The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.

Methods: In retrospectively collected data, 149 patients who underwent single-level ACDF for degenerative disease were enrolled and divided into non-plating (n=66) and plating (n=83). Interspinous motion (ISM) at the arthrodesis segment, Numeric Rating Scale (NRS) for neck pain, and Neck Disability Index (NDI) were serially evaluated at 3, 6, and 12 months postoperatively. Predictable factors for fusion, including age, sex, plating, diabetes, smoking, and type of grafts, were investigated, and fusion was defined as ISM <1 mm. Results: In both groups, ISM was the highest at 3 months and gradually decreased thereafter, and the plating group showed significantly lower serial ISM than the non-plating group at 12 months. The plating group had lower NRS and NDI scores than the nonplating group at 12 months, and the difference in the NRS scores was statistically significant, particularly at 3 and 6 months, although that of the NDI scores was not. In a multivariate analysis, plating was the most powerful predictor for fusion. Conclusions Plating significantly decreases the serial ISM compared with non-plating in single-level ACDF, and such decreased motion is correlated with decreased neck pain until 12 months postoperatively, particularly at 3 and 6 months. Given that plating was the most predictive factor for fusion, we recommend plating even in single-level ACDF for better early clinical outcomes.

Purpose: There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. Materials and Methods: Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. Results: 193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. Conclusion Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

Objective: Alcohol consumption is a frequent risk factor for trauma. The shock index is widely used to predict the prognosis of trauma, and alcohol can influence the shock index in several ways. This study investigated the usefulness of the shock index in trauma patients who had ingested alcohol. Methods: This was a retrospective, observational, single-center study. We performed a logistic regression analysis to assess the association between alcohol consumption and massive transfusions. A receiver operating characteristic (ROC) curve was constructed to determine the predictive value of the shock index for patients who had ingested alcohol. Results: A total of 5,128 patients were included in the study. The alcohol-positive group had lower systolic blood pressure and higher heart rate; consequently, the shock index in this group was higher. There was no significant difference between the proportion of the alcohol-positive and alcohol-negative groups who underwent massive transfusions and suffered hospital mortality compared to the overall proportion of patients who underwent massive transfusion based on the shock index. In the logistic regression analysis, the alcohol-negative group showed higher odds ratios for massive transfusions compared to the alcohol-positive group. The area under the ROC curve for predicting massive transfusion was 0.831 for the alcohol-positive group and 0.825 for the alcohol-negative group. However, when a cutoff value of 1 was used, the false positive rate was significantly higher in the alcohol-positive group. Conclusion The shock index is a useful tool for predicting outcomes in patients with trauma. However, in patients who have ingested alcohol, the shock index should be interpreted with caution.

Objectives: Treatment guidelines or an algorithm can help clinicians implement better practices and clinical decisions. Therefore, the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) was revised again through a consensus of expert opinion. The diagnosis and treatment of mixed features are not simple, and there are many things to discuss. We describe the preferences and recommendations from KMAP-BP 2022 for the treatment of mood episodes with mixed features. Methods: We revised the KMAP-BP 2018 questionnaire and conducted the survey with expert clinicians. Out of ninety-three members of the review committee, eighty-seven completed the survey. We analyzed the answers, discussed the data, and held a clinician hearing. Results: In first-step strategies for mixed features with more manic symptoms, a combination of a mood stabilizer and an atypical antipsychotic is the treatment of choice. Mood stabilizer monotherapy and atypical antipsychotic monotherapy are preferred strategies. For mixed features with more depressive symptoms, a combination of mood stabilizer and atypical antipsychotic, a combination of atypical antipsychotic and lamotrigine (LMT), atypical antipsychotic monotherapy, a combination of mood stabilizer and LMT, and mood stabilizer monotherapy are preferred. For mixed features with similar manic symptoms and depressive symptoms, a combination of mood stabilizer and atypical antipsychotic, atypical antipsychotic monotherapy, and mood stabilizer monotherapy are preferred. Conclusion For mixed features, a combination of mood stabilizer and atypical antipsychotic is generally preferred, and LMT is preferred for depressive symptoms. Compared with KMAP-BP 2018, more diverse strategies and drugs are being attempted for the treatment of mixed features.

Objectives: After the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002, its fifth revision was completed in 2022 to reflect the recent rapid developments and research into bipolar disorder and its psychopharmacology. Methods: According to the methodology for previous versions, the depressive episode section of KMAP-BP 2022 was revised based on a survey consisting of 11 questions. Among ninetythree experts, eighty-seven members of the review committee (93.5%) completed the survey.The executive committee analyzed the results and discussed the final production of an algorithm by considering the scientific evidence. Results: Overall, the results from this study showed little change in comparison with previous versions of KMAP-BP. However, there have been significant changes in recommendations over the span of about 20 years. The preferences for lamotrigine and atypical antipsychotics, especially aripiprazole, quetiapine, and olanzapine, have shown a tendency to continuously increase, but the preferences for risperidone and ziprasidone have not increased, but have decreased. Moreover, the preference for typical antipsychotics has significantly decreased. Additionally, concerns over the use of antidepressants in bipolar depression have been raised, and their use is not recommended in KMAP-BP 2022 as a first-line treatment. Conclusion Pharmacotherapy for acute depressive episodes with various clinical progressions and various subtypes still shows diversity, compared to pharmacotherapy for mania. We look forward to the development of bipolar depressive, episode-specific therapeutic drugs in the future, and hope the fifth update of KMAP-BP will be a complementary option for clinicians and their patients with bipolar disorder.

Objectives: The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) is a consensus-based medication guideline. To reflect advances in pharmacotherapy for bipolar disorders, we updated KMAP-BP to provide more timely information for clinicians. Methods: We conducted a survey using a questionnaire on treatments formanic/hypomanic episodes. Eighty-seven members among ninety-three members of the review committee (93.5%) completed the survey. Each treatment strategy or treatment option for manic/hypomanic episodes was evaluated with an overall score of 9, and the resulting 95% confidence interval treatment options were categorized into three recommendation levels (primary, secondary, and tertiary). The executive committee analyzed the results and discussed the final production of an algorithm by considering the scientific evidence. Results: The combination of a mood stabilizer and an atypical antipsychotic, monotherapy with a mood stabilizer, or monotherapy with an atypical antipsychotic were recommended as the firstline pharmacotherapeutic strategy for the initial treatment of mania without psychotic features. The mood stabilizer and atypical antipsychotic combination was the treatment of choice, and atypical antipsychotic monotherapy was the first-line treatment for mania with psychotic features. When initial treatment fails, a combination of mood stabilizer+atypical antipsychotic and switching to another first-line agent is recommended. For hypomania, monotherapy with either mood stabilizer or atypical antipsychotic is the recommended first-line treatment, but the mood stabilizer+atypical antipsychotic combination is recommended as well. Conclusion It is notable that there were changes in the preferences for the use of individual atypical antipsychotics, and the preference for the use of mood stabilizer increased for treatment-resistant mania.

Objectives: The pharmacotherapy of bipolar disorder is complex. A treatment guideline or algorithm can help clinicians implement better practices and clinical decisions. Therefore, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was revised through expert consensus on pharmacotherapy for bipolar disorder. Methods: We revised the KMAP-BP 2018 questionnaire and conducted a survey of expert clinicians. Out of ninety-three members of the review committee, eighty-seven completed the survey. We analyzed the answers, discussed the data, and held a clinician hearing. Here, we report the results from KMAP-BP 2022. Results: The preferred first-step strategies for acute euphoric mania are a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP), MS monotherapy, and AAP monotherapy. For psychotic mania, an MS and AAP combination, and AAP monotherapy are preferred. For hypomania, MS monotherapy and AAP monotherapy are preferred. The first-step strategies for mild to moderate bipolar depression are MS monotherapy, lamotrigine (LMT) monotherapy, AAP monotherapy, an MS+AAP combination, and an AAP+LMT combination. For non-psychotic severe depression, the MS+AAP combination, the AAP+LMT combination, and the MS+LMT combination are preferred. For psychotic severe depression, MS+AAP and AAP+LMT are preferred. Conclusion We obtained expert consensus and developed KMAP-BP 2022. Compared with KMAP-BP 2018, we can figure out clinicians’ preferences and decisions in real clinical situations more clearly. The preference for AAP increased, and that of MS and an antidepressant decreased. We hope KMAP-BP 2022 is helpful for clinicians who treat patients with bipolar disorder.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) first was published in 2002, and has been revised four times, in 2006, 2012, 2017, and 2021. In this review, we compared recommendations from the recently revised KMAP-DD 2021 to four global clinical practice guidelines (CPGs) for depression published after 2010. The recommendations from the KMAP-DD 2021 were similar to those from other CPGs, although there were some differences. The KMAP-DD 2021 reflected social culture and the healthcare system in Korea and recent evidence about pharmacotherapy for depression, as did other recently published evidence-based guidelines. Despite some intrinsic limitations as an expert consensus-based guideline, the KMAP-DD 2021 can be helpful for Korean psychiatrists making decisions in clinical settings by complementing previously published evidence-based guidelines, especially for some clinical situations lacking evidence from rigorously designed clinical trials.

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.