Correlation between obstructive sleep apnea and hypoperfusion in patients with acute cerebral infarction.

Purpose: To explore the relationship between obstructive sleep apnea (OSA) and hypoperfusion during ultra-early acute cerebral infarction. Patients and methods: Data were retrospectively collected from patients admitted to our hospital with acute cerebral infarction between January 2020 and January 2022, who underwent comprehensive whole-brain computed tomography perfusion imaging and angiography examinations within 6 h of onset. The F-stroke software automatically assessed and obtained relevant data (Tmax). The patients underwent an initial screening for sleep apnea. Based on their Apnea-Hypopnea Index (AHI), patients were categorized into an AHI ≤15 (n = 22) or AHI >15 (n = 25) group. The pairwise difference of the time-to-maximum of the residue function (Tmax) > 6 s volume was compared, and the correlation between AHI, mean pulse oxygen saturation (SpO2), oxygen desaturation index (ODI), percentage of time with oxygen saturation < 90% (T90%), and the Tmax >6 s volume was analyzed. Results: The Tmax >6 s volume in the AHI > 15 group was significantly larger than that in the AHI ≤ 15 group [109 (62-157) vs. 59 (21-106) mL, p = 0.013]. Spearman's correlation analysis revealed Tmax >6 s volume was significantly correlated with AHI, mean SpO2, ODI, and T90% in the AHI > 15 group, however, no significant correlations were observed in the AHI ≤ 15 group. Controlling for the site of occlusion and Multiphase CT angiography (mCTA) score, AHI (ß = 0.919, p < 0.001), mean SpO2 (ß = -0.460, p = 0.031), ODI (ß = 0.467, p = 0.032), and T90% (ß =0.478, p = 0.026) remained associated with early hypoperfusion in the AHI > 15 group. Conclusion: In patients with acute cerebral infarction and AHI > 15, AHI, mean SpO2, ODI and T90% were associated with early hypoperfusion. However, no such relationship exists among patients with AHI ≤ 15.

Albumin-Globulin Ratio and Common Carotid Artery Intima-Media Thickness in Patients with Ischemic Stroke.

BACKGROUND: The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in acute ischemic stroke (AIS) remain uncertain. We investigated the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with AIS. METHODS: A total of 1,339 AIS patients were enrolled. Admission A/G ratio was divided into quartiles, and serum albumin and globulin levels were also categorized. Carotid atherosclerosis was detected through the assessment of common carotid artery intima-media thickness (cIMT), and abnormal cIMT was characterized by mean and maximum cIMT values of ≥1 mm. We evaluated the relationships between A/G ratio, albumin, globulin and abnormal cIMT, using multivariable logistic regression models. RESULTS: In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was linked to a 59% decreased risk of abnormal mean cIMT (OR 0.41; 95% CI 0.29-0.60) and a 58% decreased risk of abnormal maximum cIMT (OR 0.42; 95% CI 0.30-0.60) when compared to the lowest quartile (Q1), respectively. Moreover, decreased albumin and elevated globulin levels were also associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided supplementary predictive capability beyond the already established risk factors, and the C-statistic of the A/G ratio for abnormal cIMT is larger than globulin (P <0.01). CONCLUSION: Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in AIS patients. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT.

Prognostic significance of serum globulin in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: We investigated the association between serum globulin levels upon hospital admission and in-hospital short-term outcomes in acute ischemic stroke (AIS) patients. METHODS: A total of 3,127 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into 4 groups according to their level of admission serum globulin: Q1 (<23.5 g/L), Q2 (23.5-26.4 g/L), Q3 (26.4-29.9 g/L), and Q4 (≥29.9 g/L). Logistic regression models were used to estimate the effect of serum globulin on the short-term outcomes, including all cause in-hospital mortality, poor outcome upon discharge (modified Rankin Scale score ≥3) and in-hospital pneumonia in AIS patients. RESULTS: The median National Institutes of Health Stroke Scale (NIHSS) score was 4.0 (IQR, 2.0-7.0). The risk of in-hospital mortality was significantly higher in patients with highest serum globulin level (Q4) compared to those with lowest (Q1) (adjusted odds ratio [OR] 2.30; 95% confidence interval [CI], 1.12-4.70; P-trend =0.026). The highest serum globulin level (Q4) was associated with a 1.32-fold and 1.62-fold increase in the risk of poor outcome upon discharge (adjusted OR 1.32; 95% CI, 1.00-1.75; P-trend = 0.070) and in-hospital pneumonia (adjusted OR 1.62; 95% CI, 1.18-2.23; P-trend = 0.001) in comparison to Q1 after adjustment for potential covariates. CONCLUSIONS: A high level of serum globulin upon hospital admission was independently associated with all cause in-hospital mortality, poor outcome upon discharge and in-hospital pneumonia in relative mild AIS patients.

Prognostic Value of Red Blood Cell Distribution Width and Hemoglobin in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between baseline red blood cell distribution width (RDW) and hemoglobin levels and outcomes after acute intracerebral hemorrhage (ICH) is not well studied. We aimed to investigate the association between baseline RDW and hemoglobin levels with early hematoma expansion (HE) and mortality at 3 months and 1 year in acute ICH patients. METHODS: A total of 393 ICH patients from January 2014 to February 2019 were included. Patients were divided into four groups based on quartiles of RDW and hemoglobin levels at admission, respectively. Logistic regression models were used to estimate the effect of the levels of RDW and hemoglobin on early HE (absolute hematoma growth >6 mL from baseline to follow-up) and allcaused mortality at 3 months and 1 year. RESULTS: There were no significant associations between baseline RDW and hemoglobin levels and early HE. The 3-month mortality (adjusted odds ratio [OR] 2.88; 95% confidence intervals [CI] 0.96-8.64) and 1-year mortality (adjusted OR 3.16, 95% CI 1.08-9.21) was significantly higher in patients with the highest RDW level (Q4) compared to those with the lowest RDW level (Q1). Moreover, patients with the lowest hemoglobin level were significantly associated with increased odds of all-cause mortality at 3-month (adjusted OR 3.95, 95% CI 1.26-12.4) and 1-year (adjusted OR 4.42, 95% CI 1.56-12.5) compared to those with highest hemoglobin level. CONCLUSION: In patients with acute ICH, a higher level of RDW at admission significantly increased the risk of all-cause mortality at 1 year. Moreover, a decreased hemoglobin level at admission was also associated with a higher risk of all-cause mortality at 3 months and 1 year.

Knockdown of A20 attenuates microglial susceptibility to OGD/R-induced ferroptosis and upregulates inflammatory responses.

The A20 protein is considered to have a potent anti-inflammatory effect, but its mechanism of action in the regulation of ferroptosis and inflammation after stroke is still unknown. In this study, the A20-knockdown BV2 cell line (sh-A20 BV2) was constructed at first, and the oxygen-glucose deprivation/re-oxygenation (OGD/R) cell model was constructed. Both the BV2 and sh-A20 BV2 cells were treated with the ferroptosis inducer erastin for 48 h, the ferroptosis-related indicators were detected by western blot. The mechanism of ferroptosis was explored by western blot and immunofluorescence. Under OGD/R pressure, the oxidative stress level of sh-A20 BV2 cells was inhibited, but the secretion of the inflammatory factors TNF-α, IL-1ß, and IL-6 was significantly upregulated. And sh-A20 BV2 cells had higher expression levels of GPX4 and NLRP3 proteins under OGD/R induction. Western blot further confirmed that sh-A20 BV2 cells inhibited OGD/R-induced ferroptosis. Under the effect of erastin of the ferroptosis inducer (0-1000 nM), sh-A20 BV2 cells had higher cell viability than wild-type BV2 cells and significantly inhibited the accumulation of ROS and the level of oxidative stress damage. It was confirmed that A20 could promote the activation of the IκBα/NFκB/iNOS pathway. It was confirmed by an iNOS inhibitor that iNOS inhibition could reverse the resistance effect of BV2 cells to OGD/R-induced ferroptosis after A20 knockdown. In conclusion, this study demonstrated that inhibition of A20 mediates a stronger inflammatory response while enhancing microglial resistance by knocking down A20 in BV2 cells.

Higher NT-proBNP Levels are Related to Poor Functional Outcome and Pneumonia in Acute Intracerebral Hemorrhage Patients.

BACKGROUND: We investigated the association between N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) levels upon hospital admission and early hematoma growth (HG), inhospital pneumonia and major disability in patients with acute intracerebral hemorrhage (ICH). METHODS: A total of 353 ICH patients from January 2014 to February 2019 were included in the present study. Patients were divided into three groups based on the admission NT-proBNP levels (T1: <61; T2: 61-199; T3: ≥199 pg/mL). Logistic regression models were used to estimate the effect of NT-proBNP on early HG, in-hospital pneumonia, and major disability upon hospital discharge (modified Rankin Scale score ≥5) in ICH patients. RESULTS: There was no significant association observed between baseline NT-proBNP levels and early HG (P-trend =0.249). The risk of in-hospital pneumonia was significantly higher in patients with the highest NT-proBNP level (T3) (adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.11-4.08) and higher NT-proBNP level (T2) (adjusted OR 2.18; 95% CI, 1.19-4.00) compared to those with lowest NT-proBNP level (T1). The highest NT-proBNP level (T3) was associated with a 3.55-fold increase in the risk of major disability at hospital discharge (adjusted OR 3.55; 95% CI, 1.23-10.26; P-trend =0.013) in comparison to T1 after adjustment for potential covariates, including pneumonia. CONCLUSION: Increased NT-proBNP at admission was independently associated with in-hospital pneumonia and major disability upon discharge but not early hematoma growth in acute ICH patients.

The Prognostic Significance of White Blood Cell and Platelet Count for Inhospital Mortality and Pneumonia in Acute Ischemic Stroke.

BACKGROUND: We investigated the combined effect of white blood cell (WBC) and platelet count on in-hospital mortality and pneumonia in acute ischemic stroke (AIS) patients. METHODS: A total of 3,265 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into four groups according to their level of WBC and platelet count: LWHP (low WBC and high platelet), LWLP (low WBC and low platelet), HWHP (high WBC and high platelet), and HWLP (high WBC and low platelet). A logistic regression model was used to estimate the combined effect of WBC and platelet counts on all-cause in-hospital mortality and pneumonia in AIS patients. RESULTS: HWLP was associated with a 2.07-fold increase in the risk of in-hospital mortality in comparison to LWHP (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI), 1.02-4.18; P-trend =0.020). The risk of pneumonia was significantly higher in patients with HWLP than those with LWHP (adjusted OR 2.29; 95% CI, 1.57-3.35; P-trend <0.001). The C-statistic for the combined WBC and platelet count was higher than WBC count or platelet count alone for the prediction of in- -hospital mortality and pneumonia (all P < 0.01). CONCLUSION: High WBC count combined with a low platelet count level at admission was independently associated with in-hospital mortality and pneumonia in AIS patients. Moreover, the combination of WBC count and platelet count level appeared to be a better predictor than WBC count or platelet count alone.

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson's Disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, and it is characterized by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), as well as the presence of intracellular inclusions with α-synuclein as the main component in surviving DA neurons. Emerging evidence suggests that the imbalance of proteostasis is a key pathogenic factor for PD. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and autophagy, two major pathways for maintaining proteostasis, play important roles in PD pathology and are considered as attractive therapeutic targets for PD treatment. However, although ER stress/UPR and autophagy appear to be independent cellular processes, they are closely related to each other. In this review, we focused on the roles and molecular cross-links between ER stress/UPR and autophagy in PD pathology. We systematically reviewed and summarized the most recent advances in regulation of ER stress/UPR and autophagy, and their cross-linking mechanisms. We also reviewed and discussed the mechanisms of the coexisting ER stress/UPR activation and dysregulated autophagy in the lesion regions of PD patients, and the underlying roles and molecular crosslinks between ER stress/UPR activation and the dysregulated autophagy in DA neurodegeneration induced by PD-associated genetic factors and PD-related neurotoxins. Finally, we indicate that the combined regulation of ER stress/UPR and autophagy would be a more effective treatment for PD rather than regulating one of these conditions alone.

Effect of Sleep-Disordered Breathing During Rapid Eye Movement Sleep and Non-Rapid Eye Movement sleep on Acute Ischemic Stroke.

OBJECTIVES: Sleep-disordered breathing adversely impacts stroke outcomes. We investigated whether sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep differentially influenced stroke outcomes. MATERIALS AND METHODS: Acute ischemic stroke patients who finished polysomnography within 14 days of stroke onset from April 2010 to August 2018 were reviewed. Patients were divided into four groups according to apnea-hypopnea index during rapid eye movement sleep and non-rapid eye movement sleep. The modified Rankin Scale was used to evaluate short-term outcome. During January and April 2019, another follow-up was performed for long-term outcomes, including stroke-specific quality-of-life scale, modified Rankin Scale, stroke recurrence and death. RESULTS: Of 140 patients reviewed, 109 were finally recruited. Although patients with sleep-disordered breathing during non-rapid eye movement sleep only and with sleep-disordered breathing during both rapid eye movement sleep and non-rapid eye movement sleep had higher apnea-hypopnea indices and more disrupted sleep structures, short-term and long-term outcomes did not significantly different between four groups. In Logistic regression analysis, apnea-hypopnea index (p = 0.013, OR 1.023, 95%CI 1.005-1.042) was found independently associated with short-term outcome. Rapid eye movement sleep latency (p = 0.045, OR 0.994, 95%CI 0.987-1.000) was found independently associated with quality of life. Apnea-hypopnea indices during rapid eye movement sleep or non-rapid eye movement sleep were not significantly associated with short-term or long-term outcomes. CONCLUSIONS: Apnea-hypopnea index is an independent risk factor of short-term outcome of acute ischemic stroke while sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep do not affect stroke outcomes differently.

Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial.

BACKGROUND: Elevated fibrinogen (Fg) level is a known risk factor for ischemic stroke. There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention. We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention. METHODS: This is a multicenter, randomized, parallel group and controlled study that began treatment in hospitalized patients with ischemic stroke and continued for 12 months. Patients were randomized to either the control group that received the standard stroke treatment or the fibrinogen-depleting group that received the standard stroke treatment plus enteric-coated lumbrokinase capsules. The NIH Stroke Scale scores (NIHSSs) and plasma Fg level were recorded. The carotid artery intima-media thickness (IMT) and status of plaques were examined through carotid ultrasound examination. Primary outcomes included all-cause mortality, any event of recurrent ischemic stroke/transient ischemic attack (TIA), hemorrhagic stroke, myocardial infarction and angina, and other noncerebral ischemia or hemorrhage. Kaplan-Meier survival analysis and the Long-rank test were used to compare total vascular end point incidence between the two groups. Comparison of median values between two groups was done by the Student t test, one-way analysis of variance (ANOVA), or non-parametric rank sum test. RESULTS: A total of 310 patients were enrolled, 192 patients in the treatment group and 118 patients in the control group. Compared to the control group, the treatment group showed favorable outcomes in the Fg level, carotid IMT, the detection rate of vulnerable plaques, the volume of carotid plaques, NIHSS scores, and incidence of total vascular (6.78% and 2.08%, respectively) and cerebral vascular events (5.93% and 1.04%, respectively) (P < 0.05). In the treatment group, the volume of carotid plaques was significantly related to the carotid IMT, the plaque diameter, width and number (P = 0.000, 0.000, 0.000, 0.022; F = 13.51, 2.52, 11.33, -3.29, but there was a weak correlation with the Fg level (P = 0.056). After 1-year therapy, the incidence of overall vascular end points was reduced by 4.7%. CONCLUSION: Long-term oral fibrinogen-depleting therapy may be beneficial for secondary ischemic stroke prevention.