Cartilage progenitor cells derived extracellular vesicles-based cell-free strategy for osteoarthritis treatment by efficient inflammation inhibition and extracellular matrix homeostasis restoration.

Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach that can inhibit inflammation and promote cartilage matrix homeostasis. Cartilage progenitor cells (CPCs) are identified as a cell population of superficial zone in articular cartilage which possess strong migration ability, proliferative capacity, and chondrogenic potential. Recently, the application of CPCs may represent a novel cell therapy strategy for OA treatment. There is growing evidence that extracellular vesicles (EVs) are primary mediators of the benefits of stem cell-based therapy. In this study, we explored the protective effects of CPCs-derived EVs (CPCs-EVs) on IL-1ß-induced chondrocytes. We found CPCs-EVs exhibited chondro-protective effects in vitro. Furthermore, our study demonstrated that CPCs-EVs promoted matrix anabolism and inhibited inflammatory response at least partially via blocking STAT3 activation. In addition, liquid chromatography-tandem mass spectrometry analysis identified 991 proteins encapsulated in CPCs-EVs. By bioinformatics analysis, we showed that STAT3 regulatory proteins were enriched in CPCs-EVs and could be transported to chondrocytes. To promoting the protective function of CPCs-EVs in vivo, CPCs-EVs were modified with cationic peptide ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD) for surface charge reverse. In posttraumatic OA mice, our results showed PPD modified CPCs-EVs (PPD-EVs) effectively inhibited extracellular matrix catabolism and attenuated cartilage degeneration. Moreover, PPD-EVs down-regulated inflammatory factors expressions and reduced OA-related pain in OA mice. In ex-vivo cultured OA cartilage explants, PPD-EVs successfully promoted matrix anabolism and inhibited inflammation. Collectively, CPCs-EVs-based cell-free therapy is a promising strategy for OA treatment.

Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

BACKGROUND: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT. METHODS: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy. Patients were stratified into the intravenous thrombolysis (IVT) group (IVT alone) and EVT group (IVT plus EVT or EVT alone). The primary outcome was a modified Rankin Scale score 0 to 2 at 90 days. Secondary outcomes included additional thresholds and distribution of modified Rankin Scale scores, 24-hour recanalization, early neurological deterioration, and relevant complications during hospitalization. Safety outcomes encompassed intracranial hemorrhagic events at 24 hours and mortality at 90 days. Binary logistic regression analyses with propensity score matching were used. Subgroup analyses were performed based on the anatomic site of occlusion, including right versus left, proximal versus distal, dominant/co-dominant versus nondominant, single versus double/triple branch(es), and anterior versus central/posterior branch. RESULTS: Among 734 patients (43.3% were females; median age, 73 years) with M2 segment occlusion, 342 (46.6%) were in the EVT group. Propensity score matching analysis revealed no statistical difference in the primary outcome (odds ratio, 0.860 [95% CI, 0.611-1.209]; P=0.385) between the EVT group and IVT group. However, EVT was associated with a higher incidence of subarachnoid hemorrhage (odds ratio, 6.655 [95% CI, 1.487-29.788]; P=0.004) and pneumonia (odds ratio, 2.015 [95% CI, 1.364-2.977]; P<0.001). Subgroup analyses indicated that patients in the IVT group achieved better outcomes when presenting with right, distal, or nondominant branch occlusion (Pall interaction<0.05). CONCLUSIONS: Our study showed similar efficiency of EVT versus IVT alone in acute M2 segment middle cerebral artery occlusion. This suggested that only specific patient subpopulations might have a potentially higher benefit of EVT over IVT alone. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04487340.

Fabrication of versatile lignocellulose nanofibril/polymerizable deep eutectic solvent hydrogels with anti-swelling, adhesive and low-temperature resistant properties via a one-pot strategy.

Lignocellulosic nanofibril (LCNF) is indispensable in numerous potential applications because of its unsurpassed quintessential characteristics. While it still remains a challenge to assemble LCNF in a facile and environmental economy-first manner. In this work, a simple and green one-step synthetic approach was reported to prepare a series of LCNF-containing versatile hydrogels using deep eutectic solvent (DES). In particular, the LCNF5% hydrogel (namely LCNF5%-gel) in this work perfectly integrated superior stretchability (∼643 %), and displayed a dramatically improved anti-swelling ability (25 %) compared to the control sample (neat DES hydrogel, 2252 %). Simultaneously, the LCNF5% hydrogel presented underwater adhesiveness and outstanding long-term low-temperature resistance (stable at -25 °C for a month). This novel multifunctional hydrogel, prepared by a facile and eco-friendly strategy, is potentially useful in wet adhesion or underwater applications.

Association of Atrial Fibrillation with Remote Intracerebral Hemorrhage After Intravenous Thrombolysis: Results from a Multicenter Study in China.

INTRODUCTION: This study aimed to investigate the association between atrial fibrillation (AF), particularly newly diagnosed AF, and remote intracerebral hemorrhage (rICH) in patients with ischemic stroke who were treated with intravenous thrombolysis (IVT). METHODS: This observational study was conducted on patients with ischemic stroke who received IVT with recombinant tissue-type plasminogen activator. The data were taken from a multicenter prospective registry of a Chinese population. rICH was defined as any extraischemic hemorrhage detected on computerized tomography (CT) 24 h after intravenous thrombolysis. We collected and compared the demographic data and clinical characteristics of all the patients with rICH to those of patients without any type of hemorrhagic transformation. The association between AF and rICH was analyzed using univariate analysis and binary logistic regression. RESULTS: A total of 20,697 patients were included in the study, with 1566 (7.6%) experiencing intracerebral hemorrhage (ICH), 586 (2.8%) experiencing rICH, and 19,131 (92.4%) not experiencing any form of hemorrhagic transformation. Univariate analysis revealed significant differences in age, pre-thrombolysis systolic blood pressure, baseline National Institute of Health Stroke Scale score, previously known AF, newly diagnosed AF, coronary heart disease, congestive heart failure, hyperhomocysteinemia, and history of thrombolysis between the rICH and control groups (P < 0.05). Further multivariate logistic regression analysis indicated that total AF (OR 1.821, 95% CI 1.082-3.065, P < 0.05), previously known AF (OR 1.470, 95% CI 1.170-1.847), and newly diagnosed AF (OR 1.920, 95% CI 1.304-2.825) were independently associated with rICH. CONCLUSIONS: This study suggests that AF, regardless of whether it is newly diagnosed or previously known, may be associated with the occurrence of rICH following intravenous thrombolysis. Interestingly, our findings suggest that newly diagnosed AF may have a stronger impact on rICH than previously known AF, although confirmation from more studies is needed.

Demand and influencing factors of "Internet + Traditional Chinese Medicine" home nursing service for older adult patients with chronic diseases: a mixed research perspective.

Background: In the context of global aging, the characteristics of chronic diseases seriously affect the quality of life of older adults. It is urgent to carry out continuous nursing basis for older adult patients with chronic diseases. In view of the remarkable efficacy of Chinese medicine in the treatment of chronic diseases, this study may help to understand the demand for "Internet + Chinese medicine" home care service and its influencing factors of older adult chronic disease patients, and to provide a reference basis for improving the quality of life of the older adult chronic disease population. Methods: This is a mixed study. The quantitative study adopted the convenience sampling method, and a total of 308 patients in a third-grade hospital in Shaanxi Province were investigated by general data questionnaire, traditional Chinese medicine service demand questionnaire, traditional Chinese medicine knowledge questionnaire, older adult Chinese medicine attitude questionnaire, and home care demand questionnaire from March to April 2022. In the qualitative study, semi-structured interviews were adopted, and patients were interviewed until the content was saturated. Colaizzi analysis method was used to analyze and summarize the topic of the interview data. Results: 308 valid questionnaires were collected, and the patients scored (58.42 ± 17.16) on the demand for TCM nursing services, (59.86 ± 11.54) on the knowledge of TCM, (73.03 ± 9.11) on the attitude toward TCM, and (136.84 ± 46.39) on the demand for home care. The results of multiple linear regression showed that learning about the nursing service pathway, knowledge of general knowledge of Chinese medicine, and attitude toward Chinese medicine among the older adult and home care demand were the influencing factors of the demand for Chinese medicine nursing services for older adult patients with chronic diseases (p < 0.05). The results of the in-depth interviews were summarized into three themes: facilitating factor, hindering factor, and the "Internet + Chinese medicine" multiple needs of home care. Conclusion: Older adult patients with chronic diseases have a high intention of home care demand and they are affected by multiple factors. Consequently, the actual demand situation of older adult patients with chronic diseases should be used as a guide to provide directed and diversified Chinese medicine home care services to meet the individualized needs of the older adult.

Effects of emergency medical services on timely treatment and outcome in stroke patients with intravenous thrombolysis among the severity of neurologic deficits: A retrospective observational study.

Whether emergency medical service (EMS) improves the outcome of acute ischemic stroke (AIS) patients after intravenous thrombolysis (IVT) is still unknown among the severity of neurologic deficits. This study is to investigate the impact of EMS use on timely treatment and outcomes of AIS with IVT. This is a retrospective observational study. Clinical data after IVT from January 2017 to May 2020 were retrospectively analyzed, including onset-to-needle time (ONT), onset-to-door time (ODT). The patients were divided into EMS and non-EMS groups according to the method of admission. A good outcome was defined as a modified Rankin scale score of ≤2 at 3 months. The severity of neurological deficits was assessed using the national institutes of health stroke scale. A total of 2303 patients were analyzed (906 [(39.3%] female; mean age, 68 ±â€…13 year), and 1028 (44.6%) patients were transported by EMS and 1418 (67.9%) patients achieved good outcome. Among all patients, compared with non-EMS patients, EMS patients had shorter ONT (148 minutes vs 155 minutes, P = .002) and ODT (95 minutes vs 104 minutes, P < .001), but lower rate of good outcome (61.7% vs 73.0%, P < .001). The multivariate analysis showed that the use of EMS was negatively associated with ONT (ρ = -0.041, P = .048) and ODT (ρ = -0.051, P = .014). Among moderate to severe stroke patients, EMS was related with good outcome independently (OR: 3.101, 95%CI: 1.367-7.038, P = .007). In ischemic stroke, EMS can shorten the pre-hospital delay. Among moderate to severe stroke patients, EMS can further improve the outcome. But the study needs further validation.

Peptide aptamer-based time-resolved fluoroimmunoassay for CHIKV diagnosis.

BACKGROUND: Chikungunya virus (CHIKV) and Dengue virus (DENV) have similar clinical symptoms, which often induce misdiagnoses. Therefore, an antigen detection diagnostic system that can clearly identify these two viruses is desirable. METHODS: In this study, we developed a novel peptide with high affinity and specificity to CHIKV, and further constructed peptide aptamer-based TRFIA assay to efficiently detect CHIKV. Peptide aptamer B2 (ITPQSSTTEAEL) and B3 (DTQGSNWI) were obtained through computer-aided design and selected as CHIKV-specific peptide aptamers based on their high binding affinity, strong hydrogen bonding, and RMSD of molecular docking. Then, a sandwich-Time-Resolved Fluoroimmunoassay (TRFIA) was successfully constructed for the detection of the interaction between peptide aptamers and viruses. RESULTS: When using B2 as the detection element, highly specific detection of CHIKV E2 was achieved with detection limits of 8.5 ng/ml in PBS solution. Variation coefficient between inter-assay showed the disturbances received from the detection of clinical fluid specimens (including serum and urine), were also within acceptable limits. The detection limits for 10-fold dilution serum and urine were 57.8 ng/mL and 147.3 ng/mL, respectively. The fluorescent signal intensity exhibited a good linear correlation with E2 protein concentration in the range of 0-1000 ng/mL, indicating the potential for quantitative detection of E2 protein. CONCLUSIONS: These results demonstrate that the construction of peptide aptamers with high affinity and specificity provides an excellent method for rapid diagnostic element screening, and the developed peptide aptamer B2 contributed to better detection of CHIKV viral particles compared to traditional antibodies.

Buccal acupuncture combined with ultrasound-guided dry needle-evoked inactivation of trigger points to treat cervical and shoulder girdle myofascial pain syndrome.

BACKGROUND: Myofascial pain syndrome (MPS) is a common disease with easy persistence and recurrence. In clinical practice, although many methods have been adopted to prevent and treat MPS, the control of MPS is still not satisfactory. OBJECTIVE: To compare the safety and effectiveness of buccal acupuncture, inactivation of trigger points (MTrPs), and their combination in the treatment of MPS. METHODS: Two hundred MPS patients in the pain clinic were randomly divided into four groups (n= 50) to receive oral drugs (Group A), oral drugs + buccal needle (Group B), oral drugs + MTrP inactivation (Group C), or oral drugs + buccal needle + MTrP inactivation (Group D). RESULTS: The visual analogue scale (VAS) and cervical range of motion (ROM) of Group D were significantly lower than those of the other three groups, and the pressure pain threshold (PPT) value of labelled MTrPs was significantly higher than those of the other three groups (P< 0.05). The excellent rate and total effective rate of Group D were significantly higher than those of the other three groups. Group C had the highest pain score and the lowest acceptance score. The results showed that buccal acupuncture combined with ultrasound-guided dry needle-evoked inactivation of MTrPs can significantly reduce the VAS score of MPS patients, improve the range of motion of the cervical spine, and improve patient satisfaction. CONCLUSIONS: This study provides a highly accepted and satisfactory treatment for MPS, which is worthy of clinical promotion.

Late-onset mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome with mitochondrial DNA 3243A>G mutation masquerading as autoimmune encephalitis: A case report.

BACKGROUND: Here, we present a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, which initially appeared to be autoimmune encephalitis and was ultimately confirmed as MELAS with the mitochondrial DNA 3243A>G mutation. CASE SUMMARY: A 58-year-old female presented with acute-onset speech impediment and auditory hallucinations, symmetrical bitemporal lobe abnormalities, clinical and laboratory findings, and a lack of relevant prodromal history, which suggested diagnosis of autoimmune encephalitis. Further work-up, in conjunction with the patient's medical history, family history, and lactate peak on brain lesions on magnetic resonance imaging, suggested a mitochondrial disorder. Mitochondrial genome analysis revealed the m.3243A>G variant in the MT-TL1 gene, which led to a diagnosis of MELAS syndrome. CONCLUSION: This case underscores the importance of considering MELAS as a potential cause of autoimmune encephalitis even if patients are over 40 years of age, as the symptoms and signs are atypical for MELAS syndrome.

Injectable hypoxia-preconditioned cartilage progenitor cells-laden GelMA microspheres system for enhanced osteoarthritis treatment.

Osteoarthritis (OA) is the most common age-related degenerative joint disease mainly characterized by the destruction of articular cartilage. Owing to its native avascular property, intrinsic repair of articular cartilage is very limited. Thus, a chondrogenic microenvironment in the joint is essential to the preservation of healthy chondrocytes and OA treatment. Recently, cartilage progenitor cells (CPCs)-based therapy is emerging as a promising strategy to repair degenerated and damaged articular cartilage. In this study, injectable hypoxia-preconditioned three-dimensional (3D) cultured CPCs-laden gelatin methacryloyl (GelMA) microspheres (CGMs) were constructed and characterized. Compared to normoxia-pretreated 3D CPCs and two-dimensional (2D) cultured CPCs, hypoxia-preconditioned 3D cultured CPCs exhibited enhanced cartilage extracellular matrix (ECM) secretion and greater chondrogenic ability. In addition, hypoxia-preconditioned 3D cultured CPCs more effectively maintained cartilage matrix metabolism balance and attenuated articular cartilage degeneration in subacute and chronic rat OA models. Mechanistically, our results demonstrated hypoxia-preconditioned 3D cultured CPCs exerted chondro-protective effects by inhibiting inflammation and oxidative stress via NRF2/HO-1 pathway in vitro and in vivo. Together, through the 3D culture of CPCs using GelMA microspheres (GMs) under hypoxia environment, our results proposed an efficient articular cartilage regeneration strategy for OA treatment and could provide inspiration for other stem cells-based therapies.

Secreted phosphoprotein 24 kD (Spp24) inhibits the growth of human osteosarcoma through the BMP-2/Smad signaling pathway.

Autocrine stimulation of tumor cells is an important mechanism for the growth of skeletal tumors. In tumors that are sensitive, growth factor inhibitors can dramatically reduce tumor growth. In this study, our aim was to investigate the effects of Secreted phosphoprotein 24 kD (Spp24) on the growth of osteosarcoma (OS) cells in the presence and absence of exogenous BMP-2 both in vitro and in vivo. Our study demonstrated that Spp24 inhibited proliferation and promoted apoptosis of OS cells as confirmed by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay and immunohistochemical staining. We found that BMP-2 increased the mobility and invasiveness of tumor cells in vitro whereas Spp24 inhibited both of these processes alone and in the presence of exogenous BMP-2. Phosphorylation of Smad1/5/8 and Smad8 gene expression was enhanced by treatment with BMP-2 but inhibited by treatment with Spp24. Subcutaneous and intratibial tumor models in nude mice demonstrated that BMP-2 promoted OS growth in vivo, while Spp24 significantly inhibited tumor growth. We conclude that the BMP-2/Smad signaling pathway is involved in the pathogenesis of OS growth and that Spp24 inhibits the growth of human OS induced by BMP-2 both in vitro and in vivo. Interruption of Smad signaling and increased apoptosis appear to be the primary mechanisms involved. These results confirm the potential of Spp24 as a therapeutic agent for the treatment of OS and other skeletal tumors.

Psychometric evaluation of the Chinese version of the Upper Limb Lymphedema Quality of Life Questionnaire in breast cancer-related lymphedema patients.

PURPOSE: The purpose of this study was to translate and evaluate the psychometric properties of the Chinese version of the Upper Limb Lymphedema Quality of Life Questionnaire (C-ULLQoL). METHODS: Eighty-five participants completed the C-ULLQoL and the Functional Assessment of Cancer Therapy-Breast (C-FACT-B). The Cronbach's alpha (α) was used to determine the internal consistency, and intraclass correlation coefficients (ICCs) - to evaluate the test-retest reliability. The content validity index (CVI) was assessed by a group of experts. Construct validity was examined by performing factor analysis and criterion validity by observing the correlations between C-ULLQoL with C-FACT-B. RESULTS: Cronbach's α of the total scale was 0.930. ICC scores ranged from 0.874 to 0.938. The content validity of C-ULLQoL was acceptable. Two factors (65.488% of the variance) were extracted by exploratory factor analysis. A significant correlation was observed between C-ULLQoL and C-FACT-B (r = -0.611, p < 0.01). CONCLUSION: The C-ULLQoL is a reliable and valid questionnaire that can be used in clinic and scientific practice for evaluating health-related quality of life in Chinese patients with breast cancer-related lymphedema.IMPLICATIONS FOR REHABILITATIONAn effective and comprehensive scale to measure the health-related quality of life (HRQoL) is essential because breast cancer-related lymphedema (BCRL) leads to various complications for patients, caregivers, and society.The Chinese version of the Upper Limb Lymphedema Quality of Life Scale (C-ULLQoL) is a valid, reliable, and practical instrument to comprehensively assess HRQoL in Chinese patients with BCRL.The C-ULLQoL can be used in both clinical and research settings to evaluate HRQoL of BCRL patients in China.

Regulated macrophage immune microenvironment in 3D printed scaffolds for bone tumor postoperative treatment.

The 3D printing technique is suitable for patient-specific implant preparation for bone repair after bone tumor resection. However, improving the survival rate due to tumor recurrence remains a challenge for implants. The macrophage polarization induction to M2-type tumor-associated macrophages (TAMs) by the tumor microenvironment is a key factor of immunosuppression and tumor recurrence. In this study, a regenerative scaffold regulating the macrophage immune microenvironment and promoting bone regeneration in a dual-stage process for the postoperative treatment of bone tumors was constructed by binding a colony-stimulating factor 1 receptor (CSF-1R) inhibitor GW2580 onto in situ cosslinked hydroxybutylchitosan (HBC)/oxidized chondroitin sulfate (OCS) hydrogel layer covering a 3D printed calcium phosphate scaffold based on electrostatic interaction. The hydrogel layer on scaffold surface not only supplied abundant sulfonic acid groups for stable loading of the inhibitor, but also acted as the cover mask protecting the bone repair part from exposure to unhealthy growth factors in the microenvironment at the early treatment stage. With local prolonged release of inhibitor being realized via the functional material design, CSF-1R, the main pathway that induces polarization of TAMs, can be efficiently blocked, thus regulating the immunosuppressive microenvironment and inhibiting tumor development at a low therapeutic dose. At the later stage of treatment, calcium phosphate component of the scaffold can facilitate the repair of bone defects caused by tumor excision. In conclusion, the difunctional 3D printed bone repair scaffold regulating immune microenvironment in stages proposed a novel approach for bone tumor postoperative treatment.

Paroxysmal speech disorder as the initial symptom in a young adult with anti-N-methyl-D-aspartate receptor encephalitis: A case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a treatable but frequently misdiagnosed autoimmune disease. Speech dysfunction, as one of the common manifestations of anti-NMDAR encephalitis, is usually reported as a symptom secondary to psychiatric symptoms or seizures rather than the initial symptom in a paroxysmal form. We report a case of anti-NMDAR encephalitis with paroxysmal speech disorder as a rare initial manifestation, and hope that it will contribute to the literature. CASE SUMMARY: A 39-year-old man with anti-NMDAR encephalitis initially presented with paroxysmal nonfluent aphasia and was misdiagnosed with a transient ischemic attack and cerebral infarction successively. The patient subsequently presented with seizures, but no abnormalities were found on brain magnetic resonance imaging or electroencephalogram. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis and increased protein levels. Anti-NMDAR antibodies in serum and CSF were detected for a conclusive diagnosis. After immunotherapy, the patient made a full recovery. CONCLUSION: This case suggests that paroxysmal speech disorder may be the presenting symptom of anti-NMDAR encephalitis in a young patient.

U-Shaped Association Between Serum Uric Acid and Hemorrhagic Transformation After Intravenous Thrombolysis.

BACKGROUND: Uric acid (UA) has both antioxidative and pro-oxidative properties. The study aimed to investigate the relationship between serum UA and hemorrhagic transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke. METHODS: The patients undergoing intravenous thrombolysis from two hospitals in China were retrospectively analyzed. HT was evaluated using computed tomography images reviewed within 24- 36h after thrombolysis. Symptomatic intracranial hemorrhage (sICH) was defined as HT accompanied by worsening neurological function. Multivariate logistic regression and spline regression models were performed to explore the relationship between serum UA levels and the risk of HT and sICH. RESULTS: Among 503 included patients, 60 (11.9%) were diagnosed with HT and 22 (4.4%) developed sICH. Patients with HT had significant lower serum UA levels than those without HT (245 [214-325 vs. 312 [256-370] µmol/L, p < 0.001). Multivariable logistic regression analysis indicated that patients with higher serum UA levels had a lower risk of HT (OR per 10-µmol/L increase 0.96, 95%CI 0.92-0.99, p = 0.015). Furthermore, multiple-adjusted spline regression models showed a Ushaped association between serum UA levels and HT (p < 0.001 for non-linearity). Similar results were present between serum UA and sICH. Restricted cubic spline models predicted the lowest risk of HT and sICH when the serum UA levels were 386µmol/L. CONCLUSION: The data show the U-shaped relationship between serum UA levels and the risk of HT and sICH after intravenous thrombolysis.

Clinical Value of Combined Detection of UA and MMP-9 in Evaluating Bleeding Transformation and Prognosis After Thrombolysis in Acute Cerebral Infarction.

This paper presents an in-depth study and analysis of the assessment of hemorrhagic transformation and prognostic outcome after thrombolysis in acute cerebral infarction using a combined test and evaluates its clinical value. The ischemic tissue hemodynamic changes were compared and analyzed by the combined application of magnetic resonance conventional examination. Single-factor and multi-factor Logistic regression analysis was applied to the model group samples to determine the independent influencing factors of hemorrhage and to construct a risk prediction model. The Hosmer-Lemeshow chi-square test was used to test the fit of the model, and the area under the ROC curve was used to test the discriminatory ability of the model. The area under the ROC curve was used to test the discriminatory ability of the model. The main purpose of this study was to investigate the clinical diagnostic value of the combined D-D and Hcy and test for the early detection of patients with acute cerebral infarction disease. There was no significant correlation between single PWI-ASPECTS and clinical prognostic MRS score, which may be related to the site and volume of initial diffusion restriction; the percentage of the mismatched area between DWI-PWI and clinical prognostic mRS score was significantly correlated, which helps clinicians to assess the therapeutic effect of non-thrombolytic therapy and provide an important basis for clinical selection of appropriate interventions in the subacute phase of stroke. The sensitivity of D-D, Hcy, and cTnI in the acute cerebral infarction group was 59.4%, 79.6%, and 49.5%, and the specificity was 73.5%, 70.5%, and 91.1%, respectively, with the area under the curve of 0.606, 0.729, and 0.521. The sensitivity, specificity, and area under the curve of the combined assay were higher than those of the single assay. The detection level of high-risk group was the highest, followed by the low-risk group. Pearson correlation analysis suggests that there is a significant correlation between serum UA and MM-9 level and grace score.

Evaluation of a Multilevel Program to Improve Clinician Adherence to Management Guidelines for Acute Ischemic Stroke.

Importance: Promotion of clinician adherence to stroke guidelines can improve stroke outcomes. Objective: To investigate the outcomes of a multilevel system program on clinician adherence to guidelines for treatment of patients with acute ischemic stroke (AIS). Design, Setting, and Participants: This quality improvement study used a prospective interrupted time series (ITS) and difference-in-difference (DID) design, from August 1, 2018, to January 31, 2020, divided into preprogram term and short and long postprogram terms; each term had 6 months. Data were collected during hospitalization and at discharge with an automated medical record data capture system in 58 public hospitals in Zhejiang province, China. Data were analyzed from August 2018 to January 2020. Exposures: The multilevel system program included a modularized standard template for medical records, centrally supported continuing education, continuous monitoring and feedback, and collaborative workshops. Main Outcomes and Measures: The primary outcome was adherence to 12 key performance indicators (KPIs), expressed as (1) percentage of patient-applicable KPIs achieved in each participant and (2) percentage of participants among whom all applicable KPIs were achieved (dichotomous all-or-none measure). The secondary outcome was severe disability or death (modified Rankin Scale 5-6) at discharge. Results: Among 45 091 patients (mean [SD] age, 69 [12] years; 18 347 female [40.7%]), 28 721 from 30 hospitals received the program and 16 370 from 28 hospitals continued routine care. In adjusted DID analysis, the program was associated with an increase in the absolute percentage of KPIs achieved per patient (6.46%; 95% CI, 5.49% to 7.43%), absolute rate of all-or-none success (8.29%; 95% CI, 6.99% to 9.60%), and decreased rate of severe disability or death at discharge (-1.68%; 95% CI, -2.99% to -0.38%). The ITS result showed the program was associated with an increase in KPIs achieved per patient per week (slope change in short-term period, 0.36%; 95% CI, 0.20% to 0.52%; level change in long-term period, (9.64%; 95% CI, 4.58% to 14.69%) and in all-or-none success (slope change in short-term period 0.34%; 95% CI, 0.23% to 0.46%; level change in long-term period 5.89%; 95% CI, 0.19% to 11.59%). Conclusions and Relevance: The centrally supported program was associated with increases in clinician adherence to guidelines and reduced the proportion of severely disabled or deceased patients with AIS at discharge, providing support for its wider implementation.

Causative Classification of Ischemic Stroke by the Machine Learning Algorithm Random Forests.

Background: Prognosis, recurrence rate, and secondary prevention strategies differ by different etiologies in acute ischemic stroke. However, identifying its cause is challenging. Objective: This study aimed to develop a model to identify the cause of stroke using machine learning (ML) methods and test its accuracy. Methods: We retrospectively reviewed the data of patients who had determined etiology defined by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) from CASE-II (NCT04487340) to train and evaluate six ML models, namely, Random Forests (RF), Logistic Regression (LR), Extreme Gradient Boosting (XGBoost), K-Nearest Neighbor (KNN), Ada Boosting, Gradient Boosting Machine (GBM), for the detection of cardioembolism (CE), large-artery atherosclerosis (LAA), and small-artery occlusion (SAO). Between October 2016 and April 2020, patients were enrolled consecutively for algorithm development (phase one). Between June 2020 and December 2020, patients were enrolled consecutively in a test set for algorithm test (phase two). Area under the curve (AUC), precision, recall, accuracy, and F1 score were calculated for the prediction model. Results: Finally, a total of 18,209 patients were enrolled in phase one, including 13,590 patients (i.e., 6,089 CE, 4,539 LAA, and 2,962 SAO) in the model, and a total of 3,688 patients were enrolled in phase two, including 3,070 patients (i.e., 1,103 CE, 1,269 LAA, and 698 SAO) in the model. Among the six models, the best models were RF, XGBoost, and GBM, and we chose the RF model as our final model. Based on the test set, the AUC values of the RF model to predict CE, LAA, and SAO were 0.981 (95%CI, 0.978-0.986), 0.919 (95%CI, 0.911-0.928), and 0.918 (95%CI, 0.908-0.927), respectively. The most important items to identify CE, LAA, and SAO were atrial fibrillation and degree of stenosis of intracranial arteries. Conclusion: The proposed RF model could be a useful diagnostic tool to help neurologists categorize etiologies of stroke. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT01274117].

Undertreatment of Anticoagulant Therapy in Hospitalized Acute Ischemic Stroke Patients With Atrial Fibrillation.

Background: This study aimed to investigate the prevalence and factors associated with the initiation of oral anticoagulation among patients with acute ischemic stroke (AIS) and concurrent atrial fibrillation (AF) at discharge in China. Methods: We continuously included hospitalized patients with AIS with an AF diagnosis registered in the computer-based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation (CASE II) from January 2016 to December 2020 and divided them into a and non-anticoagulant groups according to the medications at discharge. Binary logistic regression was used to determine the factors associated with the prescription of anticoagulants in patients with AF. Results: A total of 16,162 patients were enrolled. The mean age was 77 ± 9 years, 8,596 (53.2%) were males, and the median baseline National Institute of Health Stroke Scale score was 5 (2-12). Of the 14,838 patients without contraindications of antithrombotic therapy, 6,335 (42.7%) patients were initiated with anticoagulation treatment at discharge. Prior history of hemorrhagic stroke (OR 0.647, p < 0.001) and gastrointestinal bleeding (OR 0.607, p = 0.003) were associated with a lower rate of anticoagulation at discharge. Patients with any intracranial hemorrhage (OR 0.268, p < 0.001), gastrointestinal bleeding (OR 0.353, p < 0.001), or pneumonia during hospitalization (OR 0.601, p < 0.001) were less likely to receive anticoagulants at discharge. Among 7,807 patients with previously diagnosed AF and high risk of stroke (CHA2DS2-VASc ≥2), only 1,585 (20.3%) had been receiving anticoagulation treatment prior to the onset of stroke. However, the mean international normalized ratio (INR) was 1.5 on the first test during hospitalization in patients receiving warfarin. Patients complicated with a previous history of ischemic stroke/transient ischemic attack (TIA; OR 2.303, p < 0.001) and peripheral artery disease (OR 1.456, p = 0.003) were more common to start anticoagulants. Conclusions: Less than half of patients with AIS and concurrent AF initiated guideline-recommended oral anticoagulation at discharge, while only 20% of patients with previously diagnosed AF with a high risk of stroke had been using anticoagulants prior to the onset of stroke, which highlights a large care gap in hospitalized stroke patients and the importance of AF management.

Stroke outcome of early antiplatelet in post-thrombolysis haemorrhagic infarction.

BACKGROUND AND PURPOSE: Initiation of early antiplatelet (EA) therapy after acute ischaemic stroke (AIS) is essential. We aimed to investigate the safety and effectiveness of EA therapy in patients who had an AIS with haemorrhagic infarction (HI) after intravenous thrombolysis (IVT). METHODS: Based on a multicentre stroke registry database, patients who had an AIS with post-thrombolysis HI at 24 hours were identified. EA users and non-EA users were defined as patients with HI who received or did not receive antiplatelet therapy between 24 and 48 hours after IVT. Primary outcome was favourable outcome defined as modified Rankin Scale scores 0-2 at 3 months. Secondary outcomes were early neurological deterioration (END) and haemorrhagic transformation expansion. RESULTS: A total of 842 patients with HI were identified from 24 061 thrombolytic patients within 4.5 hours, and 341 (40.5%) received EA therapy. EA users were more likely to have a favourable outcome (55.7% vs 39.5%, OR 1.565; 95% CI 1.122 to 2.182; p=0.008) and lower rate of END (12.6% vs 21.4%, OR 0.585; 95% CI 0.391 to 0.875; p=0.009) compared with non-EA users. EA therapy was not associated with haemorrhagic transformation expansion (p=0.125). After propensity score matching, EA therapy was still independently associated with favourable outcome (54.3% vs 46.3%, OR 1.495; 95% CI 1.031 to 2.167; p=0.038) and lower risk of END (13.5% vs 21.2%, OR 0.544; 95% CI 0.350 to 0.845; p=0.007). CONCLUSIONS: Antiplatelet therapy can be safely used between 24 and 48 hours when HI occurs after IVT, and such therapy is associated with reduced risk of END and improved neurological outcome in patients who had an AIS.