Endothelial cell metabolism in sepsis.

BACKGROUND: Endothelial dysfunction in sepsis is a pathophysiological feature of septic organ failure. Endothelial cells (ECs) exhibit specific metabolic traits and release metabolites to adapt to the septic state in the blood to maintain vascular homeostasis. METHODS: Web of Science and PubMed were searched from inception to October 1, 2022. The search was limited to the English language only. Two reviewers independently identified studies related to EC metabolism in sepsis. The exclusion criteria were duplicate articles according to multiple search criteria. RESULTS: Sixty articles were included, and most of them were cell and animal studies. These studies reported the role of glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism in EC homeostasis. including glycolysis, oxidative phosphorylation, fatty acid metabolism and amino acid metabolism. However, dysregulation of EC metabolism can contribute to sepsis progression. CONCLUSION: There are few clinical studies on EC metabolism in sepsis. Related research mainly focuses on basic research, but some scientific problems have also been clarified. Therefore, this review may provide an overall comprehension and novel aspects of EC metabolism in sepsis.

STAF score is a new simple approach for diagnosing cardioembolic stroke.

BACKGROUND AND PURPOSE: Detecting cardioembolic stroke soon after acute cerebral ischemia has a major impact on secondary stroke prevention. Recently, the Score for the Targeting of Atrial Fibrillation (STAF) was introduced to identify stroke patients at risk of atrial fibrillation. However, whether the STAF score could be a useful approach to differentiate cardioembolic stroke from other stroke subtypes is unclear. METHODS: Consecutive patients with acute ischemic stroke that were admitted to our stroke center were enrolled. Each patient was assessed (age, baseline National Institutes of Health Stroke Scale, left atrial dilatation and absence of vascular etiology) to calculate the STAF score. A follow-up visit was conducted for each patient during hospitalization to determine the diagnosed stroke etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. RESULTS: The median and interquartile range of the STAF score was significantly higher in the cardioembolic than in the non-cardioembolic group [6 (2) vs. 2 (3), p < 0.001]. The discriminating ability of the STAF score model was good as demonstrated by the receiver operating characteristic curve. The area under the curve (AUC) of STAF score (AUC = 0.98; 95% CI, 0.96-0.99) was significantly greater than B-type natriuretic peptide (AUC = 0.87; 95% CI, 0.83-0.91) (p < 0.05). The optimal STAF cut-off value was ≥ 5, which diagnosed cardioembolic stroke with a sensitivity of 90% and specificity of 95%. CONCLUSIONS: The STAF score is a simple and accurate tool that can discriminate the cardioembolic stroke from other types during hospitalization for acute ischemic stroke.

Prognostic values of 4 risk scores in Chinese patients with chest pain: Prospective 2-centre cohort study.

Four risk scores for stratifying patients with chest pain presenting to emergency departments (EDs) (namely Thrombolysis in myocardial infarction [TIMI], Global registry for acute coronary events [GRACE], Banach and HEART) have been developed in Western settings but have never been compared and validated in Chinese patients. We aimed to find out to the number of MACE within 7 days, 30 days, and 6 months after initial ED presentation, and also to compare the prognostic performance of these scores in Chinese patients with suspected cardiac chest pain (CCP) to predict 7-day, 30-day, and 6-month major adverse cardiac events (MACE).A prospective 2-center observational cohort study of consecutive patients presenting with chest pain to the EDs of 2 university hospitals in Guangdong and Hong Kong from 17 March 2012 to 14 August 2013 was conducted. Patients aged ≥18 years with suspected CCP but without ST-segment elevation myocardial infarction (STEMI) were recruited.Of 833 enrolled patients (mean age 65.1 years, SD14.5; 55.6% males), 121 (14.5%) experienced MACE within 6 months (4.8% with safety outcomes and 10.3% with effectiveness outcomes). The HEART score had the largest area under the receiver operating characteristic (ROC) curve for predicting MACE at 7-day, 30-day, and 6-month follow-up [area under curve (AUC) = 0.731, 0.726, and 0.747, respectively. The HEART score also had the largest AUC for predicting effectiveness outcome (AUC = 0.715, 0.704, and 0.721, respectively). However, there was no significant difference in AUC between HEART and TIMI scores. Banach had the largest AUC for predicting safety outcome (AUC = 0.856, 0.837, and 0.850, respectively).The HEART score performed better than the GRACE and Banach scores to predict total MACE and effectiveness outcome in Chinese patients with suspected CCP, whereas the Banach score best predicted safety outcomes.

Increased expression of microRNA-21 in peripheral blood mediates the down-regulation of IFN-γ and increases the prevalence of stroke-associated infection.

BACKGROUND: Increasing levels of microRNA (miRNA)-21 can lead to IFN-γ deficiency, thereby suppressing immune function. Whether changes in the peripheral blood expression of miRNA-21 in patients with acute stroke are related to stroke-associated infection (SAI) remains unsettled. METHODS: MiRNA-21 and IFN-γ expression levels in peripheral blood plasma were measured in stroke patients presenting within 24h of symptom onset to assess whether these expression levels are associated with the prevalence of SAI. RESULTS: The stroke with SAI group had significantly higher miRNA-21 expression and lower IFN-γ levels than the stroke without SAI group (p<0.05). A significant negative correlation was observed between miRNA-21 expression and IFN-γ levels (r=-0.303, p=0.026). ROC curves were constructed to measure the performance of the miRNA-21 and IFN-γ to judge SAI. The areas under the ROC curve (AUC) for miRNA-21 and IFN-γ were 0.667 (95% CI, 0.525 to 0.798, p=0.028) and 0.698 (95% CI, 0.558 to 0.816, p=0.005), respectively. The optimal cutoff value was miRNA-21>0.53 and IFN-γ≤72.57pg/ml. There was a significantly different prevalence of SAI between the high miRNA-21 group and the low miRNA-21 group (p=0.008, log rank test). There was also a significant difference between the high IFN-γ group and the low IFN-γ group (p=0.003, log rank test). CONCLUSIONS: Plasma up-regulated miRNA-21 and decreased IFN-γ in acute stroke can be considered new biological predictors for SAI and thus, new therapeutic targets.

Is serum total bilirubin useful to differentiate cardioembolic stroke from other stroke subtypes?

BACKGROUND: Previous studies have reported that the total bilirubin (TB) level is associated with coronary artery disease, heart failure and atrial fibrillation. These heart diseases can produce cardiogenic cerebral embolism and cause cardioembolic stroke. However, whether the serum TB could be a biomarker to differentiate cardioembolic stroke from other stroke subtypes is unclear. METHODS: Our study consisted of 628 consecutive patients with ischaemic stroke. Various clinical and laboratory variables of the patients were analysed according to serum TB quartiles and stroke subtypes. RESULTS: The higher TB quartile group was associated with atrial fibrillation, larger left atrium diameter, lower left ventricular fractional shortening and cardioembolic stroke (P < 0.001, P = 0.001, P = 0.033, P < 0.001, respectively). Furthermore, serum TB was a statistically significant independent predictor of cardioembolic stroke in a multivariable setting (Continuous, per unit increase OR = 1.091, 95%CI: 1.023-1.164, P = 0.008). CONCLUSIONS: Serum TB level was independently associated with cardioembolic stroke. The combination of clinical data and serum TB may be a feasible strategy to diagnose cardioembolic stroke in the acute phase.

Evaluation of the Recognition of Stroke in the Emergency Room (ROSIER) scale in Chinese patients in Hong Kong.

BACKGROUND AND PURPOSE: The objective of this study was to determine the performance of the Recognition Of Stroke In the Emergency Room (ROSIER) scale in risk-stratifying Chinese patients with suspected stroke in Hong Kong. METHODS: This was a prospective cohort study in an urban academic emergency department (ED) over a 7-month period. Patients over 18 years of age with suspected stroke were recruited between June 2011 and December 2011. ROSIER scale assessment was performed in the ED triage area. Logistic regression analysis was used to estimate the impacts of diagnostic variables, including ROSIER scale, past history and ED characteristics. FINDINGS: 715 suspected stroke patients were recruited for assessment, of whom 371 (52%) had acute cerebrovascular disease (302 ischaemic strokes, 24 transient ischaemic attacks (TIA), 45 intracerebral haemorrhages), and 344 (48%) had other illnesses i.e. stroke mimics. Common stroke mimics were spinal neuropathy, dementia, labyrinthitis and sepsis. The suggested cut-off score of>0 for the ROSIER scale for stroke diagnosis gave a sensitivity of 87% (95%CI 83-90), a specificity of 41% (95%CI 36-47), a positive predictive value of 62% (95%CI 57-66), and a negative predictive value of 75% (95%CI 68-81), and the AUC was 0.723. The overall accuracy at cut off>0 was 65% i.e. (323+141)/715. INTERPRETATION: The ROSIER scale was not as effective at differentiating acute stroke from stroke mimics in Chinese patients in Hong Kong as it was in the original studies, primarily due to a much lower specificity. If the ROSIER scale is to be clinically useful in Chinese suspected stroke patients, it requires further refinement.

Comparison of miR-124-3p and miR-16 for early diagnosis of hemorrhagic and ischemic stroke.

BACKGROUND: The present study aimed to investigate and compare plasma concentrations of miR-124-3p and miR-16 as diagnostic markers in acute stroke. METHODS: miR-124-3p and miR-16 concentrations in 93 stroke patients were analyzed using real-time polymerase chain reaction. The primary outcome was the differentiation of hemorrhagic and ischemic stroke. RESULTS: Of 93 patients, 74 (79.6%) were diagnosed as ischemic stroke (IS) and 19 (20.4%) were diagnosed as hemorrhagic stroke (HS). Median plasma 124-3p concentrations taken within 24h of symptom onset were higher in HS patients than that in IS patients (3.8×10(5) vs 2.0×10(5) copies/ml plasma, p=0.0109), while median miR-16 concentration in IS patients were higher than that in HS patients (1.6×10(9) vs 1.3×10(9) copies/ml plasma, p=0.0399). The odds ratio (OR) for discriminating HS and IS with miR-124-3p and miR-16 was 5.37 and 9.75 respectively. CONCLUSION: Both miR-124-3p and miR-16 are diagnostic markers to discriminate HS and IS.

Multiple atherosclerosis-related biomarkers associated with short- and long-term mortality after stroke.

OBJECTIVES: We investigated the relationships of biomarkers of various pathophysiologic pathways including high-sensitivity C-reactive protein (hs-CRP), lipocalin-2 (LCN2), myeloperoxidase (MPO) and matrix metalloproteinases 9 (MMP9) with mortality in stroke patients. DESIGN AND METHODS: hs-CRP, LCN2 and MPO concentrations in 92 patients were determined using enzyme-linked immunosorbent assays. MMP9 mRNA concentrations were determined using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Twelve patients (13.0%) died at 6 months and 34 patients (37.0%) died at 5 years. The independent predictors for 6-month mortality were hs-CRP (adjusted OR=16.0) and LCN2 (adjusted OR=16.9), while for 5-year mortality was hs-CRP (adjusted OR=5.56). For patients with hs-CRP >3.4 mg/L, an increase in LCN2 was associated with 2.5-fold higher 6-month mortality, while an increase in normalized MMP9 mRNA was associated with 5.8-fold higher 6-month and 1.5-fold higher 5-year mortality. CONCLUSION: hs-CRP was the most significant independent predictor of both short- and long-term mortality after stroke, with LCN2 and MMP9 mRNA each adding further to the risk stratification.

[The myocardium protective effects of erythropoietin (EPO) in a rat model of asphyxia-induced cardiac arrest/cardiopulmonary resuscitation (CPR)].

OBJECTIVE: To examine the effects of EPO administration on the integrity of myocardium in a rat model of asphyxia-induced cardiac arrest/CPR. METHODS: 24 male Sprague-Dawley (SD) rats were randomly divided into three groups (8 each) to receive (1) cardiac arrest (induced by tracheal catheter clamping for 8 minutes)/CPR (by chest compressions and mechanical ventilation 8 minutes after cardiac arrest), (2) cardiac arrest/CPR +EPO (5 kU/kg, i.v, 3 minutes after restoration of spontaneous circulation (ROSC), and (3) no-treatment (control). The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal positive/negative filling pressure change versus time (±dp/dt max) in the animals were recorded 30, 60, 90, and 120 minutes after ROSC. Blood and heart tissue samples were collected 120 minutes after ROSC for the examination of serum troponin I (cTnI) level, myocardium pathological change (by light/electronic microscopy), and myocardium apoptosis [by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) staining]. RESULTS: The LVSP, +dp/dt max and - dp/dt max absolute value in CPR group and EPO group were significantly lower than those of baseline at 30, 60, 90, 120 minutes after ROCS. In comparison with the control group, the LVSP( mm Hg, 1 mm Hg = 0.133 kPa: 119.52±12.68, 134.32±15.78 vs. 165.82±7.05), +dp/dt max (mm Hg/sec: 4457.14±826.22, 6019.85±1192.19 vs. 10325.93±773.09), and - dp/dt max ( mm Hg/sec: - 3956.04±952.37, - 4957.22±838.60 vs. - 8421.33±886.65) were significant lower (all P < 0.01) in the CPR and EPO group 30 minutes after ROSC, and such tendency remained till 120 minutes after ROSC: (LVSP: 124.62±8.07, 145.61±16.70 vs. 162.34±7.63; +dp/dt max: 4977.67±350.40, 7471.62±998.32 vs. 9999.39±727.96; - dp/dt max: - 4145.51±729.77, - 5895.64±787.30 vs. - 8089.75±981.52). Compared to the CPR group, the value of LVSP, + dp/dt max and - dp/dt max at all time points were significantly higher in EPO group (all P < 0.05). The LVEDP value was significantly higher ( P < 0.01) in both CPR and EPO group in comparison with the control (mm Hg/sec: 22.94±3.94, 11.18±2.58 vs. 2.89±0.70) 120 minutes after ROSC, and it was significantly lower in EPO group in comparison with CPR group ( P < 0.05). Light/electronic microscopy revealed myocardial necrosis, inflammatory cell infiltration, myocardial cell membrane integrity loss, mitochondrial swelling, and increased number of apoptotic cardiomyocyte (314.1±30.7 vs. 165.2±45.9 as in control) in CPR group samples. In contrast, the cardiomyocyte morphologic damages were significantly fewer in EPO group, so is the numbers of apoptotic cardiomyocyte (242.1±20.0 vs. 314.1±30.7, P < 0.05). In comparison with the control, the serum cTnI 120 minutes after ROSC was significantly higher (all P < 0.01) in CPR and EPO group (µg/L: 20.70±5.96,16.98±3.81 vs. 2.60±0.86), but no such difference was found between these two groups. CONCLUSION: EPO can attenuate the post resuscitation myocardial injury probably through its mitochondrial protective, anti-apoptotic effect.

[The anti-apoptosis effect of erythropoietin on neonatal rat cardiocytes during hypoxia/reoxygenation injury and its possible mechanism].

OBJECTIVE: To investigate the anti-apoptosis effect of erythropoietin (EPO) on myocardial cells after hypoxia/reoxygenation in vitro, and the relationship among protein kinase C (PKC), the mitochondrial ATP-sensitive potassium (mitoKATP) channel and EPO in the anti-apoptotic signaling pathways. METHODS: Cardiocytes were harvested from neonatal rats and cultured. Cultured myocardial cells were divided into the control group, the hypoxia/reoxygenation group, the EPO group and the chelerythrine group, and a hypoxia/reoxygenation model of cardiocytes was reproduced. Apoptosis rate was assayed by flow cytometry. Flavoprotein fluorescence was scanned by confocal laser microscope to assess the mitoKATP channel activity. RESULTS: Apoptosis rate was significantly higher in hypoxia/reoxygenation group than that of control group [(42.56+/-8.00)% vs. (17.88+/-2.00)%, P<0.05]. There was no statistically significant difference in flavoprotein fluorescence between this group and the control group [(0.278+/-0.170)x10(-2) vs. (0.149+/-0.050)x10(-2), P>0.05]. Myocardial cell apoptosis rate in EPO group was lower than that in hypoxia/reoxygenation group [(22.73+/-5.00)% vs. (42.56+/-8.00)%, P<0.05], and flavoprotein fluorescence intensity was significantly enhanced when compared with hypoxia/reoxygenation group [(2.201+/-1.090)x10(-2) vs. (0.278+/-0.170)x10(-2), P<0.01]. However, when chelerythrine was added, the anti-apoptosis effect of EPO was blocked, and the intensity of cardiocytes flavoprotein fluorescence was decreased [the apoptosis rate was (46.72+/-17.00)% and the flavoprotein fluorescence intensity was (0.986+/-0.320)x10(-2) ]. When compared with EPO group there was statistically significant difference (P<0.01 and P<0.05). CONCLUSION: Myocardial cell apoptosis occurs in hypoxia/reoxygenation injury, and EPO can protect rat cardiomyocytes from hypoxia/reoxygenation induced apoptosis. The protective effect is partly associated with the PKC/mitoKATP pathway.

[Role of macrophage migration inhibitory factor in mice with sepsis and after effect of its intervention].

OBJECTIVE: To investigate the expression profile of macrophage migration inhibitory factor (MIF) in serum and lung tissues of mice with sepsis, and to explore the effect of MIF antagonist ISO-1 on sepsis in a murine sepsis model. METHODS: Sepsis was reproduced in 40 mice by cecal ligation and puncture (CLP). Heart blood was obtained from 8 mice each at 12, 24, 36, 48 hours after CLP. The content of MIF in serum was determined by enzyme linked immunosorbent assay (ELISA). MIF mRNA and protein expressions in lung tissues of septic mice were assessed by reverse transcription-polymerase chain reaction (RT-PCR) or Western blotting. Another group of 40 mice were selected to investigate the role and the impact of MIF antagonist ISO-1 in septic mice. RESULTS: The content of MIF in serum was higher in septic mice than that in sham operation group, and it peaked at 36 hours, and decreased at 48 hours, but still higher than that in sham operation group (all P<0.01). The MIF mRNA and protein expression in lung tissues of septic mice were higher than those in sham operation group, beginning at 12 hours, and peaked at 48 hours (P<0.05 or P<0.01). ISO-1, which was the antagonist of MIF, could elevate the surviving rate of animals with sepsis [60% (12/20) vs. 25% (5/20), P<0.05]. CONCLUSION: MIF plays a role as a late mediator in sepsis, with a high expression of MIF in serum and lung tissue. ISO-1 can elevate the surviving rate in murine model of sepsis. It is concluded that MIF could be taken as a potential target of treatment of sepsis.