Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

Purpose: Triple-negative breast cancer (TNBC) has been associated with worse prognosis, and biomarkers are needed to identify high-risk patients who may benefit from clinical trials or escalated treatment after completion of standard treatment. We aimed to assess whether the post-treatment neutrophil-to-lymphocyte ratio (NLR) can reflect patient prognosis and determine the follow-up period that can provide the most feasible data. Methods: In this retrospective analysis involving patients with TNBC, clinicopathological data, including those on peripheral complete blood cell count, were collected. The prognostic powers of serial NLRs obtained at baseline and after treatment completion were compared. Kaplan-Meier curves were generated to compare the overall survival (OS) and distant disease-free survival (DDFS). Results: In total, 210 patients were enrolled. Forty-three (20.5%) events were detected. Twothirds of the events (29/43) were related to breast cancer. Most recurrent breast cancer-related diseases (27/29) were detected within 5 years of the initial diagnosis. In contrast, half of the events due to secondary malignancies or non-breast-related diseases (7/14) occurred 5 years after the initial diagnosis. Comparison of the prognostic performance of NLRs at baseline and at 6, 12, and 24 months after treatment completion revealed the strongest prognostic performance at 6 months after treatment completion (area under the curve = 0.745). The high NLR group (NLR >2.47) showed worse OS (p = 0.006) and DDFS (p < 0.001) than low NLR group. Conclusion Elevated post-treatment NLR was significantly associated with worse survival in patients with TNBC. We believe that it can be a useful surrogate marker for identifying highrisk patients with TNBC.

Background/Aims: Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database. Methods: This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]). Results: The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS. Conclusions Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.

No abstract available.
Adult ; Autoantibodies/*blood ; Gangliosides/blood/*immunology ; Humans ; Male ; Ophthalmoplegia/blood/*diagnosis/immunology ; Recurrence ; Syndrome

PURPOSE: Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. RESULTS: SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. N(G)-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. CONCLUSION: These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ; Acetylcholine ; Arginase* ; Arginine ; Blotting, Western ; Endothelium ; Human Umbilical Vein Endothelial Cells ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase Type III* ; Oxidation-Reduction ; Peroxynitrous Acid ; Phosphorylation* ; Reactive Oxygen Species

BACKGROUND: In surgeries involving the upper extremities and breast, the blood pressure is frequently measured at the ankles. As the blood pressure is used as a pain indicator in the full surgical anesthesia, the ankle blood pressure higher than the brachial blood pressure may be misinterpreted by the anesthesiologist, in determining the depth of the anesthesia. This paper investigated whether the ankle blood pressure is significantly higher than the brachial blood pressure before the anesthesia induction, during induction, and after tracheal intubation. METHODS: Two hundred seventeen patients requiring general anesthesia for elective surgery were included in this study. Ankle and brachial blood pressure were simultaneously measured before the anesthesia induction, during induction, and after tracheal intubation. RESULTS: The ankle blood pressure was higher than the brachial blood pressure before induction, during induction, and after tracheal intubation. Ankle-brachial blood pressure differences were significantly higher before induction and after intubation as compared to that during induction. The correlation coefficient between the systolic ankle-brachial blood pressure difference before induction and that after tracheal intubation was 0.623. In 33 child patients with an ankle-brachial blood pressure index > or =1 before induction, there were no significant differences in the ankle-brachial blood pressure during induction. The brachial systolic blood pressure could be predicted by simple and multiple regression equations (R2 = 0.349-0.828). CONCLUSIONS: The results of the study suggest that the anesthesiologists need to consider the ankle-brachial blood pressure differences in monitoring the anesthesia, in cases where the brachial blood pressure cannot be measured during surgery.
Anesthesia ; Anesthesia, General ; Animals ; Ankle ; Blood Pressure ; Breast ; Child ; Humans ; Intubation ; Upper Extremity

No abstract available.
Anesthesia ; Thyroid Crisis ; Thyroid Gland

OBJECTIVE: To compare clinicopathologic characteristics and surgical outcomes of laparoscopic surgery in women with endometrial cancer according to body mass index (BMI). METHODS: From June 2009 to October 2010, prospective observational study without randomization of 159 patients treated by laparoscopic surgery from 10 hospitals nationwide. RESULTS: Patients were divided according to the WHO guidelines for Asia-Pacific populations and the distributions of BMI were as follows: 3 patients (1.9%) in underweight (BMI < 18.5 kg/m2), 50 patients (31.4%) in normal weight (BMI, 18.5-22.9 kg/m2), 45 patients (28.3%) in overweight (BMI, 23.0-24.9 kg/m2), 49 patients (30.8%) in obese (BMI, 25.0-29.9 kg/m2), and 12 patients (7.5%) in morbid obese (BMI > or = 30.0 kg/m2). Age, history of previous surgery, surgery extend, and history of previous surgery were not different between non-obese patients (BMI < 25.0 kg/m2) and obese patients (BMI > or = 25.0 kg/m2). Co-morbidities were more common in obese patients but marginally significant (23.5% vs. 37.7%, p=0.072). Four patients (2.5%) were converted to abdominal surgery because of severe adhesion. Regarding to surgical outcomes, operation time was significantly longer in obese patients (199 min vs. 235 min, p=0.013) but blood loss, lymph node yield, hospital stay, Foley removal, transfusion rate and peri-operative complication were not statistically significant. Regarding to pathologic results, there were no difference in terms of lymphovasucular space invasion, tumor grade, histologic type, lymph node metastasis and FIGO stage. CONCLUSION: Clinicopathologic characteristics and surgical outcomes does not seem to be significantly influenced by BMI except operation time. So the laparoscopic approach can be the alternative method for obese patients.
Body Mass Index ; Endometrial Neoplasms ; Female ; Humans ; Laparoscopy ; Length of Stay ; Lymph Nodes ; Neoplasm Metastasis ; Obesity ; Overweight ; Prospective Studies ; Random Allocation ; Thinness

BACKGROUND: The number of cases employing thoracic endovascular aortic repair (TEVAR) has been increasing due to lower morbidity and mortality compared to open repair technique. The aim of this study is to evaluate the outcome of TEVAR for thoracic aortic diseases. MATERIALS AND METHODS: Sixteen patients underwent TEVAR from October 2003 to April 2010. Mean age at operation was 59 years (20~78 years), and 11 were male. Indications for TEVAR were large aortic diameter (>5.5 cm) upon presentation in 6 patients, increasing aortic diameter during the follow-up period in 4, traumatic aortic rupture in 3, persistent chest pain in 2, and ruptured aortic aneurysm in one. The mean diameter, length and the number of the stents were 33 mm (26~40 mm), 12 cm (9.5~16.0 cm), and 1.25 (1~2), respectively. Aortography employing Multi-detector computerized tomography (MDCT) technique was performed at one week, and patients were followed up in the out-patient department at one month, 6 months, and one year postoperatively. RESULTS: Primary technical success showing complete exclusion of the aneurysm was achieved in 15 patients. One patient showed a small endo-leak (type 1). Four patients developed perioperative stroke: Three recovered without sequelae, and one showed mild right-side weakness. There was no operative mortality. Diameter of the thoracic aorta covered by stent graft changed within 10% range in 12 patients, decreased by more than 10% in 3, and increased by more than 10% in one during mean follow-up duration of 18 months (1~73 months). There was no recurrence-related death during this period. CONCLUSION: Intermediate-term outcome after TEVAR was encouraging. Indications for TEVAR could be extended for other thoracic aortic diseases.
Aneurysm ; Aorta ; Aorta, Thoracic ; Aortic Aneurysm ; Aortic Diseases ; Aortic Rupture ; Aortography ; Chest Pain ; Follow-Up Studies ; Humans ; Male ; Outpatients ; Stents ; Transplants