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Mechanical thrombectomy using a stent retriever is a widely-used technique for recanalizing occluded cerebral arteries in acute ischemic stroke. Although rare, inadvertent stent detachment has primarily been reported with earlier stent retriever designs. We present 2 cases of inadvertent stent detachment with the pRESET stent. In the first case, an elderly patient presented with right middle cerebral artery occlusion and experienced stent detachment during the second retrieval. Despite this, successful recanalization was achieved through balloon angioplasty. In the second case, an elderly patient experienced stent detachment after the third retrieval, and recanalization of the M1 segment was unsuccessful due to the inability to pass the microcatheter. The first patient had a modified Rankin scale (mRS) score of 3, while the second had a poor prognosis with an mRS score of 5. These cases highlight that inadvertent stent detachment can impact outcomes, and balloon angioplasty may serve as a useful salvage therapy.

Background: Direct oral anticoagulants (DOACs) have been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was 2 per 100 patient-years and 1.5% per year while taking DOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with DOACs, the prognosis was likely to be better than that with warfarin., Methods and Results: Data from 2002 to 2019, sourced from a nationwide claims database, were used to identify atrial fibrillation patients using International Classification of Diseases codes. Patients who experienced an ischemic stroke during anticoagulation were categorized by the drugs used (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). The primary outcome was mortality within 3 months and 1 year after the ischemic stroke. Among the 9578 patients with ischemic stroke during anticoagulation, 3343 received warfarin, and 6235 received DOACs (965 dabigatran, 2320 apixaban, 1702 rivaroxaban, 1248 edoxaban). The DOACs group demonstrated lower risks of 3-month (adjusted hazard ratio [HR], 0.550, [95% CI, 0.473-0.639]; P <0.0001) and 1-year mortality (adjusted HR, 0.596 [95% CI, 0.536-0.663]; P <0.0001) than the warfarin group. Apixaban and edoxaban within the DOAC group exhibited particularly reduced 1-year mortality risk compared with other DOACs ( P <0.0001)., Conclusions: Our study confirmed that DOACs have a better prognosis than warfarin after ischemic stroke. The apixaban and edoxaban groups had a lower risk of death after ischemic stroke than the other DOAC groups.

Background: Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain., Aims: This study aimed to investigate whether conventional and intensive BP managements differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups., Methods: In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target: <140 mm Hg) and conventional (systolic BP target = 140-180 mm Hg) BP managements during the 24 h after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 h and mortality within 3 months., Results: Of the 305 patients (median = 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs conventional, 54.9%, adjusted odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12-0.90, p  = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs conventional, 54.2%, adjusted OR = 0.73, 95% CI = 0.38-1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups., Conclusions: Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 h resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: No comprehensive study has been conducted on the effects of high tibial osteotomy (HTO) on the coronal, sagittal, and axial alignments of the ankle joint. Therefore, this study aimed to investigate the multiplane changes in the ankle joint following HTO using the EOS biplanar X-ray imaging system., Methods: The medical records of 43 patients who underwent HTO for the treatment of medial knee osteoarthritis were retrospectively reviewed. Preoperative and postoperative EOS images and lower-extremity scanograms were evaluated; the correlations between the outcomes were evaluated., Results: After HTO, the ankle joint axis point on the weight-bearing line showed significant lateralization ( p < .001). The knee lateral ankle surface angle increased significantly in the sagittal alignment ( p < .001). The distal tibia showed a significant internal rotation in the axial plane ( p = .022). Tibial rotation showed no significant relationship with the other parameters., Conclusions: HTO induced lateralization of the ankle joint axis (coronal), increased the posterior tibial slope (sagittal), and caused the internal rotation of the distal tibia (axial). Axial changes in the distal tibia showed no significant relationship with other coronal and sagittal parameters of the ankle joint. We suggest that surgeons should consider, during HTO, that the ankle joint axis shifts laterally and distal tibia has tendency to rotate internally after HTO., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment., Methods: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis., Results: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups., Conclusion: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain., Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months., Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea., Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups., Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months., Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46)., Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Background: Many studies have evaluated stroke using claims data; most of these studies have defined ischemic stroke using an operational definition following the rule-based method. Rule-based methods tend to overestimate the number of patients with ischemic stroke., Objectives: We aimed to identify an appropriate algorithm for identifying stroke by applying machine learning (ML) techniques to analyze the claims data., Methods: We obtained the data from the Korean National Health Insurance Service database, which is linked to the Ilsan Hospital database (n = 30,897). The performance of prediction models (extreme gradient boosting [XGBoost] or gated recurrent unit [GRU]) was evaluated using the area under the receiver operating characteristic curve (AUROC), the area under precision-recall curve (AUPRC), and calibration curve., Results: In total, 30,897 patients were enrolled in this study, 3145 of whom (10.18%) had ischemic stroke. XGBoost, a tree-based ML technique, had the AUROC was 94.46% and AUPRC was 92.80%. GRU showed the highest accuracy (99.81%), precision (99.92%) and recall (99.69%)., Conclusions: We proposed recurrent neural network-based deep learning techniques to improve stroke phenotyping. This can be expected to produce rapid and more accurate results than the rule-based methods., (© 2023. The Author(s).)

A disposable microfluidic channel sensor printed on a plastic platform was developed to analyze heavy metal ions (HMIs) as a model target species. Precise separation and detection of multiple targets were established by symmetrically applying a small AC potential on the carbon channel walls to induce an electrodynamic force. The separation device was constructed by covering it with a plastic lid to achieve capillary action in the channel. The sample flow rate was regulated by the hydrophilicity of the lid plastic and electrodynamic convection by the AC field, which was characterized by the contact angle measurement and the additional electrodynamic force. The flow variables and their relevance to the capillary phenomena were demonstrated, and the analytical parameters were optimized. The working electrode was modified with poly(diamino terthiophene) anchored with nanosized graphene oxide (pDATT/GO) to enhance the detection performance. The experimental variables for separating and detecting the target species were optimized according to the AC frequency and amplitude, sample flow rate, electrolytes, pH, temperature, and applied potential for detection. The linear dynamic ranges were between 0.1 and 200.0 ppb, with detection limits of 0.04 ± 0.023, 0.29 ± 0.05, 0.07 ± 0.011, and 0.14 ± 0.06 ppb for Cu 2+ Cd 2+ , Hg 2+ , and Pb 2+ , respectively. Finally, the reliability of the proposed method was evaluated through analysis of HMIs in real water samples. The results were matched to those obtained through parallel analysis using ICP-MS at a 95% confidence level.

Purpose: Changes in coronal and sagittal alignment of the knee joint after HTO have been reported in several previous studies. However, only few of them investigated the changes only on coronal alignment of the ankle joint. The purpose of this study was to investigate changes in both coronal and sagittal alignment of the ankle joint after HTO., Methods: 46 patients (49 cases) who underwent HTO were retrospectively analyzed. Preoperative and postoperative lower extremity scanogram and EOS imaging system were investigated. The hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA), and knee tibia plafond angle (KTPA) were measured by scanogram to evaluate coronal alignment of the knee. Tibial anterior surface angle (TAS), talar tilt (TT), tibial plafond inclination (TPI), and ankle joint axis point on the weight-bearing-line (AAWBL) ratio were measured by scanogram to investigate coronal alignment of the ankle. Knee lateral ankle surface angle (KLAS) and tibial lateral surface angle (TLS) were measured by EOS to evaluate sagittal alignment of the ankle., Results: Varus alignment of the knee was corrected by significant change of the HKA angle (5.8 ± 3.1° vs. - 2.1 ± 2.8°, p < 0.001), MPTA (85.7 ± 2.9° vs. 91.7 ± 3.3°, p < 0.001), and KTPA (5.0 ± 3.5° vs. - 2.1 ± 4.2°, p < 0.001) after HTO. Regarding the ankle coronal alignment, there was significant change in TPI (3.9 ± 3.4° vs. - 0.9 ± 3.8°, p < 0.001) and AAWBL ratio (45.5 ± 14.7% vs. 61.6 ± 13.3%, p < 0.001). In sagittal alignment of the ankle, KLAS (4.5 ± 3.1° vs. 7.7 ± 3.7°, p < 0.001) significantly increased. Among the variables, the amount of correction in AAWBL ratio (R = 0.608, p < 0.01) showed strongest relationship with tibial correction angle., Conclusion: Based on the present study, coronal and sagittal alignment of ankle joint was significantly affected by HTO. After HTO, AAWBL ratio increased due to lateralization of the ankle joint axis, and KLAS increased due to increased posterior tibial slope., Level of Evidence: III., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear., Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT., Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion)., Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment., Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months., Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31)., Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke., Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

The present study was performed to determine the incidence and risk factors of contralateral Achilles tendon rupture after an initial tendon rupture, and to identify the associated patient characteristics. Medical records of 181 adult patients with acute Achilles tendon rupture were reviewed. We investigated the risk factors for contralateral Achilles tendon rupture and calculated the incidence density (per 100 person-years), survival rate, hazard ratios, and 95% confidence intervals. The risk factors were extracted, including blood type, age, body mass index (BMI), occupation, underlying comorbidities, history of alcohol intake or smoking, injury mechanism, and fluoroquinolone antibiotic or steroid use. Military personnel and manual laborers, including farmers and firefighters were considered to have an occupation involving physical activity. Ten patients (5.5%) were identified as having nonsimultaneous, contralateral Achilles tendon rupture a mean of 3.3 years (range 1.0-8.3 years) after the initial tendon rupture. The incidence density of contralateral tendon rupture was 0.89 per 100 person-years. The 8-year survival rate of contralateral tendon rupture was 92.2%. Unadjusted and adjusted hazard ratios (with 95% confidence intervals, p value) of blood type O were 3.71 (1.07-12.82, p = .038) and 2.90 (0.81-10.32, p = .101), respectively, and those of occupations involving physical activity were 5.87 (1.64-20.98, p = .006) and 4.69 (1.27-17.28, p = .02), respectively. Based on the present data, blood type O and occupations involving physical activity are significantly associated with an increased risk of contralateral tendon rupture in adult patients who have sustained Achilles tendon rupture., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy., Methods: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke., Results: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%., Conclusions: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy., Competing Interests: Disclosures None.

Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs) has been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation (AF) since 2014. Many studies based on claim data revealed that NOACs had comparable effect to warfarin in preventing ischemic stroke with fewer hemorrhagic side effects. We analyzed the difference in clinical outcomes according to the drugs in patients with AF based on the clinical data warehouse (CDW)., Methods: We extracted data of patients with AF from our hospital's CDW and obtained clinical information including test results. All claim data of the patients were extracted from National Health Insurance Service, and dataset was constructed by combining it with CDW data. Separately, another dataset was constructed with patients who could obtain sufficient clinical information from the CDW. The patients were divided NOAC and warfarin groups. The occurrence of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, and death were confirmed as clinical outcome. The factors influencing the risk of clinical outcomes were analyzed., Results: The patients who were diagnosed AF between 2009 and 2020 were included in the dataset construction. In the combined dataset, 858 patients were treated with warfarin, 2,343 patients were treated with NOACs. After the diagnosis of AF, the incidence of ischemic stroke during follow-up was 199 (23.2%) in the warfarin group, 209 (8.9%) in the NOAC group. Intracranial hemorrhage occurred in 70 patients (8.2%) among the warfarin group, 61 (2.6%) of the NOAC group. Gastrointestinal bleeding occurred in 69 patients (8.0%) in the warfarin group, 78 patients (3.3%) in the NOAC group. NOAC's hazard ratio (HR) of ischemic stroke was 0.479 (95% CI 0.39-0.589, p < 0.0001), HR of intracranial hemorrhage was 0.453 (95% CI 0.31-0.664, p < 0.0001), and HR of gastrointestinal bleeding was 0.579 (95% CI 0.406-0.824, p = 0.0024). In the dataset constructed using only CDW, the NOAC group also had a lower risk of ischemic stroke and intracranial hemorrhage than warfarin group., Conclusions: In this CDW based study, NOACs are more effective and safer than warfarin in patients with AF even with long-term follow-up. NOACs should be used to prevent ischemic stroke in patients with AF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Hong and Seo.)

Background: Mechanical thrombectomy (MT) of ischemic stroke was recommended as a clinical guideline in 2015, and the indication for time was expanded in 2018 based on two clinical studies. We aimed to compare and analyze the prognosis of patients treated under the extended time indication before and after the introduction of advanced software., Methods: We obtained data from medical records between 2016 to 2020. From 2016 to 2017, patients who did not receive MT who visited the hospital within 24 hours from the last normal time (LNT) were classified as standard medical treatment (SMT) group. Among patients who underwent MT between 2019 and 2020, patients who visited the hospital between 6-24 hours from the LNT were classified into the extended MT (EMT) group. Good outcome was defined as 3-months modified rankin scale (mRS) ≤ 2, and a poor outcome as mRS ≥ 4., Results: From 2016 to 2017, 1,058 patients were hospitalized for ischemic stroke, of which 60 (5.7%) received MT, and 27 patients were classified into the SMT group. Among 1,019 patients between 2019 and 2020, 85 (8.3%) received MT, and 24 patients were in the EMT group. Among the SMT group, only 3 had a good prognosis, and 24 (88.9%) had a poor prognosis. However, in the EMT group, 10 (41.7%) had a good prognosis, and 9 (37.5%) had a poor prognosis. The SMT group had a 49.1 times higher risk of poor prognosis compared to the EMT group ( P = 0.008)., Conclusion: The number of patients with ischemic stroke who receive MT has increased by using advanced imaging software. It was confirmed that patients treated based on the extended time indication also had a good prognosis., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy., Methods: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR., Results: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P <0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P =0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P =0.001). These associations persisted regardless of treatment modality or various baseline characteristics., Conclusions: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Purpose: The purpose of this study was to evaluate trends in medical costs and prognosis in acute ischemic stroke (AIS) patients in Korea from 2008 to 2017 using medical claims data., Materials and Methods: All data for the past decade was collected from a big data hub provided by the Health Insurance Review & Assessment Service. Using several Korean Standard Classification of Disease codes, we estimated the number of patients, the costs of medical insurance, and prognosis according to the treatment with or without endovascular thrombectomy (EVT) among in-patients with AIS., Results: Since 2014, when EVT was covered by insurance, the number of patients who underwent EVT for AIS has increased significantly. Also, in the past decade, the medical costs following inpatient care for AIS with EVT have increased gradually, and the overall medical costs for the first year post-stroke have also increased. The prognosis of AIS patients with EVT was different according to the time of treatment. Annual trends for both mortality and cerebral hemorrhage after treatment of AIS with EVT have gradually decreased., Conclusion: In this study, we found that both inpatient medical costs and 1-year cumulative medical costs have gradually increased, and the prognosis has gradually improved in patients receiving EVT treatment among AIS patients.

Background: CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores are used to estimate thromboembolism risk. We aimed to investigate the association between unfavorable outcomes and stroke risk scores in patients who received endovascular thrombectomy (EVT). Methods: This study was performed using data from a nationwide, multicenter registry to explore the selection criteria for patients who would benefit from reperfusion therapies. We calculated pre-admission CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores for each patient who received EVT and compared the relationship between these scores and 3-month modified Rankin Scale (mRS) records. Results: Among the 404 patients who received EVT, 213 (52.7%) patients had unfavorable outcomes (mRS 3−6). All scores were significantly higher in patients with unfavorable outcomes than in those with favorable outcomes. Multivariable logistic regression analysis indicated that CHADS2 and the ATRIA score were positively correlated with unfavorable outcomes after adjusting for body mass index and variables with p < 0.1 in the univariable analysis (CHADS2 score: odds ratio [OR], 1.484; 95% confidence interval [CI], 1.290−1.950; p = 0.005, ATRIA score, OR, 1.128; 95% CI, 1.041−1.223; p = 0.004). Conclusions: The CHADS2 and ATRIA scores were positively correlated with unfavorable outcomes and could be used to predict unfavorable outcomes in patients who receive EVT.

For the early diagnosis of lung cancer, a novel strategy to detect microRNAs encapsulated in exosomes with immunomagnetic isolation was demonstrated for the selective extraction of exo-miRNAs from patient serum. Here, miRNA was captured from lysed exosomes in specially designed capture probe modified magnetic beads, followed by T4 DNA polymerase-mediated in situ formation of chimeric 5'-miRNA-DNA-3' (Target). The poly-(2,2':5',2''-terthiophene-3'-(p-benzoic acid)) (pTBA)-modified electrode harbors Probe-1 DNA that hybridizes to the 5' end of the chimera, followed by hybridization of Probe-2 DNA to the 3' end of the chimera, resulting in the formation of a 20-nucleotide-long dsDNA consensus sequence for p53 protein binding. A bioconjugate composed of p53 and hydrazine assembled on AuNPs (p53-AuNPs-Hyd) recruits the p53 protein to recognize a specific sequence, forming the final sensor probe (pTBA-Probe-1:Target/Probe-2:bioconjugate), where hydrazine functions as an electrocatalyst to generate amperometric signal from the reduction of H 2 O 2 . This sensor has double specificity via selective capture of the target in Probe-1 and p53 recognition, which shows excellent analytical performance, revealing a dynamic range between 100 aM and 10 pM with a detection limit of 92 (±0.1) aM. For practical applications, we prepared a multiplexed array sensor to simultaneously detect four exo-miRNAs (miRNA-21, miRNA-155, miRNA-205, and miRNA-let-7b) up to femtomolar levels from 1.0 mL to 125 μL of cell culture (A549, MCF-7 and BEAS-2B) media and lung cancer patient serum samples, respectively., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year., Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020)., Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths., Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Self-assembly of AgPF 6 with a pair of chiral tridentate ligands (1 S ,1' S ,1'' S ,2 R ,2' R ,2'' R ) and (1 R ,1' R ,1'' R ,2 S ,2' S ,2'' S )-(benzenetricarbonyltris(azanediyl))tris(2,3-dihydro-1 H -indene-2,1-diyl)triisonicotinate ( s , r -L) and ( r , s -L) in a mixture of methanol and dioxane yields 2D sheets consisting of [Ag( s , r -L)](PF 6 )·3C 4 H 8 O 2 ·0.5H 2 O and [Ag( r , s -L)](PF 6 )·3C 4 H 8 O 2 ·0.5H 2 O, respectively. The differential pulse voltammetric (DPV) technique using the pair of chiral 2D-sheet enantiomers was employed for chiral discrimination of amino acid enantiomers, and was found to be an effective tool for enantio-recognition of L- and D-histidines. Both the size and the binding site of amino acids were strongly dependent on electrochemical enantio-recognition via the chiral 2D sheets.

A disposable amperometric biosensor with a dual monomers-based bioconjugate was developed for granzyme B (GzmB) detection and for monitoring of the cancer progression of patients before and after immunotherapy. The biosensor was fabricated by immobilizing a GzmB monoclonal antibody (Ab 1 ) on a poly3'-(2-aminopyrimidyl)-2,2':5',2''-terthiophene/gold nanoparticle (pPATT/AuNP) layer. The bioconjugate nanoparticles were synthesized through self-assembly of a monomer mixture of 2,2:5,2-terthiophene-3-(p-benzoic acid) (TBA) and PATT onto AuNPs, followed by chemical binding of brilliant cresyl blue (BCB) on TBA and GzmB polyclonal antibody (Ab 2 ) on the PATT layer. Each sensing layer was investigated by surface analysis and electrochemical experiments. The sensor performance was assessed with selectivity, stability, reproducibility, detection limit, and real sample analysis. Under the optimized conditions, the dynamic range of GzmB was in two slopes from 3.0 to 50.0 pg/ml and from 50.0 to 1000.0 pg/ml with a detection limit of 1.75 ± 0.14 pg/ml (RSD ≤5.2%). GzmB monitoring was performed for the patient's serum samples, where a low level of GzmB was observed for lung cancer patients before immunotherapy (10.51 ± 0.99 pg/ml, RSD ≤6.2%), and the level was increased after therapy (17.19 ± 2.22 pg/ml, RSD ≤2.6%). Moreover, a significantly higher level was present in healthy persons (34.40 ± 3.92 pg/ml, RSD ≤1.4%). The cancer progression of patients before and after therapy was evaluated by monitoring GzmB levels in human serum using the proposed sensor., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The CHADS 2 , CHA 2 DS 2 -VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT)., Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient., Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS 2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198-2.009, p = 0.001; CHA 2 DS 2 VASc score: OR 1.269, 95% CI 1.080-1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011-1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167-1.849, p = 0.001). The CHADS 2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS 2 score; 0.618, 95% CI 0.554-0.681)., Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

Rationale: Very early stage blood pressure (BP) levels may affect outcome in stroke patients who have successfully undergone recanalization following intra-arterial treatment, but the optimal target of BP management remains uncertain., Aim: We hypothesized that the clinical outcome after intensive BP-lowering is superior to conventional BP control after successful recanalization by intra-arterial treatment., Sample-Size Estimates: We aim to randomize 668 patients (334 per arm), 1:1., Methods and Design: We initiated a multicenter, prospective, randomized, open-label trial with a blinded end-point assessment (PROBE) design. After successful recanalization (thrombolysis in cerebral infarction score ≥ 2 b), patients with elevated systolic BP level, defined as the mean of two readings ≥ 140 mmHg, will be randomly assigned to the intensive BP-lowering (systolic BP < 140 mm Hg) group or the conventional BP-lowering (systolic BP, 140-180 mm Hg) group., Study Outcomes: The primary efficacy outcomes are from dichotomized analysis of modified Rankin Scale (mRS) scores at three months (mRS scores: 0-2 vs. 3-6). The primary safety outcomes are symptomatic intracerebral hemorrhage and death within three months., Discussion: The OPTIMAL-BP trial will provide evidence for the effectiveness of active BP control to achieve systolic BP < 140 mmHg during 24 h in patients with successful recanalization after intra-arterial treatment., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Background: Mechanical thrombectomy (MT) of ischemic stroke was demonstrated to be effective in clinical trials and was reported to have favorable outcomes in real clinical settings since 2015. We aimed to determine the national trends of MT and compare the outcomes between the different levels of treating hospital., Methods: We obtained data from the nationwide database from 2008 to 2017. Patients with ischemic stroke who received MT were identified using the International Classification of Disease Codes. Good outcome was defined as discharge to home, and a poor outcome was defined as cerebral hemorrhage, physical disability, or death. The study period was divided into three (off-label MT, transitional, MT period). Hospital groups where MT was performed were divided into tertiary and non-tertiary hospitals., Results: In MT period, 47.0% of the MT procedures were performed in non-tertiary hospitals compared with 36.1% in off-label MT period. Comparison of the 3-month mortality between patients who were treated in tertiary vs . non-tertiary hospitals revealed significant lower mortality in tertiary hospital through all period. The incidence of cerebral hemorrhage and physical disability did not differ between hospital groups. However, the percentage of patients discharged home was 41.4% for tertiary hospitals and 42.4% for non-tertiary hospitals, which was not statistically different in MT period (P=0.4671)., Conclusions: Analysis of the nationwide data confirmed that the extent of increase in MT was higher in non-tertiary hospitals than tertiary hospitals. In addition, no significant difference was revealed in the number of favorable clinical outcome between the hospital groups during MT period., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-2342). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: anemia is known to be a risk factor for developing ischemic stroke in long-term follow-up studies, and it is also known to increase the risk of death in ischemic stroke patients. We aimed to determine the association of anemia with the risk of ischemic stroke and the risk of death after ischemic stroke., Methods: The study included patients from National Health Insurance Service cohort, from January 2005 to December 2015. Anemia patients were defined as those with confirmed diagnostic codes and related medications in the sample cohort, and patients under the age of 18 were excluded. To perform a comparative analysis with the control group, twice as many patients were extracted by propensity score matching. The effects of anemia on the development of ischemic stroke were analyzed., Results: A total of 58,699 patients were newly diagnosed with anemia during the study period. In anemia group, the rate of ischemic stroke occurring within 1 year was 0.550%, and the rate was 0.272% in the control group. The odds ratio of anemia related to ischemic stroke was 1.602 (95% confidence intervals (CI) 1.363-1.883). During the follow-up period, 175 out of 309 (56.6%) died in anemia group, and 130 out of 314 (41.4%) died in control group. The anemia group showed a higher risk of death than the control group (Hazard ratio 1.509, 95% CI 1.197-1.902)., Conclusion: Analysis of the nationwide health insurance data revealed that anemia is one of the risk factors for the development of ischemic stroke, and also an independent prognostic factor affecting post-stroke mortality.

The meniscus has poor intrinsic regenerative capability, and its injury inevitably leads to articular cartilage degeneration. Although there are commercialized off-the-shelf alternatives to achieve total meniscus regeneration, each has its own shortcomings such as individualized size matching issues and inappropriate mechanical properties. We manufactured a polycaprolactone-based patient-specific designed framework via a Computed Tomography scan images and 3D-printing technique. Then, we completed the hybrid-scaffold by combining the 3D-printed framework and mixture micro-size composite which consists of polycaprolactone and sodium chloride to create a cell-friendly microenvironment. Based on this hybrid-scaffold with an autograft cell source (fibrochondrocyte), we assessed mechanical and histological results using the rabbit total meniscectomy model. At postoperative 12-week, hybrid-scaffold achieved neo-meniscus tissue formation, and its shape was maintained without rupture or break away from the knee joint. Histological and immunohistochemical analysis results showed obvious ingrowth of the fibroblast-like cells and chondrocyte cells as well as mature lacunae that were embedded in the extracellular matrix. Hybrid-scaffolding resulted in superior shape matching as compared to original meniscus tissue. Histological analysis showed evidence of extensive neo-meniscus cell ingrowth. Additionally, the hybrid-scaffold did not induce osteoarthritis on the femoral condyle surface. The 3D-printed hybrid-scaffold may provide a promising approach that can be applied to those who received total meniscal resection, using patient-specific design and autogenous cell source.

Teriparatide (TPTD) is a bone-forming agent used to treat postmenopausal osteoporosis. Since hip fractures are related to higher morbidity and mortality rates than other fractures, efficacious osteoporosis drugs for the hip are critical. We reviewed research articles reporting the efficacy of TPTD in terms of bone mineral density (BMD), fractures prevention, changes in the outer diameter, cortical thickness and porosity, post-operative periprosthetic BMD loss, and healing of typical and atypical fractures of the hip. Data meta-analyses indicated that TPTD not only increased the BMD of the proximal femur but also decreased the risk of hip fractures. Even though TPTD increases the cortical bone porosity of the proximal femur, the bone strength does not decrease as the majority of the porosity is located at the endocortex; further, it increases the outer diameter and thickens the cortical bone. TPTD stimulates bone remodeling and facilitates callus maturity and fracture healing. There have been many reports on improving the effect of TPTD on the healing of atypical fractures; therefore it is advisable to use TPTD considering the increase benefit compared to the risk., Competing Interests: CONFLICT OF INTEREST: The authors declare that there is no potential conflict of interest relevant to this article., (Copyright © 2021 by Korean Hip Society.)

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke., Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy., Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245])., Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Objectives: While the prevalence of active cancer patients experiencing acute stroke is increasing, the effects of active cancer on reperfusion therapy outcomes are inconclusive. Thus, we aimed to compare the safety and outcomes of reperfusion therapy in acute stroke patients with and without active cancer., Materials and Methods: A comprehensive literature search was conducted for studies comparing the effects of intravenous thrombolysis (IVT) or endovascular treatment (EVT) in ischemic stroke patients with and without active cancer. The literature was screened using both a manual and machine learning algorithm approach. The outcomes evaluated were symptomatic intracerebral hemorrhage (sICH), all-type intracerebral hemorrhage (aICH), successful recanalization, favorable outcomes (modified Rankin Scale, 0-2), and mortality. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) using the random-effects model from the included studies., Results: Seven studies were analyzed in this meta-analysis. IVT (n = 1012) was associated with an increased risk of sICH (OR, 9.80; 95% CI, 3.19-30.13) in the active cancer group. However, no significant differences in aICH, favorable outcomes, and mortality were found between groups. Although sICH and successful recanalization in the EVT group (n = 2496) were similar, we observed fewer favorable outcomes (OR, 0.55; 95% CI, 0.33-0.93) and a high prevalence of mortality (OR, 2.91; 95% CI, 1.89-4.47) in the active cancer group., Conclusions: Reperfusion therapy may benefit selected patients with acute ischemic stroke with active cancer, considering the comparable clinical outcomes of IVT and procedure-related outcomes of EVT. These results should be cautiously interpreted and confirmed in future well-designed large-scale studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Purpose: We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion., Methods: Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization., Results: Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032)., Conclusions: The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

The template-free synthesis and the characterization of an active electrocatalyst are performed for both the hydrogen evolution and oxygen reduction reactions in acidic media. In this work, the unique chelation mode of benzene-1,4-dithiocarboxamide (BDCA) is first used to synthesize a novel palladium-BDCA coordination polymer (PdBDCA) as a precursor of palladium sulfide nanoparticles-decorated nitrogen and sulfur doped carbon (Pd 4 S-SNC). The newly synthesized PdBDCA and Pd 4 S-SNC nanoparticles are characterized using chemical, electrochemical, and surface analysis methods. Notably, the nanoparticles obtained at 700 °C exhibit the remarkable catalytic property for the hydrogen evolution reaction in 0.5 m H 2 SO 4 , showing the overpotential of 32 mV (vs reversible hydrogen electrode (RHE)) and Tafel slope of 52 mV dec -1 , which are comparable to that of Pt/C. The catalyst also shows a high oxygen reduction activity, offering the half-wave and onset potentials of 0.92 and 0.77 V (vs RHE) in 0.5 m H 2 SO 4 , with improved methanol tolerance and long-term stability compared with Pt/C. The present study gives a way for the design of excellent electrocatalyst for the energy conversion devices in the corrosive acidic environment., (© 2021 Wiley-VCH GmbH.)

The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p < 0.001). Six out of the 19 comorbidities were included for developing the reperfusion comorbidity index on the basis of the odds ratios in the multivariate logistic regression analysis. This index showed good prediction of 6-month mortality in the retrospective cohort (area under the curve [AUC], 0.747; 95% CI, 0.704-0.790) and in 333 patients in the prospective cohort (AUC, 0.784; 95% CI, 0.709-0.859). Consideration of comorbidities might be helpful for the prediction of the 6-month mortality in patients with acute ischemic stroke who receive reperfusion therapy.

Background and Purpose: We aimed to determine whether the care process and outcomes in patients with acute stroke who received recanalization therapy changed during the outbreak of coronavirus disease 2019 (COVID-19) in South Korea., Methods: We used data from a prospective multicenter reperfusion therapy registry to compare the care process-including the time from symptom onset to treatment, number of treated patients, and discharge disposition-and treatment outcomes between before and during the COVID-19 outbreak in South Korea., Results: Upon the COVID-19 outbreak in South Korea, the number of patients receiving endovascular treatment to decrease temporarily but considerably. The use of emergency medical services by stroke patients increased from 91.5% before to 100.0% during the COVID-19 outbreak ( p =0.025), as did the median time from symptom onset to hospital visit [median (interquartile range), 91.0 minutes (39.8-277.0) vs. 176.0 minutes (56.0-391.5), p =0.029]. Furthermore, more functionally dependent patients with disabilities were discharged home (59.5% vs. 26.1%, p =0.020) rather than staying in a regional or rehabilitation hospital. In contrast, there were no COVID-19-related changes in the times from the hospital visit to brain imaging and treatment or in the functional outcome, successful recanalization rate, or rate of symptomatic intracerebral hemorrhage., Conclusions: These findings suggest that a prehospital delay occurred during the COVID-19 outbreak, and that patients with acute stroke might have been reluctant to visit and stay in hospitals. Our findings indicate that attention should be paid to prehospital care and the behavior of patients with acute stroke during the COVID-19 outbreak., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 Korean Neurological Association.)

Of the drugs developed to prevent and treat osteoporosis, bisphosphonate has played a very important role in preventing osteoporotic fractures. However, case reports describing atypical femoral fractures in patients using long-term bisphosphonates have emerged. The majority of atypical femur fractures occurs in the lateral aspect of the subtrochanteric or femur diaphysis, which is explained by accumulation of tensile stress in these areas. Although the superior cortex of the femur neck withstands maximum tensile stress, to our knowledge, there have been only two reports (three cases) of atypical femoral neck fracture. In addition, none of those case reports revealed detailed pathology related to suppressed bone turnover rate. We encountered an incomplete femoral neck fracture and diagnosed it as "atypical" on the basis of the patient's lack of trauma and medication history and pathological findings. For patients with groin pain, minimal or no trauma, and a history of long-term bisphosphonate use, an atypical femoral neck fracture should be considered.

The self-assembly of PdX 2 (X - = ClO 4 - and PF 6 - ) with C 3 -symmetric l - and d -L [L = (2 S ,2' S ,2″ S )- and (2 R ,2' R ,2″ R )-[benzenetricarbonyltris(azanediyl)]tris(3-phenylpropane-2,1-diyl)triisonicotinate] produces the chiral nanocube pair [Pd 6 ( l -L) 8 ](X) 12 and [Pd 6 ( d -L) 8 ](X) 12 (X - = ClO 4 - and PF 6 - , respectively) with an inner cavity of 12.3 × 12.3 × 12.3 Å 3 . These chiral nanocubes are effective for the enantiorecognition of various chiral amino acids via the square-wave-voltammetry technique. In the present study, the site of enantiorecognition was confirmed by density functional theory calculated interactions between each nanocube and the chiral amino acids, and the calculated interactions were coincident with the shifts of the electrochemical oxidation potentials.

A robust amperometric sensor was developed for the lactate detection in the extracellular matrix of cancer cells. The sensor was fabricated by separately immobilizing nicotinamide adenine dinucleotide (NAD + ) onto a carboxylic acid group and lactate dehydrogenase (LDH) onto an amine group of bi-functionalized conducting polymer (poly 3-(((2,2':5',2″-terthiophen)-3'-yl)-5-aminobenzoic acid (pTTABA)) composited with N, S-doped porous carbon. Morphological features of the composite layer and sensor performance were investigated using FE-SEM, XPS, and electrochemical methods. The experimental parameters were optimized to get the best results. The calibration plot showed a linear dynamic range between 0.5 μM and 4.0 mM with the detection limit of 112 ± 0.02 nM. The proposed sensor was applied to detect lactate in a non-cancerous (Vero) and two cancer (MCF-7 and HeLa) cell lines. Among these cell lines, MCF-7 was mostly affected by the administration of lactate transport inhibitor, α-cyano-4-hydroxycinnamate (αCHC), followed by HeLa and Vero, respectively. Furthermore, the effect of αCHC concentration and treatment time on the lactate level in the cell lines were demonstrated. Finally, cytotoxicity studies were also performed to evaluate the effect of αCHC on cell viability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Dental implant surgeries involve the insertion of implant fixtures into alveolar bones to replace missing teeth. When the availability of alveolar bone at the surgical site is insufficient, bone graft particles are filled in the insertion site for successful bone reconstruction. Bone graft particles induce bone regeneration over several months at the insertion site. Subsequently, implant fixtures can be inserted at the recipient site. Thus, conventional dental implant surgery is performed in several steps, which in turn increases the treatment period and cost involved. Therefore, to reduce surgical time and minimize treatment costs, a novel hybrid scaffold filled with bone graft particles that could be combined with implant fixtures is proposed. This scaffold is composed of a three-dimensionally (3D) printed polycaprolactone (PCL) frame and osteoconductive ceramic materials such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Herein, we analyzed the porosity, internal microstructure, and hydrophilicity of the hybrid scaffold. Additionally, Saos-2 cells were used to assess cell viability and proliferation. Two types of control scaffolds were used (a 3D printed PCL frame and a hybrid scaffold without HA/β-TCP particles) for comparison, and the fabricated hybrid scaffold was verified to retain osteoconductive ceramic particles without losses. Moreover, the fabricated hybrid scaffold had high porosity and excellent microstructural interconnectivity. The in vitro Saos-2 cell experiments revealed superior cell proliferation and alkaline phosphatase assay results for the hybrid scaffold than the control scaffold. Hence, the proposed hybrid scaffold is a promising candidate for minimizing cost and duration of dental implant surgery.

We investigated whether there was an annual change in outcomes in patients who received the thrombolytic therapy or endovascular treatment (EVT) in Korea. This analysis was performed using data from a nationwide multicenter registry for exploring the selection criteria of patients who would benefit from reperfusion therapies in Korea. We compared the annual changes in the modified Rankin scale (mRS) at discharge and after 90 days and the achievement of successful recanalization from 2012 to 2017. We also investigated the determinants of favorable functional outcomes. Among 1230 included patients, the improvement of functional outcome at discharge after reperfusion therapy was noted as the calendar year increased ( p < 0.001). The proportion of patients who were discharged to home significantly increased (from 45.6% in 2012 to 58.5% in 2017) ( p < 0.001). The successful recanalization rate increased over time from 78.6% in 2012 to 85.1% in 2017 ( p = 0.006). Time from door to initiation of reperfusion therapy decreased over the years ( p < 0.05). These secular trends of improvements were also observed in 1203 patients with available mRS data at 90 days ( p < 0.05). Functional outcome was associated with the calendar year, age, initial stroke severity, diabetes, preadmission disability, intervals from door to reperfusion therapy, and achievement of successful recanalization. This study demonstrated the secular trends of improvement in functional outcome and successful recanalization rate in patients who received reperfusion therapy in Korea.

Low interfacial energy, an intrinsic property of complex coacervate, enables the complex coacervate to easily encapsulate desired cargo substances, making it widely used in encapsulation applications. Despite this advantage, the low interfacial energy of the complex coacervate makes it unstable against mechanical mixing, and changes in pH and salt concentration. Hence, a chemical cross-linker is usually added to enhance the stability of the complex coacervate at the expense of sacrificing all intrinsic properties of the coacervate, including phase transition of the coacervate from liquid to solid. In this study, we observed an abrupt increase in the interfacial energy of the coacervate phase in mineral oil. By controlling the interfacial energy of the coacervate phase using a microfluidic device, we successfully created double engulfed PEG-diacrylate (PEGDA) coacervate microparticles, named DEPOT, in which the coacervate is engulfed in a cross-linked PEGDA shell. The engulfed coacervate remained as a liquid phase, retained its original low interfacial energy property to encapsulate the desired cargo substances, and infiltrated into the target site by a simple solvent exchange from oil to water.

In this study, we have established the separation of Au nanoparticles (AuNPs) using a symmetrical AC electric field applied-electrochemical microfluidic device composed of carbon channel and detection electrodes. The lateral movement of AuNPs in the channel under the AC field was analyzed by simulation using the mathematically derived equations, which were formulated from Newtonian fluid mechanics. It shows that the nanoparticles are precisely separated according to their respective mass or size difference in a short time. The experimental parameters affecting the separation and detection of AuNPs were optimized in terms of applied frequency, amplitude, flow rate, buffer concentration, pH dependency, and temperature. The final separation was performed at 1.0 V amplitude with 8.0 MHz frequency at 0.4 μL/min flow rate for the separation, and the potential of 1.0 V was applied for the amperometric detection of AuNPs in a 0.1 M PBS. Before and after the separation, AuNPs (diameter range: 3-60 nm) were confirmed by UV-visible spectroscopy and transmission electron microscopy. In this case, the separation resolution was 3 nm with an enhanced separation efficiency of up to 597,503 plates/m for the AuNPs. In addition, the amperometric current response of the detection electrode under the AC field application was also enhanced by the sensitivity 5-fold compared with the absence of the AC field.

Purpose: Although carotid endarterectomy (CEA) is recommended as a treatment for carotid stenosis rather than carotid artery stenting (CAS), CAS has been preferred in Korea. The aim of this study was to analyze long-term outcomes after CAS compared with CEA using Korean nationwide insurance data., Materials and Methods: We obtained all data from the nationwide database of the Health Insurance Review & Assessment Service (HIRA) during the study period using several codes regarding the procedure or operation. We included the HIRA data, which included at least oneyear follow-up after the procedures. The outcomes associated with both procedures were death, recurrence of ischemic stroke, and admission for cerebral hemorrhage., Results: A total of 16,065 eligible patients who were treated with CAS or CEA between 1 January 2007 and 31 December 2016 were analyzed. The number of patients with CAS and CEA was 12,173 (75.8%) and 3,892 (24.2%), respectively. 8,976 patients (55.9%) were classified as symptomatic patients. CAS was associated with a higher risk of all-cause mortality (adjusted hazard ratio [HR], 1.282; 95% confidence interval [CI], 1.173-1.400). The adjusted rates for recurrent ischemic stroke and cerebral hemorrhage between CAS versus CEA were 24.9% versus 15.9% (HR, 1.474; 95% CI, 1.325-1.639) and 1.5% versus 0.9% (HR, 2.026; 95% CI, 1.322-3.106), respectively. In young symptomatic patients, there was no statistically significant difference in all-cause mortality and cardiovascular death between CAS and CEA., Conclusion: Our study using Korean nationwide insurance data demonstrated similar results to previous studies. Until further evidence of CAS is established through prospective studies, CAS should be performed in selected patients according to current guidelines.

Although a conventional method of utilizing thermoresponsive grafted poly(N-isopropylacrylamide) (PNIPAAm) enables the harvest of a healthy confluent cell-to-cell junction preserved cell sheet while limiting the use of the trypsin enzyme, the absolute necessity in the delicate control of a sensitive nm-scale PNIPAAm chain length inevitably decelerates the advancement of cell sheet engineering. In this study, we demonstrate, for the first time, a thermoresponsive cell culture platform composed only of a 'bulk' form of a PNIPAAm hydrogel with the Young's modulus being increased up to the MPa scale. The surface roughness of the bulk PNIPAAm hydrogel initially modulated by the cross-linker concentration was altered from the nm- to μm-scale in response to a change in temperature above/below the low critical solution temperature (LCST) of 32 °C. The appropriate control of the surface roughness allowed the stable attachment (above the LCST) and easy detachment (below the LCST) of diverse cells and enabled the harvest of cell sheets composed of cell lines (C2C12 and NIH3T3) or even primary cells (human umbilical vein endothelial cells and keratinocytes). During their incubation at 37 °C, the cell lines were able to be attached on every surface of the prepared PNIPAAm cell culture platforms, whereas the primary cells were found to be only attached on a surface having a roughness below ∼30 nm. Furthermore, in the aspect of cell sheet detachment at the incubation temperature of 20 °C, the cell sheets composed of cell lines were fully detached from the surface of the platform having a roughness of ∼10 μm or higher, while the cell sheets composed of primary cells were entirely detached from the surface with a roughness of ∼19 μm or higher. Based on such behaviors of the diverse cells at a given surface roughness, this study further suggests a universal thermoresponsive cell culture platform which allows the harvest of all types of cells from cell lines to primary cells in a desired shape. Our suggested universal cell culture platform could play a powerful and versatile role in accelerating the advancement of cell sheet engineering.

Background and Purpose: Previous studies have reported conflicting results about the prevalence of seizures in Alzheimer's disease (AD). There are few epidemiological studies on this topic in Asia. Thus, the objective of this study was to examine demographic and clinical characteristics as well as incidence for seizures in AD patients compared to non-AD patients in a prospective, longitudinal, community-based cohort with a long follow-up., Methods: Data were collected from National Health Insurance Service-National Elderly Cohort (NHIS-elderly) Database to define patients with AD from 2004-2006 using Korean Classification Diseases codes G30 and F00. We performed a 1:5 case-control propensity score matching based on age, sex, and household income. We conducted Cox proportional hazards regression analysis to estimate the risk of epilepsy in AD patients., Results: In the cohort study, patients with AD had higher risk for epilepsy than those without AD, with hazard ratio of 2.773 (95% confidence interval [CI], 2.515-3.057). This study also showed that male gender and comorbidities such as hypertension, hyperlipidemia, diabetes, and chronic kidney disease increased the risk of developing epilepsy. Patients with AD had 1.527 (95% CI, 1.375-1.695) times higher mortality rate than those in the control group., Conclusions: AD patients have significantly higher risk of developing epilepsy than non-AD patients., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest.

Purpose: As endovascular therapy (EVT) has been approved as a treatment guideline for acute ischemic stroke (AIS), it has been increasing in Korea. We conducted a nationwide survey to evaluate the current status of EVT for patients with AIS in Korea., Materials and Methods: An electronic survey was sent to a representative clinician at each hospital where EVT was available in Korea. A Google survey was used to distribute the questionnaires and receive responses from October 2017 to December 2017., Results: Among 120 hospitals in our society, 76 participated in this survey. In 26% of the hospitals, more than 50 annual cases of EVT were performed, and 25-50 annual cases in 37%. Fifty-six hospitals (73.7%) achieved successful recanalization (thrombolysis in cerebral infarction ≥2b) in more than 80% of patients. Computed tomography (CT) angiography was the most common imaging modality for AIS treatment, and magnetic resonance (MR) diffusion, MR-perfusion/diffusion, and perfusion CT were frequently used in order. Non-eligibility criteria for EVT included a National Institutes of Health Stroke Scale <4 (64.5%), the absence of MR perfusion/diffusion mismatch (52.6%), and a low Alberta Stroke Program Early CT Score (42.1%). For anterior circulation stroke, 60% of Korean hospitals adopted a wider time range of "8 hours" from symptom onset, while 70% of hospitals had a time limitation of 12-24 hours for posterior circulation stroke. The most preferred EVT device was a stentriever (89.4%). In the failed cases due to underlying stenosis, 79% of Korean hospitals performed angioplasty or stenting for revascularization., Conclusion: This first nationwide survey showed that most Korean hospitals conducted EVT for AIS patients according to the present guideline in the era of mechanical thrombectomy by integrating the clinical experiences of many medical institutions and specialists.

Background and Purpose: There is an uncertainty about the association between intracranial aneurysms and aortic dissection. We aimed to determine the prevalence of intracranial aneurysms in patients with aortic dissection and evaluate the independent risk factors for the presence of intracranial aneurysms in these patients., Materials and Methods: Seventy-one patients with a confirmed aortic dissection who underwent additional brain imaging were enrolled as the aortic dissection group, and 2118 healthy individuals with brain imaging, as controls. Demographic data were obtained from their medical records, including age, sex, comorbidities, and arch vessel involvement of aortic dissection. Two readers reviewed all brain images independently regarding the presence, morphology, size, and location of intracranial aneurysms. Baseline characteristics were compared between the aortic dissection group and controls by propensity score matching, and logistic regression analysis was performed for independent risk factors for the presence of intracranial aneurysms., Results: The prevalence of intracranial aneurysms was 12.96% in the aortic dissection group and 1.85% in controls ( P = .022). The mean diameter of intracranial aneurysms was significantly larger in the aortic dissection group (5.79 ± 3.26 mm in aortic dissection versus 3.04 ± 1.57 mm in controls; P = .008), and intracranial aneurysms of >7 mm were also more common in the aortic dissection group (28.6% in aortic dissection versus 5.3% in controls, P = .003). On multivariate analysis, arch vessel involvement of aortic dissection was an independent risk factor for the presence of intracranial aneurysms (odds ratio, 6.246; 95% confidence interval, 1.472-26.50; P = .013)., Conclusions: Patients with aortic dissection have a high prevalence of intracranial aneurysms, and selective screening for brain vessels could be considered in these patients with arch vessel involvement. A further prospective study is needed to demonstrate a substantial prevalence of intracranial aneurysms., (© 2017 by American Journal of Neuroradiology.)