Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated. Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated. Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated. Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Background: The purpose of this study was to evaluate the clinical and radiological outcomes of high-flexion total knee arthroplasty (TKA) using Vega Knee System (B. Braun, Aesculap) at a long-term follow-up and to analyze the implant survivorship. Methods: We enrolled 165 patients (232 knees) with a minimum 7-year follow-up after TKA (VEGA Knee System). For clinical assessment, range of motion (ROM), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used. For radiologic assessment, hip-knee-ankle angle, component position, and the existence of radiolucent lines and loosening were used. Survival analysis was conducted using the Kaplan-Meier method. Results: The mean follow-up period was 9.8 years. The mean ROM increased from 124.4° to 131.4° at the final follow-up. The WOMAC score decreased from 38.5 to 17.4 at the final follow-up (p < 0.001). All 5 subscales of the KOOS improved at the final follow-up (all subscales, p < 0.001). Revision TKA was performed in 10 cases (4.3%), which included 9 cases of aseptic loosing and 1 case of periprostatic joint infection. Of the 9 aseptic loosening cases (3.9%), 8 cases (3.4%) were loosening of the femoral component and 1 case (0.4%) was loosening of the tibial component. When revision for any reason was considered an endpoint, the 10-year survivorship was 96.2% (95% confidence interval [CI], 93.9%–98.5%). On the other hand, when revision for aseptic loosening was considered the endpoint, the 10-year survivorship was 96.6% (95% CI, 94.4%–98.8%). Conclusions The Vega Knee System provided good clinical results in the long-term follow-up period. Although the VEGA Knee System showed acceptable implant survivorship, loosening of the femoral component occurred in about 3.4% of the patients. For more accurate evaluation of the survivorship of high-flexion design TKA with a short posterior flange, it is necessary to conduct more long-term follow-up studies targeting diverse races, especially Asians who frequently perform high-flexion activities.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Background/Aims: Recently, 1-L polyethylene glycol-ascorbic acid (PEG-Asc) has been used to reduce the volume of preparation agents in colonoscopy. This clinical trial aimed to compare the efficacy and safety of two types of 1-L PEG-Asc (CleanViewAL ® [Tae Joon Pharmaceutical Company, Seoul, Korea] and Plenvu ® [Norgine, Harefield, United Kingdom]) in average-aged adults. Methods: This study was a prospective, randomized, non-inferiority, open-label, phase 4 clinical trial. The primary endpoint was the efficacy evaluated using the Boston bowel preparation scale (BBPS), and the secondary endpoint was clinical safety. Results: In total, 173 patients were assigned to either the CleanViewAL ® (n=84) or Plenvu ® (n=89) group. Overall cleansing successes of 97.6% (82/84) and 98.8% (88/89) were achieved in the CleanViewAL ® group and in the Plenvu ® group, respectively, showing that CleanViewAL ® has similar bowel cleansing efficacy to Plenvu ® (95% CI, -0.052 to 0.027; p=0.207). The total BBPS score was 8.67±1.00 and 8.70±0.76 in the CleanViewAL ® group and Plenvu ® group, respectively (p=0.869). The most common adverse symptom was nausea, and no adverse symptoms requiring hospitalization were reported in either group. There were no cases of critical hypernatremia and liver dysfunction exceeding the common terminology criteria for adverse events grade I. An overall satisfaction score (scale of 1 to 10) showed no difference between the two groups (p=0.289). However, the CleanViewAL ® group showed a higher taste satisfaction score (scale of 1 to 5) than the Plenvu ® group (CleanViewAL ® : 2.90±0.91, Plenvu ® : 2.60±0.86, p=0.028). Conclusions Both types of 1-L PEG-Asc, CleanViewAL ® and Plenvu ® , are effective and safe bowel cleansing agents in average-aged adults. CleanViewAL ® was preferred in terms of taste satisfaction.

Objectives: In this study, we investigated and organized the maintenance-treatment strategies for Bipolar I and II disorders outlined in The Korean Medication Algorithm Project for Bipolar disorder 2022 (KMAP-BP 2022). Methods: The questionnaire sought to survey expert opinion on medication for bipolar disorders and was completed by a review committee consisting of 87 experienced Korean psychiatrists. It comprised 56 questions, and each question included various sub-items. The questionnaire for the maintenance treatments covered overall treatment strategies after acute mood episodes in bipolar I and II disorders, the choice of mood stabilizers and atypical antipsychotics and antidepressants, duration of medication, and treatment strategies for breakthrough symptoms. Results: In the case of bipolar I disorder, mood stabilizer monotherapy, atypical antipsychotics monotherapy, and a combination of mood stabilizers and atypical antipsychotics were selected as the first-line treatments. In maintenance management of bipolar II disorder, mood stabilizer monotherapy, atypical antipsychotics monotherapy, and combinations of mood stabilizers were selected as the preferred first-line treatments. Conclusion There has been a growing body of evidence that atypical antipsychotics have a greater preference than observed in the previous KMAP-BP of 2018. Also, monotherapy of mood stabilizers or atypical antipsychotics was more frequently selected in KMAP-BP 2022 than in the KMAP-BP 2018.

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: 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.

Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.