Purpose: While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. Materials and Methods: We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. Results: A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Conclusion Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Purpose: While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. Materials and Methods: We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. Results: A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Conclusion Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Purpose: While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. Materials and Methods: We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. Results: A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Conclusion Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

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.

Background/Aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge. Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab. Results: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of antitumor macrophages and activated T-cells, potentially explaining its better response. Conclusions Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

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.