Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Purpose: The incidence and prognostic implications of atrial fibrillation (AF) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are controversial, especially for Korean patients. Furthermore, the pattern of antithrombotic therapy for these patients is unknown. The present study sought to identify the impact of AF on Korean patients undergoing TAVI and demonstrate the status of antithrombotic therapy for these patients. Materials and Methods: A total of 660 patients who underwent TAVI for severe AS were recruited from the nationwide K-TAVI registry in Korea. The enrolled patients were stratified into sinus rhythm (SR) and AF groups. The primary endpoint was all-cause death at 1-year. Results: AF was recorded in 135 patients [pre-existing AF 108 (16.4%) and new-onset AF 27 (4.1%)]. The rate of all-cause death at 1 year was significantly higher in patients with AF than in those with SR [16.2% vs. 6.4%, adjusted hazard ratio (HR): 2.207, 95% confidence interval (CI): 1.182–4.120, p=0.013], regardless of the onset timing of AF. The rate of new pacemaker insertion at 1 year was also significantly higher in patients with AF than in those with SR (14.0% vs. 5.5%, adjusted HR: 3.137, 95%CI: 1.621–6.071, p=0.001).Among AF patients, substantial number of patients received the combination of multiple antithrombotic agents (77.8%), and the most common combination was that of aspirin and clopidogrel (38.1%). Conclusion AF was an independent predictor of 1-year mortality and new pacemaker insertion in Korean patients undergoing TAVI.

Objective: We evaluated the incidence of newly diagnosed gestational diabetes mellitus (GDM) during the 3rd trimester in women with suspected large for gestational age (LGA) fetuses on ultrasound and assessed their perinatal outcomes. Methods: A retrospective cohort study was performed. Singleton pregnant women with suspected LGA on the 3rd trimester ultrasound and whose results of GDM screening at midpregnancy had been normal were enrolled. All participants were retested with 100-g oral glucose tolerance test (OGTT) within 2 days after diagnosis of LGA. We compared perinatal outcomes between the newly diagnosed with GDM group and the non-GDM group. Results: Among 169 pregnant women, 13% (23/169) were newly diagnosed with GDM. The women in the GDM group had a higher HbA1c level at diagnosis (5.8 vs. 5.3, P<0.01) and earlier gestational age at delivery (38.0 vs 38.9 weeks of gestation, P=0.003) than those in the non-GDM group. The rate of cesarean delivery (CD) was significantly higher in the GDM group than that in the non-GDM group (73.9%, vs. 49.3%, P=0.028) with similar proportions for the indications of CD except CD on maternal request (CDMR). The CDMR rate was higher in the GDM group than nonGDM group (41.2% vs. 23.6%) but it did not reach statistical significance. There were no significant differences in the obstetrical and neonatal complications between the two groups. Conclusion Among pregnant women with suspected LGA, 13% were newly diagnosed with GDM in late pregnancy. Nonetheless, there were no differences in the perinatal outcomes between women with newly diagnosed GDM and those without GDM. However, concerns over shoulder dystocia appear to increase CD rates in the GDM group.

Objective: This study examined the characteristics of the patients taking poison intentionally at the pre-hospital stage to prevent it at the community level. Methods: We retrospectively reviewed the data that had been reported to fire stations from January 2017 to December 2018. This data included sex, age, occupation, the season of the year, time, place, methods, alcohol ingestion, transferred to the hospital or not, and we examined how taking poison had an effect on the suicide success rate. Results: The subjects were a total of 1,356 patients who had been reported to fire stations due to intentionally taking poison. Forty-five point five percent of them were male, and 54.5% were female. The most common method of intentional taking poison was sedatives (58.3%), followed by pesticides (24.6%), antidepressants (19.0%), and other methods (12.6%). The home place was preferred more than any other places. The suicide success rate was 2.1% in males and 1.4% in females. For the age groups, those patients 40-64 years old tried taking poison much more than the other age groups. In the aspect of the season of the year, summer was the highest season for taking poison, at 30.3%. The daytime was more preferred than the night time. Conclusion In this study, we analyzed the characteristics of the pre-hospital intentional poisoning cases according to gender, age, occupation, season of the year, time, and between the transferred and the untransferred groups. Efforts should be made in cooperation with the community to prevent suicide attempts by intentionally taking poison.

Objective: We evaluated the incidence of newly diagnosed gestational diabetes mellitus (GDM) during the 3rd trimester in women with suspected large for gestational age (LGA) fetuses on ultrasound and assessed their perinatal outcomes. Methods: A retrospective cohort study was performed. Singleton pregnant women with suspected LGA on the 3rd trimester ultrasound and whose results of GDM screening at midpregnancy had been normal were enrolled. All participants were retested with 100-g oral glucose tolerance test (OGTT) within 2 days after diagnosis of LGA. We compared perinatal outcomes between the newly diagnosed with GDM group and the non-GDM group. Results: Among 169 pregnant women, 13% (23/169) were newly diagnosed with GDM. The women in the GDM group had a higher HbA1c level at diagnosis (5.8 vs. 5.3, P<0.01) and earlier gestational age at delivery (38.0 vs 38.9 weeks of gestation, P=0.003) than those in the non-GDM group. The rate of cesarean delivery (CD) was significantly higher in the GDM group than that in the non-GDM group (73.9%, vs. 49.3%, P=0.028) with similar proportions for the indications of CD except CD on maternal request (CDMR). The CDMR rate was higher in the GDM group than nonGDM group (41.2% vs. 23.6%) but it did not reach statistical significance. There were no significant differences in the obstetrical and neonatal complications between the two groups. Conclusion Among pregnant women with suspected LGA, 13% were newly diagnosed with GDM in late pregnancy. Nonetheless, there were no differences in the perinatal outcomes between women with newly diagnosed GDM and those without GDM. However, concerns over shoulder dystocia appear to increase CD rates in the GDM group.

The Acknowledgements was published incorrectly. The authors apologize for any inconvenience that it may have caused.

OBJECTIVE: This study was conducted to determine the effectiveness and safety of medical treatment with sublingual misoprostol (MS) in the 1st trimester miscarriage under the approval by Health Insurance Review and Assessment Service (HIRA) for off-label usage by the single medical center in Korea. METHODS: A retrospective cohort study was performed in one institution between April 2013 and June 2016. Ninety-one patients diagnosed with miscarriage before 14 weeks of gestation and wanted to try medical treatment were included. A detailed ultrasound scan was performed to confirm the diagnosis. Patients took 600 microgram (mcg) of MS sublingually at initial dose, and repeated the same dose 4–6 hours apart. Successful medical abortion was defined as spontaneous expulsion of gestational products (including gestational sac, embryo, fetus, and placenta). If gestational products were not expelled, surgical evacuation was performed at least 24 hours later from the initial dose. Information about side effects was obtained by medical records. RESULTS: About two-thirds of patients had a successful outcome. The median interval time from pill to expulsion was 18 hours in the successful medical treatment group. There was no serious systemic side effect or massive vaginal bleeding. Presence or absence of vaginal spotting before diagnosis of miscarriage, uterine leiomyomas, subchorionic hematoma, or distorted shape of gestational sac on ultrasound scan were not statistically different between the two groups. CONCLUSION: Medical treatment with sublingual MS can be a proper option for the 1st trimester miscarriage, especially for the patient who want to avoid surgical procedure. We can reduce the unnecessary sedation or surgical intervention in the patients with the 1st trimester miscarriage.
Abortion, Incomplete ; Abortion, Missed ; Abortion, Spontaneous* ; Administration, Sublingual ; Cohort Studies ; Diagnosis ; Embryonic Structures ; Female ; Fetus ; Gestational Sac ; Hematoma ; Humans ; Insurance, Health ; Korea* ; Leiomyoma ; Medical Records ; Metrorrhagia ; Misoprostol* ; Off-Label Use* ; Pregnancy ; Retrospective Studies ; Ultrasonography ; Uterine Hemorrhage

OBJECTIVES: The objective of this study was to investigate the relationship between the level of Electronic Medical Record (EMR) system adoption and healthcare information technology (IT) infrastructure. METHODS: Both survey and various healthcare administrative datasets in Korea were used. The survey was conducted during the period from June 13 to September 25, 2017. The chief information officers of hospitals were respondents. Among them, 257 general hospitals and 273 small hospitals were analyzed. A logistic regression analysis was conducted using the SAS program. RESULTS: The odds of having full EMR systems in general hospitals statistically significantly increased as the number of IT department staff members increased (odds ratio [OR] = 1.058, confidence interval [CI], 1.003–1.115; p = 0.038). The odds of having full EMR systems was significantly higher for small hospitals that had an IT department than those of small hospitals with no IT department (OR = 1.325; CI, 1.150–1.525; p < 0.001). Full EMR system adoption had a positive relationship with IT infrastructure in both general hospitals and small hospitals, which was statistically significant in small hospitals. The odds of having full EMR systems for small hospitals increased as IT infrastructure increased after controlling the covariates (OR = 1.527; CI, 1.317–4.135; p = 0.004). CONCLUSIONS: This study verified that full EMR adoption was closely associated with IT infrastructure, such as organizational structure, human resources, and various IT subsystems. This finding suggests that political support related to these areas is indeed necessary for the fast dispersion of EMR systems into the healthcare industry.
Dataset ; Delivery of Health Care* ; Electronic Health Records* ; Health Care Sector ; Hospitals, General ; Humans ; Korea ; Logistic Models ; Surveys and Questionnaires

OBJECTIVE: Pregnancy is a major risk factor of thromboembolism, and the patients with preeclampsia (PE) are known to have higher risk of thromboembolic complications than normal pregnant women. D-dimer is a well-established laboratory marker for the screening of venous thromboembolism (VTE), but the concentrations of d-dimer tend to increase physiologically in pregnant women throughout the gestational age. We performed this study to evaluate the clinical significance of d-dimer concentrations in patients with gestational hypertensive disorders (GHD) according to the severity. METHODS: Retrospective cohort study was performed in one institution. Singleton pregnant women with GHD were enrolled, and their antepartum concentrations of d-dimer were measured as a part of routine evaluation for patients suspected with PE. Patients with multiple gestations, rheumatic diseases, autoimmune diseases, or suspected VTE were excluded. A categorization of severity about PE was based on the general criteria. RESULTS: In 73.3% of study population, their d-dimer concentrations exceeded the normal range (>0.55 mg/L). A significantly greater proportion of pregnant women had excessive concentrations of d-dimer in the severe GHD than in the non-severe GHD (89.8% vs. 53.7%; P<0.01). Patients with severe GHD had significantly higher median concentrations of d-dimer than those with non-severe GHD (median [range], 2.00 mg/L [0.11 to 7.49] vs. 0.71 mg/L [0.09 to 5.39]; P<0.01) although their earlier gestational ages of sampling. CONCLUSION: Maternal concentrations of d-dimer were significantly elevated in patients with severe features than those without severe features among those with GHD. Some pregnant women with GHD can have markedly elevated concentrations of d-dimer without any evidence of current VTE.
Autoimmune Diseases ; Biomarkers ; Cohort Studies ; Female ; Gestational Age ; Humans ; Hypertension, Pregnancy-Induced ; Mass Screening ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Reference Values ; Retrospective Studies ; Rheumatic Diseases ; Risk Factors ; Thromboembolism ; Venous Thromboembolism

Endoscopic Retrograde Cholangiopancreatography (ERCP) is an essential endoscopic technique in diagnosis and treatment of pancreatobiliary diseases. Although its diagnostic role is decreasing because of less invasive modalities such as magnetic resonance cholangiopancreatography or endoscopic ultrasound, it is still very important in treatment of pancreatobiliary diseases. However, there is a trend of hesitation to learn ERCP by the fellows in Korea because of following reasons; concentration of ERCP in a few high volume centers, high risk of post-procedural complications, and long training courses. In this background, the education committee of Korean Pancreatobiliary Association has prepared for ERCP educational guidelines for fellows in Korea. This guideline should be helpful to fellows who are currently under the training.
Cholangiopancreatography, Endoscopic Retrograde* ; Cholangiopancreatography, Magnetic Resonance ; Diagnosis ; Education ; Fellowships and Scholarships ; Korea ; Ultrasonography