulation. Abbreviations used: AGI: Acute gastrointestinal injury; FO: Fish oil; TPN: Total parenteral nutrition; IAP: Intra-abdominal pressure; ICU: Intensive Care Unit; MODS: Multiple organ dysfunction syndrome; TLR4: Toll-like receptor 4; DNR: Do Not Resuscitate; WGAP: Working Group of Abdominal Problem; EN: Enteral nutrition; BP: Low blood pressure; CRI: Catheter-related infection; PBS: Phosphate-buffered saline; ELFA: Enzyme-linked fluorescent assay; SD: Standard deviation; PUFAs: Polyunsaturated fatty acids; EPA: Eicosapentenoic acid; DHA: Docosahexaenoic acid.

Single-blinded, randomized, and controlled clinical trial evaluating the effects of Omega-3 fatty acids among septic patients with intestinal dysfunction: A pilot study.

Sepsis is a systemic inflammatory reaction, which is aggravated by aspects of the immune response that are thought to be inhibited by Omega-3 fatty acids. The aim of the present study was to determine if Omega-3 fatty acid could modulate immunological function and improve survival rate among septic patients with intestinal dysfunction. A total of 48 mechanically ventilated patients with intestinal dysfunction were included in this prospective, randomized and single-blind clinical study. Patients were randomly divided into control (group A) and treatment groups (group B). The treatment protocol for all the participants followed the Sepsis Survival Campaign guidelines, and group B received total parenteral nutrition containing 100 ml of Omega-3 fatty acids (containing 10 g refined fish oil) per day in addition to the standard treatment applied in group A. Group B had a significantly lower mortality rate compared with group A (12.5 vs. 41.7%, P<0.05) during the 28-day follow-up. Group B also had lower Acute Physiology and Chronic Health Evaluation II scores (P<0.05) and lower Marshall scores (P<0.05) at day 7. In addition, group B had a higher ratio of T helper to inducer lymphocytes as well as a higher ratio of CD4 to CD8 lymphocytes (P<0.01 for both) than group A. It was concluded that Omega-3 fatty acids improved T helper/inducer and CD4/CD8 ratios, and may have reduced mortality, among septic patients with intestinal dysfunction.