Ipsilateral orolingual angioedema following rhTNK-tPA administration for acute ischemic stroke.

Recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA), a genetically modified variant of conventional alteplase with longer half-life and higher fibrin specificity, has now emerged as a reasonable choice for thrombolytic treatment of acute ischemic stroke (AIS) in China. Orolingual angioedema is a rare but potentially life-threatening complication of intravenous thrombolysis. Currently, there is no documented evidence of orolingual angioedema occurring after thrombolysis with rhTNK-tPA. In this report, we present a unique case of a 75-year-old Chinese man who developed ipsilateral orolingual angioedema following the administration of rhTNK-tPA for AIS. Our case emphasizes the need for caution when using rhTNK-tPA due to its potential to induce ipsilateral orolingual angioedema.

Procalcitonin related to stroke-associated pneumonia and clinical outcomes of acute ischemic stroke after IV rt-PA treatment.

To investigate the possible relationship between procalcitonin (PCT) and stroke-associated pneumonia (SAP) as well as clinical outcomes after recombinant tissue plasminogen activator (rt-PA) treatment of AIS. From June 2015 to December 2019, 173 consecutive patients with AIS after IV rt-PA treatment were prospectively enrolled. Serum PCT concentrations were measured after admission. Multivariate logistic regression analysis was used to examine the potential risk factors of SAP, poor outcome and mortality. Of the 173 patients, 49 (28.3%) participants were identified with SAP, 87 (50.3%) with poor outcome, and 28 (16.2%) with mortality. Multivariate logistic regression analysis demonstrated that patients with PCT in the second [odds ratio (OR) 4.413; 95% confidence interval (CI) 1.331-14.634; P = 0.015] and third tertile (OR 10.958; 95% CI 3.524-34.071; P < 0.001) were more likely to have SAP compared with the first tertile. Besides, PCT was an independent predictor of 3-month poor outcome (OR 3.219, 95% CI 1.291-8.028, P = 0.007) and mortality (OR 7.538, 95% CI 2.061-27.564, P = 0.002). In receiver operating characteristic (ROC) curve analysis, the diagnostic and prognostic accuracy of PCT was higher than hs-CRP. This study demonstrated that PCT was a reliable diagnostic and prognostic biomarker of SAP and poor clinical outcomes in Chinese AIS patients after IV rt-PA treatment.

Long noncoding RNA Nespas inhibits apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway.

Epilepsy is one of the most common neurological diseases with spontaneous recurrent seizures. Long noncoding RNAs (lncRNAs) are crucial modulators in numerous diseases, including epilepsy. However, the functional role and potential mechanism of lncRNA Nespas in epilepsy remain unknown. Our study clarified that Nespas was underexpressed in epileptiform hippocampal tissues and neurons. Furthermore, Nespas promoted hippocampal neuron viability and proliferation, and inhibited hippocampal neuron apoptosis. Mechanistically, Nespas interacted with microRNA 615-3p (miR-615-3p) in epileptiform hippocampal neurons. 26S proteasome non-ATPase regulatory subunit 11 (Psmd11) was a downstream target of miR-615-3p, and Nespas elevated Psmd11 expression via competitively binding to miR-615-3p in epileptiform hippocampal neurons. In addition, rescue assays suggested that Nespas promoted hippocampal neuron viability and proliferation, and suppressed hippocampal neuron apoptosis by upregulation of Psmd11. Furthermore, Nespas suppressed the PI3K/Akt/mTOR pathway via upregulating Psmd11 in epileptiform hippocampal neurons. This report explored the function and regulatory mechanism of Nespas in epileptiform hippocampal neurons for the first time. Our findings revealed that Nespas suppressed the apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway via upregulation of Psmd11 at a miR-615-3p dependent way, indicating that Nespas may offer a new direction for the treatment of epilepsy.

Pontine warning syndrome and restless legs syndrome secondary to paramedian pontine infarction: a case report.

Pontine warning syndrome (PWS) occurs rarely and is characterized by recurrent, stereotyped episodes of motor or sensory dysfunction, dysarthria, or ophthalmoplegia leading to pontine infarction. Restless legs syndrome (RLS) is a distinct neurological sensorimotor disorder. Pontine infarction is a rare but possible cause of RLS. Here, we report the case of a 58-year-old woman who experienced unilateral RLS in concomitance with stereotyped episodes of left-sided weakness and dysarthria, and developed an acute paramedian pontine infarction eventually. To the best of our knowledge, no other cases of PWS coinciding with RLS in the progression of pontine infarction have been reported in the literature. Furthermore, we discussed the potential mechanisms of PWS and RLS secondary to pontine infarction, which may be helpful for managing such patients.

Profile and 1-Year Outcome of Ischemic Stroke in East China: Nanjing First Hospital Stroke Registry.

BACKGROUND: The profile and 1-year outcome after acute ischemic stroke (AIS) in Nanjing, China, is uncertain. This study aimed to investigate the profile and outcome after 1-year follow-up of AIS in East China. METHODS: In a prospective cohort study, 2168 patients with AIS were recruited consecutively. The primary outcome was death or dependency defined as a modified Rankin Scale score of 3-6 at 12 months. Plausible risk factors of death or dependency, such as demographics, risk factors of cardiovascular diseases, clinical features, laboratory results, and complications after a stroke, were selected from available variables to perform multivariable logistic regression analyses. RESULTS: Eight hundred thirty-seven (38.6%) patients died or suffered from dependency. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03-1.05), history of diabetes mellitus (OR, 1.50; 95% CI, 1.10-2.04), prior stroke (OR, 2.08; 95% CI, 1.51-2.87), National Institutes of Health Stroke Scale (NIHSS) score (OR, 23.06; 95% CI, 14.24-37.34), estimated glomerular filtration rate (OR, 1.65; 95% CI, 1.02-2.66), pulmonary infection (OR, 2.98; 95% CI, 2.17-4.09), and gastrointestinal bleeding (OR, 7.81; 95% CI, 2.76-22.09) were significantly and independently associated with higher rates of mortality or disability (all P values < .05). Male gender (P values < .001) was the only factor associated with lower mortality or disability. CONCLUSIONS: The main dominating predictors for death or dependency were older age, female gender, diabetes mellitus, prior stroke, NIHSS score, estimated glomerular filtration rate, pulmonary infection, and gastrointestinal bleeding.

Correlation of LP-PLA2 and MMP-9 with the occurrence of early neurological deterioration in patients with acute ischemic stroke.

Early neurological deterioration is a common complication of acute ischemic stroke (AIS), which aggravates symptoms, worsens the condition, and counteracts the benefits of clinical treatment. The aim of this paper was to analyze the correlation between lipoprotein-associated phospholipase A2 (Lp-PLA2), matrix metalloproteinase-9 (MMP-9), and the occurrence of early neurological deterioration (END) in patients with AIS and to explore the clinical prediction of END by the combination of the 2 assays for the clinical prediction of END. A total of 500 AIS patients admitted to our hospital from October 2022 to October 2023 were included as study subjects, and the clinical data of all AIS patients were collected and organized to detect the levels of Lp-PLA2 and MMP-9. Categorized into END and non-END groups according to whether END occurred within 7 days of the onset of AIS, and comparing the clinical baseline data and laboratory index levels of the 2 groups. Logistic regression analysis was performed to determine the independent predictors of END, and the predictive effects of Lp-PLA2 and MMP-9 levels on END were assessed by subject work characteristics (ROC) curves. END occurred in 111 (22.2%) of 500 AIS patients. Multivariate logistic regression analysis showed that diabetes (OR 2.717, 95% CI:1.53-4.81, P < .001), baseline NIHSS score (OR 1.65, 95% CI:1.41-1.94, P < .001), Lp-PLA2 (OR 1.07, 95% CI:1.05-1.09, P < .001) and MMP-9 (OR 1.12, 95% CI:1.09-1.16, P < .001) levels were independent influences on the occurrence of END in patients with AIS after correcting for confounders. ROC curve analysis showed that Lp-PLA2, MMP-9, and a combination of both predicted END with an area under the curve was 0.730, 0.763, and 0.831, respectively, and the area under the curve for the combination of both predicting END was significantly higher than that for any of the inflammatory markers alone (P < .05). Both inflammatory markers, Lp-PLA2 and MMP-9, were independent predictors of the development of END in patients with AIS, and the combination of the two had a higher predictive value.

Glial Fibrillary Acidic Protein as a Potential Indicator for Symptomatic Intracranial Hemorrhage in Acute Ischemic Patients Undergoing Endovascular Thrombectomy.

Background: The correlation between glial fibrillary acidic protein (GFAP) and symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) treatment remains uncertain. We aimed to assess the association between levels of GFAP in the bloodstream and the occurrence of sICH. Methods: Between June 2019 and May 2023, 142 consecutive AIS patients undergoing EVT at Stroke Center and 35 controls from the Physical Examination Center were retrospectively included. The levels of GFAP in the bloodstream were quantified using enzyme-linked immunosorbent assay prior to endovascular treatment (T1) and 24 h after the procedure (T2). The identification of sICH was based on the Heidelberg Bleeding Classification. Results: Serum GFAP levels at T1 in AIS patients were significantly higher than those in the controls (0.249 [0.150-0.576] versus 0.065 [0.041-0.110] ng/mL, p = 0.001), and there was a notably elevation in GFAP levels at T2 compared to T1 (3.813 [1.474, 5.876] versus 0.249 [0.150-0.576] ng/mL, p = 0.001). Of the 142 AIS patients, 18 (14.5%) had sICH after EVT. Serum GFAP levels at T2 showed significant associations with sICH in both the unadjusted model (OR 1.513, 95% CI 1.269-1.805, p = 0.001) and multivariable adjusted model (OR 1.518, 95% CI 1.153-2.000, p = 0.003). Furthermore, the addition of GFAP at T2 to conventional model resulted in a significant enhancement of risk reclassification for sICH (integrated discrimination improvement [IDI] 0.183, 95% CI 0.070-0.295, p = 0.001). Conclusion: Serum GFAP levels were notably increased in AIS patients 24 h after EVT. Elevated GFAP levels were correlated to an elevated risk of sICH. GFAP could potentially serve as a dependable indicator for sICH in AIS individuals who treated with EVT.

Serum YKL-40 Levels and White Matter Hyperintensities in Patients with Acute Ischemic Stroke.

Background: White matter hyperintensity (WMH) is associated with risk of acute ischemic stroke (AIS) and poor outcomes after AIS. The purpose of this prospective study was to evaluate the association between serum YKL-40 levels and WMH burden in patients with AIS. Methods: From February 2020 to March 2021, a total of 672 consecutive AIS patients with magnetic resonance imaging data were prospectively recruited form two centers. Serum YKL-40 levels were quantified using enzyme-linked immunosorbent assay. The burden of WMH was semiquantitatively measured by the Fazekas visual grading scale. According to severity of overall WMH, patients were dichotomized into none-mild WMH group (Fazekas score 0-2) or moderate-severe WMH group (Fazekas score 3-6). Besides, based on severity of periventricular WMH (PV-WMH) and deep WMH (D-WMH), patients were categorized as none-mild (Fazekas score 0-1) or moderate-severe (Fazekas score 2-3). Results: Among the 672 patients, 335 (49.9%) participants were identified with moderate-severe overall WMH, 326 (48.5%) with moderate-severe PV-WMH and 262 (39.0%) with moderate-severe D-WMH. Compared with the first quartile of serum YKL-40, the adjusted odds ratio (OR) of the fourth quartile for moderate-severe PV-WMH was 2.473 (95% confidence interval [CI] 1.316-4.646; P=0.005). No significant association was observed between YKL-40 and overall WMH (OR 0.762; 95% CI 0.434-1.336; P=0.343) or D-WMH (OR 0.695; 95% CI 0.413-1.171; P=0.172). Conclusion: Our results suggested that higher YKL-40 levels appeared to be associated with PV-WMH, but not with overall WMH or D-WMH in patients with AIS.

Prognostic performance of serum YKL-40 for one-year clinical outcomes in acute ischemic stroke.

BACKGROUND: Effects of YKL-40 on one-year clinical outcomes including poor clinical outcome, all-cause mortality, and stroke recurrence among acute ischemic stroke (AIS) patients remained elusive. The purpose of this study was to explore the association between serum YKL-40 at admission and one-year clinical outcomes in AIS patients. METHODS: In this prospective cohort study, a total of 1002 participants out of 1361 AIS patients from two centers were included for current analysis. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. Multivariable logistic or Cox regression were performed to explore the independent association of YKL-40 with one-year clinical outcomes, including poor outcome (modified Rankin Scale of 3-6), all-cause mortality, and recurrent stroke. C-statistic, net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discriminatory and predictive power of YKL-40 when added to conventional model. RESULTS: Compared with the first quartile of YKL-40, the adjusted odds ratios or hazard ratios with 95% confidence intervals of the fourth quartile were 3.032 (1.627-5.650) for poor outcome, 2.886 (1.320-6.308) for all-cause mortality and 1.694 (0.906-3.169) for recurrent stroke. The addition of serum YKL-40 to conventional model significantly improved reclassification for poor outcome (NRI 0.053, P = 0.031; IDI 0.018, P = 0.001) and all-cause mortality (NRI 0.162, P = 0.036). CONCLUSIONS: Elevated serum YKL-40 at admission might be independently associated with one-year poor outcome and all-cause mortality but not stroke recurrence among Chinese AIS patients.

The Association between High Mobility Group Box 1 and Stroke-Associated Pneumonia in Acute Ischemic Stroke Patients.

Objective: This study aimed to investigate the association between high-mobility-group box 1 (HMGB1) and stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients. Methods: AIS patients were enrolled in two centers. The serum samples were collected within the first 24 h after admission, and HMGB1 levels were measured by enzyme-linked immunosorbent assay. Logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) of SAP for HMGB1 concentrations. Restricted cubic splines (RCS) were performed to explore the shapes of the association between HMGB1 concentrations and SAP. Results: From January 2022 to May 2022, a total of 420 AIS patients were enrolled. Ninety-six (22.9%) patients develop SAP. The levels of HMGB1 in the SAP group were higher than those in the non-SAP group (p < 0.001). Using the first quartile of HMGB1 group as a reference, patients in the fourth quartile of HMGB1 group had the highest likelihood of experiencing SAP in the unadjusted model (OR = 3.687; 95% CI: 1.851−7.344), age- and sex-adjusted model (OR = 3.511; 95% CI: 1.725−7.147), and multivariable-adjusted model (OR = 2.701; 95% CI: 1.045−6.981). HMGB1 was also independently associated with SAP as a continuous variable in the unadjusted model (OR = 1.132; 95% CI: 1.069−1.199), age- and sex-adjusted model (OR = 1.131; 95% CI: 1.066−1.200), and multivariable-adjusted model (OR = 1.096; 95% CI: 1.011−1.188). RCS showed a linear association between HMGB1 and SAP (p for linear trend = 0.008) Conclusions: HMGB1 might be able to act as a potential biomarker of SAP in AIS patients.

The efficacy and risk factors of mechanical thrombectomy for the treatment of vertebrobasilar artery occlusion: a single center study.

BACKGROUND: The mortality of acute ischemic stroke patients caused by vertebrobasilar artery occlusion (VBAO) is high and mechanical thrombectomy has gradually become a promising treatment for acute ischemic stroke. This study analyzed the efficacy of mechanical thrombectomy and the risk factors associated with poor outcomes in VBAO patients caused by severe local atherosclerotic stenosis. METHODS: This retrospective study enrolled patients with acute ischemic stroke caused by VBAO between March 1, 2016 and August 31, 2019. Patient demographic and clinical data were collected retrospectively. All enrolled patients were retrospectively interviewed for at least 3 months. Patients with a modified Rankin scale (mRS) score between 0 and 3 points were defined as having satisfactory outcomes while those with more than 3 points were defined as having unsatisfactory outcomes. In-hospital mortality, the rates of recanalization, and the rates of intracerebral hemorrhage were also recorded. Multivariable logistic regression was used to determine the risk factors of unsatisfactory outcomes in enrolled patients. RESULTS: A total of 65 patients were enrolled in this study with a median age 69.0 (63.0-78.0) years and 48 patients (73.8%) were male. Approximately 50% of patients had a mRS score of 0 or 1 point within 90 days after treatment with mechanical thrombectomy and 14 patients had a mRS score of 6 points. A total of 11 patients died in hospital. Out of the 65 patients, 7 required recanalization and 9 patients suffered from intracerebral hemorrhage. Multivariate logistic regression analysis showed that older age, lower baseline posterior circulation acute stroke prognosis early CT score (pcASPECTS), higher baseline National Institutes of Health stroke scale (NIHSS) score, and residual stenosis were independent risk factors of both unsatisfactory outcomes and mortality of VBAO patients. CONCLUSIONS: This study confirmed the important role of mechanical thrombectomy in the treatment of acute ischemic stroke caused by VBAO and may provide some guidance for improving the prognosis of patients.

The Relationship Between Serum YKL-40 Levels on Admission and Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke.

BACKGROUND: Stroke-associated pneumonia (SAP) is a standout complication after acute ischemic stroke (AIS), with a prevalence of 7-38%. The aim of this prospective study was to investigate the relationship between serum YKL-40 levels at admission and SAP. METHODS: Between August 2020 and February 2021, consecutive AIS patients from two centers were enrolled prospectively. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. We performed logistic regression analyses to explore the relationship between YKL-40 and SAP. Receiver operating characteristic curve was also used to assess the predictive ability of YKL-40 in predicting SAP. RESULTS: Ultimately, a total of 511 AIS patients were recruited. Multivariate logistic regression analysis showed that YKL-40 was independently related to SAP, whether as a continuous variable or as quartiles (P=0.001). The area under curve of YKL-40 to predict SAP was 0.765. The optimal cutoff value of YKL-40 as a predictor of SAP was determined to be 206.4 ng/mL, where the sensitivity was 63.1% and the specificity was 82.0%. CONCLUSION: Our study demonstrated that YKL-40 might be considered as a useful biomarker to predict SAP in AIS patients.

Efficacy and safety of omega-3 fatty acids on liver-related outcomes in patients with nonalcoholic fatty liver disease: A protocol for a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis, which is considered as the hepatic manifestation of metabolic syndrome, has a great prevalence all over the world. New drugs are urgently needed for the treatment of NAFLD. This review will be to assess the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on liver-related outcomes (liver histology and liver enzymes) in patients with NAFLD. METHODS: We will search 5 databases for relative studies: Medline, the Cochrane Library, EMBASE, Web of Science, and ClinicalTrials.gov and identified all reports of randomized controlled trials published prior to July 2020. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Fixed-effects model or random-effects model will be used to calculate pooled estimates of weighted mean difference with 95% confidence intervals. RESULTS: This systematic review aims to examine the effect of n-3 PUFAs on liver histology and liver enzymes in patients with NAFLD. CONCLUSIONS: These findings will provide guidance to clinicians and patients on the use of n-3 PUFAs for NAFLD. ETHICS AND DISSEMINATION: This study is a protocol for a systematic review of n-3 PUFAs as a treatment of NAFLD patients. This review will be published in a journal and disseminated in print by peer-review. SYSTEMATIC REVIEW REGISTRATION: INPLASY202050008.

Intensive or standard: a meta-analysis of blood pressure lowering for cerebral haemorrhage.

The ideal target blood pressure(BP) has remaining controversial for patients with cerebral haemorrhage, so we performed a meta-analysis to assess the effects of intensive BP lowering therapy. Clinical trials in which acute-phase patients were randomly assigned to an intensive BP lowering group or a standard BP lowering group were included. The primary outcome was mortality and dependency at 90 days. The secondary outcomes were mortality at 90 days, the proportion of cases involving haematoma extension during the acute phase and early neurological deterioration. Although intensive BP lowering was associated with reduced mortality and dependency at 90 days, this result was not statistically significant (OR 0.89, 95% CI 0.77-1.02, P=0.09). No differences between the two groups were found with respect to the secondary outcomes. Significant differences remained absent in sensitivity analyses. The results suggested that intensive BP lowering does not affect 90-day outcomes, but appears to be safe.

Carotid Endarterectomy and Carotid Artery Stenting Lead to Improved Cognitive Performance in Patients with Severe Carotid Artery Stenosis.

In patients with severe carotid artery stenosis, the effects of carotid artery reopening, achieved either by carotid endarterectomy (CEA) or carotid artery stenting (CAS), on cognitive functions remain elusive. Herein, we conducted a prospective study to determine whether and to what extent CEA and CAS affected cognitive performance. Patients admitted to the Department of Neurology or Vascular Surgery in Nanjing First Hospital from December 2012 to March 2015 with a diagnosis of severe carotid artery stenosis (>70%) were included in the study. Among them, 77 patients underwent CEA, 81 patients underwent CAS, and 77 patients who refused to receive aforementioned interventions were enrolled in control group. Of note, all patients in this study received basic pharmacological treatment according to the American Heart Association/American Stroke Association guidelines. Cognitive functions were evaluated by a broad spectrum of neuropsychological tests including the Mini-mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and event related potential P300 on the day prior to and at 3 months after indicated intervention. When compared with basic pharmacological treatment, both CEA and CAS significantly increased the scores of MMSE and MoCA at 3 months following procedures. Meanwhile, a significant reduction of P300 score was also observed in patients underwent CEA or CAS. In addition, the changes in MMSE, MoCA and P300 scores over time between CEA and CAS groups were not statistically significant. Taken together, our findings suggest an improvement of cognitive functions following carotid artery reopening. Meanwhile, the beneficial effects of CEA and CAS on cognitive performance seem to be equivalent.

Association between human leukocyte antigen-G 14-bp insertion/deletion polymorphism and cancer risk: a meta-analysis and systematic review.

BACKGROUND: Human leukocyte antigen-G (HLA-G) is involved in the development and progression of human cancers, and numerous molecular epidemiological studies have been conducted to explore the potential relationship of HLA-G 14-bp insertion/deletion (ins/del) polymorphism with cancer risk. However, results from published studies were inconclusive. METHODS: Both PUBMED and EMBASE databases were searched comprehensively to identify eligible studies investigating the association of HLA-G 14-bp ins/del polymorphism with cancer risk. Statistical analysis was performed by using STATA 12.0 and Review Manager 5.0. RESULTS: Fourteen eligible studies with 2340 cancer patients and 3967 controls were included and analyzed with odds ratio (OR) and its corresponding 95% confidence interval (CI). Overall, no significant association between HLA-G 14-bp ins/del polymorphism and overall cancer risk was detected in all comparison models. Further subgroup analyses based on ethnicity and cancer types demonstrated the significant association among Asians (ins/del vs. del/del: OR = 0.80, 95% CI, 0.66-0.95; ins/ins+ins/del vs. del/del: OR = 0.80, 95% CI, 0.65-0.97) and for breast cancer (ins allele vs. del allele: OR = 0.76, 95% CI, 0.61-0.96; ins/ins vs. del/del: OR = 0.57, 95% CI, 0.37-0.87; and ins/ins vs. ins/del+del/del: OR = 0.60, 95% CI, 0.42-0.87). CONCLUSION: This study suggested that HLA-G 14-bp ins/del polymorphism might contribute to breast cancer susceptibility and overall cancer risk among Asians. Further well-designed studies with larger sample size are warranted to validate our conclusion.