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.

Purpose: Reliable landmarks of ankle syndesmosis change in various positions is important for managing ankle injury. The purpose of our study was to investigate and compare radiographic landmarks of normal ankle in various positions. Methods: The study involved both ankle radiographs of 30 subjects (15 males, 15 females) without clinical or radiographic abnormality. Tibiofibular clear space (TFCS) and tibiofibular overlap (TFO) were measured on anteroposterior (AP) and mortise radiographs in non-standing (NS) and standing (S) neutral and dorsiflexion 10° (DF10) and 20° (DF20). The radiographic measurements were used to calculate means, standard deviations, and intra- and interobserver reliabilities, and compare TFCS and TFO in various positions and genders. Results: On the AP view, the mean TFCS in NS, S, DF10, and DF20 positions were 4.00±0.97, 4.00±0.83, 4.35±0.95, and 4.45±0.89 mm and the mean TFO on the same positions were 6.58±2.27, 4.27±1.90, 3.44±1.96, and 2.38±1.91 mm. On the mortise view, the mean TFCS in NS, DF10, and DF20 positions were 3.62±0.88, 4.08±0.86, and 3.88±0.97 mm and the mean TFO on the same positions were 3.57±2.13, 2.31±1.77, and 3.57±2.14 mm. The reliabilities in all positions except TFCS on some positions were excellent. No measurement was significantly different between females and males except TFO in NS on mortise view (p=0.006) and DF10 on AP view (p=0.032). Conclusion Increase of TFCS and decrease of TFO on AP view reflects syndesmosis change from NS to DF20 on standing. Clinically, the effect of weight-bearing and reliability of TFO should be considered.

PURPOSE: In clinical studies, patients may experience several types of events during follow up under the competing risks (CR) framework. Patients are often classified into low- and high-risk groups based on prognostic factors. We propose a method to determine an optimal cutpoint value for prognostic factors on censored outcomes in the presence of CR. MATERIALS AND METHODS: We applied our method to data collected in a study of lung cancer patients. From September 1, 1991 to December 31, 2005, 758 lung cancer patients received tumor removal surgery at Samsung Medical Center in Korea. The proposed statistic converges in distribution to that of the supremum of a standardized Brownian bridge. To overcome the conservativeness of the test based on an approximation of the asymptotic distribution, we also propose a permutation test based on permuted samples. RESULTS: Most cases considered in our simulation studies showed that the permutation-based test satisfied a significance level of 0.05, while the approximation-based test was very conservative: the powers of the former were larger than those of the latter. The optimal cutpoint value for tumor size (unit: cm) prior to surgery for classifying patients into two groups (low and high risks for relapse) was found to be 1.8, with decent significance reflected as p values less than 0.001. CONCLUSION: The cutpoint estimator based on the maximally selected linear rank statistic was reasonable in terms of bias and standard deviation in the CR framework. The permutation-based test well satisfied type I error probability and provided higher power than the approximation-based test.
Bias (Epidemiology) ; Follow-Up Studies ; Humans ; Korea ; Lung Neoplasms ; Lung ; Methods

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.
Aphasia, Primary Progressive ; Cognition ; Comprehension ; Humans ; Magnetic Resonance Imaging ; Neurofibrillary Tangles ; Neuropsychological Tests ; Parietal Lobe ; Positron-Emission Tomography ; Prefrontal Cortex ; Rabeprazole ; Semantics ; Temporal Lobe

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.
Alzheimer Disease ; Brain ; Brain Injury, Chronic* ; Cell Line ; Craniocerebral Trauma ; Gene Expression Profiling* ; Humans ; Models, Animal ; Neurodegenerative Diseases ; Phosphoprotein Phosphatases ; Phosphotransferases ; Sequence Analysis, RNA ; Tauopathies* ; Transcriptome*

No abstract available.
Corpus Callosum* ; Diffusion* ; Hypoxia, Brain*