Previously, we reported the concept of a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local emergency rooms in rural and medically underserved areas in Gangwon state by combining artificial intelligence and remote consultation with a neurosurgeon. Developing a telemedicine ICH treatment protocol exclusively for doctors with less ICH expertise working in emergency rooms should be part of establishing this system. Difficulties arise in providing appropriate early treatment for ICH in rural and underserved areas before the patient is transferred to a nearby hub hospital with stroke specialists. This has been an unmet medical need for decade. The available reporting ICH guidelines are realistically possible in university hospitals with a well-equipped infrastructure. However, it is very difficult for doctors inexperienced with ICH treatment to appropriately select and deliver ICH treatment based on the guidelines. To address these issues, we developed an ICH telemedicine protocol. Neurosurgeons from four university hospitals in Gangwon state first wrote the guidelines, and professors with extensive ICH expertise across the country revised them. Guidelines and recommendations for ICH management were described as simply as possible to allow more doctors to use them easily. We hope that our effort in developing the telemedicine protocols will ultimately improve the quality of ICH treatment in local emergency rooms in rural and underserved areas in Gangwon state.

Objective: : We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. Methods: : We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. Results: : Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56–0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80–1.47; p=0.5929). Three other variants, rs16944 (IL-1β), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01Conclusion : Our updated meta-analysis with increased statistical power highlights that rs1800796 which maps on the IL-6 gene is associated with IA, and in particular confers a protective effect against occurrence of IA in the East-Asian population.

Objective: : Surgical site infection is the most detrimental complication following cranioplasty. In other surgical fields, intrawound vancomycin powder application has been introduced to prevent surgical site infection and is widely used based on results in multiple studies. This study evaluated the effect of intrawound vancomycin powder in cranioplasty compared with the conventional method without topical antibiotics. Methods: : This retrospective study included 580 patients with skull defects who underwent cranioplasty between August 1, 1998 and December 31, 2021. The conventional method was used in 475 (81.9%; conventional group) and vancomycin powder (1 g) was applied on the dura mater and bone flap in 105 patients (18.1%; vancomycin powder group). Surgical site infection was defined as infection of the incision, organ, or space that occurred after cranioplasty. Surgical site infection within 1-year surveillance period was compared between the conventional and vancomycin powder groups with logistic regression analysis. Penalized likelihood estimation method was used in logistic regression to deal with zero events. All local and systemic adverse events associated with topical vancomycin application were also evaluated. Results: : Surgical site infection occurred in 31 patients (5.3%) and all were observed in the conventional group. The median time between cranioplasty and detection of surgical site infection was 13 days (range, 4–333). Staphylococci were the most common organisms and identified in 25 (80.6%) of 31 cases with surgical site infections. The surgical site infection rate in the vancomycin powder group (0/105, 0.0%) was significantly lower than that in the conventional group (31/475, 6.5%; crude odds ratio [OR], 0.067; 95% confidence interval [CI], 0.006–0.762; adjusted OR, 0.068; 95% CI, 0.006–0.731; p=0.026). No adverse events associated with intrawound vancomycin powder were observed during the follow-up. Conclusion : Intrawound vancomycin powder effectively prevented surgical site infections following cranioplasty without local or systemic adverse events. Our results suggest that intrawound vancomycin powder is an effective and safe strategy for patients undergoing cranioplasty.

We aimed to develop a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local hospitals in rural and underserved areas in Gangwon-do using artificial intelligence and non-face-to-face collaboration treatment technology. This is a prospective and multi-center development project in which neurosurgeons from four university hospitals in Gangwondo will participate. Information technology experts will verify and improve the performance of the cloud-based telemedicine collaboration platform while treating ICH patients in the actual medical field. Problems identified will be resolved, and the function, performance, security, and safety of the telemedicine platform will be checked through an accredited certification authority. The project will be carried out over 4 years and consists of two phases. The first phase will be from April 2022 to December 2023, and the second phase will be from April 2024 to December 2025. The platform will be developed by dividing the work of the neurosurgeons and information technology experts by setting the order of items through mutual feedback. This article provides information on a project to develop a cloud-based telemedicine platform for acute ICH patients in Gangwon-do.

Objective: This study aimed to validate the risk stratification system (RSS) and biopsy criteria for cervical lymph nodes (LNs) proposed by the Korean Society of Thyroid Radiology (KSThR). Materials and Methods: This retrospective study included a consecutive series of preoperative patients with thyroid cancer who underwent LN biopsy, ultrasound (US), and computed tomography (CT) between December 2006 and June 2015. LNs were categorized as probably benign, indeterminate, or suspicious according to the current US- and CT-based RSS and the size thresholds for cervical LN biopsy as suggested by the KSThR. The diagnostic performance and unnecessary biopsy rates were calculated. Results: A total of 277 LNs (53.1% metastatic) in 228 patients (mean age ± standard deviation, 47.4 years ± 14) were analyzed. In US, the malignancy risks were significantly different among the three categories (all P < 0.001); however, CTdetected probably benign and indeterminate LNs showed similarly low malignancy risks (P = 0.468). The combined US + CT criteria stratified the malignancy risks among the three categories (all P < 0.001) and reduced the proportion of indeterminate LNs (from 20.6% to 14.4%) and the malignancy risk in the indeterminate LNs (from 31.6% to 12.5%) compared with US alone. In all image-based classifications, nodal size did not affect the malignancy risks (short diameter [SD] ≤ 5 mm LNs vs. SD > 5 mm LNs, P ≥ 0.177). The criteria covering only suspicious LNs showed higher specificity and lower unnecessary biopsy rates than the current criteria, while maintaining sensitivity in all imaging modalities. Conclusion Integrative evaluation of US and CT helps in reducing the proportion of indeterminate LNs and the malignancy risk among them. Nodal size did not affect the malignancy risk of LNs, and the addition of indeterminate LNs to biopsy candidates did not have an advantage in detecting LN metastases in all imaging modalities.

Background: Inflammation induces dysfunction of endothelial cells via inflammatory cell adhesion, and this phenomenon and reactive oxygen species accumulation are pivotal triggers for atherosclerosis-related vascular disease. Although exosomes are excellent candidate as an inhibitor in the inflammation pathway, it is necessary to develop exosome-mimetic nanovesicles (NVs) due to limitations of extremely low release rate and difficult isolation of natural exosomes. NVs are produced in much larger quantities than natural exosomes, but due to the low flexibility of the cell membranes, the high loss caused by hanging on the filter membranes during extrusion remains a challenge to overcome. Therefore, by making cell membranes more flexible, more efficient production of NVs can be expected. Methods: To increase the flexibility of the cell membranes, the suspension of umbilical cord-mesenchymal stem cells (UC-MSCs) was subjected to 5 freeze and thaw cycles (FT) before serial extrusion. After serial extrusion through membranes with three different pore sizes, FT/NVs were isolated using a tangential flow filtration (TFF) system. NVs or FT/NVs were pretreated to the human coronary artery endothelial cells (HCAECs), and then inflammation was induced using tumor necrosis factor-α (TNF-α). Results: With the freeze and thaw process, the production yield of exosome-mimetic nanovesicles (FT/NVs) was about 3 times higher than the conventional production method. The FT/NVs have similar biological properties as NVs for attenuating TNF-α induced inflammation. Conclusion We proposed the efficient protocol for the production of NVs with UC-MSCs using the combination of freeze and thaw process with a TFF system. The FT/NVs successfully attenuated the TNF-α induced inflammation in HCAECs.

Objective: : The purpose of this study was to evaluate the impact of time interval between index event and stenting on the periprocedural risk of stenting for symptomatic carotid stenosis and to determine the optimal timing of stenting. Methods: : This retrospective study included 491 (322 symptomatic [65.6%] and 169 asymptomatic [34.4%]) patients undergoing carotid stenting. The symptomatic patients were categorized into Day 0–3, 4–7, 8–10, 11–14, 15–21, and >21 groups according to the time interval between index event and stenting. Periprocedural (≤30 days) risk for clinical (any neurological deterioration) and radiological (new infarction on postprocedural diffusion-weighted imaging) events of stenting in each time interval versus asymptomatic stenosis was calculated with logistic regression analysis adjusted for confounders, and provided as odds ratio (OR) and 95% confidence interval (CI). Results: : Overall clinical event rate (4.3%) of stenting for symptomatic carotid stenosis was higher than that for asymptomatic stenosis (1.2%; OR, 3.979 [95% CI, 1.093–14.489]; p=0.036). Stenting in Day 0–3 (13.2%; OR, 10.997 [95% CI, 2.333–51.826]; p=0.002) and Day 4–7 (8.3%; OR, 6.775 [95% CI, 1.382–33.227]; p=0.018) was associated with high risk for clinical events. However, the clinical event rates in stenting after 7 days from index event (Day 8–10, 1.8%; Day 11–14, 2.5%; Day 15–21, 0%; Day >21, 2.9%) were not different from that in stenting for asymptomatic stenosis. Overall radiological event rate (55.6%) in symptomatic stenosis was also higher than that in asymptomatic stenosis (35.5%; OR, 2.274 [95% CI, 1.553–3.352]; p<0.001). The high risk for radiological events was maintained in all time intervals (Day 0–3 : 55.3%; OR, 2.224 [95% CI, 1.103–4.627]; p=0.026; Day 4–7 : 58.3%; OR, 2.543 [95% CI, 1.329–4.949]; p=0.005; Day 8–10 : 53.6%; OR, 2.096 [95% CI, 1.138–3.889]; p=0.018; Day 11–14 : 57.5%; OR, 2.458 [95% CI, 1.225–5.021];p=0.012; Day 15–21 : 55.6%; OR, 2.271 [95% CI, 1.099–4.764]; p=0.028; Day >21 : 54.8%; OR, 2.203 [95% CI, 1.342–3.641]; p=0.002). Conclusion : This study showed that as stenting was delayed, the periprocedural risk for clinical events decreased. The clinical event risk was high only in stenting within 7 days and comparable with that for asymptomatic stenosis in stenting after 7 days from index event, although the radiological event risk was not affected by stenting timing. Therefore, our results suggest that delayed stenting after 7 days from symptom onset is a safe strategy for symptomatic stenosis.

Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons (100 µM, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner (1–50 µM) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of Ca²⁺ and ROS, mitochondrial membrane potential (ΔΨ(m)) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.
Adenine ; Brain ; Cell Death ; Cell Survival ; Cell-Free System ; Glutamic Acid* ; Heme Oxygenase-1 ; Membrane Potential, Mitochondrial ; Mitochondria ; Neurodegenerative Diseases ; Neurons ; Reactive Oxygen Species*

BACKGROUND: Standardized postoperative airway management is essential for patients undergoing anterior cervical spine surgery (ACSS). The paucity of clinical series evaluating these airway complications after ACSS has been resulted in a significant limitation in statistical analyses. METHODS: A retrospective cohort study was performed regarding airway distress (intubation for more than 24 hours or unplanned reintubation within 7 days of operation) developed after ACSS. If prevertebral soft tissue swelling was evident after the operation, patients were managed with prolonged intubation (longer than 24 hours). Preoperative and intraoperative patient data, and postoperative outcome (time to extubation and reintubation) were analyzed. RESULTS: Between 2008 and 2016, a total of 400 ACSS were performed. Of them, 389 patients (97.25%) extubated within 24 hours of surgery without airway complication, but 11 patients (2.75%) showed postoperative airway compromise; 7 patients (1.75%) needed prolonged intubation, while 4 patients (1.00%) required unplanned reintubation. The mean time for extubation were 2.75 hours (range: 0–23 hours) and 50.55 hours (range: 0–250 hours), respectively. Age (P = 0.015), diabetes mellitus (P = 0.003), operative time longer than 5 hours (P = 0.048), and estimated blood loss (EBL) greater than 300 mL (P = 0.042) were associated with prolonged intubation or reintubation. In prolonged intubation group, all patients showed no airway distress after extubation. CONCLUSION: In ACSS, postoperative airway compromise is related to both patients and operative factors. We recommend a prolonged intubation for patients who are exposed to these risk factors to perform a safe and effective extubation.
Airway Management ; Cohort Studies ; Diabetes Mellitus ; Humans ; Intubation* ; Operative Time ; Retrospective Studies ; Risk Factors* ; Spine*

Quercetin is a flavonoid usually found in fruits and vegetables. Aside from its antioxidative effects, quercetin, like other flavonoids, has a various neuropharmacological actions. Quercetin-3-O-rhamnoside (Rham1), quercetin-3-O-rutinoside (Rutin), and quercetin-3-(2(G)-rhamnosylrutinoside (Rham2) are mono-, di-, and tri-glycosylated forms of quercetin, respectively. In a previous study, we showed that quercetin can enhance α7 nicotinic acetylcholine receptor (α7 nAChR)-mediated ion currents. However, the role of the carbohydrates attached to quercetin in the regulation of α7 nAChR channel activity has not been determined. In the present study, we investigated the effects of quercetin glycosides on the acetylcholine induced peak inward current (I(ACh)) in Xenopus oocytes expressing the α7 nAChR. I(ACh) was measured with a two-electrode voltage clamp technique. In oocytes injected with α7 nAChR copy RNA, quercetin enhanced I(ACh), whereas quercetin glycosides inhibited I(ACh). Quercetin glycosides mediated an inhibition of I(ACh), which increased when they were pre-applied and the inhibitory effects were concentration dependent. The order of I(ACh) inhibition by quercetin glycosides was Rutin≥Rham1>Rham2. Quercetin glycosides-mediated I(ACh) enhancement was not affected by ACh concentration and appeared voltage-independent. Furthermore, quercetin-mediated I(ACh) inhibition can be attenuated when quercetin is co-applied with Rham1 and Rutin, indicating that quercetin glycosides could interfere with quercetin-mediated α7 nAChR regulation and that the number of carbohydrates in the quercetin glycoside plays a key role in the interruption of quercetin action. These results show that quercetin and quercetin glycosides regulate the α7 nAChR in a differential manner.
Acetylcholine* ; Carbohydrates ; Flavonoids ; Fruit ; Glycosides* ; Humans* ; Oocytes ; Quercetin* ; Receptors, Nicotinic ; RNA ; Rutin ; Vegetables ; Xenopus