Inflammatory biomarkers may be associated with poor outcomes after mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) has become the mainstay of treatment for acute ischemic stroke (AIS) recently. This case-control study aimed to identify the pivotal role of inflammation in the prognosis of AIS patients after MT. METHODS: Altogether, 70 AIS patients who underwent MT were retrospectively recruited for this study. Receiver operating characteristic analysis was performed to demonstrate the sensitivity and specificity of the inflammatory variables for predicting prognosis. A meta-analysis was performed to pool the published results together. Stata software was used for analysis. RESULTS: There was no differences in pre-MT inflammatory biomarkers between patients who survived and those who died, as well as patients with modified Rankin Scale (mRS) 0-2 and mRS ≥ 3. In contrast, post-MT C-reactive protein (CRP) levels might be a potential parameter to predict death after thrombectomy [area under the curve (AUC), 95%confidence interval (CI), 0.737, 0.587-0.887; p = 0.005; optimal cutoff value = 4.565]. Moreover, post-MT monocyte count might be an appropriate parameter to predict poor long-term prognosis after thrombectomy (AUC, 95%CI, 0.704, 0.575-0.833; p = 0.017; optimal cutoff value = 0.345). A meta-analysis revealed that the pre-MT inflammatory indices, including white blood cell count (weighted mean difference, 95%CI, 1.32, 1.01-1.63), neutrophil count (1.23, 0.95-1.51), monocyte count (0.05, 0.02-0.09), neuthrophil-to-lymphocyte ratio (2.42, 1.98-2.87) and platelet-to-lymphocyte ratio (24.65, 7.99-41.32), were higher in patients with 3-month mRS ≥ 3, and the lymphocyte count (-0.31,-0.43 to -0.18) was lower in this cohort. CONCLUSIONS: Inflammatory indices were significantly associated with the prognosis of patients undergoing MT, especially post-MT CRP and monocyte count, which can predict long-term outcomes.

Association between inflammatory biomarkers and venous thromboembolism: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a common thrombotic vascular disease that has a significant impact on people's well-being and quality of life. A plethora of clinical studies explore the relationship between inflammatory biomarkers and VTE but yield conflicting results. This article proposed to pool these studies to draw a more convincing conclusion. METHODS: We searched several databases for studies before April 2023. Available data was processed using Stata software (version 15.0 SE) and R (version 4.1.2). This meta-analysis has been registered in PROSPERO (CRD42022321815). The VTE in this review encompassed pulmonary embolism, deep vein thrombosis, and cerebral venous thrombosis. RESULTS: A total of 25 articles were finally involved in this study. Our results revealed that higher levels of high-sensitivity C-reactive protein (hs-CRP, MD, 0.63, 95%CI, 0.21-1.05) and C-reactive protein (CRP)> 3ug/ml (OR, 1.52, 95%CI, 1.18-1.96) might be regarded as risk factors for future VTE occurrence. The elevated levels of monocyte (MD, 0.03, 95%CI, 0.00-0.05), hs-CRP (0.85, 0.61-1.08), CRP (0.66, 0.20-1.13) and IL-6 (0.47, 0.25-0.70) might represent the previous VTE; a series of markers such as white blood cell (1.43, 0.88-1.98), neutrophil (1.79, 1.02-2.56), monocyte (0.17, 0.14-0.21), hs-CRP (3.72, 1.45-5.99), IL-6 (5.99, 4.52-7.46), platelet-lymphocyte ratio (33.1, 24.45-41.78) and neutrophil-lymphocyte ratio (1.34, 0.95-1.73) increased during the acute phase of VTE. CONCLUSIONS: In general, activated inflammatory biomarkers might not only be correlated with an increased risk of VTE, but may also give a hint of the occurrence of VTE in clinical settings.

KDELR2 Promotes Glioblastoma Tumorigenesis Targeted by HIF1a via mTOR Signaling Pathway.

The KDEL (Lys-Asp-Glu-Leu) receptors (KDELRs), proteins with seven transmembrane domains, are primarily responsible for endoplasmic reticulum (ER) homeostasis. Recent studies have found additional function of KDELRs in growth, cellular secretory traffic, immune response, and autophagy; however, its role in tumorigenesis is still poorly understood. Here, we showed that KDELR2 is highly expressed in glioblastoma (GBM) tissues. Reviewing the expression of KDELR2 in TCGA and REMBRANDT database, we found that higher expression of KDELR2 is associated with shorter survival of GBM patients. We explored the effect of KDELR2 on tumorigenesis in GBM cells and animal model (nude mice), and identified KDELR2 as oncogene promoting cell proliferation. Additionally, KDELR2 expression in GBM cells correlated positively with HIF1alpha (HIF1α) expression, and we demonstrated by ChIP-qPCR and luciferase reporter assay that the upstream region of the KDELR2 gene is directly targeted by HIF1alpha. Taken together, our data suggest that KDELR2 is a target gene downstream of HIF1-alpha driving the malignancy of GBM and could eventually serve as a therapeutic target for the treatment of GBM patients.

Remote ischemic conditioning improves cognition in patients with subcortical ischemic vascular dementia.

BACKGROUND: Subcortical ischemic vascular dementia (SIVD) is very common among the older people, but has no approved treatment. Preclinical trials show that remote ischemic conditioning (RIC) reduces recurrence of ischemic stroke. We hypothesize that RIC may also be an effective therapy for patients with SIVD. METHODS: Thirty-seven consecutive SIVD cases were enrolled in this randomized control study. Eighteen RIC patients underwent five brief cycles of conditioning (bilateral upper limb compression at 200 mmHg) followed by reperfusion twice daily over 6 consecutive months. Nineteen control patients underwent the same process, but at a pressure of 60 mmHg which caused no restriction on the blood flow of the upper limb. The primary outcome measures were changes in neuropsychological assessments. The secondary outcomes included the changes in high-sensitive C-reactive protein (hs-CRP) concentration, white matter lesion volume (WMLV), diffusion tension imaging (DTI) metrics of white matter. All data were collected at baseline and follow-up. RESULTS: A significant treatment difference favoring RIC at 6 months was observed on performance of Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association Test (COWAT), Trail Making Test A and B (TMT-A & TMT-B), and Judgment of Line Orientation (JLO) (p < 0.05). The control group did not show much improvement after the treatment, and only with a slight change in HVLT-R and TMT-R (p < 0.05). Covariance analysis of efficacy between the two groups suggested that RIC patients performed better on JLO than control patients at the 6-month follow-up (RIC 23.10 vs. control 18.56; p = 0.013). Although DTI metrics were comparable, Hs-CRP levels and WMLV in RIC patients showed a declining trend. CONCLUSIONS: Over the 6-month treatment period, we found that RIC was safe and effective for improving cognitive function in SIVD patients. TRIAL REGISTRATION: Clinical Trial Registration ( http://www.clinicaltrials.gov ), Unique identifier: NCT03022149; Retrospectively registered; Date of registration: January 16, 2017.

Dehydration in cerebral venous sinus thrombosis.

AIMS: This study aimed to unravel the dehydration status of patients with cerebral venous sinus thrombosis (CVST) to facilitate the understanding of dehydration in CVST. METHODS: This was a multicenter retrospective study and three populations were recruited, namely, patients with CVST, CVST mimics, and healthy subjects. Blood samples were obtained 1-2 days after admission to assess dehydration status. Stata 15.1 was performed for statistical analysis. RESULTS: A total of 208 patients were diagnosed with CVST, 237 with CVST mimics, and 200 healthy individuals were enrolled. The urine specific gravity (USG, 1.020 [1.014, 1.029] vs. 1.017 [1.011, 1.021]) was higher in patients with CVST than in those with mimics (all p < 0.001). The percentage of USG >1.03 was also higher in CVST (22.6%) than in its mimics (6.3%, p < 0.001). With the development of CVST, USG (acute vs. sub-acute vs. chronic, 1.022 [1.015, 1.033] vs. 1.021 [1.015, 1.031] vs. 1.019 [1.014, 1.025]) decreased. All dehydration-related markers could not differentiate CVST from its mimics and healthy populations, and they were not associated with CVST severity and prognosis (p > 0.05). CONCLUSION: High levels of USG, especially USG >1.013, were more common in patients with CVST. Dehydration-related indices could not characterize CVST and were not associated with CVST severity and prognosis.

[Detection of anti-aquaporin 4 antibody in neuromyelitis optical].

OBJECTIVE: To assess the sensitivity and specificity of anti-aquaporin 4 antibody in the diagnosis of neuromyelitis optical (NMO) and analyze the relationship between clinical features and different NMO-IgG status. METHODS: A total of 269 serum specimens were collected from the patients with NMO, high-risk for NMO, multiple sclerosis (MS) and miscellaneous diseases and analyzed with HEK-293T cells transfected by aquaporin 4 cDNA. The sensitivity and specificity of anti-aquaporin 4 antibody in the diagnosis of NMO were calculated, Spearman correlation coefficients were used to examine the relationship between clinical features and antibody titer. RESULTS: (1) The results of cell-based immunofluorescence assay showed 36 examples of 47 NMO patient serums (76.6%) were positive, 7/23 high-risk for NMO positive (30.4%), 3/85 multiple sclerosis (3.5%) positive, 1/48 miscellaneous neurological disorders (2.1%), 2/16 immune system diseases positive (12.5%) and negative in all 50 healthy serum specimens. Sensitivity and specificity were 76.6% and 97.0% for discriminating NMO from MS and other diseases. (2) Anti-AQP4 antibody titer had no obvious correlation to relapses, spinal lesion length and EDSS (P > 0.05). (3) Anti-AQP4 antibody titer became lower after a high dose of intravenous methylprednisolone (P < 0.05). CONCLUSION: Anti-AQP4 antibody in NMO has a high specificity and sensitivity so as to contribute to early diagnosis and optimized treatment of NMO. And its titer decreases after a high dose of intravenous methylprednisolone. But there is no correlation between its titer and length of spinal cord lesions, relapsing frequency or expanded disability status scale (EDSS) score.

[The clinical and magnetic resonance imaging studies of brain damages in neuromyelitis optica].

OBJECTIVE: To investigate the feature brain damage and clinical manifestations in neuromyelitis optica (NMO) patients; To investigate the relationship between serum NMO-IgG antibody and NMO brain damage. METHODS: Clinical data of 37 NMO patients and their head and spinal cord MRI by 1.5T superconducting MR scanner, were analyzed; serum NMO-IgG antibody were measured by immunofluorescence. RESULTS: 17 cases were found to have abnormal signals on MRI, which were mainly in the white matter, pons, medulla, ventricle, aqueduct, and around the corpus callosum; According to pathological changes, brain damage can be divided into scattered irregularity (13 cases), fusion (3 cases), multiple sclerosis-like (1 case), with scattered irregularity more common, 5 cases had clinical manifestations of brain damage: somnolence, vomiting, diplopia, visual rotation, 11 cases patients with brainstem damage show positive serum NMO-IgG antibodies. CONCLUSIONS: Brain damage can be seen in half of NMO patients, they often located in the high expression area of AQP4: brain white matter, periventricular, brainstem and so on. Clinical symptoms has nothing to do with the size of lesions but the location, they often occur when brainstem was involved. Serum NMO-IgG is helpful in differentiating NMO with brain damage and MS.

[Comparison of three anti-aquaporin 4 antibody detection methods in neuromyelitis optical].

OBJECTIVE: To evaluate three methods of detecting anti-aquaporin 4(AQP4) antibody in neuromyelitis optical(NMO), including indirect immunofluorescence assay organization (IIF), cell immunofluorescence method (CBA) and ELISA. METHODS: The patients were divided into NMO group (n = 29), multiple sclerosis (MS) group (n = 23), and healthy controls group (n = 50). IIF, CBA and ELISA were used in 3 groups to detect serum anti-AQP4 antibody. The sensitivity and specificity as well as the consistency of positive results were compared. RESULTS: In the aspect of the sensitivity of the three anti-AQP4 antibody to diagnosis NMO, CBA (72.4%) > IIF (62.1%) > ELISA (51.7%); in the aspect of specificity, CBA (100.0%) > ELISA (98.6%) > IIF (97.3%). Kappa testing and evaluation method showed that the three detection methods were all in good consistency, particular in CBA and ELISA (P < 0.01). CONCLUSIONS: CBA method showed a highest specificity and sensitivity in all these three anti-AQP4 antibody detection methods. CBA and ELISA are in better consistency of positive results.

[Neuromyelitis optica IgG and related clinical features of patients with neuromyelitis optica].

OBJECTIVE: To investigate the differential diagnostic value of NMO-IgG for neuromyelitis optica (NMO) versus multiple sclerosis (MS) and to analyze its possible clinical features related to NMO-IgG. METHODS: Forty-one NMO patients and 44 MS patients in acute phase and 40 healthy controls were investigated. Serum NMO-IgG was tested by indirect immunofluorescence assay. The disability severity in NMO and MS patients was assessed by Expanded Disability Status Scale (EDSS). Clinical features and MRI imaging profiles were analyzed between NMO-IgG positive patients and negative ones. RESULTS: 70.7% (29/41) NMO patients were NMO-IgG positive compared to 9.1% (4/44) MS patients and all healthy controls were NMO-IgG negative (P < 0.01). The sensitivity and specificity were 70.7% and 90.9% respectively when NMO-IgG was used to discriminate NMO from MS. NMO patients with positive NMO-IgG had significantly higher EDSS scores (P < 0.05). More NMO-IgG seropositive patients had longitudinally extensive cord lesions (≥ 3 segments) than the NMO-IgG seronegative patients (93.1% vs 66.7%). But the difference was insignificant. CONCLUSION: NMO-IgG is a specific biomarker of NMO. NMO-IgG can facilitate an early differentiation of NMO from MS. NMO-IgG seropositivity is related to graver symptoms and it may predict an aggravation.

[Construction and clinical application of lentivirus-AQP4 expressing vector].

OBJECTIVE: To construct the human aquaporin-4 (AQP4) expressing vector and detect anti-AQP4 antibody in serum of patients with neuromyelitis optica (NMO). METHODS: RNA was extracted from human glioblastoma and AQP4 cDNA obtained through RT-PCR.The fragment was cloned into the lentiviral expressing vector (iDUET101) and transformed into competent strain Hb101 for later amplification; plasmids were extracted from the amplified positive-bacteria-colony, sequenced and transfected into HEK-293T cells. Expression of AQP4 was identified by RT-PCR, Western blot and immunofluorescence assay. And anti-AQP4 antibody in human serum was tested. RESULTS: The sequence of target fragment matched with that of human AQP4 fragment sequences (NM_001650) completely. The constructed AQP4 fragment transfected in HEK-293T cell was tested by immunofluorescent examination and it exhibited obvious fluorescence located in cell membrane. Western blot test was positive. And the fragment was about 34 KD. Cellular immunofluorescence examination showed 11 examples of 12 NMO patient serums (91.7%) were positive, 4 in 34 multiple sclerosis (11.8%) positive and negative in all 50 serum samples of healthy controls. CONCLUSION: The HEK-293T cell transfected with lentivirus-AQP4 vector can express stably. And the expressed fragment may be applied in clinical examination.

Comparison of grey matter atrophy between patients with neuromyelitis optica and multiple sclerosis: a voxel-based morphometry study.

PURPOSE: Previous studies have established regional grey matter (GM) loss in multiple sclerosis (MS). However, whether there is any regional GM atrophy in neuromyelitis optica (NMO) and the difference between NMO and MS is unclear. The present study addresses this issue by voxel-based morphometry (VBM). METHODS: Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 26 NMO patients, 26 relapsing-remitting MS (RRMS) patients, and 26 normal controls. An analysis of covariance model assessed with cluster size inference was used to compare GM volume among three groups. The correlations of GM volume changes with disease duration, expanded disability status scale (EDSS) and brain T2 lesion volume (LV) were analyzed. RESULTS: GM atrophy was found in NMO patients in several regions of frontal, temporal, parietal lobes and insula (uncorrected, p < 0.001). While extensive GM atrophy was found in RRMS patients, including most cortical regions and the deep grey matter (corrected for multiple comparisons, p < 0.01). Compared with NMO, those with RRMS had significant GM loss in bilateral thalami, caudate, left parahippocampal gyrus, right hippocampus and insula (corrected, p < 0.01). In RRMS group, regional GM loss in right caudate and bilateral thalami were strongly correlated with brain T2LV. CONCLUSIONS: Our study found the difference of GM atrophy between NMO and RRMS patients mainly in deep grey matter. The correlational results suggested axonal degeneration from lesions on T2WI may be a key pathogenesis of atrophy in deep grey matter in RRMS.