PURPOSE: Mortality in emergency department sepsis (MEDS), sepsis-related organ failure assessment (SOFA), multiple organ dysfunction score (MODS), and serum lactate levels have shown their efficacy in the early detection of patients with a bad prognosis. However, those studies did not consider differences in treatment protocols and could not rule out the interference of these differences in treatment modalities. Hence, we aimed to assess the performance of MEDS, MODS, SOFA, and serum lactate levels for predicting a bad prognosis in patients scheduled for identical, standardized treatment protocols, EGDT. METHODS: Medical records of patients who visited a tertiary level teaching hospital and were enrolled in an EGDT program between October 2009 and May 2010, were retrospectively reviewed. MEDS, SOFA, and MODS scores were calculated and recorded along with serum lactate levels. Receiver operating characteristics (ROC) curves of those predictors of mortality were plotted, Bivariate correlation analyses with overall lengths of admission and ICU lengths of stay were done for surviving patients. RESULTS: None of the diagnostic methods (serum lactate level, MEDS, SOFA, MODS) showed a significant difference on ROC analysis (p=0.819, 0.506, 0.811, 0.873, respectively). Bivariate correlation analyses of MEDS, SOFA, MODS and overall lengths of admission showed significant results (p=0.048, 0.018, and 0.003, respectively. Pearson correlation coefficients were, 0.263, 0.312, and 0.381). Only MEDS showed a significant correlation with intensive care unit (ICU) length of stay (p=0.032, Pearson correlation coefficient = 0.332). CONCLUSION: Neither MEDS, SOFA, MODS, nor serum lactate level can predict mortality in EGDT-enrolled patients. MEDS may be correlated with ICU length of stay.
Clinical Protocols ; Emergencies ; Hospitals, Teaching ; Humans ; Intensive Care Units ; Lactic Acid ; Length of Stay ; Medical Records ; Multiple Organ Failure ; Organ Dysfunction Scores ; Prognosis ; Retrospective Studies ; ROC Curve ; Sepsis ; Severity of Illness Index ; Treatment Outcome

PURPOSE: Image-based computational models with fluid-structure interaction (FSI) can be used to perform plaque mechanical analysis in intracranial artery stenosis. We described a process in FSI study applied to symptomatic severe intracranial (M1) stenosis before and after stenting. MATERIALS AND METHODS: Reconstructed 3D angiography in STL format was transferred to Magics for smoothing of vessel surface and trimming of branch vessels and to HyperMesh for generating tetra volume mesh from triangular surface-meshed 3D angiogram. Computational analysis of blood flow in the blood vessels was performed using the commercial finite element software ADINA Ver 8.5. The distribution of wall shear stress (WSS), peak velocity and pressure was analyzed before and after intracranial stenting. RESULTS: The wall shear stress distributions from Computational fluid dynamics (CFD) simulation with rigid wall assumption as well as FSI simulation before and after stenting could be compared. The difference of WSS between rigid wall and compliant wall model both in pre- and post-stent case is only minor except at the stenosis region. These WSS values were greatly reduced after stenting to 15~20 Pa at systole and 3~5 Pa at end-diastole in CFD simulation, which are similar in FSI simulations. CONCLUSION: Our study revealed that FSI simulation before and after intracranial stenting was feasible despite of limited vessel wall dimension and could reveal change of WSS as well as flow velocity and wall pressure.
Angiography ; Arteries ; Atherosclerosis ; Blood Vessels ; Cerebral Arteries ; Characidae ; Constriction, Pathologic ; Glycosaminoglycans ; Hydrodynamics ; Magic ; Stents ; Systole

Objective: Rotational atherectomy (RA) and newly developed second-generation drug-eluting stent (DES) support the strategy of longer stent deployment in comparison to short stent implantations in the past. However, studies analyzing the outcome of patients who received long stent implantation following RA are few in number. The present study compared the clinical outcomes of patients with the coronary arterial disease (CAD) who underwent RA with long stent implantation using first- and second-generation DES. Methods: A retrospective cohort study was performed at the single center from March 2003 to October 2019. Eighty-seven patients with CAD who underwent RA with ≥32 mm long stent implantation were enrolled in the study and divided into two groups according to the type of DES. As a primary endpoint, the cumulative 2-year incidence of major adverse cardiac events (MACE) including death, myocardial infarction (MI), target vessel revascularization, and stent thrombosis (ST) was compared by DES type. Adjusted interaction between the type of stent and clinical variables was estimated to determine the predictor variables of MACE. Results: The second-generation DES group was associated with a shorter procedure duration and more common usage of intravascular ultrasound in procedural characteristics. In the second-generation DES group, a trend toward a lower rate of MI and ST existed. All-cause mortality and cardiovascular mortality were not significantly different. When combined with MACE, we could identify a significant reduction in the second-generation DES group. Conclusion In comparison to the first-generation DES group, the second-generation DES group was associated with a lower rate of MACE for 2 years in patients who underwent RA with long stent implantation.

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.
Apoptosis* ; Autophagy ; Calcium Channels, L-Type ; Cell Death ; Cytokines ; Down-Regulation* ; Felodipine ; Humans ; Necrosis ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; RNA Interference ; Tumor Necrosis Factor-alpha

OBJECTIVE: Since the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002, the third revision of KMAP-BP was performed in 2014 in order to reflect the recent rapid development and research of bipolar disorder and psychopharmacology. METHODS: According to methodology of previous versions, KMAP-BP 2014 was revised using the same questionnaire consisting of 14 questions. Sixty-four experts of the review committee completed the survey. The executive committee analyzed the results and discussed the final production of algorithm considering scientific evidence. RESULTS: The first-line pharmacotherapeutic strategy for acute bipolar depressive episode with moderate, non-psychotic severe and psychotic severe episode was mood stabilizer combined with atypical antipsychotic (AAP) or AAP with lamotrigine. Compared to KMAP-BP 2010, preference of AAP has been increased in the treatment of bipolar depressive episode in KMAP-BP 2014. Among AAPs, olanzapine, quetiapine and aripiprazole were preferred. When considering the efficacy and safety simultaneously, (es)citalopram, bupropion, and sertraline were recommended among antidepressants for bipolar depression. CONCLUSION: Compared with the previous version, we found that more aggressive pharmacological strategies as an initial treatment were preferred, although various strategies were recommended as same as previous studies. Increased preference of AAP was prominent in KMAP-BP 2014. We expect this algorithm may be helpful in the treatment of bipolar disorder, depressive episode.
Advisory Committees ; Antidepressive Agents ; Bipolar Disorder* ; Bupropion ; Drug Therapy ; Psychopharmacology ; Surveys and Questionnaires ; Sertraline ; Aripiprazole ; Quetiapine Fumarate

OBJECTIVE: The pharmacotherapy of bipolar disorder has many difficulties such as various clinical feature according to each episode, recurrence, breakthroughs, treatment resistance, switching and worsening of its course. Recent rapid development and research of bipolar disorder and psychopharmacology, including atypical antipsychotics and new anticonvulsants, make it more difficult to choose the appropriate pharmacological options. Therefore, we decided to revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) 2010 in order to provide more proper guideline for clinicians. METHODS: Like the previous version, KMAP-BP 2010, we performed the survey using questionnaire comprising 55 main questions in which 8 main questions and 478 sub-items for treatment of manic or hypomanic episode were included. Sixty-four members of the review committee completed the survey. The executive committee analyzed the results and discussed the final production of algorithm considering scientific evidence. RESULTS: The first-line pharmacotherapeutic strategy for acute manic episode is combination of mood stabilizer and an atypical antipsychotic, and it is the treatment of choice for euphoric, psychotic and dysphoric/mixed mania. The preference for monotherapy with atypical antipsychotic (for all three types of mania) or mood stabilizer (for euphoric mania) was increased in KMAP-BP 2014. Valproic acid and lithium are chosen as the preferred mood stabilizer of the first-line treatment of acute manic episode and valproic acid was the treatment of choice for all types of mania. Atypical antipsychotics is more widely accepted than before in manic and hypomanic episode. Moreover, the preference for combination treatment in manic patients who failed to respond in early stage treatment was increased. CONCLUSION: Compared with the previous version, we found that 'no-consensus' decreases in this revision. These suggest that the many clinicians agree with others in the treatment of acute manic/hypomanic episode, and the pharmacotherapy of manic/hypomanic episode become more obvious than before. Atypical antipsychotics such as aripiprazole, olanzapine and quetiapine gain more awareness in the treatment of bipolar mania and hypomania. We expect this algorithm may provide clinicians good information and help about the treatment of bipolar disorder, manic/hypomanic episode.
Advisory Committees ; Anticonvulsants ; Antipsychotic Agents ; Bipolar Disorder* ; Drug Therapy ; Humans ; Lithium ; Psychopharmacology ; Surveys and Questionnaires ; Recurrence ; Valproic Acid ; Aripiprazole ; Quetiapine Fumarate

OBJECTIVE: The Korean Medication Algorithm for Bipolar Disorder (KMAP-BP) was firstly published in 2002, with updates in 2006 and 2010. This third update reviewed the experts' consensus of opinion on the pharmacological treatments of bipolar disorder. METHODS: The newly revised questionnaire composed of 55 key questions about clinical situations including 223 sub-items was sent to the experts. Sixty-four of 110 experts replied. For the newly added section (treatment guideline for child and adolescent bipolar disorders) in KMAP-BP 2014, 23 of 38 experts replied to this special section. Data were analyzed according to the same methods to be used in conjunction with the previous publications. RESULTS: The recommendations for the management of acute mania remained largely unchanged. Combination of mood stabilizer (MS) and atypical antipsychotic (AAP) was the first-line treatment option in acute mania. Valproic acid (VP), lithium (Li), and several AAPs continued to be first-line treatments. MS or AAP monotherapy was the first-line treatment in hypomania. More frequent use of AAP as a first-line agent was noted in KMAP-BP 2014. For management of mild to moderate bipolar depression, MS monotherapy, combination of MS and AAP, combination of AAP and lamotrigine (LTG) was the first-line treatments. In severe non-psychotic depression, combination of MS and AAP, combination of AAP and LTG, and combination of MS and antidepressant (AD) was the first-line treatments. For the management of severe psychotic bipolar depression, combination of MS and AAP, combination of AAP and LTG, combination of MS, AAP and AD or LTG, combination of AAP and AD, and combination of AAP, AD and LTG was the first-line treatments. Li, VP, LTG, aripiprazole (ARP), olanzapine (OLZ) and quetiapine (QT) were the first-line treatment for bipolar depression. Although many treatment options were recommended, there were few consensus of opinion in bipolar depression. Treatment of mixed features was firstly added in KMAP-BP 2014. Combination of MS and AAP was the treatment of choice for management of mixed features. AAP monotherapy was also the first-line treatment. VP, Li, ARP, OLZ and QT were the first-line treatment for management of all phases of mixed features. Risperidone was added in mixed mania and LTG in mixed depressive features. There have been many treatment options for management of rapid cycling in bipolar disorder, when considered the combination of MS and AAP was only first-line treatment in KMAP-BP 2014. Combination of MS and AAP, MS or AAP monotherapy was the first-line options for management of maintenance phase after manic episode. For maintenance treatment after bipolar I depression, combination of MS and AAP, combination of MS and LTG, combination of AAP and LTG, MS or LTG monotherapy, and combination of MS, AAP and LTG were the first-line options. For management of maintenance phase of bipolar II depression, combination of AAP and LTG, combination of MS and LTG, combination of MS and AAP, AAP or LTG monotherapy were recommended as the first-line options. CONCLUSION: The experts' opinion of consensus was markedly changed in KMAP-BP 2014 than in previous publications. Preferred treatment with AAP and LTG was especially noted for management of bipolar disorder. We confirmed the treatment options recommended in KMAP-BP 2014 were much in concordance with current updated treatment guidelines for bipolar disorder. Despite the limitations of expert consensus guideline, KMAP-BP 2014 may reflect the current patterns of clinical practice and recent researches.
Adolescent ; Bipolar Disorder* ; Child ; Consensus ; Depression ; Humans ; Lithium ; Surveys and Questionnaires ; Risperidone ; Valproic Acid ; Aripiprazole ; Quetiapine Fumarate

OBJECTIVE: The complexity of the treatment for bipolar disorder is often caused by the presence of side effects of various psychiatric medications. In particular, weight gain and metabolic syndrome are currently major concerns in the medication for bipolar disorders. Therefore, we undertook a survey of expert opinion to help make clinical decisions in these special situations. METHODS: A written survey which asked about treatment strategies in the safety and tolerability was prepared; 1) weight gain, 2) antipsychotic related hyperprolactinemia, 3) lamotrigine related skin rash, 4) treatment non-adherence, and 5) genetic counselling. Treatment options were scored using a 9-point scale for rating appropriateness of clinical decisions in some issues. In other issues, experts were asked to choose to determine the ranking of preferences on the list. Sixty-four experts of the review committee completed the survey. We classified the expert opinions about preferences by chi2 test. RESULTS: Experts preferred behavioral and diet modification for weight gain, switching to prolactin-sparing-antipsychotics for antipsychotic-induced hyperprolactinemia, reducing dose of lamotrigene for its related benign skin rash, and prescribing once a day for treatment adherence. CONCLUSION: With the limitation of expert opinion, authors hope that the results of this study provide valuable information to make clinical decision about the treatment of bipolar disorder in the complicated situations.
Advisory Committees ; Bipolar Disorder* ; Exanthema ; Expert Testimony ; Food Habits ; Hope ; Hyperprolactinemia ; Weight Gain

OBJECTIVE: The third revision of Korean Medication Algorithm Project for Bipolar Disorder was performed in 2014 in order to provide more proper guideline for clinicians. In this study, we undertook a survey of expert opinion to help clinical decisions in medical comorbidities. METHODS: The questionnaire to survey the expert opinion of medication for bipolar disorder was completed by the review committee consisting of 64 experienced psychiatrists. This survey was composed of 56 main questionnaires of which the contents covered from overall treatment strategies to treatment strategies under the specific situations. The executive committee analyzed the results and discussed the final production of algorithm. RESULTS: In bipolar patients with cardiovascular, diabetic, or hepatic comorbidities, aripiprazole was first-line treatment strategy. In case of renal comorbidity accompanying bipolar disorder, aripiprazole, valproate, and quetiapine were preferred. Valproate was recommended as the first-line strategy in case of bipolar disorder with cerebrovascular diseases. CONCLUSION: This study provided information about the consensus among experts in regard to treatment strategies for bipolar disorder in the medically ill.
Advisory Committees ; Bipolar Disorder* ; Comorbidity* ; Consensus ; Drug Therapy ; Expert Testimony ; Humans ; Psychiatry ; Surveys and Questionnaires ; Valproic Acid ; Aripiprazole ; Quetiapine Fumarate

OBJECTIVE: The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was first published in 2002 through an expert consensus of opinion, and updated in 2006, 2010, and 2014. This study constitutes the fourth revision of the KMAP-BP. METHODS: A 50-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of adult bipolar disorder and six items for pediatric bipolar disorder. The review committee included 84 Korean psychiatrists and 43 child and adolescent psychiatry experts. RESULTS: The preferred first-step strategies for acute mania were the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP), MS monotherapy, and AAP monotherapy. A combination of a MS and an AAP, and AAP monotherapy were preferred for psychotic mania. The first-step strategies for mild to moderate bipolar depression were monotherapy with MS, AAP, or lamotrigine (LMT), and the combination of a MS and an AAP or LMT, or a combination of an AAP and LMT. The combination of two among a MS, AAP, and LMT were preferred for non-psychotic severe depression. A combination of a MS and an AAP or the combination of an AAP with an antidepressant or LMT were the first-line options for psychotic severe depression. CONCLUSION: The recommendations of the KMAP-BP 2018 have changed from the previous version by reflecting recent developments in pharmacotherapy for bipolar disorder. KMAP-BP 2018 provides clinicians with a wealth of information regarding appropriate strategies for treating patients with bipolar disorder.
Adolescent ; Adolescent Psychiatry ; Adult ; Advisory Committees ; Bipolar Disorder* ; Child ; Consensus ; Depression ; Drug Therapy ; Humans ; Psychiatry