Introduction: Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS), however, the presence of DAD in the clinical criteria of ARDS patients by Berlin definition is little known. This study is designed to investigate the role of DAD in ARDS patients who underwent open lung biopsy. Methods: We retrospectively reviewed all ARDS patients who met the Berlin definition and underwent open lung biopsy from January 1999 to January 2014 in a referred medical center. DAD is characterized by hyaline membrane formation, lung edema, inflammation, hemorrhage and alveolar epithelial cell injury. Clinical data including baseline characteristics, severity of ARDS, clinical and pathological diagnoses, and survival outcomes were analyzed. Results: A total of 1838 patients with ARDS were identified and open lung biopsies were performed on 101 patients (5.5 %) during the study period. Of these 101 patients, the severity of ARDS on diagnosis was mild of 16.8 %, moderate of 56.5 % and severe of 26.7 %. The hospital mortality rate was not significant difference between the three groups (64.7 % vs 61.4 % vs 55.6 %, p = 0.81). Of the 101 clinical ARDS patients with open lung biopsies, 56.4 % (57/101) patients had DAD according to biopsy results. The proportion of DAD were 76.5 % (13/17) in mild, 56.1 % (32/57) in moderate and 44.4 % (12/27) in severe ARDS and there is no significant difference between the three groups (p = 0.113). Pathological findings of DAD patients had a higher hospital mortality rate than non-DAD patients (71.9 % vs 45.5 %, p = 0.007). Pathological findings of DAD (odds ratio: 3.554, 95 % CI, 1.385–9.12; p = 0.008) and Sequential Organ Failure Assessment score on the biopsy day (odds ratio: 1.424, 95 % CI, 1.187–1.707; p<0.001) were significantly and independently associated with hospital mortality. The baseline demographics and clinical characteristics were not significantly different between DAD and non-DAD patients. Conclusions: The correlation of pathological findings of DAD and ARDS diagnosed by Berlin definition is modest. A pathological finding of DAD in ARDS patients is associated with hospital mortality and there are no clinical characteristics that could identify DAD patients before open lung biopsy.

The survival predictors and optimal mechanical ventilator settings in patients with severe acute respiratory distress syndrome (ARDS) undergoing extracorporeal membrane oxygenation (ECMO) are uncertain. This study was designed to investigate the influences of clinical variables and mechanical ventilation settings on the outcomes for severe ARDS patients receiving ECMO. We reviewed severe ARDS patients who received ECMO due to refractory hypoxemia from May 2006 to October 2015. Serial mechanical ventilator settings before and after ECMO and factors associated with survival were analyzed. A total of 158 severe ARDS patients received ECMO were finally analyzed. Overall intensive care unit (ICU) mortality was 55.1%. After ECMO initiation, tidal volume, peak inspiratory pressure and dynamic driving pressure were decreased, while positive end-expiratory pressure levels were relative maintained. After ECMO initiation, nonsurvivors had significantly higher dynamic driving pressure until day 7 than survivors. Cox proportional hazards regression model revealed that immunocompromised [hazard ratio 1.957; 95% confidence interval (CI) 1.216–3.147; p = 0.006], Acute Physiology and Chronic Health Evaluation (APACHE) II score (hazard ratio 1.039; 95% CI 1.005–1.073; p = 0.023), ARDS duration before ECMO (hazard ratio 1.002; 95% CI 1.000–1.003; p = 0.029) and mean dynamic driving pressure from day 1 to 3 on ECMO (hazard ratio 1.070; 95% CI 1.026–1.116; p = 0.002) were independently associated with ICU mortality. For severe ARDS patients receiving ECMO, immunocompromised status, APACHE II score and the duration of ARDS before ECMO initiation were significantly associated with ICU survival. Higher dynamic driving pressure during first 3 days of ECMO support was also independently associated with increased ICU mortality.

Staphylococcus aureus is one of most common pathogens in humans. Methicillin-resistant S. aureus (MRSA) accounts for 64 % of S. aureus bacteremia isolated in intensive care units (ICUs), and heteroresistant vancomycin-intermediates S. aureus (hVISA) is a phenotype of MRSA. However, studies focusing on the hVISA impact on critically ill patients are scarce. This was a retrospective study conducted in a tertiary medical center from January 2009 to December 2010. All adult patients in ICUs with MRSA bloodstream infection were eligible. A modified population analysis profile and area under the curve method was applied to all isolates to confirm hVISA phenotype. Multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) and the accessory gene regulator (agr) typing were performed individually. Clinical outcomes including in-hospital mortality, length of stay in intensive care unit and hospital after MRSA bacteremia of the patients were also analyzed. A total of 48 patients were enrolled and 14 patients were confirmed to have the hVISA phenotype. The prevalence of hVISA was 29.2 %. There was no difference in the age, sex, comorbidity, Charlson’s comorbidity score and previous vancomycin therapy between the hVISA and VSSA groups. The hVISA group had a significantly higher in-hospital mortality than the VSSA group (13/14 versus 22/34; p = 0.046). All of the 14 hVISA patients had an MIC = 2 mg/L by E-test and this represented a significant association between high MIC and the development of hVISA (p < 0.001). MLST analysis showed all the isolates in the hVISA group were ST239, while ST239 (14/34; 41.2 %) and ST5 (12/34; 35.3 %) were predominant in the VSSA group (p = 0.007). A comparison of the survivor and non-survivor group showed that the hVISA phenotype (OR 11.8; 95 % CI 1.1–126.99; p = 0.042) and sequential organ failure assessment (SOFA) score (OR 1.39; 95 % CI 1.07–1.81; p = 0.014) were independent factors significantly associated with in-hospital mortality. Patients in ICUs with MRSA bacteremia may have a higher in-hospital mortality if they have the hVISA phenotype. SOFA score is also predictor of mortality.

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.

Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized.

Background: The experience of using consolidation durvalumab in post-concurrent chemoradiation (CCRT) unresectable stage III non-small cell lung cancer (NSCLC) is rare in real-world clinical practice, and the factors associated with its efficacy are also unclear. We sought to analyze the efficacy of consolidation durvalumab and the factors associated with its efficacy using a multicenter observational study. Methods: The data for 61 patients with post-CCR unresectable stage III NSCLC receiving consolidation durvalumab at the Chang Gung Memorial Hospitals in Linkou, Keelung, Chiayi, and Kaohsiung from November 2017 to March 2020 were analyzed. (3) Results: The median post-CCRT progression-free survival (PFS) and time to metastatic disease or death (TMDD) for consolidation durvalumab were 14.0 months and 16.7 months, respectively. In multiple variant factors analysis, we found that an epidermal growth factor receptor (EGFR) mutation was an independently unfavorable predictive factor for consolidation durvalumab therapy regarding PFS. The median post-CCRT PFS was 6.50 months for EGFR-mutated patients and 33.63 months for EGFR wild-type and unknown patients (HR = 10.47; 95% CI, 4.55–24.07; p < 0.001). Conclusions: Consolidation durvalumab is effective and safe for post-CCRT unresectable stage III NSCLC in clinical practice, but EGFR mutation is an unfavorable factor for consolidation durvalumab. Thus, searching for a better consolidation therapy for EGFR-mutated patients is warranted.