Background: and Purpose Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients.Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset.Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days. Conclusion This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

BACKGROUND: Microsatellite instability (MSI) analysis is becoming increasingly important in many types of tumor including colorectal cancer (CRC). The commonly used MSI tests are either time-consuming or labor-intensive. A fully automated MSI test, the Idylla MSI assay, has recently been introduced. However, its diagnostic performance has not been extensively validated in clinical CRC samples.METHODS: We evaluated 133 samples whose MSI status had been rigorously validated by standard polymerase chain reaction (PCR), clinical next-generation sequencing (NGS) cancer panel test, or both. We evaluated the diagnostic performance of the Idylla MSI assay in terms of sensitivity, specificity, and positive and negative predictive values, as well as various sample requirements, such as minimum tumor purity and the quality of paraffin blocks.RESULTS: Compared with the gold standard results confirmed through both PCR MSI test and NGS, the Idylla MSI assay showed 99.05% accuracy (104/105), 100% sensitivity (11/11), 98.94% specificity (93/94), 91.67% positive predictive value (11/12), and 100% negative predictive value (93/93). In addition, the Idylla MSI assay did not require macro-dissection in most samples and reliably detected MSI-high in samples with approximately 10% tumor purity. The total turnaround time was about 150 minutes and the hands-on time was less than 2 minutes.CONCLUSIONS: The Idylla MSI assay shows good diagnostic performance that is sufficient for its implementation in the clinic to determine the MSI status of at least the CRC samples. In addition, the fully automated procedure requires only a few slices of formalin-fixed paraffin-embedded tissue and might greatly save time and labor.
Colorectal Neoplasms ; Microsatellite Instability ; Microsatellite Repeats ; Paraffin ; Polymerase Chain Reaction ; Sensitivity and Specificity

Brucellosis is an emerging infectious disease affecting humans and animals. In this study, we investigated the in vitro and in vivo effects of tannic acid (TA) against Brucella abortus infection. After infection, F-actin polymerization and mitogen-activated protein kinases (MAPKs) (ERK 1/2 and p38α) phosphorylation were reduced in TA-treated cells compared with that in control cells. The mice were infected via an intraperitoneal route and were orally given TA or phosphate-buffered saline for 14 days. Spleen weights of the TA-treated and control mice were not different; however, splenic proliferation of B. abortus was significantly reduced in the TA-treated group. Immune response analysis showed that, compared with the control group, non-infected TA-treated mice displayed increased levels of interferon-γ (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), and interleukin-10 at 3 days post-infection and a further increase in IFN-γ and MCP-1 at 14 days post-infection. In contrast, compared with the control group, infected TA-treated mice displayed elevated levels of IFN-γ at 3 days post-infection, which continued to increase at 14 days post-infection, as was also observed for tumor necrosis factor. Taken together, the results showing TA activation of cytokine production and inhibition of bacterial proliferation in the host highlight a potential use of TA treatment in the control of Brucella infection.
Actins ; Animals ; Brucella abortus ; Brucella ; Brucellosis ; Chemokine CCL2 ; Communicable Diseases, Emerging ; Cytokines ; Humans ; In Vitro Techniques ; Interleukin-10 ; Mice ; Mitogen-Activated Protein Kinases ; Phosphorylation ; Polymerization ; Polymers ; Spleen ; Tannins ; Tumor Necrosis Factor-alpha ; Weights and Measures

Successful recovery from brain ischemia is limited due to poor vascularization surrounding the ischemic zone. Cell therapy with strong angiogenic factors could be an effective strategy to rescue the ischemic brain. We investigated whether cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable and potent Ang1 variant, enhances the angiogenesis of human cord blood derived endothelial progenitor cells (hCB-EPCs) for rescuing brain from ischemic injury. COMP-Ang1 markedly improved the tube formation of capillaries by EPCs and incorporation of EPCs into tube formation with human umbilical vein endothelial cells (HUVECs) upon incubation on matrigel in vitro. COMP-Ang1 stimulated the migration of EPCs more than HUVECs in a scratch wound migration assay. The transplanted EPCs and COMP-Ang1 were incorporated into the blood vessels and decreased the infarct volume in the rat ischemic brain. Molecular studies revealed that COMP-Ang1 induced an interaction between Tie2 and FAK, but AKT was separated from the Tie2-FAK-AKT complex in the EPC plasma membrane. Tie2-FAK increased pp38, pSAPK/JNK, and pERK-mediated MAPK activation and interacted with integrins alphanubeta3, alpha4, beta1, finally leading to migration of EPCs. AKT recruited mTOR, SDF-1, and HIF-1alpha to induce angiogenesis. Taken together, it is concluded that COMP-Ang1 potentiates the angiogenesis of EPCs and enhances the vascular morphogenesis indicating that combination of EPCs with COMP-Ang1 may be a potentially effective regimen for ischemic brain injury salvage therapy.
Angiogenesis Inducing Agents ; Animals ; Blood Vessels ; Brain ; Brain Injuries* ; Brain Ischemia ; Capillaries ; Cartilage Oligomeric Matrix Protein ; Cell Membrane ; Cell- and Tissue-Based Therapy ; Fetal Blood ; Human Umbilical Vein Endothelial Cells ; Humans ; Integrins ; Ischemia ; Morphogenesis ; Rats ; Salvage Therapy ; Stem Cells ; Wounds and Injuries

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of cervical midline-splitting French-door laminoplasty with a polyether ether ketone (PEEK) plate. The authors retrospectively analyzed the results of patients with cervical laminoplasty miniplate (MAXPACER(R)) without bone grafts in multilevel cervical stenosis. METHODS: Fifteen patients (13 males and 2 females, mean age 50.0 years (range 35-72)) with multilevel cervical stenosis (ossification of the posterior longitudinal ligament and cervical spondylotic myelopathy) underwent a combined surgery of midline-splitting French-door laminoplasty with or without mini plate. All 15 patients were followed for at least 12 months (mean follow-up 13.3 months) after surgery, and a retrospective review of the clinical, radiological and surgical data was conducted. RESULTS: The radiographic results showed a significant increase over the postoperative period in anterior-posterior diameter (9.4+/-2.2 cm to 16.2+/-1.1 cm), open angles in cervical lamina (46.5+/-16.0degrees to 77.2+/-13.1degrees), and sectional volume of cervical central canal (100.5+/-0.7 cm2 to 146.5+/-4.9 cm2) (p<0.001). The sagittal alignment of the cervical spine was well preserved (31.7+/-10.0degrees to 31.2+/-7.6degrees, p=0.877) during the follow-up period. The clinical results were successful, and there were no significant intraoperative complications except for screw displacement in two cases. The mini plate constructs did not fail during the 12 month follow-up period, and the decompression was maintained. CONCLUSION: Despite the small cohort and short follow-up duration, the present study demonstrated that combined cervical expansive laminoplasty using the mini plate is an effective treatment for multilevel cervical stenosis.
Cohort Studies ; Constriction, Pathologic ; Decompression ; Ether* ; Female ; Follow-Up Studies ; Humans ; Intraoperative Complications ; Longitudinal Ligaments ; Male ; Postoperative Period ; Retrospective Studies ; Spine ; Spondylosis* ; Transplants