Study on the correlation between serum indole-3-propionic acid levels and the progression and prognosis of acute ischemic stroke.

OBJECTIVE: This study aimed to explore the correlation between the serum level of indole-3-propionic acid (IPA) and the progression and prognosis of acute cerebral infarction (ACI). METHODS: This study enrolled 197 patients with ACI, and 53 participants from a community-based stroke screening program during the same period were included as the control group. The patients with ACI were divided into quartiles of serum IPA. A logistic regression model was used for comparison. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of the IPA. RESULTS: Compared with the healthy control group, the ACI group had lower serum IPA (P < 0.05). The serum IPA was an independent factor for acute ischemic stroke (OR=0.992, 95% CI: 0.984-0.999, P=0.035). The serum IPA was lower in patients with progressive stroke or poor prognosis than in patients with stable stroke or good prognosis (P < 0.05). Patients with ACI with low serum IPA are prone to progression and poor prognosis. The best cutoff value for predicting progression was 193.62 pg/mL (sensitivity, 67.5%; specificity 83.7%), and that for poor prognosis was 193.77 pg/mL (sensitivity, 71.1%; specificity, 72.5%). CONCLUSION: The serum level of IPA was an independent predictor of ACI and had certain clinical value for predicting stroke progression and prognosis in patients with ACI.

External validation of the iScore, ASTRAL score, DRAGON score, and THRIVE score and development of a nomogram to predict outcome in patients with large vessel occlusion-acute ischemic stroke.

OBJECTIVE: This study aimed to validate the iScore, ASTRAL score, DRAGON score, and THRIVE score for assessing large vessel occlusion-acute ischemic stroke (AIS-LVO) and establish a predictive model for AIS-LVO patients that has better performance to guide clinical practice. METHODS: We retrospectively included 439 patients with AIS-LVO and collected baseline data from all of them. External validation of the iScore, ASTRAL score, DRAGON score, and THRIVE score was performed. All variables were compared between groups via univariate analysis, and the results are expressed as ORs and 95 % CIs. Independent variables with P < 0.25 were included in the multivariate logistic analysis, and statistically significant differences (P < 0.05) were identified as risk factors for prognosis in AIS-LVO patients. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive value of our model. RESULTS: Our external validation resulted in an iScore under the curve (AUC) of 0.8475, an ASTRAL AUC of 0.8324, a DRAGON AUC of 0.8196, and a THRIVE AUC of 0.8039. In our research, multivariate Cox regression revealed 8 independent predictors. We used a nomogram to visualize the results of the data analysis. The AUC for the training cohort was 0.8855 (95 % CI, 0.8487-0.9222), and that in the validation cohort was 0.8992 (95 % CI, 0.8496-0. 9488). CONCLUSIONS: In this study, we verified that the above scores have excellent efficacy in predicting the prognosis of AIS-LVO patients. The nomogram we developed was able to predict the prognosis of AIS-LVO more accurately and may contribute to personalized clinical decision-making and treatment for future clinical work.

Effectiveness and safety of emergency transcatheter aortic valve replacement in patients with severe aortic stenosis complicated by cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: The application of transcatheter aortic valve replacement (TAVR) has been developed on different populations in many clinical studies. However, research dedicated to the application of emergency TAVR in patients with aortic stenosis (AS) experiencing cardiogenic shock is limited. OBJECTIVE: To investigate the safety and effectiveness of emergency TAVR in AS patients with circulatory collapse. METHODS: Studies on the application of emergency TAVR in AS patients with cardiogenic shock were screened from PubMed, Web of Science, and Embase databases. Two researchers independently screened the literature-extracted data and conducted a meta-analysis was conducted using STATA 16.0 software. RESULTS: 17 studies comprising 36,886 patients undergoing emergency TAVR and 8,530 patients undergoing emergency SAVR or BAV. Emergency TAVR showed no difference in valve implantation success rate compared to elective TAVR. At 30-day endpoints comparison, emergency TAVR exhibited significantly higher all-cause mortality and readmission rates than elective TAVR (RR=2.73 95 %CI 2.04-3.65, P < 0.01; RR=1.2 95 %CI 0.9-1.6, P < 0.01), but reduced mortality risk compared to emergency SAVR/BAV (RD=-0.15 95 %CI -0.25 to -0.04, P = 0.005). At one year post-operation, people with emergency TAVR continued to have higher all-cause mortality than elective TAVR (RR=1.55 95 %CI 1.37-1.74, P < 0.01) but similar with emergency SAVR/BAV (RD=-0.04 95 %CI -0.33 to 0.25, P = 0.796). Rates of severe bleeding and new-onset renal dialysis were higher after emergency TAVR, compared to elective TAVR, while the incidences of permanent pacemaker implantation, severe paravalvular leakage and stroke were similar. CONCLUSION: Despite emergency TAVR having higher readmission and mortality rates compared to elective TAVR, it is a relatively safe and effective treatment in cases of cardiogenic shock compared to emergency BAV/SAVR.

Machine Learning-Based Clinical Prediction Models for Acute Ischemic Stroke Based on Serum Xanthine Oxidase Levels.

OBJECTIVE: Early prediction of the onset, progression and prognosis of acute ischemic stroke (AIS) is helpful for treatment decision-making and proactive management. Although several biomarkers have been found to predict the progression and prognosis of AIS, these biomarkers have not been widely used in routine clinical practice. Xanthine oxidase (XO) is a form of xanthine oxidoreductase (XOR), which is widespread in various organs of the human body and plays an important role in redox reactions and ischemia‒reperfusion injury. Our previous studies have shown that serum XO levels on admission have certain clinical predictive value for AIS. The purpose of this study was to utilize serum XO levels and clinical data to establish machine learning models for predicting the onset, progression, and prognosis of AIS. METHODS: We enrolled 328 consecutive patients with AIS and 107 healthy controls from October 2020 to September 2021. Serum XO levels and stroke-related clinical data were collected. We established 5 machine learning models-the logistic regression (LR), support vector machine (SVM), decision tree, random forest, and K-nearest neighbor (KNN) models-to predict the onset, progression, and prognosis of AIS. The area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were used to evaluate the predictive performance of each model. RESULTS: Among the 5 machine learning models predicting AIS onset, the AUROC values of 4 prediction models were over 0.7, while that of the KNN model was lower (AUROC = 0.6708, 95% CI 0.576-0.765). The LR model showed the best AUROC value (AUROC = 0.9586, 95% CI 0.927-0.991). Although the 5 machine learning models showed relatively poor predictive value for the progression of AIS (all AUROCs <0.7), the LR model still showed the highest AUROC value (AUROC = 0.6543, 95% CI 0.453-0.856). We compared the value of 5 machine learning models in predicting the prognosis of AIS, and the LR model showed the best predictive value (AUROC = 0.8124, 95% CI 0.715-0.910). CONCLUSIONS: The tested machine learning models based on serum levels of XO could predict the onset and prognosis of AIS. Among the 5 machine learning models, we found that the LR model showed the best predictive performance. Machine learning algorithms improve accuracy in the early diagnosis of AIS and can be used to make treatment decisions.

Development of a model to predict the risk of multi-drug resistant organism infections in ruptured intracranial aneurysms patients with hospital-acquired pneumonia in the neurological intensive care unit.

OBJECTIVE: This study was developed to explore the incidence of multi-drug resistant organism (MDRO) infections among ruptured intracranial aneurysms(RIA) patient with hospital-acquired pneumonia(HAP) in the neurological intensive care unit (NICU), and to establish risk factors related to the development of these infections. METHODS: We collected clinical and laboratory data from 328 eligible patients from January 2018 to December 2022. Bacterial culture results were used to assess MDRO strain distributions, and risk factors related to MDRO infection incidence were identified through logistic regression analyses. These risk factors were further used to establish a predictive model for the incidence of MDRO infections, after which this model underwent internal validation. RESULTS: In this study cohort, 26.5 % of RIA patients with HAP developed MDRO infections (87/328). The most common MDRO pathogens in these patients included Multidrug-resistant Klebsiella pneumoniae (34.31 %) and Multidrug-resistant Acinetobacter baumannii (27.45 %). Six MDRO risk factors, namely, diabetes (P = 0.032), tracheotomy (P = 0.004), history of mechanical ventilation (P = 0.033), lower albumin levels (P < 0.001), hydrocephalus (P < 0.001) and Glasgow Coma Scale (GCS) score ≤8 (P = 0.032) were all independently correlated with MDRO infection incidence. The prediction model exhibited satisfactory discrimination (area under the curve [AUC], 0.842) and calibration (slope, 1.000), with a decision curve analysis further supporting the clinical utility of this model. CONCLUSIONS: In summary, risk factors and bacterial distributions associated with MDRO infections among RIA patients with HAP in the NICU were herein assessed. The developed predictive model can aid clinicians to identify and screen high-risk patients for preventing MDRO infections.

The clinical value of serum xanthine oxidase levels in patients with acute ischemic stroke.

Xanthine oxidase (XO), a form of xanthine oxidoreductase, is widely distributed in various human tissues. As a major source for the generation of superoxide radicals, XO is involved in the induction of oxidative stress and inflammation during ischemic and hypoxic tissue injury. Therefore, we designed this study to identify the role of serum XO levels in acute ischemic stroke (AIS) pathogenesis. In this single-center prospective study, 328 consecutive patients with AIS for the first time were included, and 107 age- and sex-matched healthy controls from a community-based stroke screening population were also included. The serum levels of XO and several conventional stroke risk factors were assessed. Multivariate analysis was applied to evaluate the relationship between serum levels of XO and clinical outcomes, and nomogram models were developed to predict the onset, progression and prognosis of AIS. Compared with the healthy control group, the serum level of XO was significantly higher in the AIS group (P < 0.05) and was an independent risk factor for AIS (OR 8.68, 95% CI 4.62-14.33, P < 0.05). Patients with progressive stroke or a poor prognosis had a much higher serum level of XO than patients with stable stroke or a good prognosis (all P < 0.05). In addition, the serum level of XO was an independent risk factor for stroke progression (OR 1.98, 95% CI 1.12-3.50, P = 0.018) and a poor prognosis (OR 2.51, 95% CI 1.47-3.31, P = 0.001). The nomogram models including XO to predict the onset, progression and prognosis of AIS had good prediction and differentiation abilities. The findings of this study show that the serum level of XO on admission was an independent risk factor for AIS and had certain clinical predictive value for stroke progression and prognosis in patients with AIS.

Correlation Between Plasma Levels of RIP3 and Acute Ischemic Stroke with Large-Artery Atherosclerosis.

BACKGROUND: Receptor-interacting serine-threonine protein kinase 3 (RIP3) was previously discovered to be an important medium in the occurrence and development of major atherosclerotic cerebral infarction. However, the role of RIP3 in acute ischemic stroke remains unclear. OBJECTIVE: This study aimed to explore the correlation between plasma levels of RIP3 and acute ischemic stroke with large-artery atherosclerosis (LAA). METHODS: This prospective study enrolled 116 patients with LAA, 40 healthy controls, and 30 acute ischemic stroke patients with small-artery occlusion. The patients with LAA were divided according to the quartile of plasma levels of RIP3. A logistic regression model was used for comparison. The ROC curve was performed to evaluate the predictive value. RESULTS: In patients with LAA, the RIP3 levels in patients with poor outcomes as well as neurological deterioration were significantly higher than those with good outcomes (P < 0.001) and without neurological deterioration (P = 0.014). Patients in the highest levels of plasma RIP3 quartile were more likely to have neurological deterioration (OR, 11.07; 95% CI, 1.990-61.582) and poor outcomes (OR, 35.970; 95% CI, 5.392-239.980) compared with the lowest. The optimal cut-off value for neurological deterioration was 1127.75 pg/mL (specificity, 66.7%; sensitivity, 69.2%) and that for poor prognosis was 1181.82 pg/mL (specificity, 89.7%; sensitivity, 62.1%). CONCLUSION: Elevated levels of plasma RIP3 were significantly associated with neurological deterioration and poor prognosis in patients with LAA. A significant increase in plasma RIP3 levels can predict neurological deterioration and the poor prognosis of these patients.

Maraviroc, an inhibitor of chemokine receptor type 5, alleviates neuroinflammatory response after cerebral Ischemia/reperfusion injury via regulating MAPK/NF-κB signaling.

Neuroinflammation is a key factor that contributes to the secondary damage after cerebral ischemia/reperfusion (CI/R) injury. Chemokine receptor type 5 (CCR5) has shown its pro-inflammatory effects during central nervous system (CNS) diseases. However, the role of CCR5 in CI/R injury is still unclear. In this study, we administered maraviroc (MVC, APEXBIO, UK-427857), a CCR5 antagonist, to the middle cerebral artery occlusion (MCAO) mice. In vivo studies showed that MVC was successively intraperitoneally (i.p.) injected with doses (20 mg/kg body weight) for 3 days after mice MCAO. MVC showed its neuroprotective effects in alleviating neurological deficits and infarct volumes after MCAO. The level of apoptosis and inflammation were remarkably decreased by MVC treatment after CI/R injury. Subsequently, primary microglia cells were stimulated with doses of MVC (20 nM) for 12 h after oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. MVC significantly increased the viability of primary microglia after OGD/R. The expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in microglia was down-regulated by MVC treatment. Mechanistically, MVC also inhibited the secretion of these cytokines by microglia after OGD stimulation. Furthermore, the key components of NF-κB pathway were measured in vivo and in vitro after MCAO and OGD. MVC significantly inhibited the activity of NF-κB pathway in the above pathological environments. Finally, our data indicated that MVC treatment decreased the activation of JNK signaling pathway after CI/R injury in vivo and in vitro. The JNK activator anisomycin (AN, Beyotime, SC0132) reversed the neuroprotective effects of MVC, indicating that the JNK pathway is involved in the anti-inflammatory and anti-apoptotic mechanisms of MVC in CI/R injury. Our data demonstrated that CCR5 inhibition exhibits neuroprotective effects after CI/R injury. MVC, which is widely used for HIV treatment by its anti-virus effect, is a potential drug for the treatment of ischemic stroke in the future clinical trials. MVC has been widely used in HIV treatment which showed its safety. Based on its anti-inflammatory and anti-apoptotic mechanisms, we speculate that MVC may be a potential drug for treating ischemic stroke in future clinical trials.