Autophagy is a process of eliminating damaged or unnecessary proteins and organelles, thereby maintaining intracellular homeostasis. Deregulation of autophagy is associated with several diseases including cancer. Contradictory dual roles of autophagy have been well established in cancer. Cytoprotective mechanism of autophagy has been extensively investigated for overcoming resistance to cancer therapies including radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Selective autophagy inhibitors that directly target autophagic process have been developed for cancer treatment. Efficacies of autophagy inhibitors have been tested in various pre-clinical cancer animal models. Combination therapies of autophagy inhibitors with chemotherapeutics are being evaluated in clinal trials. In this review, we will focus on genetical and pharmacological perturbations of autophagy-related proteins in different steps of autophagic process and their therapeutic benefits. We will also summarize combination therapies of autophagy inhibitors with chemotherapies and their outcomes in pre-clinical and clinical studies. Understanding of current knowledge of development, progress, and application of cytoprotective autophagy inhibitors in combination therapies will open new possibilities for overcoming drug resistance and improving clinical outcomes.

Purpose: Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. Materials and Methods: Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. Results: Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC50of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC50 of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.

OBJECTIVE: Patients with low acuity who need hospitalization may be at risk if they do not receive proper treatment in overcrowded emergency rooms. This study was conducted to investigate factors affecting the hospitalization of patients with low acuity of Korean Triage and Acuity Scale (KTAS). METHODS: This study was a retrospective chart review analysis of patients aged 15 years or older who had triaged as KTAS 4 and 5 grades when visiting a local emergency medical center from January 1, 2016 to December 31, 2017. Multivariate logistic analysis was performed to analyze the effects of age, sex, reasons for visiting, visiting route, ambulance utilization, KTAS grade and major category on patient admission. RESULTS: A total of 10,540 patients were enrolled and the odds ratio (OR) increased with age from those aged over 34 years (P < 0.001). Patients that triaged as KTAS grade 5 (adjusted OR, 1.57; 95% confidence interval [CI], 1.36–1.82), had a condition caused by disease (adjusted OR, 2.31; 95% CI, 2.00–2.68), and visited by using an ambulance (public: adjusted OR, 1.05; 95% CI, 0.91–1.22; private: adjusted OR, 4.60; 95% CI, 3.85–5.49) were more likely to be hospitalized. Individuals in the “general” major category were more likely to be hospitalized than those falling into other major categories (P < 0.001). CONCLUSION: The factors influencing the hospitalization of patients with low acuity were age, reasons for visiting, visiting route, ambulance utilization, KTAS grade and major category on patient admission.
Accidental Falls ; Ambulances ; Emergencies* ; Emergency Service, Hospital* ; Hospitalization ; Humans ; Odds Ratio ; Patient Admission ; Retrospective Studies ; Risk Factors ; Triage

PURPOSE: Korean Acuity and Triage Scale (KTAS) has been used nationally since 2016 for triage in emergency departments. After the newly developed triage tool was applied, there have been few studies of the validity of pediatric KTAS. The purpose of this study was to evaluate the validity of KTAS in children under the age of 15 who visited a single children's hospital. METHODS: This retrospective study was conducted on 7,011 pediatric patients under the age of 15 who visited a single child hospital between January 1 and December 31, 2016, the difference in the admission rate, intensive care unit admission rate, length of stay in the emergency department, and total hospital cost in emergency department were analyzed using the KTAS level. RESULTS: The number of patients triaged as KTAS IV was highest with 48.2%. The length of stay was longest in KTAS I and shortest in KTAS V. The medical cost in emergency department was highest in KTAS I and lowest in KTAS V. All dependent variables except for the intensive care unit admission rate showed significant differences according to the KTAS level. CONCLUSION: When the KTAS of the newly developed five level triage system was applied to pediatric patients, there were statistically significant difference in hospitalization, length of stay in emergency department, and total cost to the emergency department according to the KTAS level. Therefore, it will be necessary to evaluate the validity of KTAS through multicenter studies including hospitals with various characteristics.
Child ; Emergencies* ; Emergency Service, Hospital* ; Hospital Costs ; Hospitalization ; Humans ; Intensive Care Units ; Length of Stay ; Retrospective Studies ; Triage*

PURPOSE: In Korea, emergency department overcrowding in large hospitals have caused social concern. Moreover, patients with low socioeconomic status visit the emergency department more frequently. This kind of visitation also causes a burden on the national budget, but emergent patient should be treated in emergency department regardless of economic state. So, on establishment of policy about the patient with low socioeconomic status, the frequency of emergency visitation alone is difficult to obtain a sufficient basis for policy-making. METHODS: We retrospectively analyzed adult patients with a disease who visited the Pusan Wide-regional Emergency Center in 2015. Korean Triage and Acuity Scale level I, II or III were defined as emergency, and level IV or V was defined as non-emergency. The ratio of emergency and non-emergency was compared in the National Health Insurance and Medicaid database. RESULTS: The number of patients with National Health Insurance was 16,208 (90.3%) and with Medicaid was 1,737 (9.7%). Among those with National Health Insurance, there were 12,720 (78.5%) emergency cases and 3,488 (21.5%) non-emergency cases. Among those with Medicaid, 1,379 (79.4%) emergency cases and 358 (20.6%) non-emergency cases. Between National Health Insurance and Medicaid, there was no statistically significant difference in the ratio of emergency and non-emergency (p=0.380) CONCLUSION: Accessibility of emergency and non-emergency patients with National Health Insurance and Medicaid to Pusan Wide-regional Emergency Center was not different.
Adult ; Budgets ; Busan ; Emergencies* ; Emergency Service, Hospital ; Humans ; Insurance Coverage* ; Insurance* ; Korea ; Medicaid ; National Health Programs ; Retrospective Studies ; Social Class ; Triage

PURPOSE: To analyze delayed diagnosis, we collected date on pediatric and adolescent patients who had been admitted to the Emergency Department with injuries due to minor trauma METHODS: We retrospectively analyzed the age distribution, trauma mechanism, time interval for each affected body region at delayed diagnosis, hospital stay, and outcome for 161 pediatric and adolescent patients who had been admitted to the Emergent Department of Gachon University Gil Hospital from January 2006 to September 2008. RESULTS: The incidence of delayed diagnosis in pediatric and adolescent trauma was 11.8% in our retrospective review of 161 pediatric and adolescent patients. Lengths of hospitalization were longer in patients with delayed diagnosis (p<0.05). Patients with delayed diagnosis were more often transferred to other hospitals than patients with non-delayed diagnosis (p<0.05). The time intervals for each different affected body regions at delayed diagnosis were significantly different, but the hospital stays were not. There were no statistical significance to age on affected body region. CONCLUSION: From this study, we found that admission result and hospital stay were statistically significant differences between the delayed-diagnosis patient group and the non-delayed-diagnosis patient group. Finally, we must follow up pediatric and adolescent patients with minor trauma, closely considering missed injuries.
Adolescent ; Age Distribution ; Body Regions ; Delayed Diagnosis ; Emergencies ; Follow-Up Studies ; Hospitalization ; Humans ; Incidence ; Length of Stay ; Pediatrics ; Retrospective Studies

No abstract available.

BACKGROUND: A diagnosis of coronary artery disease (CAD) in the early phase of acute chest pain is often difficult in an emergency department (ED) due to the lower sensitive ECG and delayed expression of the cardiac necrosis markers. Ischemia modified albumin (IMA) has recently been reported to be an early sensitive biochemical marker of ischemia. The aim of this study was to evaluate the diagnostic value of IMA in patients with suspected CAD and less sensitive ECG/delayed cardiac necrosis markers. METHODS: 100 consecutive patients (mean age: 5413 years, male: 66%) presenting to the ED with suspected CAD and chest pain within 6 hours of chest pain were enrolled in this study. An ECG check and blood sampling for IMA and CK-MB, cardiac troponin-T (TnT) were done within 1 hour at the ED. The diagnosis of CAD was based upon the clinical findings, results of serial ECG/TnT and coronary angiography. The ideal cutoff value of IMA for CAD was calculated by the Receiver Operator Characteristic (ROC) curve analysis. RESULTS: CAD including acute coronary syndrome was diagnosed in 69/100 (69%). The optimum diagnostic cutoff point for the IMA levels in these study populations was found by ROC analysis to be 99.5 U/mL. The ROC curve area for the IMA test was 0.901 (95% confidential interval, 0.840-0.961, p=0.001). The IMA levels >99.5 U/mL demonstrated a sensitivity of 86%, specificity of 81%, positive predictive value of 90% and negative predictive value of 74% for the diagnosis of CAD. The combination of IMA-ECG-CKMB/TnT increased the sensitivity for detecting ischemia to 94%, with a negative predictive value of 85%. IMA is a highly sensitive with a high negative predictive value, and might improve the utility of standard biomarkers for CAD. CONCLUSIONS: IMA might be a useful ischemic marker of coronary artery disease in patients presenting within 6 hours after the onset of chest pain.
Acute Coronary Syndrome ; Biomarkers ; Chest Pain* ; Coronary Angiography ; Coronary Artery Disease* ; Coronary Vessels* ; Diagnosis ; Electrocardiography ; Emergencies* ; Emergency Service, Hospital* ; Humans ; Ischemia* ; Male ; Necrosis ; ROC Curve ; Sensitivity and Specificity ; Thorax* ; Troponin T

Vascular catheters are associated with complications such as infection, thrombosis and stenosis. The embolization of a venous catheter fragment is a rare complication. A 39-year-old woman underwent placement of a totally implantable venous access device for chemotherapy to treat a recurrent liposarcoma of the left thigh. The "pinch-off sign" was noted on a routine chest X-ray but that was ignored. Three-months after implantation of the intravenous access device, the indwelling central catheter was fractured and embolized to the pulmonary trunk. The catheter in the pulmonary trunk was successfully removed through a percutaneous femoral vein approach using a pigtail catheter and goose neck snare.
Thigh/pathology ; Pulmonary Artery/*injuries/surgery ; Liposarcoma/drug therapy ; Humans ; Foreign-Body Migration/*complications/surgery ; Female ; *Equipment Failure ; Embolism/*etiology/surgery ; Catheters, Indwelling/*adverse effects ; Catheterization, Central Venous/*adverse effects/instrumentation ; Adult