PURPOSE: Paraquat is a lethal herbicide and induces acute renal failure, hepatic dysfunction, and progressive respiratory failure. The aims of this study are to investigate the correlation between plasma paraquat concentrations and initial laboratory data at Emergency Medical Center and to investigate whether initial laboratory data is useful for predicting outcomes of paraquat-poisoned patients. METHODS: A retrospective analysis by chart review was done on 83 patients who ingested paraquat and who had presented to Emergency center of within 24 hours. Plasma paraquat concentrations, urine dithionite test and initial laboratory parameters including white blood cell count, urine pH, and AST, ALT, BUN, Creatinine, Amylase, Glucose, pH, PaCO2, PaO2, HCO3. Base Excess, Na, K, Cl were obtained at the time of Emergency Center visit. We compared urine dithionite test, plasma paraquat concentrations and Severity Index of Paraquat Pisoning (SSPI) of the survival group to those of the dead group. The patients were divided into four subgroups based on the level of plasma paraquat concentration, their initial laboratory data was compared and analyzed. RESULTS: The mean plasma paraquat concentration in the mortality group was higher than that in the survival group (88.44+/-81.56 vs. 1.32+/-1.72 microgram/mL). Among the initial laboratory data of four subgroups, WBC, Glucose, Cr, pH, HCO3, Bass excess were significantly different between the group of low level of plasma paraquat concentration and higher group. ANCOVA analysis revealed that WBC, HCO3, Bass excess correlated with the level of plasma paraquat concentration significantly. CONCLUSION: The plasma paraquat concentration and SIPP were higher in the mortality group significantly. Initial laboratory data including WBC, Glucose, Cr, pH, HCO3, Bass excess were proven to be significant prognostic factors. Especially WBC, HCO3, Bass excess can be used to predict the outcome of paraquat poisoning.
Acute Kidney Injury ; Amylases ; Bass ; Creatinine ; Dithionite ; Emergencies ; Glucose ; Humans ; Hydrogen-Ion Concentration ; Leukocyte Count ; Paraquat ; Plasma ; Prognosis ; Respiratory Insufficiency ; Retrospective Studies

Cellular and gene therapies (CGT) are promising fields that are bringing significant clinical benefits to patients by directly targeting the underlying cause of disease. In line with this trend, regulatory agencies in every country have been making efforts to accelerate CGT product development. For acceleration, it is necessary to increase the efficiency of clinical trials, thus the early-phase clinical trials for CGT products should be elaborate and productive. The guidelines of international regulatory agencies were compared and analyzed to examine the considerations for the design of early-phase CGT products. The guidelines described a safety evaluation, preliminary evidence of effectiveness gathering, dose exploration, and a feasibility assessment as common objectives of early-phase clinical trials for CGT products. In addition, the considerations for the design of early-phase CGT products included pretreatment effects and problems in the manufacturing and administration process. The guidelines also covered selection of a study population, control group/blinding, and dose/regimen planning. There were differences in the degree of detail, description, and the scope of the content covered by each guideline. The guideline published by FDA was the most specific. However, when compared with the previous guidelines for designing earlyphase clinical trials for small molecules and biologics, the current guidelines need to be revised to suggest more detailed and practical principles and rules.

This study was conducted to evaluate the efficacy and safety of once-weekly dulaglutide therapy as add-on to oral antidiabetic drugs (OADs) and basal insulin in Korean patients with type 2 diabetes mellitus (T2DM) in real-world clinical practice. We retrospectively reviewed the medical records of 112 patients who received dulaglutide in a tertiary referral center. The primary efficacy endpoint was a change in glycated hemoglobin (HbA1c) between baseline and 6 months. The secondary endpoints were the percentage of patients achieving HbA1c <7.0% or ≤6.5% and the change of body weight at 6 months. At baseline, the mean HbA1c was 8.7 % (8.8% in the OAD combination and 8.5% in the basal insulin combination group). The mean adjusted HbA1c at 6 months decreased by −1.13% in all patients (p<0.001), and by −1.36 and −0.74% in the OAD combination and basal insulin combination group, respectively. A significant reduction of −2.9 kg in body weight was observed in all patients at 6 months (p<0.001). Approximately 34.8% and 23.2% of patients achieved HbA1c <7.0% and ≤6.5%, respectively. Higher baseline HbA1c and no previous insulin therapy were associated with positive responses to dulaglutide on multivariate analysis. Mild gastrointestinal issues (23.2%) were the most frequently observed adverse events. Dulaglutide is an effective and durable treatment option as OAD and basal insulin combination therapy in Korean patients with T2DM.

This study was conducted to evaluate the efficacy and safety of once-weekly dulaglutide therapy as add-on to oral antidiabetic drugs (OADs) and basal insulin in Korean patients with type 2 diabetes mellitus (T2DM) in real-world clinical practice. We retrospectively reviewed the medical records of 112 patients who received dulaglutide in a tertiary referral center. The primary efficacy endpoint was a change in glycated hemoglobin (HbA1c) between baseline and 6 months. The secondary endpoints were the percentage of patients achieving HbA1c <7.0% or ≤6.5% and the change of body weight at 6 months. At baseline, the mean HbA1c was 8.7 % (8.8% in the OAD combination and 8.5% in the basal insulin combination group). The mean adjusted HbA1c at 6 months decreased by −1.13% in all patients (p<0.001), and by −1.36 and −0.74% in the OAD combination and basal insulin combination group, respectively. A significant reduction of −2.9 kg in body weight was observed in all patients at 6 months (p<0.001). Approximately 34.8% and 23.2% of patients achieved HbA1c <7.0% and ≤6.5%, respectively. Higher baseline HbA1c and no previous insulin therapy were associated with positive responses to dulaglutide on multivariate analysis. Mild gastrointestinal issues (23.2%) were the most frequently observed adverse events. Dulaglutide is an effective and durable treatment option as OAD and basal insulin combination therapy in Korean patients with T2DM.

Objective: This study investigated associations of life stressors and serum ghrelin levels with suicidal ideation (SI), and evaluated the potential mediating effect of ghrelin on associations between life stressors and SI in patients with acute coronary syndrome (ACS). Methods: In total, 969 ACS patients recruited from a tertiary university hospital in Korea within 2 weeks of disease onset were evaluated in terms of life stressors (using the List of Threatening Events Questionnaire), serum ghrelin levels, and SI (using the “suicidal thoughts” item of the Montgomery–Asberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI; logistic regression was performed with adjustment for covariates. Results: Life stressors were significantly associated with SI at baseline and follow-up. Serum ghrelin showed no such associations, but high levels thereof mediated associations of life stressors with SI; significant interaction terms were also observed after adjustment for covariates. Conclusion By evaluating life stressors and serum ghrelin levels, clinical prediction of SI in the acute and chronic phases of ACS could be improved.

Objective: To investigate individual and interactive associations of baseline serum leptin levels and physical comorbidity with short- and long-term treatment outcomes in outpatients with depressive disorders who received stepwise antidepressant treatment in a naturalistic prospective study design. Methods: Baseline serum leptin levels were measured, and the number of concurrent physical disorders ascertained from 1,094 patients. These patients received initial antidepressant monotherapy; then, for patients with an insufficient response or who experienced uncomfortable side effects, treatment was administered using alternative strategies every 3 weeks in the acute treatment phase (at 3, 6, 9, and 12 weeks) and every 3 months in the continuation treatment phase (at 6, 9, and 12 months). Then, 12-week and 12-month remission, defined as a Hamilton Depression Rating Scale score of ≤7, was estimated. Results: In multivariable logistic regression analyses, individual effects were found only between higher baseline serum leptin levels and 12-week non-remission. Significant interactive effects between higher leptin levels and fewer physical disorders (＜ 2 physical disorders) on 12-week non-remission were observed. However, neither individual nor interactive effects between leptin levels and physical comorbidity were associated with 12-month remission. Conclusion The combination of serum leptin level and number of physical disorders may be a useful predictor of short-term treatment responses in patients with depressive disorders receiving pharmacotherapy.

Objective: To investigate associations between baseline serum serotonin levels and short- and long-term treatment outcomes in outpatients with depressive disorders in a naturalistic one-year prospective study design. Methods: Patients were recruited at a University hospital in South Korea from March 2012 to April 2017. At baseline, blood samples were obtained from 1,094 patients who received initial antidepressant monotherapy (Step 1). After the Step 1 treatment, further treatment steps (at least Steps 2−4) could be administered every 3 weeks during the acute treatment phase (3, 6, 9, and 12 weeks; n = 1,086), and every 3 months during the continuation treatment phase (6, 9, and 12 months; n = 884). In cases showing an insufficient response or intolerable side effects, patients were asked to choose whether to remain at the current step or enter the next treatment step, with alternative strategies including switching, augmentation, combination, and a mixture of these approaches. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. Results: The remission group had significantly higher baseline serum serotonin levels among patients who received Step 1 monotherapy in both acute and continuation treatment phases. These associations remained significant after adjustment for relevant covariates. No associations were found with any other treatment steps. Conclusion Baseline serum serotonin levels may be used as a biomarker for predicting short- and long-term treatment outcomes in antidepressant monotherapy-treated patients with depressive disorders in a real-world clinical setting.

Objective: We investigated effects of serum serotonin and interleukin 18 levels on suicidal ideation (SI) at acute and chronic phases of acute coronary syndrome (ACS). Methods: Recent-onset 969 ACS patients were evaluated for serum serotonin and interleukin 18 levels; and SI by the“suicidal thoughts” item of the Montgomery–Åsberg Depression Rating Scale. After 1-year, 711 patients were re-evaluated for SI. Logistic regression models were used adjustment for potential covariates. Results: Associations between serum interleukin 18 and SI at both phases were significant only in the lower serotonin group. Conclusion By evaluating serum serotonin and interleukin 18 levels, the clinical prediction of SI of ACS may be improved.

Objective: Obsessive-compulsive symptoms (OCS) and suicidal ideation (SI) are common in patients with acute coronary syndrome (ACS). This study investigated the associations of OCS and serum cortisol levels with SI, and further evaluated the possible modifying effects of cortisol on the associations between OCS and SI in acute and chronic phases of ACS. Methods: In total, 969 ACS patients were recruited from a tertiary university hospital in Korea within 2 weeks of disease onset and evaluated in terms of OCS (using the OCS dimension of the Symptom Checklist-90–Revised), serum cortisol levels, and SI (using the “suicidal thoughts” item of the Montgomery–Åsberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI. Logistic regression analysis was performed with adjustment for covariates. Results: Higher OCS was significantly associated with SI both at baseline and follow-up. Serum cortisol showed no such association, but modified the association between OCS and SI. That was the associations were significant only in the higher but not in the lower serum cortisol levels, with significant interaction terms after adjusted for relevant covariates. Conclusion Evaluating OCS and serum cortisol levels at the acute phase could improve the accuracy of clinical predictions of SI both in the acute and chronic phases of ACS.

Objective: This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in outpatients with depressive disorders receiving stepwise psychopharmacotherapy, according to the main antidepressant used during the treatment period. Methods: This study included 1,024 depressive outpatients initially treated using antidepressant monotherapy, followed by alternating pharmacological strategies during the acute phase (3−12 weeks; 3-week interval). Fourteen serum biomarkers, sociodemographics, and clinical characteristics were evaluated at baseline. Based on the use frequency and mechanism of action, four main antidepressant types were distinguished: escitalopram, other selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. A Hamilton Depression Rating Scale score ≤ 7 was take to indicate remission. Results: Lower high-sensitivity C-reactive protein levels were correlated with remission at 12 weeks for all antidepressant types. Lower interleukin (IL)-6 levels and tumor necrosis factor-alpha levels were associated with remission using escitalopram and other SSRIs respectively. Lower IL-1β and leptin levels, predicted remission in association with SSRIs including escitalopram. For SNRIs, remission at 12 weeks was predicted by lower IL-4 and IL-10 levels. For mirtazapine, remission at 12 weeks was associated with lower leptin levels, and higher serotonin and folate levels. Conclusion Baseline serum status, as estimated by nine serum markers, may help clinicians determine the most appropriate antidepressant to achieve remission in the acute phase of depression.