Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Integration of molecular pathology with histopathology to accurately evaluate the biological behaviour of WHO grade 2 meningiomas and patient prognosis.

PURPOSE: A molecular pathological grading method was tested in WHO grade 2 meningiomas to judge whether this molecular grading can more accurately evaluate meningioma biological behaviour. METHODS: The medical records and paraffin-embedded tissues of surgically resected WHO grade 2 meningioma patients in our department from January 1, 2010, to December 31, 2020, were collected. The molecular pathological risk grading suggested by Sahm et al. was adopted and the patients were graded as low, intermediate and high risk. Progression-free survival (PFS), malignant progression-free survival (MPFS) and overall survival (OS) were analysed. Univariate and multivariate analysis were performed to determine the relationship between molecular risk grading and patient survival. RESULTS: Of the 98 patients, 13 (13.2%) were graded as low risk, 63 patients (64.3%) were graded as intermediate risk, and 22 patients (22.4%) were graded as high risk. With increasing molecular risk grade, the rates of tumour recurrence, malignant progression and mortality increased significantly (P < 0.05). Multivariate analysis showed that molecular risk grading was negatively associated with PFS (HR 0.018, 95% CI 0.003-0.092), MPFS (HR 0.040, 95% CI 0.006-0.266) and OS (HR 0.088, 95% CI 0.016-0.472) (P < 0.01), and gross total resection (Simpson grade I-III) significantly prolonged PFS (HR 5.882, 95% CI 2.538-13.699) and OS (HR 2.611, 95% CI 1.117-7.299) (P < 0.05). CONCLUSION: Sahm et al.'s molecular risk grading can further refine the classification of WHO grade 2 meningiomas and more accurately evaluate their biological behaviour and patient prognosis.

Risk factors for the rupture of mirror middle cerebral artery aneurysm using computer-assisted semiautomated measurement and hemodynamic analysis.

OBJECTIVES: To identify the morphologic and hemodynamic risk factor of mirror middle cerebral artery (MCA) aneurysms. METHODS: We conducted a retrospective analysis of 40 paired mirror MCA aneurysms. Aneurysms were divided into ruptured and unruptured groups. Seventeen morphological and nine hemodynamic parameters were measured using computer-assisted semiautomated measurement (CASAM) and computer flow dynamic (CFD) simulation. We performed a paired t-test (for normally distributed data) or a paired Wilcoxon rank-sum (for non-normally distributed data) to analyze all parameters between the groups. Multivariate conditional logistic regression analysis identified independent risk factors. The receiver operating characteristic curve was analyzed to acquire the area under the curve (AUC) and the cutoff values of the independent risk factors. RESULTS: There were significant differences in morphological and hemodynamic parameters between the ruptured and unruptured mirror aneurysms. The multivariate logistic analysis showed that the greater size (odds ratio [OR] = 9.807, p = 0.003), smaller neck diameter (OR = 0.285, p = 0.018) and maximum oscillatory shear index (OSI) (OR = 0.000001, p = 0.046) were independently correlated with aneurysm rupture. AUCs for size, N. and maximum OSI were 0.794, 0.695, and 0.701, respectively. The cutoff values of the size, neck diameter, and maximum OSI were 6.30, 5.07, and 0.356437, respectively. CONCLUSIONS: Morphology and hemodynamics can help predict aneurysm rupture risks. The more significant size, smaller neck diameter and maximum OSI were independent risk factors for the rupture of MCA aneurysms. The variables could aid practical risk evaluation.

Development and validation of a nomogram using on admission routine laboratory parameters to predict in-hospital survival of patients with COVID-19.

To develop and validate a nomogram using on admission data to predict in-hospital survival probabilities of coronavirus disease 2019 (COVID-19) patients. We analyzed 855 COVID-19 patients with 52 variables. The least absolute shrinkage and selection operator regression and multivariate Cox analyses were used to screen significant factors associated with in-hospital mortality. A nomogram was established based on the variables identified by Cox regression. The performance of the model was evaluated by C-index and calibration plots. Decision curve analysis was conducted to determine the clinical utility of the nomogram. Six variables, including neutrophil (hazard ratio [HR], 1.088; 95% confidence interval [CI], [1.0004-1.147]; p < .001), C-reactive protein (HR, 1.007; 95% CI, [1.0026-1.011]; p = .002), IL-6 (HR, 1.001; 95% CI, [1.0003-1.002]; p = .005), d-dimer (HR, 1.034; 95% CI, [1.0111-1.057]; p = .003), prothrombin time (HR 1.086, 95% CI [1.0369-1.139], p < .001), and myoglobin (HR, 1.001; 95% CI, [1.0007-1.002]; p < .001), were identified and applied to develop a nomogram. The nomogram predicted 14-day and 28-day survival probabilities with reasonable accuracy, as assessed by the C-index (0.912) and calibration plots. Decision curve analysis showed relatively wide ranges of threshold probability, suggesting a high clinical value of the nomogram. Neutrophil, C-reactive protein, IL-6, d-dimer, prothrombin time, and myoglobin levels were significantly correlated with in-hospital mortality of COVID-19 patients. Demonstrating satisfactory discrimination and calibration, this model could predict patient outcomes as early as on admission and might serve as a useful triage tool for clinical decision making.

Inflammation-associated factors for predicting in-hospital mortality in patients with COVID-19.

The aim is to explore the relation between inflammation-associated factors and in-hospital mortality and investigate which factor is an independent predictor of in-hospital death in patients with coronavirus disease-2019. This study included patients with coronavirus disease-2019, who were hospitalized between February 9, 2020, and March 30, 2020. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO) were used to select variables. Multivariate Cox regression analysis was applied to identify independent risk factors in coronavirus disease-2019. A total of 1135 patients were analyzed during the study period. A total of 35 variables were considered to be risk factors after the univariate regression analysis of the clinical characteristics and laboratory parameters (p < .05), and LASSO regression analysis screened out seven risk factors for further study. The six independent risk factors revealed by multivariate Cox regression were myoglobin (HR, 5.353; 95% CI, 2.633-10.882; p < .001), C-reactive protein (HR, 2.063; 95% CI, 1.036-4.109; p = .039), neutrophil count (HR, 2.015; 95% CI, 1.154-3.518; p = .014), interleukin 6 (Il-6; HR, 9.753; 95% CI, 2.952-32.218; p < .001), age (HR, 2.016; 95% CI, 1.077-3.773; p = .028), and international normalized ratio (HR, 2.595; 95% CI, 1.412-4.769; p = .002). Our results suggested that inflammation-associated factors were significantly associated with in-hospital mortality in coronavirus disease-2019 patients. C-reactive protein, neutrophil count, and interleukin 6 were independent factors for predicting in-hospital mortality and had a better independent predictive ability. We believe these findings may allow early identification of the patients at high risk for death, and can also assist in better management of these patients.

Machine learning classifier based on FE-KNN enabled high-capacity PAM-4 and NRZ transmission with 10-G class optics.

Modified by special feature engineering, a powerful and low-order equalizer based on K-nearest neighbors (KNN) classifier is applied to improve performance of high-speed system with bandwidth-limited optics. The feature construction and feature weighting are specially designed to conduct an appropriate a feature engineering-based KNN (FE-KNN) scheme, which contains more data characteristics to enhance the equalization performance. Experimental comparisons of KNN classifier with/without feature engineering, decision feedback equalizer (DFE) and feed-forward equalizer (FFE) are implemented to prove the feasibility of our scheme in both 25-Gb/s NRZ and 50-Gb/s PAM-4 transmission experiments with 10-G optics system. The corresponding results show that, without the feature engineering, the performance achieved by the common KNN is not improved even in the case of hard decision (HD). In contrast, compared to the common 11-taps DFE, the performance achieved by FE-KNN with only 5 taps is improved by 1-dB at KP4-FEC threshold (BER=2.2E-4) for 25-Gb/s NRZ transmission. While, for 50-Gb/s PAM-4 case, 0.5-dB sensitivity improvement is achieved by our scheme compared to the common 11-taps DFE under the HD-FEC limit (BER=3.8E-3).

Increased Expression of Caspase-12 After Experimental Subarachnoid Hemorrhage.

Convincing evidences have proved that apoptosis plays a vital role in the pathogenesis of early and delayed brain injury following subarachnoid hemorrhage (SAH). Recently, a novel caspase-12-mediated apoptotic pathway has been reported to be induced by excess endoplasmic reticulum (ER) stress. Extensive protein damage occurs after SAH, which may trigger ER stress-associated apoptotic pathway. Thus, we hypothesized that caspase-12, as the major molecular marker of this novel apoptotic pathway, may be activated and involved in the pathogenesis of apoptotic injury after SAH. This study sought to investigate the changes of caspase-12 expressions in both in vitro and in vivo SAH models. Western blot analysis found significantly increased protein expressions of both pro- and active forms of caspase-12 after SAH. Quantitative real-time PCR and immunohistochemistry assays confirmed elevated caspase-12 level after SAH in vivo. Further, double immunofluorescence staining revealed obvious caspase-12 over-expression in both cortical neurons and astrocytes. Moreover, immunofluorescent co-staining in vivo demonstrated that neural cells with high immunoreactivity of caspase-12 also expressed caspase-3, and dual-immunofluorescent staining for caspase-12 and TUNEL in vitro showed that TUNEL-positive cells were more likely to exhibit higher caspase-12 immunoreactivity, indicating a potential contribution of caspase-12 activation to apoptosis in SAH. Collectively, our results showed significant upregulation of caspase-12 expression after experimental SAH. These findings also offer important implications for further investigations of the therapeutic potential of caspase-12 associated apoptosis in SAH.

Association between primary biliary cholangitis with diabetes and cardiovascular diseases: A bidirectional multivariable Mendelian randomization study.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs). METHODS: Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836). RESULTS: SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models. CONCLUSION: Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.

Ethanol-Induced Hepatic Ferroptosis Is Mediated by PERK-Dependent MAMs Formation: Preventive Role of Quercetin.

SCOPE: Iron deposition is frequently observed in alcoholic liver disease (ALD), which indicates a potential role of ferroptosis in its development. This study aims to explore the effects of quercetin on ferroptosis in ALD and elucidates the underlying mechanism involving the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) mediated by protein kinase RNA-like endoplasmic reticulum kinase (PERK). METHODS AND RESULTS: C57BL/6J mice are fed either a regular or an ethanol-containing liquid diet (with 28% energy form ethanol) with or without quercetin supplementation (100 mg kg-1 BW) for 12 weeks. Ethanol feeding or treatment induced ferroptosis in mice and AML12 cells, which is associated with increased MAMs formation and PERK expression within MAMs. Quercetin attenuates these changes and protects against ethanol-induced liver injury. The antiferroptotic effect of quercetin is abolished by ferroptosis inducers, but mimicked by ferroptosis inhibitors and PERK knockdown. The study demonstrates that PERK structure, rather than its kinase activity (transfected with the K618A site mutation that inhibits kinase activity-ΔK plasmid or protein C terminal knockout-ΔC plasmid of PERK), mediates the enhanced MAMs formation and ferroptosis during the ethanol exposure. CONCLUSION: Quercetin ameliorates ethanol-induced liver injury by inhibiting ferroptosis via modulating PERK-dependent MAMs formation.

Potential of body mass index as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial.

BACKGROUND: To investigate the association between body mass index (BMI) and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial-intracranial bypass surgery. MATERIALS AND METHODS: We analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, we compared the primary endpoint of CMOSS-stroke or death within 30 days, or IIS after 30 days up to two years-among patients with varying BMIs who underwent either surgery or medical treatment. RESULTS: Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within two years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m2; 95% confidence interval: 1.06-1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m2. Patients with BMI ≥24.5 kg/m2 experienced a higher incidence of IIS compared to those with BMI <24.5 kg/m2 (17.4% vs. 0.0%, P<0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m2 (5.3% vs. 19.8%, P<0.01) and those with BMI <24.5 kg/m2 (10.6% vs. 1.4%; P=0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m2. CONCLUSION: Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.

Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS.

BACKGROUND: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. METHODS AND RESULTS: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). CONCLUSIONS: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

TRIM32 Inhibits NEK7 Ubiquitylation-Dependent Microglia Pyroptosis After Spinal Cord Injury.

Spinal cord injury (SCI) is a disabling disease associated with microglial activation. Tripartite motif containing 32 (TRIM32) is an E3 ubiquitin ligase that plays a role in SCI. This study aimed to explore the role of TRIM32 in SCI and its potential mechanisms. We established an SCI mouse model to assess the function of TRIM32 using quantitative real-time polymerase chain reaction (qPCR), and hematoxylin and eosin staining. Additionally, a lipopolysaccharides (LPS)-induced cell injury model was generated to explore the impact of TRIM32 on pyroptosis using qPCR, propidium iodide staining, and western blotting. The ubiquitylation of NEK7 was analyzed using western blotting, co-immunoprecipitation, and immunofluorescence staining. The results showed that TRIM32 expression was increased in SCI mice and LPS-induced BV-2 cells. Overexpression of TRIM32 ameliorated SCI in mice and suppressed pyroptosis in LPS-treated BV-2 cells. Additionally, the E3 ligase TRIM32 promoted the ubiquitylation of NEK7 at the K64 site, leading to the downregulation of NEK7 levels. Inhibiting NEK7 ubiquitylation reversed the suppression of pyroptosis by TRIM32. In conclusion, TRIM32 inhibits microglia pyroptosis by facilitating the ubiquitylation of NEK7 at the K64 site, thereby alleviating the progression of SCI. The findings suggest that TRIM32 has the potential to be a therapeutic target of SCI.

Animal Models of Ischemic Stroke with Different Forms of Middle Cerebral Artery Occlusion.

Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical treatments are urgently needed. The middle cerebral artery occlusion (MCAO) model is currently the most widely used animal model of ischemic stroke. This review discusses various methods for constructing the MCAO model and compares their advantages and disadvantages in order to provide better approaches for studying ischemic stroke.

Morphological evaluation of the risk of posterior communicating artery aneurysm rupture: a mirror aneurysm model.

OBJECTIVE: The aim of this study was to use morphological parameters of mirror posterior communicating artery (PCoA) aneurysms to evaluate aneurysm rupture risk. METHODS: The morphological parameters of 45 pairs of ruptured mirror PCoA aneurysms were analyzed. Conditional univariate and multivariate logistic regression of the following paired morphological parameters was performed: aneurysm with a daughter sac, aneurysm height, aneurysm width, neck width, internal carotid artery diameter, PCoA diameter, flow angle, PCoA angle, aspect ratio, bottleneck factor, size ratio, height/width ratio, fetal posterior cerebral artery, and aneurysm with height > width. A scoring system was established according to the odds ratios (ORs). The receiver operating characteristic was used to test the prediction accuracy of this scoring system in the authors' database of 523 PCoA aneurysms and the threshold value was used to define higher risk. RESULTS: Aneurysm width (OR 1.676, p = 0.014), aneurysm with daughter sac (OR 7.775, p = 0.016), and aneurysm with height > width (OR 9.067, p = 0.012) were independent risk factors for rupture. The scoring system consisted of aneurysm width (1 point per mm), aneurysm with a daughter sac (5 points), and aneurysm with height > width (5 points). The area under the curve (AUC) of the scoring system was 0.842, and its threshold value was 7.97. A score ≥ 8 points was defined as higher risk. The AUC using this definition was 0.802. CONCLUSIONS: Aneurysm width, aneurysms with height > width, and aneurysms with a daughter sac were independent risk factors for PCoA aneurysm rupture. The scoring system devised in this study accurately predicts rupture risk.

Prognostic capacity of the systemic inflammation response index for functional outcome in patients with aneurysmal subarachnoid hemorrhage.

Objective: We aimed to investigate the relationship between systemic inflammatory response index (SIRI) and functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). Methods: A retrospective cohort study was performed involving all consecutive aSAH patients admitted to our institution. The modified Rankin Scale (mRS) score was performed to determine the functional outcomes of all patients at 3 months after aSAH. Results were categorized as favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Univariate and multivariate logistic regressive analyses were utilized to identify the prognostic significance of SIRI. To minimize the effects of confounding factors, patients were stratified according to the optimal cut-off value of SIRI with propensity score matching (PSM). Further subgroup analysis was conducted to verify the consistency of our findings and Pearson's correlation analysis was used to assess the relationship between SIRI and the severity of aSAH. Results: In this study, 350 patients were enrolled and 126 (36.0%) of them suffered unfavorable outcomes. The SIRI of 5.36 × 109/L was identified as the optimal cut-off value. Two score-matched cohorts (n = 100 in each group) obtained from PSM with low SIRI and high SIRI were used for analysis. A significantly higher unfavorable functional outcome rate was observed in patients with high SIRI before and after PSM (p < 0.001 and 0.017, respectively). Multivariate logistic regression analysis demonstrated that SIRI value ≥ 5.36 × 109/L was an independent risk factor for poor outcomes (OR 3.05 95% CI 1.37-6.78, p = 0.006) after adjusting for possible confounders. A identical result was discovered in the PSM cohort. In ROC analysis, the area under the curve (AUC) of SIRI was 0.774 which shown a better predictive value than other inflammatory markers observed in previous similar studies. Pearson's correlation analysis proved the positive association between SIRI and aSAH severity. Conclusions: Elevated SIRI at admission is associated with worse clinical status and poorer functional outcomes among patients with aSAH. SIRI is a useful inflammatory marker with prognostic value for functional outcomes after aSAH.

Effect of Intraarticular Injection of Platelet-Rich Plasma on Knee Osteoarthritis: A Multicenter Retrospective Clinical Study.

This study aimed to evaluate the effect of intraarticular injection with platelet-rich plasma on knee osteoarthritis. A total of 250 patients with stages I-III osteoarthritis from December 2018 to June 2020 were included in this study. All the patients had received autologous PRP injection (3 ml) into the affected knee joint every week for totally 3 injections. The VAS score and WOMAC index were used to evaluate knee function before and at 3 days, 1 month, and 3 months after injection. A total of 250 patients were enrolled in this study, including 130 patients in the PRP group and 120 patients in the control group. The content of platelets in PRP of patients in the PRP group was 958.0 ± 283.1 × 109/L. The VAS score and WOMAC index of patients in the PRP group before treatment were not significantly different from those in the control group. At 3 days, 1 month, and 3 months after PRP treatment, the VAS score and WOMAC index of the PRP group were significantly lower than those of the control group. PRP is effective in treatment of knee osteoarthritis. The pain symptoms can be alleviated at 3 days after injection.

Inhibiting RGS1 attenuates secondary inflammation response and tissue degradation via the TLR/TRIF/NF-κB pathway in macrophage post spinal cord injury.

Macrophage-dominated inflammation by the activation of Toll-like receptor (TLR) pathway leads to neurological disruption after spinal cord injury (SCI). Regulator of G-protein signaling 1 (RGS1) is reported to be a regulator in inflammation. The present study thus purposes to identify the unknown role of RGS1 mediating TLR on inflammation post SCI. A mouse model of traumatic SCI was established by a mechanical trauma at T10. The mice underwent SCI and a macrophage line activated by lipopolysaccharide (LPS) were treated with shRNA-RGS1 to elucidate the role of RGS1 in inflammatory progression. The inflammatory factors were measured, and the degree of histology and function protection were determined. The expression levels of RGS1, myeloid differentiation primary response protein 88 (Myd88), (TIR-domain-containing adaptor inducing interferon-ß (TRIF), p38, metalloproteinase (MMP)-2, and MMP-9 were determined. RGS1 was robustly increased both in LPS-activated macrophage and SCI mice. The TLR signaling pathway-induced inflammation was suppressed by RGS1 knockdown. shRNA-mediated silence of RGS1 was exhibited a prominent decrease in TNF-α, IL-1ß and IL-6 via TLR/TRIF/ nuclear factor kappa-B (NF-κB) axis. Depletion of RGS1 also inhibited MMP-induced tissue degradation via MAPK-p38 pathway in SCI mice. Moreover, suppression of RGS1 improved spinal cord histology and function recovery. These findings suggest that RGS1 regulates inflammation and tissue disruption via TLR/TRIF/NF-κB signaling pathway in mice with SCI, thereby explaining a novel target that regulates macrophage inflammation post SCI.

Analysis of the Effect of Percutaneous Cone Shaping in Patients with Osteoporotic Vertebral Fractures.

Objective: To study and analyze the clinical effect of percutaneous cone shaping in patients with osteoporotic vertebral fractures. Methods: A total of 100 patients with vertebral osteoporotic fracture treated in our hospital from June 2019 to September 2020 were selected, and there were 50 patients with vertebral osteoporotic fracture in each group. Patients could be divided into two groups according to different treatment plans: one group was vertebroplasty patients for group A, and the other group was nonsurgical treatment patients for group B. The incidence of complications during treatment and follow-up was recorded in both groups. Results: According to a study, both groups of patients completed the treatment and follow-up, no patients lost to follow-up or death, the VAS scores and ADL scores of patients before treatment were higher, and there was no significant difference at baseline (P > 0.05). After different treatment methods, the VAS score and ADL score of group A showed good improvement after treatment compared with that before treatment, and there were certain differences within the group, with statistical significance (P < 0.05). Intragroup comparison. The VAS scores of group B at 1 week, 1 month, 3 months, and 12 months after treatment were all superior to those before treatment, and the ADL scores at 1 month, 3 months, and 12 months after treatment were all superior to those before treatment, with statistically significant differences (P < 0.05). VAS scores and ADL scores showed good improvement 1 day, 1 week, and 1 month after treatment compared with those before treatment. However, there were no significant differences in the VAS score and ADL score between the two groups at 3 and 12 months after treatment. The incidence of complications in group A is lower than that in group B. The incidence of complications in group A is as follows: there was 1 case of recurrent vertebral fracture and 1 case of urinary tract infection, and the overall incidence of complications was 4.00%. In group B, there were 1 case of recurrent fracture, 3 cases of bedsore, 2 cases of urinary tract infection, and 2 cases of pulmonary infection, and the incidence of total complications was 16.00%. After comparison between groups, there was a significant difference in the incidence of complications between the two groups, and the difference was statistically significant (P < 0.05). Conclusions: Percutaneous cone plasty can provide rapid relief of pain symptoms in patients with osteoporotic vertebral fractures and significantly improve their daily activities. However, there was no significant difference in long-term recovery from group B. In terms of the incidence of complications, the incidence of complications in group A was lower than that in group B after certain treatment.

Prognostic significance of combined score of fibrinogen and neutrophil-lymphocyte ratio for functional outcome in patients with aneurysmal subarachnoid hemorrhage.

Objective: To explore the relationship between fibrinogen and neutrophil to lymphocyte ratio (F-NLR) score and functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Method: A retrospective study was conducted that involved all consecutive patients with aSAH admitted to our institution from March 2018 to October 2021. Factors, such as demographics, comorbidities, clinical characteristics, neuroradiological data, and laboratory parameters, were collected from institutional databases. All patients achieved neurological assessment using the modified Rankin Scale (mRS) score 3 months after discharge to clarify the functional outcomes. The results were classified as favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Univariate and multivariable analyses were performed to identify the relevant factors between inflammatory markers and functional outcomes after aSAH. Subsequently, a receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predicting performance of variables. A propensity score match (PSM) was performed to correct imbalances in patients' baseline characteristics. Results: Finally, 256 patients with aSAH were included in the study cohort. A total of 94 (36.7%) patients had an unfavorable outcome. F-NLR scores were 0 [interquartile range (IQR) 0-1] and 1 (IQR 1-2) in patients with favorable and unfavorable outcomes, respectively (p < 0.001). After adjustment, the F-NLR score on admission remained significantly associated with unfavorable outcomes in patients with aSAH. In the multivariable analysis, the F-NLR score was regarded as an independent risk factor of unfavorable outcomes [odds ratio (OR) 3.113, 95% CI 1.755-5.523, p < 0.001]. In ROC analysis, the optimal cutoff value of the F-NLR score was 0.5 points. Two cohorts (n = 86 in each group) obtained from PSM with low F-NLR scores (0 points) and high F-NLR scores (1-2 points) were used for analysis. A significantly higher unfavorable functional outcome rate was observed in patients with high F-NLR scores (33.7 vs. 9.3%, p < 0.001). The area under the curve (AUC) values of F-NLR scores before and after PSM were 0.767 and 0.712, respectively. Conclusion: Fibrinogen and neutrophil to lymphocyte ratio score was an independent risk parameter associated with unfavorable functional outcomes at 3 months after aSAH. A higher F-NLR score predicts the occurrence of poor functional outcomes.

Predictors of complete recovery of oculomotor nerve palsy induced by posterior communicating artery aneurysms in patients aged eighteen to sixty.

OBJECTIVE: To explore prognostic factors of complete recovery of oculomotor nerve palsy (ONP) induced by posterior communicating artery aneurysm (PcomAA). METHOD: PcomAA patients aged 18-60 years combined with ONP who underwent surgical clipping or endovascular embolization at our institution between January 2014 and January 2020 were enrolled. Characteristics included maximum diameter of aneurysm, width of aneurysm, subarachnoid hemorrhage (SAH), duration of ONP, age, sex, ONP type, treatment method were compared. Based on the recovery of ONP, patients were separated into two groups: complete recovery group, partial and no recovery group. Analyzing by univariate and multivariate logistic regressions to identify the independent prognostics for complete ONP recovery. We established a score based on these prognostics. Receiver operating characteristics (ROC) were conducted to under the performance of the predictors and score. RESULTS: Finally, ONP type (OR 6.457 95% CI 1.664-25.052, p = 0.007), treatment method (OR 5.051, 95% CI 1.332-19.158, p = 0.017), and interval to treatment ≤2 weeks (OR 25.601 95% CI 6.222-105.340, p < 0.001) were independent predictors of complete ONP recovery. The score had an area under the curve (AUC) value of 0.870. We defined that the score higher than 5 points as easier to achieve complete ONP recovery, and the AUC value of this definition was 0.821. CONCLUSIONS: For ONP induced by PcomAA in patients aged 18-60 years, the best prognostic factor for complete ONP recovery was timely treatment. The ONP type and treatment methods were correlated with complete ONP recovery.