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Abstract Rationale The prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests. Objectives To identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs). Methods We conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria. Measurements and main results Of the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality. Conclusions An aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes.

Abstract Background Pathogenesis of acute respiratory distress syndrome (ARDS) involves immune cell death and removal from the injured lungs. ARDS severity is related to lung compliance. However, the correlation between the respiratory mechanics and alveolar immune cell death in patients with ARDS remains unclear. Methods Twenty-four patients with respiratory failure and ARDS were enrolled in the intensive care unit between November 2019 and November 2021. Neutrophil extracellular traps (NETs) and cell death of lymphocytes and monocytes in bronchoalveolar lavage fluid were detected on days 1 and 8. Results Lung compliance was positively correlated with the cell death percentage of alveolar CD4/CD8 lymphocytes and monocytes on day 8 (Pearson’s correlation coefficient (r) = 0.554, p = 0.005; r = 0.422, p = 0.040; r = 0.569, p = 0.004, respectively). There was no association between lung compliance and the percentage of alveolar NETs on days 1 and 8. The cell death percentages of alveolar CD4/CD8 lymphocytes and monocytes were negatively correlated with driving pressure (DP) on days 1 (r = − 0.440, p = 0.032; r = − 0.613, p = 0.001; r = -0.557, p = 0.005, respectively) and 8 (r = − 0.459, p = 0.024; r = − 0.407, p = 0.048; r = − 0.607, p = 0.002, respectively). The cell death percentages of alveolar CD4/CD8 lymphocytes and monocytes were also negatively correlated with mechanical power (MP) on days 1 (r = − 0.558, p = 0.005; r = − 0.593, p = 0.002; r = − 0.571, p = 0.004, respectively) and 8 (r = − 0.539, p = 0.007; r = − 0.338, p = 0.107; r = − 0.649, p

Sepsis may induce immunosuppression and result in death. S100A12 can bind to the receptor for advanced glycation end-products (RAGE) and Toll-like receptor (TLR)4 following induction of various inflammatory responses. It is unclear whether S100A12 significantly influences the immune system, which may be associated with sepsis-related mortality. We measured plasma S100A12 levels and cytokine responses (mean ± standard error mean) of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) after S100A12 inhibition in healthy controls and patients with sepsis on days one and seven. Day one plasma soluble RAGE (sRAGE) and S100A12 levels in patients with sepsis were significantly higher than those in controls (2481.3 ± 295.0 vs. 1273.0 ± 108.2 pg/mL, p < 0.001; 530.3 ± 18.2 vs. 310.1 ± 28.1 pg/mL, p < 0.001, respectively). Day seven plasma S100A12 levels in non-survivors were significantly higher than those in survivors (593.1 ± 12.7 vs. 499.3 ± 23.8 pg/mL, p = 0.002, respectively). In survivors, plasma sRAGE levels were significantly decreased after 6 days (2297.3 ± 320.3 vs. 1530.1 ± 219.1 pg/mL, p = 0.009, respectively), but not in non-survivors. Inhibiting S100A12 increased the production of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in stimulated PBMCs for both controls and patients. Therefore, S100A12 plays an important role in sepsis pathogenesis. S100A12 may competitively bind to TLR4 and RAGE, resulting in decreased IL-10 and TNF-α production.

Abstract Background Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Methods We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. Results A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214–4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018–1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002–1.007], p 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p

Driving pressure (ΔP) and mechanical power (MP) are associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). We aimed to investigate which was better to predict mortality between changes in ΔP and MP. We reanalyzed data from a prospective observational cohort study of patients with ARDS in our hospital. Serial ΔP and MP values were calculated. The factors associated with survival were analyzed. Binary logistic regression showed that age (odds ratio (OR), 1.012; 95% confidence interval (CI), 1.003–1.022), Sequential Organ Failure assessment (SOFA) score (OR, 1.144; 95% CI, 1.086–1.206), trauma (OR, 0.172; 95% CI, 0.035–0.838), ΔP (OR, 1.077; 95% CI, 1.044–1.111), change in ΔP (OR, 1.087; 95% CI, 1.054–1.120), and change in MP (OR, 1.018; 95% CI, 1.006–1.029) were independently associated with 30-day mortality. Change in MP, change in ΔP, and SOFA scores were superior to ΔP in terms of the accuracy of predicting 30-day mortality. In conclusion, calculating change in ΔP is easy for respiratory therapists in clinical practice and may be used to predict mortality in patients with ARDS.

Critically ill patients, such as those in intensive care units (ICUs), can develop herpes simplex virus (HSV) pneumonitis. Given the high prevalence of acute respiratory distress syndrome (ARDS) and multiple pre-existing conditions among ICU patients with HSV pneumonitis, factors predicting mortality in this patient population require further investigation. In this retrospective study, the bronchoalveolar lavage or sputum samples of ICU patients were cultured or subjected to a polymerase chain reaction for HSV detection. Univariable and multivariable Cox regressions were conducted for mortality outcomes. The length of hospital stay was plotted against mortality on Kaplan–Meier curves. Among the 119 patients with HSV pneumonitis (age: 65.8 ± 14.9 years), the mortality rate was 61.34% (73 deaths). The mortality rate was significantly lower among patients with diabetes mellitus (odds ratio [OR] 0.12, 95% confidence interval [CI]: 0.02–0.49, p = 0.0009) and significantly higher among patients with ARDS (OR: 4.18, 95% CI: 1.05–17.97, p < 0.0001) or high (≥30) Acute Physiology and Chronic Health Evaluation II scores (OR: 1.08, 95% CI: 1.00–1.18, p = 0.02). Not having diabetes mellitus (DM), developing ARDS, and having a high Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independent predictors of mortality among ICU patients with HSV pneumonitis.

Recent studies have reported that mechanical power (MP) is associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). We aimed to investigate the association between 28-day mortality and MP in patients with severe pneumonia. In total, the data of 313 patients with severe pneumonia were used for analysis. Serial MP was calculated daily for either 21 days or until ventilator support was no longer required. Compared with the non-ARDS group, the ARDS group (106 patients) demonstrated lower age, a higher Acute Physiology and Chronic Health Evaluation II score, lower history of diabetes mellitus, elevated incidences of shock and jaundice, higher MP and driving pressure on Day 1, and more deaths within 28 days. Regression analysis revealed that MP was an independent factor associated with 28-day mortality (odds ratio, 1.048; 95% confidence interval, 1.020–1.077). MP was persistently high in non-survivors and low in survivors among the ARDS group, the non-ARDS group, and all patients. These findings indicate that MP is associated with the 28-day mortality in ventilated patients with severe pneumonia, both in the ARDS and non-ARDS groups. MP had a better predicted value for the 28-day mortality than the driving pressure.

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome caused by direct (local damage to lung parenchyma) or indirect lung injury (insults from extrapulmonary sites with acute systemic inflammatory response), the clinical and biological complexity can have a profound effect on clinical outcomes. We performed a retrospective analysis of 152 severe ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Our objective was to assess the differences in clinical characteristics and outcomes of direct and indirect ARDS patients receiving ECMO. Overall hospital mortality was 53.3%. A total of 118 patients were assigned to the direct ARDS group, and 34 patients were assigned to the indirect ARDS group. The 28-, 60-, and 90-day hospital mortality rates were significantly higher among indirect ARDS patients (all p < 0.05). Cox regression models demonstrated that among direct ARDS patients, diabetes mellitus, immunocompromised status, ARDS duration before ECMO, and SOFA score during the first 3 days of ECMO were independently associated with mortality. In indirect ARDS patients, SOFA score and dynamic compliance during the first 3 days of ECMO were independently associated with mortality. Our findings revealed that among patients receiving ECMO, direct and indirect subphenotypes of ARDS have distinct clinical outcomes and different predictors for mortality.

Extracorporeal membrane oxygenation (ECMO) is considered a salvage therapy in cases of severe acute respiratory distress syndrome (ARDS) with profound hypoxemia. However, the need for high-volume fluid resuscitation and blood transfusions after ECMO initiation introduces a risk of fluid overload. Positive fluid balance is associated with mortality in critically ill patients, and conservative fluid management for ARDS patients has been shown to shorten both the duration of mechanical ventilation and time spent in intensive care, albeit without a significant effect on survival. Nonetheless, few studies have addressed the influence of fluid balance on clinical outcomes in severe ARDS patients undergoing ECMO. In the current retrospective study, we examined the impact of cumulative fluid balance (CFB) on hospital mortality in 152 cases of severe ARDS treated using ECMO. Overall hospital mortality was 53.3%, and we observed a stepwise positive correlation between CFB and the risk of death. Cox regression models revealed that CFB during the first 3 days of ECMO was independently associated with higher hospital mortality (adjusted hazard ratio 1.110 [95% CI 1.027–1.201]; p = 0.009). Our findings indicate the benefits of a conservative treatment approach to avoid fluid overload during the early phase of ECMO when dealing with severe ARDS patients.

The high mortality rate of patients with severe acute respiratory distress syndrome (ARDS) warrants aggressive clinical intervention. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for life-threatening hypoxemia. Randomized controlled trials of ECMO for severe ARDS comprise a number of ethical and methodological issues. Therefore, indications and optimal timing for implementation of ECMO, and predictive risk factors for outcomes have not been adequately investigated. We performed propensity score matching to match ECMO-supported and non-ECMO-supported patients at 48 h after ARDS onset for comparisons based on clinical outcomes and hospital mortality. A total of 280 severe ARDS patients were included, and propensity score matching of 87 matched pairs revealed that the 90-d hospital mortality rate was 56.3% in the ECMO group and 74.7% in the non-ECMO group (p = 0.028). Subgroup analysis revealed that greater severity of ARDS, higher airway pressure, or a higher Sequential Organ Failure Assessment score tended to benefit from ECMO treatment in terms of survival. Multivariate logistic regression revealed that hospital mortality was significantly lower among patients who received ECMO than among those who did not. Our findings suggested that early initiation of ECMO (within 48 h) may increase the likelihood of survival for patients with severe ARDS.

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) increases the mortality of acute respiratory distress syndrome (ARDS) patients. The aim of this study was to investigate the outcomes and predictors of RRT in patients with influenza pneumonia-related ARDS. This retrospective cohort study includes patients from eight tertiary referral centers in Taiwan between January and March 2016, and all 282 patients with influenza pneumonia-related ARDS were enrolled. Thirty-four patients suffered from AKI requiring RRT, while 16 patients had underlying end stage renal disease (ESRD). The 30- and 60-day mortality rates were significantly higher in patients with AKI requiring RRT compared with those not requiring RRT (50.0% vs. 19.8%, p value < 0.001; 58.8% vs. 27.2%, p value = 0.001, respectively), but the patients with ESRD had no significant difference in mortality (12.5% vs. 19.8%, p value = 0.744; 31.3% vs. 27.2%, p value = 0.773, respectively). The predictors for AKI requiring RRT included underlying chronic liver disease and C-reactive protein. The mortality predictors for patients with AKI requiring RRT included the pneumonia severity index, tidal volume, and continuous renal replacement therapy. In this study, patients with influenza pneumonia-related ARDS with AKI requiring RRT had significantly higher mortality compared with other patients.