Purpose: Resectable pancreatic ductal adenocarcinoma (PDAC) has a high risk of recurrence after curative resection; despite this, the preoperative risk factors for predicting early recurrence remain unclear. This study therefore aimed to identify preoperative inflammation and nutrition factors associated with early recurrence of resectable PDAC. Methods: From March 2021 to November 2021, a total of 20 patients who underwent curative resection for PDAC were enrolled in this study. We evaluated the risk factors for early recurrence within 1 year by univariate and multivariate analyses using Cox hazard proportional regression. The cutoff values for predicting recurrence were examined using receiver operating characteristic (ROC) curves. Results: In our univariate and multivariate analyses, C-reactive protein (CRP), CRP-albumin ratio, and CRP-prealbumin ratio, as well as sex and age, were significant independent prognostic factors for early recurrence in PDAC. However, known inflammatory factors (neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios), nutritional factors (albumin, prealbumin, ferritin, vitamin D), and inflammatory-nutritional factors (Glasgow Prognostic Score, modified Glasgow Prognostic Score, albumin-bilirubin) showed no association with early recurrence. In addition, using cutoff values by ROC curve analysis, a high preoperative CRP level of >5 mg/L, as well as high CRP-to-albumin (>5.3) and CRP-to-prealbumin (>1.3) ratios showed no prognostic value. Conclusion Our results showed that inflammatory and perioperative nutritional factors, especially CRP-to-prealbumin ratio, have significant associations with early recurrence after curative resection in resectable PDAC. Therefore, for such patients, a cautious approach is needed when inflammation and poor nutritional status are present.

PURPOSE: No previous study has assessed elderly pedestrian traffic accidents based on a nationwide database. This study aimed to help primary physicians who examine patients in emergency departments to determine and make prompt and accurate treatment decisions. METHODS: This study used data from the Emergency Department-based Injury Indepth Surveillance from 2013 to 2017, managed by the Korea Centers for Disease Control and Prevention. Pedestrians aged ≥65 years were included, and using multivariate logistic regression multiple factors were analyzed to determine their relationship with injury severity. RESULTS: Of 227,695 subjects, 6,498 were included, of whom 2,065 (31.8%) were severely injured. There were more female than male patients in all severity groups. Most accidents occurred in the afternoon and on general roads. In the multivariate analysis, the odds ratio (OR) of injury severity for male pedestrians was 1.165 (95% confidence interval: 1.034–1.313, p=0.012). Older age of patients and the use of ambulances were associated with greater injury severity. The accident time affected the degree of injury severity; i.e., compared to dawn, injury severity increased in the morning (OR: 1.246, p=0.047) and decreased at night (OR: 0.678, p<0.001). A significant difference was noted in the correlation between the type of vehicle causing the accident and the accident severity; i.e., motorcycle accidents had lower severity than bicycle accidents (OR: 0.582, p=0.047). CONCLUSIONS Injury severity was correlated with sex, age, transportation to the ED, TA onset time, and type of vehicle. The study results suggest that injury severity may be positively reflected in initial assessments and overall integrated treatments by physicians and in the related policies.

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*

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the “fit for purpose” application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in C(max) of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.
Area Under Curve ; Caffeine* ; Ciprofloxacin* ; Computer Simulation ; Drug Discovery ; Humans ; In Vitro Techniques ; Permeability ; Pharmacokinetics* ; Solubility ; Tissue Distribution

Leptomeningeal carcinomatosis (LMC) is rare metastatic form of gastric cancer. Most cases are diagnosed in the final stage after multiple distant metastasis. An 84-year-old woman was admitted with melena, headache and vomiting. Esophagogastro-duodenoscopy showed an ulceroinfiltrating lesion at the stomach (Borrmann class III), and biopsy revealed a signet ring cell carcinoma. The abdominal-pelvic CT showed no evidence of metastasis. A sudden decrease of consciousness was noted, but the brain CT showed no active lesion while the brain MRI revealed enhancement of leptomeninges. A lumbar puncture was performed and the cerebrospinal fluid study revealed malignant neoplastic cells. With family consent, no further evaluation and treatment were administered and she died six weeks after the diagnosis of gastric cancer. We report an extremely rare case of a patient who initially presented with neurologic symptoms, and was diagnosed LMC from advanced gastric cancer without any evidence of metastasis in abdomen and pelvis.
Abdomen ; Aged, 80 and over ; Biopsy ; Brain ; Carcinoma, Signet Ring Cell ; Cerebrospinal Fluid ; Consciousness ; Diagnosis ; Female ; Headache ; Humans ; Magnetic Resonance Imaging ; Melena ; Meningeal Carcinomatosis* ; Neoplasm Metastasis ; Neurologic Manifestations ; Pelvis ; Spinal Puncture ; Stomach ; Stomach Neoplasms* ; Vomiting

BACKGROUND: The objective of this study was to investigate the time-course of the expression of TNF-alpha, IL-6, and IL-1beta after L5 spinal nerve transection (SNT), and to determine the effect of small interfering RNA (siRNA) targeting these cytokines on neuropathic pain. METHODS: Rats received control siRNA (CON group, n = 80) or a cocktail of siRNAs targeting these cytokines (COCK group, n = 70). The siRNAs were given via intrathecal catheter 1 d prior to SNT, on the operation day, and 1, 2 and 3 d postoperatively. Behavioral tests and levels of the cytokine mRNAs and proteins as well as glial cell activity were following the L5 SNT. RESULTS: In the CON group, TNF-alpha and IL-1beta mRNA levels increased immediately after SNT and remained high for 6 d, while IL-6 transcripts only began to increase after 12 h. TNF-alpha and IL-1beta mRNA levels in the COCK group were lower than in the CON group at all time points (P < 0.05). In the behavioral tests, allodynia and hyperalgesia were significantly lower in the COCK group from 2 d after SNT (P < 0.05). CONCLUSIONS: The time courses of TNF-alpha, IL-6 and IL-1beta mRNA expression after L5 SNT differ. RNA interference may be a method of reducing the development of mechanical allodynia and hyperalgesia in response to nerve injury.
Animals ; Catheters ; Cytokines ; Hyperalgesia ; Interleukin-6* ; Neuralgia* ; Neuroglia ; Rats* ; RNA Interference* ; RNA, Messenger ; RNA, Small Interfering ; Spinal Nerves* ; Tumor Necrosis Factor-alpha*

This article was inadvertently omitted Acknowledgments section for grant support.

Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.
Apoptosis ; Carcinoma, Squamous Cell* ; Caspase 3 ; Cell Death ; Cell Nucleus ; Cell Proliferation ; Curcuma ; Curcumin* ; Drug Therapy ; Humans ; Intestinal Absorption ; Rhizome ; Salivary Glands*

Metformin, a dimethylbiguanide, is an oral antihyperglycemic drug used in treatment of type 2 diabetes mellitus. It has been reported that metformin may be associated with lactic acidosis in patients with clinical conditions such as renal failure and heart failure. Metformin-associated lactic acidosis (MALA) is a rare, but serious complication with a mortality rate of approximately 30~50%. Therefore, an aggressive treatment strategy including hemodialysis is recommended for these patients. Although continuous renal replacement therapy (CRRT) has been administered in hemodynamically unstable patients with MALA, there are few case reports describing the use of CRRT as a therapeutic modality in Korea. Here, we describe the case histories of two MALA patients who underwent treatment with CRRT.
Acidosis ; Acidosis, Lactic* ; Diabetes Mellitus, Type 2 ; Heart Failure ; Humans ; Korea ; Metformin ; Mortality ; Renal Dialysis ; Renal Insufficiency ; Renal Replacement Therapy