Objective: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). Methods: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women.In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. Results: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (−98.61%; 95% confidence interval=−99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. Conclusion The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads.

Objective: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). Methods: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women.In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. Results: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (−98.61%; 95% confidence interval=−99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. Conclusion The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads.

Objective: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). Methods: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women.In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. Results: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (−98.61%; 95% confidence interval=−99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. Conclusion The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads.

Purpose: The incidence and prognostic implications of atrial fibrillation (AF) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are controversial, especially for Korean patients. Furthermore, the pattern of antithrombotic therapy for these patients is unknown. The present study sought to identify the impact of AF on Korean patients undergoing TAVI and demonstrate the status of antithrombotic therapy for these patients. Materials and Methods: A total of 660 patients who underwent TAVI for severe AS were recruited from the nationwide K-TAVI registry in Korea. The enrolled patients were stratified into sinus rhythm (SR) and AF groups. The primary endpoint was all-cause death at 1-year. Results: AF was recorded in 135 patients [pre-existing AF 108 (16.4%) and new-onset AF 27 (4.1%)]. The rate of all-cause death at 1 year was significantly higher in patients with AF than in those with SR [16.2% vs. 6.4%, adjusted hazard ratio (HR): 2.207, 95% confidence interval (CI): 1.182–4.120, p=0.013], regardless of the onset timing of AF. The rate of new pacemaker insertion at 1 year was also significantly higher in patients with AF than in those with SR (14.0% vs. 5.5%, adjusted HR: 3.137, 95%CI: 1.621–6.071, p=0.001).Among AF patients, substantial number of patients received the combination of multiple antithrombotic agents (77.8%), and the most common combination was that of aspirin and clopidogrel (38.1%). Conclusion AF was an independent predictor of 1-year mortality and new pacemaker insertion in Korean patients undergoing TAVI.

Purpose: Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. Results The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.

Purpose: Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. Results The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.

Objective: To assess the safety and efficacy of lymphopseudoaneurysm (LPA) glue (n-butyl cyanoacrylate [NBCA]) embolization in the management of chylous ascites after retroperitoneal surgery. Materials and Methods: A retrospective analysis from January 2014 to October 2018 was performed in six patients (4 females and 2 males; mean age, 45.3 ± 14.2 years; range, 26–61 years) who underwent LPA embolization for chylous ascites developing after retroperitoneal surgery involving the perirenal space (four donor nephrectomies, one partial nephrectomy, and one retroperitoneal lymphadenectomy). After placing a percutaneous drainage catheter into the LPA or adjacent lymphocele, embolization was performed by filling the LPA itself with a mixture of glue and Lipiodol (Guerbet). Results: Daily drainage from percutaneously placed drains exceeded 300 mL/day despite medical and surgical treatment (volume: mean, 1173 ± 1098 mL; range, 305–2800 mL). Intranodal lymphangiography was performed in four of the six patients and revealed leakage in 2 patients. Percutaneous embolization of the LPA was successful in all patients using an NBCA and Lipiodol mixture in a ratio of 1:1–1:2 (volume: mean, 4.3 ± 1.1 mL; range, 3–6 mL). Chylous ascites was resolved and the drainage catheter was removed in all patients within 4 days after the procedure (mean, 2.0 ± 1.8 days; range, 0–4 days). No procedure-related complications or recurrence of chylous ascites occurred during a mean follow-up period of 37.3 months (range, 21.1–48.4 months). Conclusion Glue embolization of LPA has the potential to be a feasible and effective treatment method for the management of chylous ascites after retroperitoneal surgery.

PURPOSE: Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults.METHODS: A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated.RESULTS: PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis.CONCLUSIONS: In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.
Adult ; Anaphylaxis ; Anxiety ; C-Reactive Protein ; Depression ; Hospitals, University ; Humans ; Hypersensitivity ; Interleukin-6 ; Korea ; Multivariate Analysis ; Necrosis ; Prevalence ; Prospective Studies ; Stress Disorders, Post-Traumatic ; Tryptases

The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Background/Aims: To date, prospective data are limited on efficacy and safety profiles of statin therapy in Korean hypercholesterolemic patients. Hence, the aim of this study was to evaluate the practice patterns of statin therapy and its efficacy and safety through the prospective Daegu and Gyeongbuk statin registry. Methods: Statin naïve patients who were prescribed statins according to the criteria of Korean Guidelines for Management of Dyslipidemia were enrolled. Clinical and laboratory evaluations were performed at baseline and at week 8, where the efficacy was assessed with the same guidelines. Results: Of 908 patients, atorvastatin and rosuvastatin were most frequently prescribed statins (63.1% and 29.3%, respectively). High intensity statins (atorvastatin 40 mg or rosuvastatin 20 mg) were prescribed in 24.7% of all patients and in 79.5% of high and very high risk groups. The total and low density lipoprotein (LDL) cholesterol levels decreased from 203.7 ± 43.0 to 140.6 ± 28.6 mg/dL and 134.4 ± 35.7 to 79.5 ± 21.3 mg/dL, respectively. The achievement rate of the LDL target goal was 98.6% in low risk, 95.0% in moderate risk, 88.1% in high risk, and 42.1% in very high risk patients (59.7% in overall). There was no significant difference in the efficacy between atorvastatin and rosuvastatin. Adverse events were observed in 12.0% of patients and led to 1.4% of treatment cessation. Conclusions The efficacy of the usual starting dose of statins in daily practice was relatively insufficient for Korean hypercholesterolemic patients with high or very high risks. Short-term adverse events of statin therapy were not common in Korean patients with a low discontinuation rate.