Li-Chung Chiu

Lung-protective mechanical ventilation using lower airway pressures remains a cornerstone of the management of acute respiratory distress syndrome (ARDS). However, positive pressure ventilation may contribute to positive fluid balance, which has been associated with adverse clinical outcomes. We prospectively enrolled patients with ARDS and collected clinical characteristics and mechanical ventilation parameters during the first 3 days after ARDS onset. The associations between airway pressures and cumulative fluid balance (CFB) were evaluated. The analysis included 287 patients with ARDS, and the all-cause hospital mortality rate was 45.6%. Patients were divided into the positive CFB group (n = 173, 60.3%) and the negative CFB group (n = 114, 39.7%). Compared with patients in the negative CFB group, those in the positive CFB group had a higher risk of organ failure, higher white blood cell counts, higher C-reactive protein levels, more severe hypoxemia, higher peak inspiratory pressures (Ppeak), and higher hospital mortality (all p < 0.05). Multivariable logistic regression analysis showed that higher Ppeak was independently associated with increased odds of positive CFB (adjusted OR, 1.076; p = 0.011). These findings highlight the potential relationship between airway pressures and fluid accumulation during mechanical ventilation in patients with ARDS.

Background and Objectives: Metabolic perturbations frequently occur during the acute phase of critical illness and may disrupt lipid homeostasis. Acute respiratory distress syndrome (ARDS) is a severe condition and is associated with high mortality in critically ill patients with sepsis. This study aimed to evaluate the association between conventional plasma lipid parameters and clinical outcomes in critically ill sepsis patients. Materials and Methods: We conducted a prospective observational cohort study of critically ill sepsis patients in Taiwan between October 2020 and July 2025. Conventional plasma lipid parameters and clinical variables were measured at intensive care unit admission. Clinical outcomes were compared between patients stratified by plasma HDL-C levels. Results: A total of 285 critically ill patients with sepsis were included. Pneumonia was the presumed source of infection in 91% of patients, and 78% met the criteria for ARDS. The overall hospital mortality rate was 37.9%. Patients with ARDS had significantly higher C-reactive protein (CRP) and interleukin-6 (IL-6) levels, higher risk of organ failure (i.e., APACHE II and SOFA scores), and lower plasma HDL-C levels (all p < 0.05). Non-survivors exhibited significantly greater organ failure severity and lower HDL-C levels compared with survivors (all p < 0.05). Patients with low HDL-C (≤17.5 mg/dL; n = 106, 37.2%) had significantly higher CRP and IL-6, greater organ failure severity, and increased 28-, 60-, 90-day, and hospital mortality, compared with those with high HDL-C (> 17.5 mg/dL; n = 179, 62.8%) (all p < 0.05). In multivariable analyses, lower HDL-C were independently associated with hospital mortality. Conclusions: Lower HDL-C levels were associated with hospital mortality in critically ill patients with sepsis, most of whom had pneumonia and concomitant ARDS. These findings suggest that HDL-C may have prognostic value in this selected critically ill population, although external validation in broader sepsis populations is warranted. An easily accessible and useful for early risk stratification.

Lung-protective mechanical ventilation using lower airway pressures remains a cornerstone of the management of acute respiratory distress syndrome (ARDS). However, positive pressure ventilation may contribute to positive fluid balance, which has been associated with adverse clinical outcomes. We prospectively enrolled patients with ARDS and collected clinical characteristics and mechanical ventilation parameters during the first 3 days after ARDS onset. The associations between airway pressures and cumulative fluid balance (CFB) were evaluated. The analysis included 287 patients with ARDS, and the all-cause hospital mortality rates was 45.6%. Patients were divided into the positive CFB group (n = 173, 60.3%) and the negative CFB group (n = 114, 39.7%). Compared with patients in the negative CFB group, those in the positive CFB group had a higher risk of organ failure, higher white blood cell counts, higher C-reactive protein levels, more severe hypoxemia, higher peak inspiratory pressures (Ppeak), and higher hospital mortality (all p < 0.05). Multivariable logistic regression analysis showed that higher Ppeak was independently associated with increased odds of positive CFB (adjusted OR, 1.076; p = 0.011). These findings highlight the potential relationship between airway pressures and fluid accumulation during mechanical ventilation in patients with ARDS.

Background and Objectives: Metabolic perturbations frequently occur during the acute phase of critical illness and may disrupt lipid homeostasis. Acute respiratory distress syndrome (ARDS) is a severe condition that contributes to multiple organ failure and is associated with high morbidity and mortality in critically ill patients with sepsis. This study aimed to evaluate the association between conventional plasma lipid parameters and clinical outcomes in critically ill sepsis patients. Materials and Methods: We conducted a prospective observational cohort study of critically ill sepsis patients in Taiwan between October 2020 and July 2025. Conventional plasma lipid parameters and clinical variables were measured at intensive care unit (ICU) admission. Clinical outcomes were compared between patients stratified by plasma HDL-C levels. Results: A total of 285 critically ill patients with sepsis were included. The overall all-cause hospital mortality rate was 37.9%. Patients with ARDS had significantly higher C-reactive protein (CRP) and interleukin-6 (IL-6) levels, higher risk of organ failure (i.e., APACHE II and SOFA scores), and lower plasma HDL-C levels (all p < 0.05). Non-survivors exhibited significantly greater organ failure severity and lower HDL-C levels compared with survivors (all p < 0.05). Patients with low HDL-C (≤ 22.5 mg/dL; n = 162, 56.8%) had significantly higher CRP and IL-6, greater organ failure severity, and increased 28-, 60-, 90-day, and hospital mortality, compared with those with high HDL-C (> 22.5 mg/dL; n = 123, 43.2%) (all p < 0.05). In multivariable logistic regression analyses, lower HDL-C were independently associated with hospital mortality. Conclusions: Plasma HDL-C levels at ICU admission are independently associated with hospital mortality in critically ill patients with sepsis. HDL-C may serve as a simple, accessible, and useful for early risk stratification in critically ill patients with sepsis.

Background/Objectives: Mechanical power (MP) refers to ventilator-delivered energy to the lungs, which may induce lung injury. We examined the relationship between MP and mortality in patients with acute respiratory distress syndrome (ARDS) who underwent prone positioning. Methods: This multicenter retrospective study included data on all patients admitted to the intensive care units of eight referral hospitals in Taiwan from October 2015 to March 2016, and in Chang Gung Memorial Hospital Linkou branch from January 2017 to October 2023. The data were obtained from the electronic medical records of each hospital by using a standard case report form. MP was calculated as follows: MP (J/min) = 0.098 × VT × RR × (Ppeak − 1/2 × ΔP). Results: We included 135 patients who underwent prone positioning. Among them, 28-day survivors had significantly lower MP (22.6 ± 6.5 vs. 25.3 ± 6.2 J/min, p = 0.024), MP/predicted body weight (PBW) (396.9 ± 118.9 vs. 449.3 ± 118.8 10⁻³ J/min/kg, p = 0.018), MP/compliance values (0.8 ± 0.3 vs. 1.1 ± 0.4 J/min/mL/cmH₂O, p = 0.048) after prone positioning, and significantly lower changes in MP, MP/PBW, and MP/compliance (−0.6 ± 5.7 vs. 2.5 ± 7.4 J/min, p = 0.007; −9.2 ± 97.5 vs. 42.1 ± 127.9 10⁻³ J/min/kg, p = 0.010; −0.1 ± 0.3 vs. 0.2 ± 0.3 J/min/mL/cmH₂O, p < 0.001, respectively). Multivariate Cox regression revealed that the change in MP/compliance (HR: 7.972, p < 0.001) was an independent predictive factor for 28-day mortality. Conclusions: In ARDS patients treated with prone positioning, MP/compliance, and change in MP, MP/PBW, and MP/compliance after prone positioning differed significantly between 28-day survivors and nonsurvivors. Further randomized controlled research is required to elucidate the potential causality of decreased MP and improved clinical outcomes.

Backgroud: This prospective randomized trial evaluated the clinical efficacy of inhaled colistin administered through two distinct nebulizer types, a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN), in the treatment of ventilator-associated pneumonia caused by multidrug-resistant bacteria. In addition, an in vitro model was used to determine the optimal delivery of colistin. Method: Thirty-two patients prescribed intravenous (IV) colistin inhalation were randomized to receive either a VMN (n = 17) or a JN (n = 15), then compared to the control group (IV alone) over a 7-to 10-day period. The primary endpoint was the clinical pulmonary infection score (CPIS), and the secondary endpoints were the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACE) score, and duration of ventilator use. Results: Results from in vitro testing demonstrated that VMN delivered a significantly higher colistin dose than JN (35.68 ± 3.55% vs. 23.56 ± 3.31%; p < 0.001) when positioned at the humidifier inlet. Compared to the IV alone group, the IV with inhalation group yielded significant improvements in CPIS, SOFA score, and APACHE score on day 7; nevertheless, clinical outcomes between the two nebulizers were statistically indistinguishable. Conclusions: In conclusion, although VMN delivers a higher dose in vitro, both nebulizers yielded comparable clinical outcomes. This study was registered at US Clinical Trial Registration (NCT04633317).

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25–8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12–17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).

Background: This study aimed to investigate the factors associated with prolonged progression‐free survival (PFS) (>36 months) of advanced non‐small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations treated with first‐line afatinib.Methods: We performed a retrospective analysis of data of patients with advanced EGFR‐mutated NSCLC receiving first‐line afatinib at two tertiary care referral centers, Linkou and Kaohsiung Chang Gung Memorial Hospital, in Taiwan between June 2014 and April 2022.Results: The data of 546 treatment‐naïve EGFR‐mutated advanced NSCLC patients were analyzed. Median PFS and overall survival were 14.5 months and 27.2 months, respectively. The PFS of 462 patients (84.6%) was less than 36 months and of 84 patients (15.4%) was more than 36 months. The PFS > 36 months group had a significantly higher percentage of patients with uncommon mutations (p = 0.002). The PFS ≤36 months group had significantly higher incidences of bone, liver, and adrenal metastases (all p < 0.05) and a higher rate of multiple distant metastases. Multivariate logistic regression analysis showed that liver metastasis was negatively and independently associated with prolonged PFS (adjusted odds ratio = 0.246 [95% CI: 0.067–0.908], p = 0.035). The median overall survival of the PFS >36 months group was 46.0 months and that of the PFS ≤36 months group was 22.9 months (log‐rank test, p < 0.001).Conclusions: We found that EGFR‐mutated NSCLC patients receiving first‐line afatinib were prone to shorter PFS if they had distant organ metastasis, especially liver metastasis.

Acute respiratory distress syndrome (ARDS) involves dysregulated immune-inflammatory responses, characterized by severe oxidative stress and high mortality. Metabolites modulating the inflammatory and immune responses may play a central role in the pathogenesis of ARDS. Most biogenic amines may induce the production of reactive oxygen species, oxidative stress, mitochondrial dysfunction, and programmed cell death. We conducted a prospective study on metabolic profiling specific to the amino acids and biogenic amines of 69 patients with ARDS. Overall, hospital mortality was 52.2%. Between day 1 and day 7 after ARDS onset, plasma kynurenine levels and the kynurenine/tryptophan ratio were significantly higher among non-survivors than in survivors (all p < 0.05). Urine metabolic profiling revealed a significantly higher prevalence of tryptophan degradation and higher concentrations of metabolites downstream of the kynurenine pathway among non-survivors than among survivors upon ARDS onset. Cox regression models revealed that plasma kynurenine levels and the plasma kynurenine/tryptophan ratio on day 1 were independently associated with hospital mortality. The activation of the kynurenine pathway was associated with mortality in patients with ARDS. Metabolic phenotypes and modulating metabolic perturbations of the kynurenine pathway could perhaps serve as prognostic markers or as a target for therapeutic interventions aimed at reducing oxidative stress and mortality in ARDS.