Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). Conclusion Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Purpose: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL. Materials and Methods: Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS). Results: Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation. Conclusion There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

Purpose: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. Materials and Methods: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). Results: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Purpose: Classical swine fever (CSF) reemerged on CSF-free Jeju Island where vaccination is not practiced by the unintentional injection of a live attenuated vaccine (modified live attenuated vaccines–low-virulence Miyagi [MLV-LOM]) in 2014. Since the Jeju provincial authority is considering adopting a voluntary immunization policy using a CSF-E2 subunit vaccine to combat LOM-derived CSF endemic, this study aimed to evaluate in Jeju herds. Materials and Methods: Two vaccination trials using the Bayovac CSF-E2 vaccine licensed for use in South Korea assessed the safety and humoral immunity of the CSF-E2 vaccine in breeding (trial 1) and nursery animals (trial 2) under farm application conditions. Results: Neither local nor systemic (including reproductive) adverse effects were objectively observed in pregnant sows and young piglets following a respective vaccination regime at pregnancy or weaning, respectively. Trial 1 showed that sows immunized with the CSF-E2 vaccine possessed high and consistent E2-specific and neutralizing antibody levels. The CSF-E2 vaccine-immunized pregnant sows subsequently conferred appropriate and steady passive immunity to their offspring. In trial 2, a double immunization scheme of the CSF-E2 vaccine in piglets at 40 and 60 days of age could elicit a consistent and long-lasting adequate antibody response. Additionally, the two trials detected no E rns -specific antibody responses, indicating that CSF-E2 vaccine can differentiate infected from vaccinated animals (DIVA). Conclusion Our trial data collectively provide invaluable information on applying the CSFE2 subunit vaccine to circumvent the possible drawbacks associated with the MLV-LOM concerning the safety, efficacy, and DIVA, in the LOM-endemic field farms and contribute to advanced CSF eradication on Jeju Island.

PURPOSE: Glyphosate herbicides (GHs) are widely used and increasingly associated with poisoning cases. Acute pancreatitis (AP) is among the many complications associated with the toxicity of GHs. We investigated the relationship between incidence of AP and its prognosis in patients with GH poisoning. METHODS: This was a retrospective cohort study conducted at a single tertiary hospital between January 2004 and December 2014. We enrolled all patients presented to the emergency department with GH poisoning. The Clinical and laboratory variables were analyzed to investigate the relationship between GH intoxication and AP. RESULTS: We studied 245 patients. Incidence of AP after GH poisoning was 6.5%. Patients with AP (mean 66 years) were older than the non-AP group (56 years). Systolic blood pressure, Glasgow Coma Scale, and amount of ingested poison differed significantly between the two groups. In the blood tests, white blood cell count, alanine aminotransferase, glucose, potassium, amylase, and lipase showed significant differences. The pH, bicarbonate, and lactate levels also differed significantly. Patients with AP demonstrated higher incidence of respiratory failure, pneumonia, acute kidney injury, rhabdomyolysis, and intensive care unit stay time. Additionally, 30-day mortality (n=11, 68.8%) was significantly higher in the AP group. On multivariate analysis, adjusted age, amount of ingestion, and lactate correlated with occurrence of AP. CONCLUSION: The incidence of GH-induced AP was 6.5% with a 30-day mortality of 68.8%. The patient's age, ingested dosage, and lactate levels were associated with GH-induced AP.
Acute Kidney Injury ; Alanine Transaminase ; Amylases ; Blood Pressure ; Cohort Studies ; Eating ; Emergency Service, Hospital ; Glasgow Coma Scale ; Glucose ; Hematologic Tests ; Herbicides ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Intensive Care Units ; Lactic Acid ; Leukocyte Count ; Lipase ; Mortality ; Multivariate Analysis ; Pancreatitis* ; Pneumonia ; Poisoning ; Potassium ; Prognosis* ; Respiratory Insufficiency ; Retrospective Studies ; Rhabdomyolysis ; Tertiary Care Centers

PURPOSE: This study was conducted to examine the efficacies of susceptibility weighted images (SWI) for predicting the clinical prognosis of comatose patients following cardiac arrest. METHODS: Thirty-two patients who were resuscitated from cardiac arrest and underwent brain magnetic resonance imaging (MRI) were retrospectively investigated and compared to 32 subjects with normal brain MRI findings who served as controls. The SWI readings were divided into three categories: prominent, diminished, and normal. Comatose patients were divided into two groups: those with a Glasgow-Pittsburgh cerebral performance category (CPC) of 1-2 (good outcome group) and those with a CPC of 3-5 (poor outcome group). RESULTS: Of the 32 patients, 17 (53.1%) showed good neurological outcomes upon hospital discharge. Normal patterns on SWI were mainly seen in the good outcome group (15 patients, 88.2%), while diminished patterns and prominent patterns were frequently found in the poor outcome group (13 patients, 88.7%). The combination of diminished pattern and prominent pattern predicted poor outcome with 86.7% sensitivity (95% confidence interval, 69.5%-100%) and 88.2% specificity (95% confidence interval, 72.9%-100%). CONCLUSION: The SWI findings correlate with the outcome of hypoxic-ischemic encephalopathy and may be a useful adjunct of vegetative state or death in comatose patients after cardiac arrest.
Brain ; Coma* ; Heart Arrest* ; Humans ; Hypoxia-Ischemia, Brain ; Magnetic Resonance Imaging ; Persistent Vegetative State ; Prognosis ; Reading ; Retrospective Studies ; Sensitivity and Specificity

PURPOSE: Flumazenil is an effective benzodiazepine antagonist. However, serious adverse effects, including seizures, cardiac arrhythmias, and even death, have been reported in patients treated with flumazenil. These adverse effects are commonly associated with co-ingested tricyclic antidepressants and benzodiazepine withdrawal. Herein, we examined the safety, effectiveness, and risk of using flumazenil to treat suspected benzodiazepine overdose in the emergency department (ED). METHODS: This is a retrospective observational study of adult patients administered with flumazenil for a known or suspected benzodiazepine overdose in the ED between July 2010 and January 2016. The outcomes included mental status improvement, incidence of seizures, and intubation rate after flumazenil administration. RESULTS: Seventy-six patients were included in the analysis. Thirty-eight (50%) patients experienced clinically significant mental status improvement. One patient had a seizure (1.3%), despite 17 reported proconvulsant coingestants. No patient required endotracheal intubation, and no patient had arrhythmias after flumazenil administration. Flumazenil was given intravenously bolus in all cases, and the average dose was 0.44mg. There were no significant changes in the vital signs after flumazenil administration. CONCLUSION: Flumazenil was effective and associated with a low frequency of seizure. However, patients with contraindications may develop seizures. The benefits with respect to risk of adverse effects should be considered carefully in all patients.
Adult ; Antidepressive Agents, Tricyclic ; Arrhythmias, Cardiac ; Benzodiazepines* ; Drug Overdose ; Emergencies* ; Emergency Service, Hospital* ; Flumazenil* ; Humans ; Incidence ; Intubation ; Intubation, Intratracheal ; Observational Study ; Retrospective Studies ; Seizures ; Vital Signs

PURPOSE: Patients suffering from acute poisoning by different substances often visit the emergency department (ED) and receive various prognoses according to the toxic material and patients' condition. Hyperlactatemia, which is an increased blood lactate level that generally indicates tissue hypoperfusion, is commonly utilized as a prognostic marker in critically ill patients such as those with sepsis. This study was conducted to investigate the relationships between blood lactate and clinical prognosis in acute poisoned patients. METHODS: This retrospective study was conducted from January 2013 to June 2014 at a single and regional-tertiary ED. We enrolled study patients who were examined for blood test with lactate among acute intoxicated patients. The toxic materials, patient demographics, laboratory data, and mortalities were also reviewed. Additionally, we analyzed variables including blood lactate to verify the correlation with patient mortality. RESULTS: A total of 531 patients were enrolled, including 24 (4.5%) non-survivors. Patient age, Glasgow coma scale (GCS), serum creatinine (Cr), aspartate transaminase (AST), and serum lactate differed significantly between survivors and non-survivors in the binary logistic regression analysis. Among these variables, GCS, AST, and lactate differed significantly. The median serum lactate levels were 2.0 mmol/L among survivors and 6.9 mmol/L among non-survivors. The AUC with the ROC curve and odds ratio of the initial serum lactate were 0.881 and 3.06 (0.89-8.64), respectively. CONCLUSION: Serum lactate was correlated with fatalities of acute poisoning patients in the ED; therefore, it may be used as a clinical predictor to anticipate their prognoses.
Area Under Curve ; Aspartate Aminotransferases ; Creatinine ; Critical Illness ; Demography ; Emergencies* ; Emergency Service, Hospital* ; Glasgow Coma Scale ; Hematologic Tests ; Humans ; Hyperlactatemia ; Lactic Acid* ; Logistic Models ; Mortality* ; Odds Ratio ; Poisoning ; Prognosis ; Retrospective Studies ; ROC Curve ; Sepsis ; Survivors

The change of compressing personnel will inevitably accompany hands off time when cardiopulmonary resuscitation (CPR) is performed by two or more rescuers. The present study assessed whether changing compression by a second rescuer located on the opposite side (OS) of the first rescuer can reduce hands-off time compared to CPR on the same side (SS) when CPR is performed by two rescuers. The scenario of this randomized, controlled, parallel simulation study was compression-only CPR by two laypersons in a pre-hospital situation. Considering sex ratio, 64 participants were matched up in 32 teams equally divided into two gender groups, i.e. , homogenous or heterogeneous. Each team was finally allocated to one of two study groups according to the position of changing compression (SS or OS). Every team performed chest compression for 8 min and 10 sec, with chest compression changed every 2 min. The primary endpoint was cumulative hands-off time. Cumulative hands-off time of the SS group was about 2 sec longer than the OS group, and was significant (6.6 +/- 2.6 sec vs. 4.5 +/- 1.5 sec, P = 0.005). The range of hands off time of the SS group was wider than for the OS group. The mean hands-off times of each rescuer turn significantly shortened with increasing number of turns (P = 0.005). A subgroup analysis in which cumulative hands-off time was divided into three subgroups in 5-sec intervals revealed that about 70% of the SS group was included in subgroups with delayed hands-off time > or = 5 sec, with only 25% of the OS group included in these subgroups (P = 0.033). Changing compression at the OS of each rescuer reduced hands-off time compared to the SS in prehospital hands-only CPR provided by two bystanders.
Cardiopulmonary Resuscitation/methods/*statistics & numerical data ; Clinical Competence/*statistics & numerical data ; Emergency Medical Services/*statistics & numerical data ; Female ; Heart Arrest/epidemiology/*prevention & control ; Heart Massage/methods/*statistics & numerical data ; Humans ; Male ; Republic of Korea/epidemiology ; Treatment Outcome ; Workload/*statistics & numerical data ; Young Adult

PURPOSE: Recently, glyphosate-surfactant herbicide has been used increasingly because it is known for its low toxicity in mammals. However, some cases presented severe clinical complications including hypotension. Previous studies have shown that hypotension is a predictor of poor outcome and mortality. Therefore, we aimed to identify factors that may be related to hypotension in glyphosate intoxication. METHODS: This retrospective study targeted patients with glyphosate intoxication who were admitted to the emergency department of a single hospital from January 1st, 2004 to November 2014. The data were collected retrospectively from clinical records and laboratory files. Using multivariate logistic analysis, data were analyzed retrospectively for association with hypotension. RESULTS: Of the 245 patients, 63 patients (25.7%) had hypotension. The results of this study showed statistically significant differences in old age, underlying disease, amount of ingestion, GCS (Glasgow coma scale), White blood cell, hemoglobin, total bilirubin, glucose level, pH, bicarbonate, base excess, lactate level, AST (aspartate aminotransferase), creatinine level, saturation, Chest X-ray abnormality, and prolonged QTc (corrected QT interval) between hypotension group and non-hypotension group. By multivariate logistic analysis, GCS, creatinine level, chest X-ray abnormality, and prolonged QTc interval were associated with the cases presenting with hypotension. CONCLUSION: GCS, creatinine level, chest X-ray abnormality, and prolonged QTc interval were significant factors associated with hypotension in patients with glyphosate intoxication.
Bilirubin ; Coma ; Creatinine ; Eating ; Emergency Service, Hospital ; Glucose ; Humans ; Hydrogen-Ion Concentration ; Hypotension* ; Lactic Acid ; Leukocytes ; Mammals ; Mortality ; Poisoning* ; Retrospective Studies ; Statistics as Topic ; Thorax