Postoperative delirium prediction after cardiac surgery using machine learning models.

OBJECTIVE: Postoperative delirium (POD) is a common postoperative complication in elderly patients, especially those undergoing cardiac surgery, which seriously affects the short- and long-term prognosis of patients. Early identification of risk factors for the development of POD can help improve the perioperative management of surgical patients. In the present study, five machine learning models were developed to predict patients at high risk of delirium after cardiac surgery and their performance was compared. METHODS: A total of 367 patients who underwent cardiac surgery were retrospectively included in this study. Using single-factor analysis, 21 risk factors for POD were selected for inclusion in machine learning. The dataset was divided using 10-fold cross-validation for model training and testing. Five machine learning models (random forest (RF), support vector machine (SVM), radial based kernel neural network (RBFNN), K-nearest neighbour (KNN), and Kernel ridge regression (KRR)) were compared using area under the receiver operating characteristic curve (AUC-ROC), accuracy (ACC), sensitivity (SN), specificity (SPE), and Matthews coefficient (MCC). RESULTS: Among 367 patients, 105 patients developed POD, the incidence of delirium was 28.6 %. Among the five ML models, RF had the best performance in ACC (87.99 %), SN (69.27 %), SPE (95.38 %), MCC (70.00 %) and AUC (0.9202), which was far superior to the other four models. CONCLUSION: Delirium is common in patients after cardiac surgery. This analysis confirms the importance of the computational ML models in predicting the occurrence of delirium after cardiac surgery, especially the outstanding performance of the RF model, which has practical clinical applications for early identification of patients at risk of developing POD.

[Effects of myocardial platelet rich plasma injection on rats with acute myocardial infarction:(99)Tc(m)-MIBI gated SPECT imaging evaluation results].

OBJECTIVE: To observe the effect of direct myocardial injection of platelet rich plasma (PRP) on cardiac function, ventricular remodeling and myocardial perfusion. METHODS: Myocardial infarction was induced in 30 Fisher rats by left anterior descending coronary artery (LAD) ligation. One week after LAD ligation, rats in control group (n = 15) received 0.5 ml saline myocardial injection and rats in PRP group (n = 11) received 0.5 ml PRP myocardial injection.(99)Tc(m)-methoxyisobutylisonitrile (MIBI) gated single photon-emission computed tomography (SPECT) imaging was applied at 1 week post LAD ligation and prior myocardial saline/PRP injection and repeated at 4 week post LAD ligation to assess myocardial perfusion and ejection fraction (EF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and the number of infarct segments. RESULTS: EF remained unchanged between 1 and 4 weeks post LAD ligation in control group and was significantly higher at 4 weeks post LAD ligation than at 1 week post LAD ligation in PRP group (P < 0.05). LVESV was significantly increased in the control group (P < 0.05) while remained unchanged in the PAP group (P < 0.05) at 4 weeks post LAD ligation compared that at 1 week post LAD ligation. LVEDV remained unchanged in the control group (P > 0.05) and significantly increased in the PRP group (P < 0.05) from 1 week to 4 weeks post LAD ligation. Myocardial perfusion remained unchanged in the control group and significantly improved in the PRP group at 4 week post LAD ligations. Histological examination also confirmed that PRP treatment can decrease infarct size [from (47 ± 19)% to (36 ± 11)%], increase ventricular wall thickness [from (3.1 ± 0.9) mm to(4.6 ± 1.8) mm] (P < 0.05). CONCLUSION: Myocardial PRP injection could improve cardiac function and reperfusion in this rat model of acute myocardial infarction.

Adenosine postconditioning protects against myocardial ischemia-reperfusion injury though modulate production of TNF-α and prevents activation of transcription factor NF-kappaB.

Adenosine serves a number of important physiological roles in the body, which is the most widely studied endogenous signal molecules, and the underlying mechanism responsible for such cardioprotection needs more understood, particularly adenosine postconditioning in myocardial ischemia/reperfusion model. In the present study we performed to investigate the inflammatory response of adenosine postconditioning on the cardiac TNF-α expression and NF-κB activation. Eighteen rats were randomly divided into 4 groups: (1) Group A: sham operation group; (2) Group B: ischemia/reperfusion group; (3) Group C: postconditioned groups, four cycles of 30-s reperfusion/30-s occlusion were started immediately after release of the index ischemia (n=6 each); (4) Group D: adenosine was infused 40 µg kg(-1) min(-1) 5 min before the onset of reperfusion without subsequent postconditioning cycles. Hearts were removed at the termination of experiments, which were preserved in frozen tube and stored at -70°C refrigerator for Measurement of malonyldialdehyde (MDA), activities of the NF-κB and TNF-α and IL-10 assay. The results of this study indicate that adenosine postconditioning immediately after myocardial ischemia can reduce the myocardial tissue MDA generation and infarct size, improve cardiac function, which is coincidence with conventional postconditioning. The study also found that modulation of NF-κB activation and accordingly reduces inflammatory factor TNF-α expression may be a molecular mechanism of adenosine down-regulation of inflammatory cytokine production.

Protective effects of adenosine in rabbit sinoatrial node ischemia-reperfusion model in vivo: control of arrhythmia by hyperpolarization-activated cyclic nucleotide-gated (HCN)4 channels.

Disturbance of cardiac rhythm is one of the consequences of myocardial ischemia/reperfusion injury. Many researchers have prompted considerable interests in developing therapeutic approaches for its control. In present study, we want to determine whether that adenosine pre- and postconditioning have protective effects on sinoatrial node ischemia/reperfusion injury on morphology, arrhythmia score, serological markers (CK-MB and cTnT), SOD activities, MDA levels and expression of HCN4 channels in SA node cells. According to the arrhythmia score recorded, whether adenosine used in terms of ischemia or reperfusion, the total number of arrhythmia was significantly reduced, as well as the number of its episodes was also markedly decreased. We have also shown a clear correlation between HCN4 channels expression and the dysfunction of SA node cells. HCN4 immunoreactivity decreased after adenosine pre- and postconditioning, but changes were significantly smaller in the cells of the SA node compared with cells of I/R group. The content of cTnT, CK-MB and MDA in adenosine pre- and postconditioning group reduced significantly; but the level of SOD increased significantly. Histological examination and electron microscopy observations found in adenosine pre- and postconditioning group sinoatrial node injury also mitigated. These findings suggested that adenosine pre- or postconditioning were to reduce the incidence of ischemia/reperfusion arrhythmias, reduce myocardial ischemia reperfusion injury. The mechanism was to stabilize the SA node cells membrane and one possible mechanism involves modulation of HCN4 channels in pacemaker cells of the sinoatrial node.

LncRNA-MYL2-2 and miR-124-3p Are Associated with Perioperative Neurocognitive Disorders in Patients after Cardiac Surgery.

BACKGROUND: Perioperative neurocognitive disorders (PND) resulting from cardiac surgery is a complication with high morbidity and mortality. However, the pathogenesis is unknown. METHODS: For the sake of investigating the risk factors and mechanism of PND, we collected the characteristics and neurological scores of patients undergoing cardiac surgery in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and Affiliated Hospital of Southwest Medical University from Jan 1, 2016 to Dec 11, 2018. RESULTS: We found that age and left atrial thrombus are independent risk factors for PND after cardiac surgery. Furthermore, the serum of 29 patients was collected on the 7th day after cardiac surgery for detecting the expression of lncRNA-MYL2-2 and miR-124-3p. Increased lncRNA-MYL2-2 and decreased miR-124-3p in serum were associated with the decline of patients' cognition. CONCLUSIONS: LncRNA-MYL2-2 and miRNA-124-3p may jointly participate in the occurrence and development of PND after cardiac surgery. These important findings are advantaged to further understand the pathogenesis of PND and prevent it, provide new biomarkers for the diagnosis and monitoring of PND.

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD) is serious disorder in the central nervous system common in aged patients after anesthesia. Although its clinical symptoms are well recognized, however, the molecular etiology of the POCD remains unrevealed. Similarly, neither gold standard molecular diagnosis nor effective treatment is available for POCD until the present. Therefore, we aimed to explore the molecular mechanism of this disorder through investigating lncRNAs and mRNAs associated with POCD human patients and investigate their underlying regulatory pathways. In this study, we recruited 200 patients requiring hip or knee replacement surgery. Their neurological functions were assessed at two time points, 1 day before the surgery and 30 days post-surgery. In parallel, serum samples were collected from the participants to analyze lncRNAs and mRNAs differential expression profile between POCD and non-POCD patients using microarray analysis. To further investigate the role differentially expressed mRNA and lncRNAs, Gene Ontology (GO), pathway analyses on mRNAs and lncRNA-mRNA interaction network were performed. As a result, 68 lncRNAs and 115 mRNAs were dysregulated in the POCD group compared to non-POCD group. Among them, the top 10 upregulated lncRNAs and 10 downregulated lncRNAs were listed for enrichment analysis. Interestingly, we found that these lncRNA and mRNA are involved in biological process, molecular function, and cellular component in addition to various signaling pathways, suggesting that the pathogenesis of POCD involves lncRNAs and mRNAs differential expression. Consequently, the genetic dysregulation between the non-POCD and POCD patients participates in the occurrence and development of POCD, and could be served as diagnostic biomarkers and drug targets for POCD treatment.

[Construction of an in vitro carotid artery bifurcation model].

OBJECTIVE: To construct a solid carotid artery bifurcation model with general applicability that simulates the real shape. METHODS: The diameter of the carotid artery was measured using ultrasonic cardiograph. A modified carotid artery model was constructed according to the tuning fork model geometry with the geometry size being rectified. The flow fields in the carotid artery model were detected by the particle imaging velocimetry technique. RESULTS: The characteristics of the distribution of the flow fields in the carotid artery model were similar to those in the human bodies. CONCLUSION: The carotid artery we constructed well resembles the real shape and has good representativeness and practicability, which provides a reliable experimental platform for further research.

Differentiation induction of mouse cardiac stem cells into sinus node-like cells by co-culturing with sinus node.

Sinus nodal cells can generate a diastolic or "pacemaker" depolarization at the end of an action potential driving the membrane potential slowly up to the threshold for firing the next action potential. It has been proved that adult cardiac stem cells (CSCs) can differentiate into sinus nodal cells by demethylating agent. However, there is no report about adult CSCs-derived sinus nodal cells with pacemaker current (the funny current, I f). In this study, we isolated the mouse adult CSCs from mouse hearts by the method of tissue explants adherence. The expression of c-kit protein indicated the isolation of CSCs. Then we co-cultured mouse CSCs with mouse sinus node tissue to induce the differentiation of these CSCs into sinus node-like cells, which was proved by identifying the enhanced expression of marker proteins cTnI, cTnT and α-Actinin with Immunofluorescence staining. At the same time, with whole-cell patch-clamp we detected the I f current, which can be blocked by CsCl, in these differentiated cells. In conclusion, by confirming specific I f current in the induced node-like cells, our work shows a method inducing differentiation of CSCs into sinus node-like cells, which can provide helpful information for the further research on sick sinus syndrome.