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.

Objective: This study investigated the feasibility and prognostic relevance of threshold-based quantification of myocardial delayed enhancement (MDE) on CT in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods: Forty-three patients with NIDCM (59.3 ± 17.1 years; 21 male) were included in the study and underwent cardiac CT and MRI. MDE was quantified manually and with a threshold-based quantification method using cutoffs of 2, 3, and 4 standard deviations (SDs) on three sets of CT images (100 kVp, 120 kVp, and 70 keV). Interobserver agreement in MDE quantification was assessed using the intraclass correlation coefficient (ICC). Agreement between CT and MRI was evaluated using the Bland-Altman method and the concordance correlation coefficient (CCC). Patients were followed up for the subsequent occurrence of the primary composite outcome, including cardiac death, heart transplantation, heart failure hospitalization, or appropriate use of an implantable cardioverter-defibrillator. The Kaplan–Meier method was used to estimate event-free survival according to MDE levels. Results: Late gadolinium enhancement (LGE) was observed in 29 patients (67%, 29/43), and the mean LGE found with the 5-SD threshold was 4.1% ± 3.6%. The 4-SD threshold on 70-keV CT showed excellent interobserver agreement (ICC = 0.810) and the highest concordance with MRI (CCC = 0.803). This method also yielded the smallest bias with the narrowest range of 95% limits of agreement compared to MRI (bias, -0.119%; 95% limits of agreement, -4.216% to 3.978%). During a median follow-up of 1625 days (interquartile range, 712–1430 days), 10 patients (23%, 10/43) experienced the primary composite outcome. Event-free survival significantly differed between risk subgroups divided by the optimal MDE cutoff of 4.3% (log-rank P = 0.005). Conclusion The 4-SD threshold on 70-keV monochromatic CT yielded results comparable to those of MRI for quantifying MDE as a marker of myocardial fibrosis, which showed prognostic value in patients with NIDCM.

Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. Conclusions TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea

40 years or new hires with less than 1 year of service.]]>
Brain ; Cardiovascular Diseases ; Cohort Studies ; Firefighters ; Follow-Up Studies ; Health Surveys ; Hospitals, University ; Humans ; Killer Cells, Natural ; Korea ; Magnetic Resonance Imaging ; Mental Disorders ; Mental Health ; Neuropsychological Tests ; Polycyclic Hydrocarbons, Aromatic ; Prospective Studies ; Republic of Korea ; Risk Factors

Purpose: Quality of life (QOL) has become important in the trend of emphasizing patient satisfaction. This study aimed to evaluate the QOL in patients who underwent laparoscopic or robotic gastrectomy for gastric cancer. Methods: A prospective trial was performed involving patients who underwent laparoscopic or robotic gastrectomy for primary gastric cancer at 11 hospitals in Korea. Within this comparative trial, QOL, postoperative pain, and long-term complications were exanimated. The quality-of-life questionnaire (QLQ)-C30 and QLQ-STO22 developed by the European Organization for Research and Treatment of Cancer were used for the QOL survey. We compared the data after dividing it into several types of characteristics as follows; device (robotic or laparoscopic), operation type, pathological stage, and sex.Biased components were extracted by logistic regression analysis. Propensity score matching was applied to the data set with the biased components. Results: In total, 434 patients (211 for laparoscopic surgery and 223 for robotic surgery) were enrolled, out of which 321 patients who responded to both preoperative and postoperative surveys were selected for analysis. Robotic gastrectomy was not different from laparoscopic gastrectomy with respect to postoperative QOL. Distal gastrectomy showed better scores than total gastrectomy in terms of role functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, constipation, financial difficulties, dysphagia, eating restrictions, anxiety, taste, and body image. Male patients showed better scores on the 19 scales compared to female patients. Conclusion Robotic and laparoscopic approaches for gastric cancer surgery did not differ from each other with respect to QOL. Distal gastrectomy resulted in better QOL than total gastrectomy.

OBJECTIVES: Many of the patients with type 2 diabetes are associated with sleep problems, and the rate of insomnia is known to be higher in the general population. The aims of this study were to know the frequency and clnical characteristics of insomnia, and related variables to insomnia in patients diagnosed with type 2 diabetes. METHODS: For 99 patients from 18 to 80 years of age (65 males and 34 females) with type 2 diabetes, interviews were performed. Total sleep time and sleep latency was evaluated. Insomnia was evaluated using the Korean Version of the Insomnia Severity Index (ISI-K). Severity of depressive symptoms were evaluted using the Korean version of the Hamilton Depression Scale (K-HDRM). According to the cutoff score of 15.5 on the ISI-K, subjects were divided into the group of type 2 diabetics with insomnia (N=34) and those without insomnia (N=65) at first, and then statistically analyzed. RESULTS: TInsomnia could be found in 34.34% of type 2 diabetics. Type 2 diabetics with insomnia had significantly more single or divorced (respectively 11.8%, p<0.05), higher total scores of the K-HDRS (11.76±5.52, p<0.001), shorter total sleep time (5.35±2.00 hours, p<0.001), and longer sleep latency (50.29±33.80 minutes, p<0.001). The all item scores of the ISI-K in type 2 diabetics with insomnia were significantly higher than those in type 2 diabetics without insomnia, that is, total (18.38±2.69), A1 (Initial insomnia) (2.97±0.76), A2 (Middle insomnia) (3.06±0.69), A3 (Terminal insomnia) (2.76±0.61), B (Satisfaction) (3.18±0.72), C (Interference) (2.09±0.97), D (Noticeability) (2.12±1.09) and E (Distress) (2.21±0.81) (respectively p<0.001). Variables associated with insomnia in type 2 diabetics were as following. Age had significant negative correlation with A3 items of the ISI-K (β=−0.241, p<0.05). Total scores of the K-HDRS had significant positive correlation, while total sleep time had significant negative correlation with all items of the ISI-K (respectively p<0.05). Sleep latency had significant positive correlation with total,, A1, B and E item scores of the ISI-K (respectively p<0.05). CONCLUSIONS: Insomnia was found in about 1/3 of type 2 diabetics. According to the presence of insomnia, clinical characteristics including sleep quality as well as quantity seemed to be different. Because depression seemed to be correlated with insomnia, clinicians should pay attention to early detection and intervention of depression among type 2 diabetics
Depression ; Divorce ; Humans ; Male ; Sleep Initiation and Maintenance Disorders

OBJECTIVES: The aims of this study were to know the frequency and the nature of cognitive dysfunction in type 2 diabetics, and to reveal influencing variables on it. METHODS: From eighty type 2 diabetics (42 males and 38 females), demographic and clinical data were obtained by structured interviews. Cognitive functions were measured using the MMSE-K (Korean Version of the Mini-Mental State Examination) and the Korean Version of the Montreal Cognitive Assessment (MoCA-K) tests. Severity of depression was evaluated by the Korean Version of the Hamilton Depression Rating Scale (K-HDRS). RESULTS: 1) Among eighty type 2 diabetics, 13.75% were below 24 on the MMSE-K, while 38.8% were below 22 on the MoCA-K. 2) The total scores and subtest scores of the MoCA-K including visuospatial/executive, attention, language, delayed recall and orientation were significantly lower in type 2 diabetics with cognitive dysfunction (N=31) than those without cognitive dysfunction (N=49) (p < 0.001, respectively). 3) There were significant difference between type 2 diabetics with and those without cognitive dysfunction in age, education, economic status, body mass index, duration of diabetes, total scores of the K-HDRS, the MMSE-K and the MoCA-K (p < 0.05, respectively). 4) The total scores of the MoCA-K had significant correlation with age, education, body mass index, family history of diabetes, duration of diabetes, total scores of the K-HDRS (p < 0.05, respectively). 5) The risks of cognitive dysfunction in type 2 diabetics were significantly influenced by sex, education, fasting plasma glucose and depression. CONCLUSIONS: The cognitive dysfunction in type 2 diabetics seemed to be related to multiple factors. Therefore, more comprehensive biopsychosocial approaches needed for diagnosis and management of type 2 diabetes.
Blood Glucose ; Body Mass Index ; Cognition ; Depression ; Diagnosis ; Education ; Fasting ; Humans ; Male

PURPOSE: The information committee of the Korean Society for Metabolic and Bariatric Surgery (KSMBS) performed the nationwide survey of bariatric and metabolic operations to report IFSO (International Federation for the Surgery of Obesity and Metabolic Disorders) worldwide survey annually. This study aimed to report the trends of bariatric and metabolic surgery in Korea in 2014–2017. MATERIALS AND METHODS: We analyzed the accumulated nationwide survey data conducted for annual ISFO survey from 2014 to 2017. Trends such as the number of operations by hospital type and the number of operations by surgical method were analyzed. RESULTS: The number of operations has decreased sharply in 2015 comparing to 2014 (913⇒550). The number of operations performed in private hospitals dropped sharply from 529 to 250, 198, and 103 cases. The number of revisional surgeries increased to 223 in 2015. The primary surgery number fell from 757 in 2014 to 327 in 2015. In primary surgery, sleeve gastrectomy was gradually increased from 2014 to 143 (18.9%), 105 (32.1%), 167 (47.2%) and 200 (56.3%) and became the most frequently performed surgery. On the other hand, the incidence of adjustable gastric band decreased gradually from 439 (58.0%) to 117 (35.8%), 112 (31.6%) and 59 (16.6%). CONCLUSION: The overall number of obesity metabolic operations has decreased since 2014, especially the number of adjustable gastric band, and the number of operations in private hospitals declined sharply. On the other hand, the number of operations in university hospitals did not change much, and the number of sleeve gastrectomy increased.
Bariatric Surgery ; Gastrectomy ; Hand ; Hospitals, Private ; Hospitals, University ; Incidence ; Korea ; Methods ; Obesity

OBJECTIVES: The aims of this study were to know the frequency of cognitive dysfunction among patients with autoimmune thyroid disorders, and to reveal influencing factors on it, especially to clarify association with autoimmune thyroid antibodies. METHODS: From sixty-five female patients with autoimmune thyroid disorders, demographic data were obtained by structured interview. Their cognitive funtions were measured using the MMSE-K and the MoCA-K tests. Depression was evaluated by the K-HDRS. RESULTS: 1) Among patients with autoimmune thyroid disorders, 7.69% of them were below 24 on the MMSE-K, while 10.77% were below 22 on the MoCA-K. The frequency of cognitive deficit was not significantly different according to having positivity to antimicrosomal antibodies or not. 2) The antimicrosomal antibody-positive patients had significantly higher antithyroglobulin antibody titers, antimicrosomal antibody titers, and TSH concentration, while had significantly lower free T4 levels(p<0.05, respectively). 3) The total scores of the MMSE-K and the MoCA-K had significant correlation with age, marital status, antithyroglobulin antibody titers and K-HDRS(p<0.05, respectively). 4) The regression analysis revealed that variables such as age, education, autoimmune thyroid antibodies, thyroid function and depression did not influence on cognitive function of patients with autoimmune thyroid disorders. CONCLUSIONS: Our results could not support that cognitive function of patients with autoimmune thyroid disorders had correlation with autoimmune thyroid antibodies.
Antibodies ; Cognition ; Cognition Disorders ; Depression ; Education ; Female ; Humans ; Marital Status ; Thyroid Gland*

OBJECTIVE: Magnetic resonance imaging (MRI) is useful for staging endometrial cancer. The treatment and prognosis of MRI-invisible endometrial cancer remain unclear. The purpose of this study was to retrospectively evaluate the long-term outcomes of patients with MRI-invisible endometrial cancer. METHODS: Between February 1995 and December 2011, we reviewed the medical records of 433 patients with endometrial cancer, which was staged IA on MRI. Of these patients, 89 had MRI-invisible cancer and 344 had MRI-visible cancer. Both cancers were treated with simple hysterectomy with or without lymph node dissection according to the surgeon's decision. Both cancers were compared regarding pathologic findings, recurrence rates, and survival rates. RESULTS: The median sizes of MRI-invisible and MRI-visible cancers were 4 mm (0 to 40 mm) and 20 mm (0 to 89 mm), respectively (p<0.001). Myometrial invasion of these groups were detected in 20.2% (18/89) and 56.7% (195/344), respectively (p<0.001). Lymphadenectomy and follow-up imaging revealed no lymph node metastasis in patients with MRI-invisible cancers, while those revealed in 4.7% (16/344) of patients with MRI-visible cancers (p=0.052). The recurrence rates of MRI-invisible and MRI-visible cancers were 1.1% (1/89) and 7.8% (27/344), respectively (p=0.026). The recurrence-free survival rates of these groups were 98.9% (88/89) and 91.6% (315/344), respectively (p=0.022). CONCLUSION: MRI-invisible endometrial cancer can be treated with less invasive surgery because of its lower tumor burden and better prognosis. This cancer may not require lymphadenectomy because of no metastasis or recurrence in lymph nodes.
Adult ; Aged ; Aged, 80 and over ; Endometrial Neoplasms/diagnostic imaging/*pathology ; Female ; Humans ; Lymphatic Metastasis ; *Magnetic Resonance Imaging ; Middle Aged ; Retrospective Studies