Objective: : The latest version of the Leksell Gamma Knife IconTM allows for mask- and frame-based fixation. Although mask fixation provides fractionated treatment and immobilization using a noninvasive method, it is not free from collision. The authors investigated the collision problem with a modified mask fixation method. Methods: : This study presents a case of two meningiomas in the frontal area, where a collision occurs in the occipital area. A modified mask fixation method was introduced to avoid the collision : first, the edges of the head cushion were cut off and polystyrene beads with a diameter of approximately 5 cm were removed. Next, the head cushion was sealed using a stapler. Finally, the head cushion was flattened in the adapter. We compared the shot coordinates, 3-dimensional (3D) error, clearance distance, and vertical depth of the head cushion between the initial and modified mask fixations. Results: : When comparing the initial and modified mask fixations, the difference in the shot coordinates was +10.5 mm along the y-axis, the difference in the 3D error was approximately 18 mm, and the difference in clearance was -10.2 mm. The head cushion was approximately 8 mm deeper in the modified mask fixation. Conclusion : Based on these findings, we recommend a modified mask fixation method for gamma knife radiosurgery using ICON with a collision.

Purpose: DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. Methods: This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients’ subjective responses were analyzed. Results: In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. Conclusions Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.

Purpose: Isolated distal deep vein thrombosis (IDDVT) is a localized lesion; nonetheless, the risk of proximal vein propagation makes it difficult to decide on the treatment protocol—that is, whether immediate anticoagulation after diagnosis or surveillance via serial imaging should be employed. This study aimed to investigate the appropriate treatment protocol for IDDVT in kidney transplant recipient (KTR). Methods: Surveillance for venous thromboembolism (VTE) was performed using duplex ultrasonography (DUS) before transplant surgery and at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year after transplant surgery. Dual mechanical prophylaxis was administered to prevent VTE. Results: In total, 60 out of 829 patients (7.2%) developed VTE, with 49 cases (81.6%) of IDDVT. Among IDDVT patients, 15 patients were treated using anticoagulation-first strategy, whereas the remaining 34 patients were treated using surveillance-first strategy. No patient in either group exhibited thrombus extension into the proximal vein or recurrence within 1 year from transplant surgery. Conclusion In Korean KTR, extension of IDDVT into the proximal vein could be prevented safely and effectively by serial DUS surveillance along with the maintenance of mechanical prophylaxis. However, the patients who have high thrombus burden or are difficult to get repeated DUS require the use of anticoagulation in early stages.

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment. RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups. CONCLUSION The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Objective: : No optimum genetic rat Huntington model both neuropathological using an adeno-associated virus (AAV-2) vector vector has been reported to date. We investigated whether direct infection of an AAV2 encoding a fragment of mutant huntingtin (AV2-82Q) into the rat striatum was useful for optimizing the Huntington rat model. Methods: : We prepared ten unilateral models by injecting AAV2-82Q into the right striatum, as well as ten bilateral models. In each group, five rats were assigned to either the 2×1012 genome copies (GC)/mL of AAV2-82Q (×1, low dose) or 2×1013 GC/mL of AAV2-82Q (×10, high dose) injection model. Ten unilateral and ten bilateral models injected with AAV-empty were also prepared as control groups. We performed cylinder and stepping tests 2, 4, 6, and 8 weeks after injection, tested EM48 positive mutant huntingtin aggregates. Results: : The high dose of unilateral and bilateral AAV2-82Q model showed a greater decrease in performance on the stepping and cylinder tests. We also observed more prominent EM48-positive mutant huntingtin aggregates in the medium spiny neurons of the high dose of AAV2-82Q injected group. Conclusion : Based on the results from the present study, high dose of AAV2-82Q is the optimum titer for establishing a Huntington rat model. Delivery of high dose of human AAV2-82Q resulted in the manifestation of Huntington behaviors and optimum expression of the huntingtin protein in vivo.

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

Extramedullary myeloma refers to the presence of myeloma deposits outside the skeletal system and typically indicates a poor prognosis associated with shorter overall survival and progression- free survival. We report a case of extramedullary myeloma with extensive, abdominal multi-organ involvement mimicking lymphoma at initial diagnosis. Bulky retroperitoneal masses with severe diffusion restriction and patency of encased vessels can be MR findings of both myeloma and lymphoma. Radiologic findings such as arterial hyperenhancement, obstructive uropathy, and the lack of associated lymphadenopathy may favor a diagnosis of myeloma over lymphoma.

PURPOSE: We investigated the clinical outcomes of deceased donor kidney transplantation (KT) using kidneys with terminal acute kidney injury (AKI). METHODS: Between February 2000 and December 2013, we performed 202 deceased donor renal transplants from 159 brain dead donors. According to the expanded criteria donor (ECD) and AKI network criteria, we divided 202 recipients into 4 groups: Group I: Non-AKI & standard criteria donor (SCD) (n = 97); group II: Non-AKI & ECD (n = 15); group III: AKI & SCD (n = 52); and group IV: AKI & ECD (n = 38). RESULTS: The incidence of delayed graft function (DFG) was significantly higher in patients with AKI than it was in the non-AKI group (P = 0.008). There were no significant differences among the 4 groups in graft survival (P = 0.074) or patient survival (P = 0.090). However, the long-term allograft survival rate was significantly lower in group IV than it was in other groups (P = 0.024). CONCLUSION: Allografts from deceased donors with terminal AKI had a higher incidence of DGF than did those from donors without AKI. However, there is no significant difference in graft and patient survival rates among the groups. So, the utilization of renal grafts from ECDs with terminal AKI is a feasible approach to address the critical organ shortage.
Acute Kidney Injury* ; Allografts ; Brain Death ; Delayed Graft Function ; Graft Survival ; Humans ; Incidence ; Kidney Transplantation* ; Kidney* ; Korea* ; Survival Rate ; Tissue Donors* ; Transplants

Tetrodes, consisting of four twisted micro-wires can simultaneously record the number of neurons in the brain. To improve the quality of neuronal activity detection, the tetrode tips should be modified to increase the surface area and lower the impedance properties. In this study, tetrode tips were modified by the electrodeposition of Au nanoparticles (AuNPs) and dextran (Dex) doped poly (3,4-ethylenedioxythiophene) (PEDOT). The electrochemical properties were measured using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A decrease in the impedance value from 4.3 MΩ to 13 kΩ at 1 kHz was achieved by the modified tetrodes. The cathodic charge storage capacity (CSC(C)) of AuNPs-PEDOT deposited tetrodes was 4.5 mC/cm², as determined by CV measurements. The tetrodes that were electroplated with AuNPs and PEDOT exhibited an increased surface area, which reduced the tetrode impedance. In vivo recording in the ventral posterior medial (VPM) nucleus of the thalamus was performed to investigate the single-unit activity in normal rats. To evaluate the recording performance of modified tetrodes, spontaneous spike signals were recorded. The values of the L-ratio, isolation distance and signal-to-noise (SNR) confirmed that electroplating the tetrode surface with AuNPs and PEDOT improved the recording performance, and these parameters could be used to effectively quantify the spikes of each cluster.
Animals ; Brain ; Dextrans ; Dielectric Spectroscopy ; Electric Impedance ; Electrodes ; Electroplating ; Microelectrodes ; Nanoparticles* ; Neurons ; Rats ; Thalamus

There is no well-stated practical guideline for mechanically ventilated patients with or without acute respiratory distress syndrome (ARDS). We generate strong (1) and weak (2) grade of recommendations based on high (A), moderate (B) and low (C) grade in the quality of evidence. In patients with ARDS, we recommend low tidal volume ventilation (1A) and prone position if it is not contraindicated (1B) to reduce their mortality. However, we did not support high-frequency oscillatory ventilation (1B) and inhaled nitric oxide (1A) as a standard treatment. We also suggest high positive end-expiratory pressure (2B), extracorporeal membrane oxygenation as a rescue therapy (2C), and neuromuscular blockage for 48 hours after starting mechanical ventilation (2B). The application of recruitment maneuver may reduce mortality (2B), however, the use of systemic steroids cannot reduce mortality (2B). In mechanically ventilated patients, we recommend light sedation (1B) and low tidal volume even without ARDS (1B) and suggest lung protective ventilation strategy during the operation to lower the incidence of lung complications including ARDS (2B). Early tracheostomy in mechanically ventilated patients can be performed only in limited patients (2A). In conclusion, of 12 recommendations, nine were in the management of ARDS, and three for mechanically ventilated patients.
Extracorporeal Membrane Oxygenation ; Humans ; Incidence ; Lung ; Mortality ; Nitric Oxide ; Positive-Pressure Respiration ; Prone Position ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult* ; Steroids ; Tidal Volume ; Tracheostomy ; Ventilation ; Ventilators, Mechanical