Purpose: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

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: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

Purpose: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

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: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

Purpose: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

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.

Background: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. Methods: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. Results: The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. Conclusion In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

Purpose: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. Materials and Methods: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. Results: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07–1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61–8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). Conclusion Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking.