Objective: We used paclitaxel and cisplatin, known to be effective in intraperitoneal chemotherapy, in a novel prototype of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) and evaluated the pharmacokinetics, tissue concentrations, and toxicities in a pig model. Methods: We developed RIPAC, including the nozzle with the conical pendulum motion, and used 10% of intravenous doses of paclitaxel and cisplatin. We used high-performance liquid chromatography followed by tandem mass spectrometry to analyze serum and tissue concentrations. We applied a non-compartment model to study pharmacokinetics to analyze the time-dependent serum concentrations measured before RIPAC to 48 hours. We evaluated the difference in tissue concentrations between twelve peritoneal regions by the modified peritoneal cancer index. For evaluating toxicities, we observed hepatic and renal function until 4 days after RIPAC. Results: Six pigs underwent RIPAC using paclitaxel (n=3) and cisplatin (n=3). The peak serum concentration (Cmax) and the area under the curve were higher for cisplatin, while the time to the peak serum concentration (Tmax) was longer for paclitaxel. Moreover, the parietal peritoneum showed higher tissue concentrations than the visceral peritoneum, and the ratio of tissue to serum concentrations using Cmax was higher for paclitaxel (172.2–6,237.9) than for cisplatin (0.1–9.3). However, there were no renal and hepatic toxicities after RIPAC with paclitaxel or cisplatin. Conclusion Delayed absorption of paclitaxel sprayed by RIPAC into the peritoneum to the bloodstream may lead to higher tissue concentrations at different regions and lower serum concentrations than cisplatin.

Purpose: To report an association between prostate cancer and vitamin D levels among different races in a single population in the United States.
Materials and Methods: We investigated whether there was an association between vitamin D level and prostate cancer in different races in the United States. We used data collected from 1,363 men during the National Health and Nutrition Examination Survey 2007–2008. Multivariate logistic regression analysis was used to evaluate the independent associations between vitamin D levels (not only 25-hydroxyvitamin D [25(OH)D], but also 25(OH)D2 and D3) and prostate cancer. Association between vitamin D levels and prostate specific antigen level was also analyzed in non-Hispanic white males without prostate cancer.
Results: Older age was significantly associated with prostate cancer in all races (p＜0.05), whereas vitamin D (p=0.024), especially 25(OH)D2 (p=0.027) was significantly higher only in non-Hispanic white males. There was no difference in vitamin D levels between non-Hispanic white males with a prostate specific antigen concentration ＞3 ng/mL and ≤3 ng/mL.
Conclusions This study revealed a positive association between vitamin D, especially 25(OH)D2, and prostate cancer only in non-Hispanic white males. And vitamin D was not associated with prostate specific antigen level causing detection bias. (Korean J Urol Oncol 2020;18:32-39)

BACKGROUND: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1(wt)/FLT3-ITD(neg/low)) has not yet been elucidated. METHODS: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. RESULTS: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1(wt)/FLT3-ITD(neg/low), complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1(wt)/FLT3-ITD(neg/low) group (P=0.233). Among the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. CONCLUSION: Among the AML patients, intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients. Well controlled studies are needed to confirm the current results.
Cell Transplantation ; Classification ; Consolidation Chemotherapy ; Gyeongsangbuk-do ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; Multivariate Analysis ; Patient Selection ; Protein-Tyrosine Kinases ; Retrospective Studies ; Transplants

No abstract available.
Leukemia, Mast-Cell* ; Mast Cells*

This paper aims to introduce, summarize, and emphasize the importance of the 'Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition'. The guideline broadly covers most aspects of the pharmacological treatment of patients in Korea diagnosed with moderate to severe major depression according to the DSM-IV TR. The guideline establishment process involved determining and answering a number of key questions, searching and selecting publications, evaluating recommendations, preparing guideline drafts, undergoing external expert reviews, and obtaining approval. A guideline adaptation process was conducted for the revised edition. The guideline strongly recommends pharmacological treatment considered appropriate to the current clinical situation in Korea, and should be considered helpful when selecting the appropriate pharmacological treatment of patients diagnosed with major depressive disorder. Therefore, the wide distribution of this guideline is recommended.
Antidepressive Agents/*therapeutic use ; Antipsychotic Agents/therapeutic use ; Databases, Factual ; Depression/complications/diagnosis/*drug therapy ; Drug Tolerance ; Evidence-Based Practice ; Humans ; Monoamine Oxidase Inhibitors/therapeutic use ; Neurotransmitter Uptake Inhibitors/therapeutic use ; Placebo Effect ; Psychotic Disorders/complications/drug therapy ; Republic of Korea ; Severity of Illness Index

OBJECTIVE: Activation of one or more serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of serotonergic antidepressants. The serotonin 2C (5HT 2C) receptor is known to be associated with antidepressant action and weight gain. We sought to determine whether the 5-HTR 2C receptor -759C/T polymorphism was associated with weight gain and treatment response to mirtazapine in major depressive disorder (MDD) patients. METHODS: The 5-HT 2C receptor -759C/T polymorphism was analyzed in 323 MDD patients. All patients were evaluated using the 21-item Hamilton Depression Rating Scale at the beginning of the study and at 1, 2, 4, and 8 weeks of mirtazapine treatment. RESULTS: There was no significant difference in the 5-HT 2C receptor -759C/T genotype distribution between responder and non-responder groups. The 5-HT 2C receptor -759C/T polymorphism was not associated with weight change over time after mirtazapine administration. CONCLUSION: The 5-HT 2C receptor -759C/T polymorphism does not appear to be a predictor of treatment response to mirtazapine. This polymorphism was not associated with weight change after 8 weeks of mirtazapine treatment. Further investigation on other polymorphisms of the 5-HT 2C gene is required to determine whether the 5-HT 2C gene influences treatment response and weight change after mirtazapine administration in patients with major depressive disorder.
Antidepressive Agents ; Depression ; Depressive Disorder, Major ; Genotype ; Humans ; Mianserin ; Negotiating ; Receptor, Serotonin, 5-HT2C ; Serotonin ; Weight Gain

OBJECTIVES: The aim of this study is to establish Korean pharmacological treatment guidelines for the initial choice of antidepressant for treatment of moderate or severe depression. METHODS: The process for establishment of guidelines involved determination of important key questions, selection of 12 international and domestic clinical practice guidelines for depression, drawing of recommendation drafts, and peer review. RESULTS: Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRI), and noradrenergic and specific serotonergic antidepressants (NaSSA) were strongly recommended as the first-line antidepressants for treatment of moderate or severe depression. SSRIs were weakly recommended for patients who had problems with tolerability. Consideration of not only efficacy but also provisional adverse effects, drug-drug interactions, history of treatment response, preference, acceptability, cost, comorbid illnesses, and other factors in the choice of first-line antidepressants was strongly recommended. The treatment recommendations for specific clinical features of depression were as follows. SSRIs were weakly recommended for atypical depression. Augmented use of antipsychotics to antidepressants was strongly recommended for psychotic depression. Bupropion and SSRIs were weakly recommended for seasonal depression. CONCLUSION: The results of this study may contribute toward improving the quality of depression treatment by providing clear and definite recommendations for the initial choice of antidepressant for treatment of moderate or severe depression.
Antidepressive Agents ; Antipsychotic Agents ; Bupropion ; Depression ; Humans ; Seasons ; Serotonin Uptake Inhibitors

Acute pulmonary embolism is considered a cardiovascular emergency and is one of the most important causes of morbidity and mortality in hospitalized patients. Tumor embolism is a rare and unique complication of malignancies, and detached thrombi or tumors may cause massive pulmonary embolism in patients with malignancies. The identification of the type of pulmonary embolism is critical because treatment and prognosis vary considerably. We report an unusual presentation of a tumor embolism that was misdiagnosed as a pulmonary thromboembolism in a young woman. The patient was initially treated with the anti-coagulants warfarin and aspirin, but her symptoms were aggravated after two months and she required emergency surgery. Histology revealed a pulmonary embolism due to metastatic chondrosarcoma. Following surgery, her condition deteriorated, and she did not survive. This case highlights the need to investigate the cause of pulmonary embolism should the patient not respond to anti-coagulatant therapy.
Aspirin ; Chondrosarcoma ; Emergencies ; Female ; Humans ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Prognosis ; Pulmonary Embolism ; Warfarin

OBJECTIVES: The aim of this study was to demonstrate the recommendations for antidepressant treatment strategy of dose increment, switching, combination, and augmentation therapy derived from Evidence-Based Korean Pharmacological Treatment Guideline for Depression, Revised Edition. METHODS: The guideline was developed through adaptation of 12 domestic and foreign clinical guidelines for depression, with key questions concerning pharmacotherapy of depression, and drawing of recommendations. RESULTS: The guideline strongly recommended dose increment, switching, and combination and augmentation therapy of antidepressant when patients with depression showed inadequate treatment outcomes from initial antidepressant treatment. The dose increment was strongly recommended when the patients had insufficient response from treatment with tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs). Switching from SSRI to non-SSRI was also strongly recommended. The combination of initial medication and other classes of antidepressants could benefit from treatment with TCAs, SSRIs, SNRIs, and noradrenergic and specific serotonergic antidepressants. Combination with norepinephrine and dopamine reuptake inhibitors or serotonin-2 antagonist/reuptake inhibitors was weakly recommended. The guideline strongly recommended use of the augmentation strategy of adding lithium or benzodiazepine to initial antidepressants. Augmentation of lamotrigine, T3, methylphenidate, and modafinil was weakly recommended. CONCLUSION: If the initial outcomes of antidepressant therapy are unsatisfactory to the patients the next-step strategies of dose increment, switching, combination and augmentation of antidepressants should be considered after rechecking the patients' drug compliance, dose, and diagnosis.
Antidepressive Agents ; Antidepressive Agents, Tricyclic ; Benzhydryl Compounds ; Benzodiazepines ; Compliance ; Depression* ; Depressive Disorder, Major ; Dopamine Uptake Inhibitors ; Drug Therapy ; Humans ; Lithium ; Methylphenidate ; Monoamine Oxidase Inhibitors ; Norepinephrine ; Serotonin ; Serotonin Uptake Inhibitors ; Triazines

OBJECTIVES: The purpose of this study was to suggest recommendations of antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy. METHODS: Using recommendations from 12 international and domestic clinical practice guidelines for depression, drawing of recommendation drafts, and peer review, the executive committee developed the guideline. RESULTS: Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOI), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRIs), norepinephrine and specific serotonergic antidepressants (NaSSAs), norepinephrine and dopamine reuptake inhibitors (NDRIs), and serotonin antagonist and reuptake inhibitors (SARIs) were strongly recommended as having antidepressant efficacy compared with placebo. Difference in efficacy of antidepressants was as follows. TCAs, MAOI, SSRI, SNRIs, and NaSSAs were strongly recommended, however, NDRIs, SARIs were weakly recommended. If there was no or minimal improvement with treatment, appropriate time of efficacy judgment in antidepressant therapy was estimated to be after two to four weeks. CONCLUSION: We hope that the results of this study will be helpful in encouraging the optimal treatment by understanding antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy.
Antidepressive Agents* ; Antidepressive Agents, Tricyclic ; Depression* ; Depressive Disorder, Major ; Dopamine Uptake Inhibitors ; Judgment* ; Monoamine Oxidase Inhibitors ; Norepinephrine ; Peer Review ; Serotonin ; Serotonin Uptake Inhibitors