Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality and poor functional outcomes. Prompt occlusion of a ruptured aneurysm at an early stage is crucial to prevent rebleeding, which can result in even higher mortality and more severe disabilities. The most critical initial decision in SAH management is the choice of treatment method with surgical clipping or endovascular coiling. We aimed to develop an evidence-based clinical guideline to select the optimal initial treatment in patients with SAH. We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer two population, intervention, comparison, outcome questions comparing clipping and coiling. The risk of bias was assessed using ROB 2.0 and the Newcastle-Ottawa Scale. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcome and mortality. We included six randomized control trials (RCTs) and 58 observational studies. Meta-analysis of RCTs showed that coiling improved functional outcomes compared to clipping (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.86–0.97). No significant mortality difference was observed in RCTs (OR, 1.38; 95% CI, 0.91–2.09), but non-RCTs favored clipping for reduced mortality (OR, 0.77; 95% CI, 0.69–0.86). However, it is difficult to generalize these findings to all clinical situations, as patients with SAH have a highly variable clinical course. Final treatment decision should be tailored to the individual patient’s status, including aneurysm location, morphology, and the expertise available at the treatment center. Such decisions are best made by specialists such as a board-certified physician and should be explained to the patient and their caregivers, along with the rationale for selecting the most appropriate treatment at the given hospital. Korea has many certified endovascular neurosurgeons, cerebrovascular surgeons, and certified cerebrovascular centers. Proper selection of the most suitable treatment method by certified physicians and centers would greatly benefit patient outcomes and healthcare professionals.

Accurate and early identification of stroke and large vessel occlusion (LVO) in emergency settings is essential for improving patient outcomes and ensuring the efficient allocation of medical resources. This clinical practice guideline systematically reviews domestic and international literature and conducts meta-analyses to evaluate the utility and diagnostic accuracy of stroke assessment tools used in prehospital emergency medical services (EMS). We developed a guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted to evaluate the usefulness of diagnostic EMS assessment tools for diagnosing stroke and LVO. Overall, 70 non-randomized control studies were selected for this study. A meta-analysis was conducted with a subgroup analysis to distinguish between patients with stroke and those with LVO. EMS tools demonstrated high sensitivity but low specificity for diagnosing stroke. In the prehospital setting, using validated EMS stroke assessment tools is recommended for the early identification of stroke and LVO. Upon hospital arrival, stroke specialists should conduct further evaluation and triage to confirm the diagnosis and guide appropriate management. Delays in diagnosing LVO are frequently unacceptable. While experts advocate for the use of EMS assessment tools to facilitate early identification of LVO, these tools alone lack adequate sensitivity. Therefore, further diagnostic evaluations and consultation with stroke specialists upon hospital arrival are recommended.

The mothership (MS) model, where patients are directly transferred to a thrombectomy-capable center, and the drip-and-ship (DS) model, where thrombolysis is initiated at the nearest primary stroke center before transfer for thrombectomy, are the primary transport modes for patients with stroke. We aimed to establish guidelines for selecting the appropriate transfer strategy based on emergent large vessel occlusion (LVO). We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer three Population, Intervention, Comparison, and Outcome questions comparing MS and DS models. The risk of bias was assessed using the Newcastle-Ottawa Scale. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcomes, mortality, and successful recanalization. Twenty-six non-randomized controlled studies showed that the MS model improved good functional outcomes by approximately 14% compared with the DS model (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.00–1.30). Fifteen studies reported that mortality in the MS and DS models showed no significant differences (OR, 0.97; 95% CI, 0.84–1.11). Twenty-four studies revealed no significant difference in successful recanalization between the MS and DS models (OR, 0.87; 95% CI, 0.68–1.10). The MS model should be considered first to improve the functional outcome of patients with LVO. However, if thrombectomy cannot be performed immediately after thrombolysis, or if a thrombectomy-enabled hospital is not nearby, the DS model should be considered by stroke specialists depending on transportation time and regional factors. We suggest a mixed approach with the DS model based on specific circumstances or regions to ensure the optimum treatment of patients with acute ischemic stroke (AIS). Appropriate transport for patients with LVO improves the prognosis of AIS.

Objectives: . Inferior turbinate (IT) hypertrophy is the main cause of chronic nasal obstruction. We developed a high-intensity focused ultrasound (HIFU) ablation device to treat patients with IT hypertrophy. Methods: . First, computed tomography images of patients with no evidence of sinonasal disease were evaluated to measure and compare the IT, medial mucosal thickness (MT), and space between the nasal septum and IT according to clinical characteristics such as septal deviation. A HIFU prototype was developed based on the above human anatomical studies. The experimental study was performed in five pigs; the nasal volume and histological changes at 1 and 4 weeks postoperatively were evaluated to compare the efficacy of HIFU turbinoplasty with that of radiofrequency turbinoplasty and a control group. Results: . The mean medial MT of the anterior, middle, and posterior portions of the IT were 4.66±1.14, 4.23±0.97, and 6.17±1.29 mm, respectively. The mean medial space was 2.65±0.79 mm. The diameter and focal depth of the prototype were 4 mm and 3 mm, respectively. HIFU showed no postoperative complications, including bleeding or scar formation. After HIFU treatment, the nasal volume increased by 196.62 mm3 (7.8%) and 193.74 mm3 (8.3%) at 1 week and 4 weeks, compared with the increase of 87.20 mm3 (3.1%) and 213.81 mm3 (9.0%), respectively,after radiofrequency therapy. A qualitative histological analysis after radiofrequency turbinoplasty showed epithelial layer disruption at 1 week and increased fibrosis, along with decreased glandular structure, at 4 weeks. The HIFU group had an intact epithelial layer at 1 week postoperatively. However, significant differences were observed at 4 weeks, including increased fibrosis and decreased glandular structure. Conclusion . The efficacy and safety of HIFU turbinoplasty were demonstrated in an animal study. Our results warrant further human clinical trials.

Objective: To evaluate the prognostic implications of preoperative magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with a focus on those with targetoid appearance based on the Liver Imaging Reporting and Data System (LI-RADS), as well as known microvascular invasion (MVI) features. Materials and Methods: This retrospective study included 242 patients (190 male; mean age, 57.1 years) who underwent surgical resection of a single HCC (≤ 5 cm) as well as preoperative gadoxetic acid-enhanced MRI between January 2012 and March 2015. LI-RADS category was assigned, and the LR-M category was further classified into two groups according to rim arterial-phase hyperenhancement (APHE). The imaging features associated with MVI were also assessed. The overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated. Results: Among the 242 HCCs, 190 (78.5%), 25 (10.3%), and 27 (11.2%) were classified as LR-4/5, LR-M with rim APHE, and LR-M without rim APHE, respectively. LR-M with rim APHE (vs. LR-4/5; hazard ratio [HR] for OS, 5.48 [p = 0.002]; HR for RFS, 2.09 [p = 0.042]) and tumor size (per cm increase; HR for OS, 6.04 [p = 0.009]; HR for RFS, 1.77 [p = 0.014]) but not MVI imaging features (p > 0.05) were independent factors associated with OS and RFS. Compared to the 5-year OS and RFS rates in the LR-4/5 group (93.9% and 66.8%, respectively), the LR-M with rim APHE group had significantly lower rates (68.0% and 45.8%, respectively, both p < 0.05), while the LR-M without rim APHE group did not significantly differ in the survival rates (91.3% and 80.2%, respectively, both p > 0.05). Conclusion Further classification of LR-M according to the presence of rim APHE may help predict the postoperative prognosis of patients with a single HCC.

OBJECTIVE: To compare the breathing effects on dynamic contrast-enhanced (DCE)-MRI between controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE), radial VIBE with k-space-weighted image contrast view-sharing (radial-VIBE), and conventional VIBE (c-VIBE) sequences using a dedicated phantom experiment. MATERIALS AND METHODS: We developed a moving platform to simulate breathing motion. We conducted dynamic scanning on a 3T machine (MAGNETOM Skyra, Siemens Healthcare) using CAIPIRINHA-VIBE, radial-VIBE, and c-VIBE for six minutes per sequence. We acquired MRI images of the phantom in both static and moving modes, and we also obtained motion-corrected images for the motion mode. We compared the signal stability and signal-to-noise ratio (SNR) of each sequence according to motion state and used the coefficients of variation (CoV) to determine the degree of signal stability. RESULTS: With motion, CAIPIRINHA-VIBE showed the best image quality, and the motion correction aligned the images very well. The CoV (%) of CAIPIRINHA-VIBE in the moving mode (18.65) decreased significantly after the motion correction (2.56) (p < 0.001). In contrast, c-VIBE showed severe breathing motion artifacts that did not improve after motion correction. For radial-VIBE, the position of the phantom in the images did not change during motion, but streak artifacts significantly degraded image quality, also after motion correction. In addition, SNR increased in both CAIPIRINHA-VIBE (from 3.37 to 9.41, p < 0.001) and radial-VIBE (from 4.3 to 4.96, p < 0.001) after motion correction. CONCLUSION: CAIPIRINHA-VIBE performed best for free-breathing DCE-MRI after motion correction, with excellent image quality.
Acceleration ; Artifacts ; Magnetic Resonance Imaging ; Respiration* ; Signal-To-Noise Ratio

Embryonic stem (ES) cells are pluripotent cells characterized by self-renewability and differentiation potential. Induced pluripotent stem (iPS) cells are ES cell-equivalent cells derived from somatic cells by the introduction of core reprogramming factors. ES and iPS cells are important sources for understanding basic biology and for generating therapeutic cells for clinical applications. Tribbles homolog 2 (Trib2) functions as a scaffold in signaling pathways. However, the relevance of Trib2 to the pluripotency of ES and iPS cells is unknown. In the present study, we elucidated the importance of Trib2 in maintaining pluripotency in mouse ES cells and in generating iPS cells from somatic cells through the reprogramming process. Trib2 expression decreased as ES cells differentiated, and Trib2 knockdown in ES cells changed their colony morphology while reducing the activity of alkaline phosphatase and the expression of the pluripotency marker genes Oct4, Sox2, Nanog and Klf4. Trib2 directly interacted with Oct4 and elevated Oct4 promoter activity. During the generation of iPS cells, Trib2 knockdown decreased the reprogramming efficiency of mouse embryonic fibroblasts, whereas Trib2 overexpression significantly increased their reprogramming efficiency. In summary, our results suggest that Trib2 is important for maintaining self-renewal in ES cells and for pluripotency induction during the reprogramming process.
Alkaline Phosphatase ; Animals ; Biology ; Embryonic Stem Cells* ; Fibroblasts ; Induced Pluripotent Stem Cells ; Mice

PURPOSE: This study investigated predictors of unresponsiveness to second-line intravenous immunoglobulin (IVIG) treatment for Kawasaki disease (KD). METHODS: This was a single-center analysis of the medical records of 588 patients with KD who had been admitted to Asan Medical Center between 2006 and 2014. Related clinical and laboratory data were analyzed by univariate and multivariate logistic regression analyses. RESULTS: Eighty (13.6%) of the 588 patients with KD were unresponsive to the initial IVIG treatment and received a second dose. For these 80 patients, univariate analysis of the laboratory results obtained before administering the second-line IVIG treatment showed that white blood cell count, neutrophil percent, hemoglobin level, platelet count, serum protein level, albumin level, potassium level, and C-reactive protein level were significant predictors. The addition of methyl prednisolone to the second-line regimen was not associated with treatment response (odds ratio [OR], 0.871; 95% confidence interval [CI], 0.216–3.512; P=0.846). Multivariate analysis revealed serum protein level to be the only predictor of unresponsiveness to the second-line treatment (OR, 0.160; 95% CI, 0.028–0.911; P=0.039). Receiver operating characteristic curve analysis to determine predictors of unresponsiveness to the second dose of IVIG showed a sensitivity of 100% and specificity of 72% at a serum protein cutoff level of <7.15 g/dL. CONCLUSION: The serum protein level of the patient prior to the second dose of IVIG is a significant predictor of unresponsiveness. The addition of methyl prednisolone to the second-line regimen produces no treatment benefit.
Blood Proteins ; C-Reactive Protein ; Chungcheongnam-do ; Humans ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Leukocyte Count ; Logistic Models ; Medical Records ; Mucocutaneous Lymph Node Syndrome* ; Multivariate Analysis ; Neutrophils ; Platelet Count ; Potassium ; Prednisolone ; ROC Curve ; Sensitivity and Specificity

PURPOSE: In 2004, the American Heart Association (AHA) had published an algorithm for the diagnosis of incomplete Kawasaki disease (KD). The aim of the present study was to investigate characteristics of supplemental laboratory criteria in this algorithm. METHODS: We retrospectively examined the medical records of 355 patients with KD who were treated with intravenous immunoglobulin (IVIG) during the acute phase of the disease. Laboratory data were obtained before the initial IVIG administration and up to 10 days after fever onset. In 106 patients, laboratory testing was performed more than twice. RESULTS: The AHA supplemental laboratory criteria were fulfilled in 90 patients (25.4%), and the frequency of laboratory examination (odds ratio [OR], 1.981; 95% confidence interval [CI], 1.391-2.821; P<0.001) was a significant predictor of it. The fulfillment of AHA supplemental laboratory criteria was significantly associated with refractoriness to the initial IVIG administration (OR, 2.388; 95% CI, 1.182-4.826; P=0.013) and dilatation of coronary arteries (OR, 2.776; 95% CI, 1.519-5.074; P=0.001). CONCLUSION: Repeated laboratory testing increased the rate of fulfillment of the AHA supplemental laboratory criteria in children with KD.
American Heart Association ; Child* ; Coronary Vessels ; Diagnosis ; Dilatation ; Fever ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Medical Records ; Mucocutaneous Lymph Node Syndrome* ; Retrospective Studies

When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellular domain. SAA also restrained the fusion of osteoclast precursors by blocking intracellular ATP release. This inhibitory response of SAA is not mediated by the well-known SAA receptors (formyl peptide receptor 2, Toll-like receptor 2 (TLR2) or TLR4). These findings provide insight into a novel inhibitory role of SAA in osteoclastogenesis and suggest that SAA is an important endogenous modulator that regulates bone homeostasis.
Adenosine Triphosphate/metabolism ; Animals ; Cell Differentiation ; Cell Line ; Gene Expression Regulation, Developmental ; Humans ; Macrophages/*cytology/metabolism ; Mice ; Osteoclasts/*cytology/metabolism ; RANK Ligand/*metabolism ; Receptor, Macrophage Colony-Stimulating Factor/genetics ; Receptors, Formyl Peptide/metabolism ; Serum Amyloid A Protein/*metabolism ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 4/metabolism