CHOROIDAL AND RETINAL ABNORMALITIES IN CUSHING SYNDROME: Correlation with the Cortisol Level.

PURPOSE: To investigate the structure and blood flow of the retina and choroid in Cushing syndrome and their relationship with cortisol levels. METHODS: A consecutive series of patients with Cushing syndrome with adrenocortical carcinoma were included in this study. Cortisol levels gradually returned to normal after adrenalectomy. Optical coherence tomography and optical coherence tomography angiography were used to assess patients with Cushing syndrome before and after the surgery for retina and choroid. Correlation analysis was performed between cortisol level and fundus changes. RESULTS: Compared with normal cortisol levels, patients with Cushing syndrome had significantly lower central macular thickness with increased cortisol level (220.82 ± 16.59 µ m and 223.68 ± 15.78 µ m, P = 0.019). However, the central choroidal thickness was higher with increased cortisol level (255.18 ± 105.89 µ m and 205.94 ± 87.04 µ m, P < 0.001). The choriocapillaris flow area was higher with increased cortisol level (2.05 ± 0.14 mm 2 and 2.00 ± 0.13 mm 2 , P = 0.02). The change of choriocapillaris flow area was correlated with the score of Huaxi Emotional-distress Index and 24-hour urine-free cortisol (24h-UFC). CONCLUSION: The increased cortisol level was correlated with lesser central macular thickness and thicker central choroidal thickness. The decrease of choriocapillaris flow area was correlated with 24h-UFC, indicating the effect of increased cortisol level on choroidal vessels.

Interleukin-6 in retinal diseases: From pathogenesis to therapy.

Interleukin-6 (IL-6) is a pleiotropic cytokine that participates in immunomodulation, inflammation, increases vascular permeability, hematopoiesis, and stimulates cell proliferation, among other biological processes. It exerts effects primarily through the classic and trans-signaling pathways. Many studies have demonstrated that IL-6 plays a critical role in the development of retinal diseases including diabetic retinopathy, uveitis, age-related macular degeneration, glaucoma, retinal vein occlusion, central serous chorioretinopathy and proliferative vitreoretinopathy. Thus, the progressive development of drugs targeting IL-6 and IL-6 receptor may play a role in the treatment of multiple retinal diseases. In this article, we comprehensively review the IL-6's biological functions of and its mechanisms in the pathogenesis of various retinal diseases. Furthermore, we summarize the drugs targeting IL-6 and its receptor and prospect their potential application in retinal diseases, hoping to provide new ideas for the treatment of retinal diseases.

A Simple Grading Scale for Predicting Symptomatic Intracranial Hemorrhage after Mechanical Thrombectomy.

INTRODUCTION: Hemorrhagic transformation, especially symptomatic intracranial hemorrhage (sICH), is a common complication after mechanical embolectomy. This study explored a grading scale based on clinical and radiological parameters to predict sICH after mechanical embolectomy. METHODS: Demographic and clinical data were retrospectively collected from patients with acute ischemic stroke treated with mechanical embolectomy at West China Hospital. Clinical and radiological factors associated with sICH were identified and used to develop the "STBA" grading scale. This score was then validated using data from an independent sample at the First Affiliated Hospital of Kunming Medical University. RESULTS: We analyzed 268 patients with acute ischemic stroke who were treated with mechanical embolectomy at West China Hospital, of whom 30 (11.2%) had sICH. Patients were rated on an "STBA" score ranging from 0 to 6 based on whether systolic blood pressure was ≥145 mm Hg at admission (yes = 2 points; no = 0 points), time from acute ischemic stroke until groin puncture was ≥300 min (yes = 1; no = 0), blood glucose was ≥8.8 mmol/L (yes = 1; no = 0), and the Alberta Stroke Program Early Computed Tomography score at admission was 0-5 (2 points), 6-7 (1 point), or 8-10 (0 points). The STBA score showed good discrimination in the derivation sample (area under the receiver operating characteristic curve = 0.858) and in the validation sample (area = 0.814). CONCLUSIONS: The STBA score may be a reliable clinical scoring system to predict sICH in acute ischemic stroke patients treated with mechanical embolectomy.

Folate and retinal vascular diseases.

Folate, a pteroylglutamic acid derivative, participates in fundamental cellular metabolism. Homocysteine, an amino acid, serves as an intermediate of the methionine cycle and can be converted back to methionine. Hyperhomocysteinemia is a recognized risk factor for atherosclerotic and cardiovascular diseases. In recent decades, elevated plasma homocysteine levels and low folate status have been observed in many patients with retinal vascular diseases, such as retinal vascular occlusions, diabetic retinopathy, and age-related degeneration. Homocysteine-induced toxicity toward vascular endothelial cells might participate in the formation of retinal vascular diseases. Folate is an important dietary determinant of homocysteine. Folate deficiency is the most common cause of hyperhomocysteinemia. Folate supplementation can eliminate excess homocysteine in plasma. In in vitro experiments, folic acid had a protective effect on vascular endothelial cells against high glucose. Many studies have explored the relationship between folate and various retinal vascular diseases. This review summarizes the most important findings that lead to the conclusion that folic acid supplementation might be a protective treatment in patients with retinal vascular diseases with high homocysteine or glucose status. More research is still needed to validate the effect of folate and its supplementation in retinal vascular diseases.

Differences in risk factors and outcome after acute stroke in patients with tandem occlusion and those with isolated intracranial occlusion after endovascular treatment.

OBJECTIVE: This study aimed to compare the clinical features, treatment, and clinical outcome of patients with tandem occlusion and isolated intracranial occlusion through endovascular treatment (EVT). METHODS: Patients with acute cerebral infarction who received EVT in two stroke centers were retrospectively included. According to MRI or CTA results, the patients were divided into tandem occlusion group or isolated intracranial occlusion group. The baseline data, etiological classification, treatment, post-stroke complications, image features, and clinical outcome were compared. Multivariate logistic regression analysis was used to evaluate the related factors affecting the prognosis of patients with EVT. RESULTS: Among 161 patients with acute cerebral infarction, there were 33 cases (20.5%) in the tandem occlusion group and 128 cases (79.5%) in the isolated intracranial occlusion group. Compared with isolated intracranial occlusion, the patients with tandem occlusion had higher rates of large artery atherosclerosis (P = 0.028), symptomatic intracerebral hemorrhage (sICH) (P = 0.023), bilateral infarction (P = 0.042), and longer time for endovascular procedure (P = 0.026). There was no significant statistical difference in 90-day mRS score between the two groups (P = 0.060). Multivariate logistic regression identified the following independent predictors of poor functional outcome: older age, high fasting blood glucose, infarction area > 1/3, and hemorrhagic transformation. CONCLUSIONS: Compared with isolated intracranial occlusion, there was not a worse prognosis among patients with tandem occlusion who received EVT.

Risk assessment of mechanic thrombectomy on post-stroke seizures: a systematical review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to evaluate the risk of early and late onset seizures following stroke mechanic thrombectomy (MT) compared with other systematic thrombolytic strategies. METHODS: A literature search was conducted to identify articles covering databases (PubMed, Embase, and Cochrane Library) published from 2000 to 2022. The primary outcome was the incidence of post-stroke epilepsy or seizures following MT or in combination with intravenous thrombolytics therapy. Risk of bias was assessed by recording study characteristics. The study was conducted according to the PRISMA guidelines. RESULTS: There were 1346 papers in the search results, and 13 papers were included in the final review.We identified 29,793 patients with stroke, of which 695 had seizures. Pooled incidence of post-stroke seizures had no significant difference between mechanic thrombolytic group and other thrombolytic strategy group (OR=0.95 (95%CI= 0.75-1.21); Z=0.43; p=0.67). In subgroup analysis, mechanic group have a lower risk of post-stroke early onset of seizures (OR=0.59 (95%CI=0.36-0.95); Z=2.18; p<0.05) but showed no significant difference in post-stroke late onset of seizures (OR=0.95 (95%CI= 0.68-1.32); Z=0.32; p=0.75). CONCLUSIONS: MT may be associated with a lower risk of post-stroke early onset of seizures, despite MT does not affect the pooled incidence of post-stroke seizures compared with other systematic thrombolytic strategies.

Association between neonatal hyperglycemia and retinopathy of prematurity: a meta-analysis.

Through a meta-analysis, we aimed to investigate whether neonatal hyperglycemia was associated with an increased risk of retinopathy of prematurity (ROP) by summarizing all available observational evidence. We searched online databases for studies published prior to December 2020; 26745 neonates with 3227 cases of ROP in 11 case-control studies and 997 neonates with 496 cases of hyperglycemia in 5 cohort studies were included. The results showed that the association between hyperglycemia and the occurrence of ROP was statistically significant in case-control studies (OR 3.93, 95% CI 2.36-6.53) and cohort studies (OR 1.70, 95% CI 1.11-2.60). Besides, the borderline significant association between the duration of hyperglycemia and ROP was observed in case-control studies (MD = 1.96, 95% CI 0.90-3.03; adjusted OR = 1.08, 95% CI 1.01-1.15). Furthermore, we found that the mean blood glucose level is higher in the ROP group than the non-ROP group in case-control studies (MD = 14.86, 95% CI 5.06-24.66) and the mean blood glucose level is higher in the hyperglycemia group than in the non-hyperglycemia group (MD = 86.54, 95% CI 11.03-162.05). However, after adjusting other confounders, the association between the mean blood glucose level and ROP varied in cohort studies (OR 1.96, 95% CI 1.23-3.13) and case-control studies (OR 1.02, 95% CI 1.00-1.05).Conclusion: This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. Further studies will be required to achieve a firm conclusion for hyperglycemia and ROP and promote a better understanding of the prevention of ROP.Trial registration: CRD42021228733 What is Known: • Hyperglycemia including the duration and daily mean blood glucose concentration has been associated with the risk of developing ROP in some clinical studies. Current evidence cannot reach a consensus on whether neonatal hyperglycemia is a risk factor for ROP. What is New: • This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. • While the association between the mean blood glucose level and ROP remains inconclusive.

Sputum microbiota as a potential diagnostic marker for multidrug-resistant tuberculosis.

The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains makes disease control more complicated, which is the main cause of death in tuberculosis (TB) patients. Early detection and timely standard treatment are the key to current prevention and control of drug-resistant TB. In recent years, despite the continuous advancement in drug-resistant TB diagnostic technology, the needs for clinical rapid and accurate diagnosis are still not fully met. With the development of sequencing technology, the research of human microecology has been intensified. This study aims to use 16 rRNA sequencing technology to detect and analyze upper respiratory flora of TB patients with anti-TB drug sensitivity (DS, n = 55), monoresistance isoniazide (MR-INH, n = 33), monoresistance rifampin (MR-RFP, n = 12), multidrug resistance (MDR, n = 26) and polyresistance (PR, n = 39) in southern China. Potential microbial diagnostic markers for different types of TB drug resistance are searched by screening differential flora, which provides certain guiding significance for drug resistance diagnosis and clinical drug use of TB. The results showed that the pulmonary microenvironment of TB patients was more susceptible to infection by external pathogens, and the infection of different drug-resistant Mtb leads to changes in different flora. Importantly, seven novel microorganisms (Leptotrichia, Granulicatella, Campylobacter, Delfitia, Kingella, Chlamydophila, Bordetella) were identified by 16S rRNA sequencing as diagnostic markers for different drug resistance types of TB. Leptotrichia, Granulicatella, Campylobacter were potential diagnostic marker for TB patients with INH single-resistance. Delftia was a potential diagnostic marker for TB patients with RFP single drug-resistance. Kingella and Chlamydophila can be used as diagnostic markers for TB patients with PR. Bordetella can be used as a potential diagnostic marker for identification of TB patients with MDR.

Different criteria for defining "spot sign" in intracerebral hemorrhage show different abilities to predict hematoma expansion and clinical outcomes: a systematic review and meta-analysis.

The "spot sign" is a well-known radiological marker used for predicting hematoma expansion and clinical outcomes in patients with intracerebral hemorrhage (ICH). We performed a meta-analysis to assess the predictive accuracy of spot sign, depending on the criteria used to identify them.We conducted a systematic review of clinical studies that clearly stated their definition of spot sign and that were indexed in the Cochrane Library, MEDLINE, EMBASE, and the China National Knowledge Infrastructure databases. We collected data on computed tomography (CT) parameters, spot sign diagnostic criteria, hematoma expansion, and clinical outcomes.Based on the eligibility criteria, we included 17 studies in this systematic review. CT imaging modality, type, time from symptom onset to CT, time from contrast infusion to scan, slice thickness, tube current, and tube electric discharge showed variation across studies. Three different definitions of the spot sign were applied: (1) a hyperdense spot within the hematoma; (2) one or more focal areas/regions of contrast pooling of any size and morphology that occurred within a hemorrhage, were discontinuous from the normal or abnormal vasculature adjacent to the hemorrhage, and showed an attenuation rate ≥ 120 UH; or (3) serpiginous or spot-like contrast density on CTA images that occurred within the hematoma margin, showed twice the density of the hematoma background, and did not contact vessels outside the hematoma. Three definitions for the spot sign were identified, all of which were associated with hematoma expansion, mortality, and unfavorable functional outcome. Subgroup analyses based on these definitions showed that spot sign identified using the second definition were more likely to be associated with hematoma expansion (OR 18.31, 95% CI 9.11-36.8) and unfavorable functional outcomes (OR 8.78, 95% CI 3.24-23.79), while those identified using the third definition were associated with increased risk of mortality (OR 6.88, 95% CI 1.43-33.13).Clinical studies identify spot sign using different CT protocols and criteria. These differences affect the ability of spot sign to predict hematoma expansion and clinical outcomes in ICH patients.

Mechanical Thrombectomy in Patients with Acute Ischemic Stroke and ASPECTS ≤5.

OBJECTIVE: This study examined the clinical features, functional outcomes, and prognostic indicators of acute ischemic stroke (AIS) patients who had an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≤ 5 and who underwent mechanical thrombectomy (MT). METHODS: We included consecutive AIS patients with ASPECTS ≤ 5 who had received MT at the same hospital. Demographic, clinical, and radiological data were collected and analyzed. Functional outcome at 90 days after treatment was classified as good or poor based on the modified Rankin Scale (mRS). RESULTS: Of the 152 included patients with ASPECTS ≤ 5 who received MT, 64 (42.11%) experienced poor functional outcomes and 32 (21.1%) experienced good functional outcomes. The independent predictors of poor functional outcomes were the presence of respiratory tract infections (OR 3.72, 95% CI 1.17-11.91), modified thrombolysis in cerebral infarction (OR 0.41, 95% CI 0.2-0.83), symptomatic intracerebral hemorrhage (sICH) (OR 4.96, 95% CI 1.36-18.13), and baseline score on the National Institute of Health Stroke Scale (NIHSS) (OR 1.18, 95% CI 1.03-1.36). Independent predictors of 90-day mortality included time from groin puncture to recanalization (OR 1.03, 95% CI 1.01-1.05), NIHSS scores (OR 1.28, 95% CI 1.12-1.47) and the occurrence of sICH (OR 1.81, 95% CI 1.25-5.75). CONCLUSION: AIS patients with ASPECTS ≤ 5 can experience good functional outcomes after MT. However, patients with sICH, respiratory infection, higher NIHSS score or failed recanalization are more likely to experience poor functional outcomes.

Intravitreal Injection of Amyloid ß1-42 Activates the Complement System and Induces Retinal Inflammatory Responses and Malfunction in Mouse.

To investigate whether intravitreal injection of amyloid ß1-42 (Aß1-42) activates the complement system and induces retinal inflammatory responses and malfunction, Aß1-42 was applied intravitreally in mice. The expressions of key components of complement system were determined by real-time PCR. Retinal function was assessed by electroretinography. We found interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in Aß1-42 treated mice retinas increased from day 1 to day 7. Compared with control group, mRNA expression of C1qa and C3 in the Aß1-42 treated retinas increased at days 1 and 7. The level of CFB, CFD, or CFH increased at day 4 and day 7. Regulator of membrane attack complex (MAC), CD59a, increased from day 1 to day 7. The expression of the main complement components in Aß1-42 treated eyes increased at days 4 and 7. Therefore, our results suggested that exogenous Aß1-42 activated CP and AP of the complement system in mice retinas, induced retinal inflammatory responses, and caused retinal malfunction.

Association Between Silent Brain Infarcts and Cognitive Function: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Silent brain infarct (SBI), which has traditionally been considered clinically silent, has been proposed as a subclinical risk marker for future cognitive function decline. METHODS: We conducted a systematic review of literature in the Cochrane Library, MEDLINE, EMBASE, and the China National Knowledge Infrastructure database. RESULTS: In the end, 19 case-control studies, comprising 6712 participants, and 3 prospective cohort studies comprising 4433 participants, met all inclusion criteria and were included in the systematic review. Meta-analysis of 9 studies showed that SBI was an important factor in cognitive function decline (Mini-Mental State score) (standardized mean difference -.47, 95% confidence interval; -.72 to -.22). Another meta-analysis of 4 studies reported the SBI was an independent factor in cognitive dysfunction (Montreal Cognitive Assessment Scale) (standardized mean difference -3.36, 95% confidence interval; -5.90 to -.82). Ten studies further reported that SBI was associated with decreases in specific areas of cognitive function. CONCLUSIONS: These results suggest that rather than being clinically silent, SBI might be a factor inducing cognitive dysfunction.

Blood metabolism study on protection of residual renal function of hemodialysis patients by traditional Chinese medicine Kidney Flaccidity Compound.

In recent years, metabolomics using high-performance liquid chromatography (UPLC) has been used to study the metabolic profiles in plasma, urine, stool and tissue in animal model of chronic kidney disease (CKD). In the previous work, we found that traditional Chinese medicine (TCM) "Kidney Flaccidity Compound" (KFC) based on "kidney flaccidity theory" can improve renal function and quality of life of patients with kidney disease. This study aimed to investigate the metabolic profiles in peripheral blood of hemodialysis patients administrated by KFC for 1.5 and 3 months and explore the potential metabolic mechanism using UPLC. Results showed that 121 metabolites were different between KFC 3-months group and untreated control, of which 75 were significantly upregulated and 46 were significantly downregulated. In the 1.5-months treatment group, there were 365 metabolites, of which 164 were significantly upregulated and 192 downregulated. There were 6 metabolites and 15 metabolites upregulated 3-fold in 3-months and 1.5-months KFC treatment group, respectively. In addition, more than 60 new metabolites were identified in the peripheral blood in KFC treated patients, including two potential diagnostic markers MGDG 30:8 and 2-(hydroxymethyl)-6-[[(1R,4S) -2,2,4-trimethyl-3-oxabicyclo[2.2.2]octan-5-yl]oxy]oxane-3,4,5-triol. The pathway enrichment analysis showed thce differential metabolites mainly enriched in Arginine and proline metabolism, Urea cycle, Tyrosine metabolism, Methionine metabolism, Tricarboxylic acid cycle, and Androgen and estrogen metabolism. The findings are helpful to reveal the mechanism of KFC protects CKD, and to provide a new strategy for recovery renal function in hemodialysis patients.

Blood Glucose Levels Are Associated with Cerebral Microbleeds in Patients with Acute Ischaemic Stroke.

BACKGROUND AND PURPOSE: There are debates about the causative role of high blood glucose in cerebral small vessel disease. The relationship between cerebral microbleeds (CMBs) and blood glucose is unclear. METHODS: Patients admitted to our department with acute ischaemic stroke were consecutively and prospectively included. Baseline demographic and clinical covariates were collected and analyzed according to the occurrence and location of CMBs and levels of blood glucose. RESULTS: Of 161 patients included in the final analysis, 69 (42.76%) were women. A total of 80 patients (49.69%) had CMBs. There was a significant trend towards the prevalence of CMBs with increasing glucose quarter (p = 0.001). Post hoc analysis showed the rate of prevalence of CMBs to be significantly higher in the third quarter (OR 1.90, 95% CI 1.20-3.02) and fourth quarter (OR 1.65, 95% CI 1.21-2.25) than that in the first. The frequencies of deep or infratentorial CMBs differed with glucose quarter. Post hoc analysis showed that frequencies of deep or infratentorial CMBs were significantly more frequent in the third quarter (OR 1.76, 95% CI 1.06-2.87) and fourth quarter (OR 1.65, 95% CI 1.19-2.31) than those in the first. CONCLUSIONS: In this prospective study of patients with acute ischaemic stroke, our results showed that glucose was associated with deep or infratentorial CMBs but not with lobar CMBs.

Accuracy of the Blend Sign on Computed Tomography as a Predictor of Hematoma Growth after Spontaneous Intracerebral Hemorrhage: A Systematic Review.

BACKGROUND: Hematoma growth is a strong independent predictor of poor outcome after intracerebral hemorrhage. However, there is no gold standard to accurately predict hematoma growth. Several noncontrast computed tomographic markers associated with hematoma growth have been reported recently. Blend sign, which is a new marker, has been reported in several studies and seems a particularly promising marker but lacks a standardized evaluation so far. METHODS: A systematic review of published literature on blend sign and hematoma growth and clinical outcomes was conducted. Systematic review of best practices was followed, and study quality was assessed. RESULTS: The 6 studies involved 1573 participants in this review. The prevalence of blend sign ranged from 8.70% to 38.46%. The sensitivity of blend sign to predict hematoma growth varied from 13.0% to 42.86%; the specificity varied from 88.51% to 95.5%. Blend sign showed lower sensitivity but superior specificity for prediction of hematoma growth. Four studies indicated that the presence of blend sign was an independent predictor of hematoma growth. Four studies showed that the prevalence of blend sign was significantly higher in patients with hematoma growth compared with those without hematoma growth (odds ratio, 9.33; 95% confidence interval, 5.20-16.74). CONCLUSION: There was an association between blend sign and hematoma growth, but this finding is tentative in light of the fact that the number of included studies was relatively small.

Activation of liver X receptor α protects amyloid ß1-40 induced inflammatory and senescent responses in human retinal pigment epithelial cells.

OBJECTIVE: To investigate whether activation of the liver X receptors (LXRs) inhibits amyloid ß1-40 (Aß1-40) induced inflammatory and senescent responses in human retinal pigment epithelial (RPE) cells. MATERIALS AND METHODS: Confluent cultures of human primary RPE and ARPE-19 cells pretreated with 5 µΜ of TO901317 (TO90), a synthetic agonist of LXR, or vehicle were incubated with 1 µΜ of Aß1-40 or Aß40-1. The optimum concentrations of Aß1-40 and TO90 were determined by cell viability assay. Pro-inflammatory cytokines IL-6, IL-8, MCP-1 were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Expression and localization of an aging protein p16INK4a (p16) were analyzed by western blotting and immunofluorescence. Expressions of LXRs and one of their target genes ATP-binding cassette transporter A1 (ABCA1) were examined by real-time PCR and western blotting. Phosphorylated transcription inhibition factor-κB-α (p-IκB-α) was assessed by western blotting. RESULTS: A negative linear relationship between the Aß1-40 concentration and the cell viability was evident, indicating Aß1-40 decreased ARPE-19 cell viability in a dose-dependent manner. Aß1-40 enhanced the expression of IL-6, IL-8, MCP-1 as well as p16 in both RPE cell lines at both mRNA and protein levels, whereas TO90 counteracted the detrimental effects. TO90 upregulated the expression of LXRα and its target gene ABCA1, but it did not affect the expression of LXRß. Meanwhile, TO90 inhibited the phosphorylation of IκB-α mediated by Aß1-40 stimulation. CONCLUSION: Activation of the LXRα-ABCA1 axis may alleviate Aß1-40 induced inflammatory and senescent responses in RPE cells. The beneficial effect appears associated with the inhibition of the NF-κB signaling pathway.

Liver Function Indicators Performed Better to Eliminate Cardioembolic Stroke than to Identify It from Stroke Subtypes.

BACKGROUND: Identifying the etiology of ischemic stroke is essential to acute management and secondary prevention. The value of liver function indicators in differentiating stroke subtypes remains to be evaluated. METHODS: A total of 1333 acute ischemic stroke patients were included. Liver function indicators collected within 24 hours from stroke onset, including alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (BILI), were collapsed into quartiles (Q) and also dichotomized by Q1. Multivariate regression analysis was conducted to identify the independent association between liver function indicators and cardioembolic stroke (SCE). Area under the curve (AUC) of receiver operating characteristic analysis was conducted, and sensitivity (Sen), specificity (Spe), positive prospective value (PPV), and negative prospective value (NPV) were determined to evaluate the predictive value of liver function indicators for SCE. RESULTS: AST, GGT, and BILI were associated with SCE. After adjustment, only AST was related to SCE independently. The incidence of SCE in the Q1 of AST, GGT, and BILI, particularly in the Q1 of AST, was quite low. The ability of AST, GGT, and BILI to identify SCE was poor, with low AUC, Sen, and PPV. The value of AST, GGT, and BILI in eliminating SCE from stroke subtypes was good, with high Spe and moderate NPV, and was enhanced after combining each liver function indicator. CONCLUSIONS: Results of present study demonstrated that AST, GGT, and BILI, particularly AST, had a potential to eliminate SCE from stroke subtypes, and the ability of eliminating SCE would be strengthened after combining each liver function indicator together.

Prognostic Significance of Intraventricular Hemorrhage in Vascular Structural Abnormality-Related Intracerebral Hemorrhage.

BACKGROUND: The prognostic significance of intraventricular hemorrhage (IVH) in patients with vascular structural abnormality-related intracerebral hemorrhage (VSARICH) is poorly understood. METHOD: We prospectively included consecutive patients diagnosed with VSARICH. Imaging of initial brain computed tomography (CT) scans within 48 hours of symptom onset was analyzed. The presence and severity of IVH were recorded. Severity of IVH was measured using the modified Graeb (mGraeb) score. Baseline characteristics and 3-month outcomes were compared between the IVH and non-IVH groups. Multivariate logistic regression was used to examine the independent association between IVH and 3-month outcomes. RESULTS: A total of 132 VSARICH patients were included for analysis, and 71 (53.8%) of them had IVH on initial CT imaging. IVH patients had a median mGraeb score of 15 (6-21), and compared to non-IVH patients, they had shorter delay to first CT scan and higher stroke severity on admission (all P ≤ .005). At 3 months, IVH patients had higher death rates (30.3% versus 7.0%; P = .001) and poor outcome rates (48.5% versus 21.1%; P = .002) than non-IVH patients. After multivariate analysis, IVH severity was associated with 3-month death (Model 1 OR 1.112, 95% CI [1.027-1.204], P = .009; Model 2 OR 1.110, 95% CI [1.027-1.200], P = .009) and poor outcome (Model 2 OR 1.053, 95% CI [1.001-1.108], P = .047), although no independent association between IVH presence and outcomes was observed. CONCLUSION: IVH severity measured by mGraeb score independently predicts death and poor functional outcome in patients with VSARICH.

Angiotensin-converting enzyme 2 activator diminazene aceturate prevents lipopolysaccharide-induced inflammation by inhibiting MAPK and NF-κB pathways in human retinal pigment epithelium.

BACKGROUND: Retinal inflammation is a devastating pathological process in ocular diseases. Functional impairment of retinal pigment epithelium (RPE) is associated with inflammatory retinal diseases. Enhancing the protective axis namely ACE2/Ang-(1-7)/Mas by activation of ACE2 presents anti-inflammatory properties. We investigated whether diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, prevented lipopolysaccharide (LPS)-induced inflammatory response by activating the protective axis and whether the effect was mediated by inhibiting the mitogen-activated protein kinase (MAPK) and the nuclear factor-κB (NF-κB) pathways. METHODS: Cell counting kit-8 (CCK-8) assay and real-time PCR were used to determine the optimum concentration and incubation time of DIZE. ARPE-19 cells and primary cultured human retinal pigment epithelia (hRPE) were incubated with or without 10 µg/mL DIZE for 6 h before stimulated with 5 µg/mL LPS for 24 h. The mRNA expression of inflammatory cytokines, AT1R, and AT2R was analyzed. The protein level of inflammatory cytokines, Ang II, and Ang-(1-7) was detected. Phosphorylation of p38 MAPK, extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphorylated transcription inhibition factor-κB-α (p-IκB-α) were measured. Inhibitors of MAPKs and NF-κB were added to verify the involvement of these pathways. A small interfering RNA (siRNA) targeted to ACE2 and a selective Ang-(1-7) antagonist A779 was used to confirm the role of ACE2 and the involvement of ACE2/Ang-(1-7)/Mas axis. RESULTS: DIZE remarkably increased the expression of ACE2 and inhibited the expression of IL-6, IL-8, and MCP-1 at both mRNA and protein levels in both RPE cell lines stimulated with LPS. Inhibitors of p38, ERK1/2, JNK, and NF-κB significantly decreased LPS-induced overproduction of IL-6, IL-8, and MCP-1. DIZE reduced the expression of Ang II and AT1R, whereas increased Ang-(1-7). Furthermore, DIZE downregulated the phosphorylation of p38MAPK, ERK1/2, JNK, and the activation of NF-κB upon stimulation with LPS. Downregulating ACE2 and pre-treatment with A779 abrogated the effects of DIZE on production of cytokines, the expression of Ang II, Ang-(1-7), AT1R, phosphorylation of MAPKs and activation of NF-κB. CONCLUSIONS: DIZE inhibits LPS-induced inflammatory response by activating ACE2/Ang-(1-7)/Mas axis in human RPE cells. The protective effect is mediated by inhibiting the p38MAPK, ERK1/2, JNK, and NF-κB pathways.

Subclinical change of liver function could also provide a clue on prognosis for patients with spontaneous intracerebral hemorrhage.

Whether subclinical change of liver function is associated with outcome of spontaneous intracerebral hemorrhage remains to be an open question. A total of 639 patients of spontaneous intracerebral hemorrhage within 7 days from stroke onset were finally enrolled. Liver function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (BIL), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), albumin (ALB), and international normalized ratio (INR), were collected and collapsed into quartiles. The main outcomes were 30-day death, 90-day death, and 90-day poor outcome (modified Rankin Scale score of 3-6). Two adjusted model, Model 1 and Model 2 (Model 1 plus GCS score), were established to identify independent association between liver function indicators and ICH outcomes. The mortality rate was 19.9 % (127/639) at 30 days and 21.3 % (136/639) at 90 days. Rate of 90-day poor outcome was 51.5 % (329/639). Among liver function indicators, AST and ALP were associated with all the three outcomes, which did not alter significantly when adjusted by Model 1. After adjusted by Model 2, ALP was still associated with outcomes. Association between AST and outcomes was, however, weakened significantly by GCS score. In conclusions, among liver function indicators, AST and ALP were associated with outcomes after spontaneous intracerebral hemorrhage.