Association of serum biomarkers with early neurologic improvement after intravenous thrombolysis in ischemic stroke.

BACKGROUND: Early neurologic improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue based on a prospective cohort. METHODS: In INTRECIS study, five centers were designed to consecutively collect blood sample from enrolled patients. The patients with ENI and without ENI were matched by propensity score matching with a ratio of 1:1. Preset 49 biomarkers were measured through microarray analysis. Enrichment of gene ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers. RESULTS: Of 358 patients, 19 patients with ENI were assigned to ENI group, while 19 matched patients without ENI were assigned to Non ENI group. A total of nine biomarkers were found different between two groups, in which serum levels of chemokine (C-C motif) ligand (CCL)-23, chemokine (C-X-C motif) ligand (CXCL)-12, insulin-like growth factor binding protein (IGFBP)-6, interleukin (IL)-5, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, plasminogen activator inhibitor (PAI)-1, platelet-derived growth factor (PDGF)-AA, suppression of tumorigenicity (ST)-2, and tumor necrosis factor (TNF)-α were higher in the ENI group, compared with those in the Non ENI group. CONCLUSIONS: We found that serum levels of CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α at admission were associated with post-thrombolytic ENI in stroke. The role of biomarkers warrants further investigation. TRIAL REGISTRATION: Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT02854592.

Change of Serum Biomarkers to Post-Thrombolytic Symptomatic Intracranial Hemorrhage in Stroke.

Background: Symptomatic intracranial hemorrhage (sICH) is a terrible complication after intravenous alteplase in stroke, and numerous biomarkers have been investigated. However, the change of biomarkers to sICH has not been well determined. Aim: To investigate the association between the change of biomarkers and sICH. Methods: This is a prospective cohort study, and patients with sICH within 24 h after thrombolysis were enrolled, while patients without sICH were matched by propensity score matching with a ratio of 1:1. The blood samples were collected before and 24 h after intravenous thrombolysis (IVT), and preset 49 serum biomarkers were measured by microarray analysis. Protein function enrichment analyses were performed to detect the association between the change of biomarkers and sICH. Results: Of consecutive 358 patients, 7 patients with sICH in 24 h were assigned to the sICH group, while 7 matched patients without any ICH were assigned to the non-sICH group. A total of 9 biomarkers were found to significantly change before vs. after thrombolysis between groups, including increased biomarkers, such as brain-derived neurotrophic factor, C-C motif chemokine ligand (CCL)-24, interleukin (IL)-6, IL-10, IL-18, and vascular endothelial growth factor, and decreased biomarkers, such as CCL-11, intercellular adhesion molecule-1, and IL-7. Conclusions: This is the first study to identify changes in serum biomarkers in patients with sICH after IVT, and found that 6 neuroinflammatory and 3 neuroprotective biomarkers may be associated with brain injury following post-thrombolytic sICH. Clinical Trial Registration: https://www.clinicaltrials.gov, identifier: NCT02854592.

The Effect of the Integrated Chinese and Western Medicine for the Treatment of Parkinson's Disease: A Meta-Analysis.

Objective: Traditional Chinese medicine (TCM) has been used to treat Parkinson's disease (PD), but the efficacy is still not clear. The aim of this study was to evaluate the effect of the integrated Chinese and Western medicine (ICWM) for PD through a meta-analysis. Methods: We searched randomized controlled trials comparing integrated Chinese and Western medicine (ICWM) versus conventional Western medicine (CWM) for Parkinson's disease. Data were extracted from eligible studies. We sought to evaluate pretreatment and posttreatment symptoms of PD patients and their quality of life and reduce adverse reactions. The results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence intervals. Results: Twenty-three studies were included in this study with a total of 1769 patients. The pooled results revealed that ICWM significantly improved the UPDRS score than CWM, the MD of UPDRS-I, II, III, and IV was -1.05 (95% CI: -1.42 to -0.69, P < 0.00001), -2.55 (95% CI: -3.19 to -1.90, P < 0.00001), -3.64 (95% CI: -4.69 to -2.60, P < 0.00001), and -0.61 (95% CI: -0.96 to -0.27, P = 0.0004), respectively, and ICWM also had a better score of PDQ-39 (MD = -8.71, 95% CI: -13.52 to -3.90, P = 0.0004) and MoCA scores (MD = 3.35, 95% CI: 1.65 to 5.04, P = 0.0001) compared with CWM. ICWM had certain advantages in terms of effective rate (RR = 1.27, 95% CI: 1.18 to 1.37, P < 0.00001) and adverse reactions (RR = 0.21, 95% CI: 0.13 to 0.36, P < 0.00001). Conclusion: Our research supported that ICWM had important health benefits for patients with PD and can effectively improve the symptoms of PD patients and their quality of life and reduce adverse reactions. Due to the lower quality of the included studies, large sample and multicenter randomized control test should be performed to verify our conclusions.

Association of Serum Biomarkers With Post-Thrombolytic Symptomatic Intracranial Hemorrhage in Stroke: A Comprehensive Protein Microarray Analysis From INTRECIS Study.

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis is closely related to the poor outcome of stroke. AIMS: To determine the serum biomarkers associated with sICH based on the INTRECIS study. METHODS: Enrolled patients with sICH and without any ICH were matched by propensity score matching with the ratio of 1:1. Preset 49 biomarkers were measured by protein microarray analysis. Gene Ontology and Pathway Enrichment Analysis and protein-protein interaction network (PPI) were analyzed in the identified biomarkers. RESULTS: Of the consecutive 358 patients, eight patients occurred with sICH, which was assigned as an sICH group, while eight matched patients without any ICH were assigned as a Non-sICH group. A total of nine biomarkers were found significantly different between groups, among which the levels of interferon (IFN)-γ and interleukin (IL)-4 were higher, while the levels of C-reactive protein (CRP), glial cell line-derived neurotrophic factor (GDNF), insulin-like growth factor-binding protein (IGFBP)-6, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, matrix metalloprotein (MMP)-2, plasminogen activator inhibitor (PAI)-1, and platelet-derived growth factor (PDGF)-AA were lower in the sICH group compared with those in the Non-sICH group. CONCLUSIONS: Our finding indicated that baseline serum CRP, GDNF, IFN-γ, IGFBP-6, IL-4, LYVE-1, MMP-2, PAI-1, and PDGF-AA levels were associated with post-thrombolytic sICH in stroke.

Painful Diabetic Peripheral Neuropathy Study of Chinese Outpatients (PDNSCOPE): A Multicentre Cross-Sectional Registry Study of Clinical Characteristics and Treatment in Mainland China.

INTRODUCTION: This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices. METHODS: A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded. RESULTS: The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350). CONCLUSION: Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.

Effectiveness of intravenous r-tPA versus UK for acute ischaemic stroke: a nationwide prospective Chinese registry study.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (r-tPA) and urokinase (UK) are both recommended for the treatment of acute ischaemic stroke (AIS) in China, but with few comparative outcome data being available. We aimed to compare the outcomes of these two thrombolytic agents for the treatment of patients within 4.5 hours of onset of AIS in routine clinical practice in China. METHODS: A pre-planned, prospective, nationwide, multicentre, real-world registry of consecutive patients with AIS (age ≥18 years) who received r-tPA or UK within 4.5 hours of symptom onset according to local decision-making and guideline recommendations during 2017-2019. The primary effectiveness outcome was the proportion of patients with an excellent functional outcome (defined by modified Rankin scale scores 0 to 1) at 90 days. The key safety endpoint was symptomatic intracranial haemorrhage according to standard definitions. Multivariable logistic regression was used for comparative analysis, with adjustment according to propensity scores to ensure balance in baseline characteristics. RESULTS: Overall, 4130 patients with AIS were registered but 320 had incomplete or missing data, leaving 3810 with available data for analysis of whom 2666 received r-tPA (median dose 0.88 (IQR 0.78-0.90) mg/kg) and 1144 received UK (1.71 (1.43-2.00)×104 international unit per kilogram). There were several significant intergroup differences in patient characteristics: r-tPA patients were more educated, had less history of stroke, lower systolic blood pressure, greater neurological impairment and shorter treatment times from symptom onset than UK patients. However, in adjusted analysis, the frequency of excellent outcome (OR 1.18, 95% CI 1.00 to 1.40, p=0.052) and symptomatic intracranial haemorrhage (OR 0.70, 95% CI 0.33 to 1.47, p=0.344) were similar between groups. CONCLUSIONS: UK may be as effective and carry a similar safety profile as r-tPA in treating mild to moderate AIS within guidelines in China. REGISTRATION: http://www.clinicaltrials.gov. unique identifier: NCT02854592.