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We describe the case of a 62-year-old man presenting 2 months after a reversed great saphenous vein femoropopliteal bypass performed for critical limb ischemia. He was found to have early, high-grade bypass graft stenosis on duplex ultrasound. Subsequent angiography demonstrated flow limitations secondary to two areas of retained venous valves in the proximal and mid-portions of the vein graft. The culprit valve lesions were successfully lysed endovascularly with a HawkOne (Medtronic) directional atherectomy device. This case demonstrates a safe, novel use of a directional atherectomy device for treatment of remnant valves causing hemodynamically significant flow problems in peripheral vein grafts.
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Processing of electrode slurry, which is highly non-Newtonian fluid, is a critical step in the mass production of lithium-ion batteries (LIBs). While extensional flow plays an important role in the electrode slurry processes such as coating, most previous studies have focused only on the shear rheology, due to the lack of a reliable method to measure the extensional rheological properties of the slurry. Here, it is demonstrated that the extensional rheological properties of the anode slurries can be successfully characterized using the stop-flow-dripping-onto-substrate/capillary break-up rheometry (SF-DoS/CaBER). Using this system, it is observed that the extensional rheology of the anode slurry is significantly affected by the blend ratio of the natural and synthetic graphite, as well as the binder and conductive concentrations. Furthermore, the shear rheology-based model predicts much shorter pinch-off times than those measured experimentally, indicating that the yield-stress of the anode slurry is much larger in extensional flow than in shear flow.
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Background@#In bone sarcomas, chemotherapy has improved the prognosis with advances in diagnostic and surgical technologies, which has led to attempts to save limbs. As early detection and multidisciplinary treatment have improved the survival rate, curative surgery is considered for selected patients with metastatic bone carcinomas. Limb salvage procedures may vary in relation to the reconstruction method, which is accompanied by different complications. To overcome them, we devised a novel concept, insitu local tumor ablation and recycling machine based on radiofrequency (RF)-induced heating and intended experiments to demonstrate its feasibility. @*Methods@#The fresh femurs of 6-month-old pigs were used after removing the epiphyses; the distal parts were placed in a heating chamber. Fiber-optic temperature sensors were inserted in the metaphysis, meta-diaphysis, and diaphysis. Temperatures were measured six times each during heating at 27.12 MHz at various powers. Additionally, the compressive and bending stiffnesses were measured six times each for the unprocessed, RF-treated, and pasteurized bones, and the results were compared. @*Results@#Under 200 W power output, the temperatures at all measurement sites reached 70 °C or higher in 6 minutes, and the temperatures were maintained. The median compressive stiffness of RF-heated bones was 79.2% higher than that of pasteurized bones, but the difference was statistically insignificant. The median bending stiffness of RF-heated bones was approximately 66.3% of that of unprocessed bones, which was 20% higher than that of pasteurized bones. @*Conclusions@#The feasibility to rapidly attain and maintain temperatures for tumor ablation is shown, which favorably preserves bone stiffness through the in-situ local tumor ablation and recycling based on RF heating. The problem of nonuniform temperature distribution might be solved by an optimal design determined from simulation research and additional experiments.
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Background@#and Purpose Exercise and physiotherapy can exert potentially beneficial effects on the motor and nonmotor features of Parkinson’s disease (PD). We conducted an email survey to assess the knowledge, attitudes, and practices of neurologists regarding exercise among patients with PD. @*Methods@#A total of 222 neurologists from the Korean Movement Disorder Society and the Korean Society of Neurologists completed the survey and were classified into 4 clusters using the k-means clustering algorithm based on their institute types, the proportions of PD patients in their clinics, and the number of years working as neurologists. @*Results@#Specialists working at referral hospitals (Clusters 1 and 2) were more confident than general neurologists (Clusters 3 and 4) about exercise improving the general motor features of PD. Specialists recommended more-frequent intense exercise compared with physicians not working at referral hospitals. The specialists in Cluster 1, representing >50% of PD patients in the clinics at referral hospitals, recommended exercise regardless of the disease stage, whereas the general neurologists in Clusters 3 and 4 recommended low-intensity exercise at an early stage of disease. Although most of the respondents agreed with the need for PD patients to exercise, less than half had prescribed rehabilitation or physiotherapy. More than 90% of the respondents answered that developing an exercise/physiotherapy protocol for PD would be helpful. @*Conclusions@#Specialists were more confident than general neurologists about the effect of exercise and recommended more-intense activities regardless of the disease stage. These results highlight the need to develop clinical practice guidelines and PD-specialized exercise protocols to provide optimal care for PD patients.
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Background@#and Purpose The influence of imaging features of brain frailty on outcomes were investigated in acute ischemic stroke patients with minor symptoms and large-vessel occlusion (LVO). @*Methods@#This was a retrospective analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute (within 24 h) minor (National Institutes of Health Stroke Scale score=0–5) ischemic stroke with anterior circulation LVO (acute minor LVO). Brain frailty was stratified according to the presence of an advanced white-matter hyperintensity (WMH) (Fazekas grade 2 or 3), silent/old brain infarct, or cerebral microbleeds. The primary outcome was a composite of stroke, myocardial infarction, and all-cause mortality within 1 year. @*Results@#In total, 1,067 patients (age=67.2±13.1 years [mean±SD], 61.3% males) were analyzed. The proportions of patients according to the numbers of brain frailty burdens were as follows: no burden in 49.2%, one burden in 30.0%, two burdens in 17.3%, and three burdens in 3.5%. In the Cox proportional-hazards analysis, the presence of more brain frailty burdens was associated with a higher risk of 1-year primary outcomes, but after adjusting for clinically relevant variables there were no significant associations between burdens of brain frailty and 1-year vascular outcomes. For individual components of brain frailty, an advanced WMH was independently associated with an increased risk of 1-year primary outcomes (adjusted hazard ratio [aHR]=1.33, 95% confidence interval [CI]=1.03–1.71) and stroke (aHR=1.32, 95% CI=1.00–1.75). @*Conclusions@#The baseline imaging markers of brain frailty were common in acute minor ischemic stroke patients with LVO. An advanced WMH was the only frailty marker associated with an increased risk of vascular events. Further research is needed into the association between brain frailty and prognosis in patients with acute minor LVO.
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Background@#Inter-hospital transfers of severely injured patients are inevitable due to limited resources. We investigated the association between inter-hospital transfer and the prognosis of pediatric injury using the Korean multi-institutional injury registry. @*Methods@#This retrospective observational study was conducted from January 2013 to December 2017; data for hospitalized subjects aged < 18 years were extracted from the Emergency Department-based Injury in Depth Surveillance database, in which 22 hospitals are participating as of 2022. The survival rates of the direct transfer group and the interhospital transfer group were compared, and risk factors affecting 30-day mortality and 72-hour mortality were analyzed. @*Results@#The total number of study subjects was 18,518, and the transfer rate between hospitals was 14.5%. The overall mortality rate was 2.3% (n = 422), the 72-hour mortality was 1.7% (n = 315) and the 30-day mortality rate was 2.2% (n = 407). The Kaplan-Meier survival curve revealed a lower survival rate in the inter-hospital transfer group than in the direct visit group (log-rank, P < 0.001). Cox proportional hazards regression analysis showed that interhospital transfer group had a higher 30-day mortality rate and 72-hour mortality (hazard ratio [HR], 1.681; 95% confidence interval [CI], 1.232–2.294 and HR, 1.951; 95% CI, 1.299–2.930) than direct visit group when adjusting for age, sex, injury severity, and head injury. @*Conclusion@#Among the pediatric injured patients requiring hospitalization, inter-hospital transfer in the emergency department was associated with the 30-day mortality rate and 72-hour mortality rate in Korea.
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Objective@#: Collateral circulation is associated with the differential treatment effect of endovascular thrombectomy (EVT) in acute ischemic stroke. We aimed to verify the ability of the collateral map to predict futile EVT in patients with acute anterior circulation ischemic stroke. @*Methods@#: This secondary analysis of a prospective observational study included data from participants underwent EVT for acute ischemic stroke due to occlusion of the internal carotid artery and/or the middle cerebral artery within 8 hours of symptom onset. Multiple logistic regression analyses were conducted to identify independent predictors of futile recanalization (modified Rankin scale score at 90 days of 4–6 despite of successful reperfusion). @*Results@#: In a total of 214 participants, older age (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.56 to 3.67; p<0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR, 1.12; 95% CI, 1.04 to 1.21; p=0.004), very poor collateral perfusion grade (OR, 35.09; 95% CI, 3.50 to 351.33; p=0.002), longer door-to-puncture time (OR, 1.08; 95% CI, 1.02 to 1.14; p=0.009), and failed reperfusion (OR, 3.73; 95% CI, 1.30 to 10.76; p=0.015) were associated with unfavorable functional outcomes. In 184 participants who achieved successful reperfusion, older age (OR, 2.30; 95% CI, 1.44 to 3.67; p<0.001), higher baseline NIHSS scores (OR, 1.12; 95% CI, 1.03 to 1.22; p=0.006), very poor collateral perfusion grade (OR, 4.96; 95% CI, 1.42 to 17.37; p=0.012), and longer door-to-reperfusion time (OR, 1.09; 95% CI, 1.03 to 1.15; p=0.003) were associated with unfavorable functional outcomes. @*Conclusion@#: The assessment of collateral perfusion status using the collateral map can predict futile EVT, which may help select ineligible patients for EVT, thereby potentially reducing the rate of futile EVT.
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Objective@#Physiotherapy (PT), which is an effective strategy for managing Parkinson’s disease (PD), can influence health care utilization. We analyzed trends in health care utilization, PT interventions, and medical costs among patients with PD. @*Methods@#Using data from the Korean National Health Insurance Service from 2011 to 2020, we analyzed the number of patients with PD and their health care utilization and assessed the odds ratio (OR) for receiving regular PTs. @*Results@#Over 10 years, 169,613 patients with PD were included in the analysis. The number of patients with PD increased annually from 49,417 in 2011 to 91,841 in 2020. The number of patients with PD receiving PT increased from 4,847 (9.81%) in 2011 to 13,163 (14.33%) in 2020, and the number of PT prescriptions increased from 81,220 in 2011 to 377,651 in 2019. Medical costs per patient with PD increased from 1,686 United States dollars (USD) in 2011 to 3,202 USD in 2020. The medical expenses for each patient with PD receiving PT increased from 6,582 USD in 2011 to 13,475 USD in 2020. Moreover, regular PTs were administered to 31,782 patients (18.74%) and were administered only through hospitalization. Those patients in their 50s with disabilities demonstrated a high OR for regular PTs, whereas those aged 80 years or older and residing outside of Seoul had a low OR. @*Conclusion@#The PD burden increased in South Korea between 2011 and 2020, as did health care utilization and medical costs. A significant increase in medical expenses can be associated with increased PD incidence and PT interventions. Regular PT applications remain restricted and have barriers to access.
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Background@#and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. @*Methods@#We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. @*Results@#Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). @*Conclusion@#The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.
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Objective@#This study aimed to improve the accuracy of PMI estimates in veterinary forensic cases by looking into how different humidity levels affect autolysis in different organs of rats. @*Methods@#The study involved 38 male rats, examining histopathological changes in their heart, liver, and pancreas. These organs were subjected to controlled humidity levels (20%, 55%, and 80%) at a constant 22°C. Tissue samples were collected at several intervals (0 h, 12 h, 24 h, 3 days, and 8 days) for comprehensive analysis. @*Results@#Distinct autolytic characteristics in animal organs emerged under varying humidity conditions. The low-humidity environment rapidly activated autolysis more than the high-humidity environment. In addition, it was found that lower humidity caused nuclear pyknosis, cytoplasmic disintegration, and myofiber interruption. The liver, in particular, showed portal triad aggregation and hepatocyte individuation. The pancreas experienced cell fragmentation and an enlarged intracellular space. High humidity also caused the loss of striations in cardiac tissues, and the liver showed vacuolation. Under these conditions, the pancreas changed eosinophilic secretory granules. @*Conclusions@#and Relevance: The study successfully established a clear connection between the autolytic process in PMIs and relative humidity. These findings are significant for developing a more accurate and predictable method for PMI estimation in the field of veterinary forensic science.
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The surveillance and epidemiological investigation systems for companion animals in South Korea are significantly underdeveloped compared to those for humans and livestock. Recent outbreaks, such as idiopathic neuromuscular syndrome and highly pathogenic avian influenza among cats, have highlighted the need for reliable systems. This short review conducts situation analysis regarding disease surveillance and epidemiological investigation for companion animals in South Korea. The current challenges include an absence of administrative leadership, a lack of legal support, and unreliable medical data. The recommendations for future directions include clear leadership by the Animal and Plant Quarantine Agency, amending the Act on the Prevention of Contagious Animal Diseases to include companion animals, and enhancing the quality of medical data through standardized coding systems, such as Systematized Nomenclature of Medicine Clinical Terms. In addition, sentinel surveillance rather than universal systems should be established to provide adequate incentives for local practitioners to provide data and develop sustainable public–private networks. These recommendations could be important for developing a comprehensive and sustainable system for disease surveillance and epidemiological investigation in the companion animal field.
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Purpose@#This study was performed to identify risk factors associated with post-tonsillectomy hemorrhage (PTH)-related hospitalization in pediatric patients visiting an emergency department (ED). @*Methods@#We retrospectively reviewed the medical records of patients who underwent tonsillectomy at a single children’s hospital ED from January 2009 through December 2020. Data were collected on patient demographics, chief complaints, surgical methods, postoperative days, initial vital signs, and laboratory findings. The study population was divided into hospitalized and discharged groups. @*Results@#Among a total of 2,716 patients reviewed, 67 met the inclusion criteria. The hospitalized group showed a lower median systolic blood pressure (108.0 [interquartile range, 82.0-134.0] vs. 118.5 [89.8-147.2] mmHg; P = 0.021) and a faster median respiratory rate (23.0 [18.0-28.0] vs. 20.0 [17.0-23.0] breaths/minute; P = 0.019), compared with the discharged group. Multivariable logistic regression identified systolic blood pressure under 100 mmHg (odds ratio, 5.21; 95% confidence interval, 1.17-37.60) and respiratory rate over 24 breaths/minute (7.31; 1.07-145.79) as the factors associated with PTH-related hospitalization. @*Conclusion@#When pediatric patients visit EDs for PTH, close monitoring or hospitalization may be needed in those with low systolic blood pressure or rapid respiratory rate.
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Purpose@#Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. @*Materials and Methods@#We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. @*Results@#Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). @*Conclusion@#Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.
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Purpose@#We aimed to investigate the association between serum lipid level and tinnitus risk in Korean older adults. @*Materials and Methods@#This study used data from the 2016–2018 Korea National Health and Nutrition Examination Survey. Overall, 6021 subjects aged ≥60 years were included. Hypertriglyceridemia was defined as a serum triglyceride level of ≥200 mg/dL.The high-risk threshold of the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio was defined as above 5.0.The presence of tinnitus was assessed via health interviews. Tinnitus severity was classified as “not annoying,” “irritating,” and “severely annoying and causing sleep problems.” Multivariate logistic regression analysis was performed to examine the association between serum lipid level and tinnitus risk. @*Results@#The odds ratio (OR) of tinnitus was 1.27-times higher in the group with hypertriglyceridemia than in the group without hypertriglyceridemia after adjusting for age, sex, hypertension, diabetes, dyslipidemia, anemia, current smoking, obesity, noise exposure, stress cognition, and depressive mood or anxiety [95% confidence interval (CI) 1.04–1.56, p=0.022]. The OR of tinnitus was 1.21-times higher in the group with a high TC/HDL-C ratio than in the group without a high TC/HDL-C ratio after adjusting for the same variables as above (95% CI 1.02–1.44, p=0.025). @*Conclusion@#This study revealed that hypertriglyceridemia and high TC/HDL-C ratio were significantly associated with an increased OR of tinnitus in Korean older adults.
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Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumor microenvironments. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies, which are being harnessed to improve solid tumor CAR T cell therapies. Here, we describe fully optimized CAR T cells targeting tumor-associated glycoprotein-72 (TAG72) for the treatment of solid tumors, identifying the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. These findings have culminated into a phase 1 trial evaluating safety, feasibility, and bioactivity of TAG72-CAR T cells for the treatment of patients with advanced ovarian cancer ( NCT05225363 ). Preclinically, we found that CAR T cell-mediated IFNγ production facilitated by IL-12 signaling was required for tumor cell killing, which was recapitulated by expressing an optimized membrane-bound IL-12 (mbIL12) molecule on CAR T cells. Critically, mbIL12 cell surface expression and downstream signaling was induced and sustained only following CAR T cell activation. CAR T cells with mbIL12 demonstrated improved antigen-dependent T cell proliferation and potent cytotoxicity in recursive tumor cell killing assays in vitro and showed robust in vivo anti-tumor efficacy in human xenograft models of ovarian cancer peritoneal metastasis. Further, locoregional administration of TAG72-CAR T cells with antigen-dependent IL-12 signaling promoted durable anti-tumor responses against both regional and systemic disease in mice and was associated with improved systemic T cell persistence. Our study features a clinically-applicable strategy to improve the overall efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting both regional and systemic disease.
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Background@#Preoperative verification of fracture morphology is essential for determining the definitive fixation strategy in the management of a pilon fracture. This study aimed to determine the correlation between fibular injury patterns and fracture morphologies and introduce clinical implications. @*Methods@#Computed tomography scans of 96 pilon fractures were retrospectively analyzed and divided into three types: intact fibula, simple fracture, and multifragment fracture. The principal fracture line and comminution zones were illustrated on a plafond template and diagrammatized on a 6 × 6 grid using PowerPoint software as fracture mapping. Correlations between fibular injury patterns and fracture morphologies, including comminution zones and principal fracture lines, were analyzed. @*Results@#The thickest comminution zone was most often located in the anterolateral quadrant. According to fibular injury patterns, the comminution zone of the multifragment group was placed two grids more lateral than that of other groups. Lateral exits of the principal fracture line in the multifragment group were much more concentrated within the fibular incisura. @*Conclusions@#In pilon fractures, a more complex fibular fracture pattern was related to the valgus position. Moreover, the articular fracture pattern of pilon fractures differed according to coronal angulation and fibular fracture pattern. These differences should influence the operative approach and placement of the plate.
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Objective@#: The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort. @*Methods@#: Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors. @*Results@#: Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene. @*Conclusion@#: BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.
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Background@#For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. @*Methods@#Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). @*Results@#The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). @*Conclusions@#In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.
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Background@#Little is known about the adverse events (AEs) associated with coronavirus disease 2019 (COVID-19) vaccination in patients with type 2 diabetes mellitus (T2DM). @*Methods@#This study used vaccine AE reporting system data to investigate severe AEs among vaccinated patients with T2DM. A natural language processing algorithm was applied to identify people with and without diabetes. After 1:3 matching, we collected data for 6,829 patients with T2DM and 20,487 healthy controls. Multiple logistic regression analysis was used to calculate the odds ratio for severe AEs. @*Results@#After COVID-19 vaccination, patients with T2DM were more likely to experience eight severe AEs than controls: cerebral venous sinus thrombosis, encephalitis myelitis encephalomyelitis, Bell’s palsy, lymphadenopathy, ischemic stroke, deep vein thrombosis (DVT), thrombocytopenia (TP), and pulmonary embolism (PE). Moreover, patients with T2DM vaccinated with BNT162b2 and mRNA-1273 were more vulnerable to DVT and TP than those vaccinated with JNJ-78436735. Among patients with T2DM administered mRNA vaccines, mRNA-1273 was safer than BNT162b2 in terms of the risk of DVT and PE. @*Conclusion@#Careful monitoring of severe AEs in patients with T2DM may be necessary, especially for those related to thrombotic events and neurological dysfunctions after COVID-19 vaccination.
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Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo.Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals.After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.