Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.

The impact and risk factors for developing pneumogenic bacteremia in carbapenem-resistant Acinetobacter baumannii nosocomial pneumonia in the intensive care unit: a multicenter retrospective study.

OBJECTIVES: This study analyzed the risk and impact of developing pneumogenic bacteremia in patients with CRAB nosocomial pneumonia in ICU. METHODS: This is multicenter retrospective study. Clinical outcomes were compared between bacteremia and non-bacteremia group, and the risk factors for mortality and developing pneumogenic CRAB bacteremia were analyzed. RESULTS: After patient recruitment, 164 cases were in the bacteremia group, and 519 cases were in the non-bacteremia group. The bacteremia group had 22.4 percentage of increase in-hospital mortality than the non-bacteremia group (68.3% vs. 45.9%, p < 0.001). Multivariate analysis showed bacteremia was an independent risk factor for in-hospital mortality (aHR = 2.399, p < 0.001). A long time-interval between ICU admission and pneumonia onset was an independent risk factor for developing bacteremia (aOR = 1.040, p = < 0.001). Spearman's rank correlation analysis indicated a high correlation between the days from ICU admission to pneumonia onset and the days of ventilator use before pneumonia onset (correlation coefficient (ρ) = 0.777). CONCLUSIONS: In patients with CRAB nosocomial pneumonia, bacteremia increased the in-hospital mortality, and a longer interval from ICU admission to pneumonia onset was an independent risk factor for developing bacteremia, which was highly associated with the use of mechanical ventilation.

Follistatin-respiratory connection predicting all-cause mortality among community-dwelling middle-to-old age individuals: Results from the I-Lan Longitudinal Study.

OBJECTIVES: The link between aging and pulmonary function decline is well-established, but the underlying mechanisms have yet to be fully revealed. Serum follistatin, a myokine implicated in muscle degeneration, may play a role in age-related pulmonary changes. This study aims to investigate the relationship between serum follistatin levels and pulmonary function decline in community-dwelling older adults, and evaluate their combined association with all-cause mortality. RESEARCH DESIGN AND METHODS: This longitudinal cohort study utilized data from 751 participants aged ≥50 years in the I-Lan Longitudinal Aging Study between 2018-2019. Serum follistatin levels, spirometry results, demographic and clinical data were retrieved. Participants were stratified based on their follistatin levels. Survival curves and group comparisons based on follistatin levels and decline in peak expiratory flow (PEF) using Kaplan-Meier analysis and log-rank tests. Multivariate Cox proportional hazards models were further used to identify independent predictors of all-cause mortality during the 52-month follow-up. RESULTS: Elevated follistatin levels significantly correlated with worse pulmonary function, particularly decreased PEF (p = 0.030). Kaplan-Meier analysis revealed the combination of elevated follistatin levels and decreased PEF was associated with increased risk of all-cause mortality (Log-rank p = 0.023). Cox proportional hazards models further identified that concurrent presence of higher follistatin levels and decreased PEF predicted higher risk of all-cause mortality (adjusted HR 3.58, 95% CI: 1.22-10.53, p = 0.020). CONCLUSION: Higher serum follistatin levels correlate with decreased pulmonary function, specifically PEF decline, in community-dwelling older adults. Furthermore, the coexistence of elevated follistatin levels and decreased PEF was associated with risk of all-cause mortality. Follistatin may serve as a biomarker for pulmonary aging and related adverse outcomes.

Influence of vaccination on critical COVID-19 patients with acute respiratory failure: a retrospective cohort study.

BACKGROUND: Despite vaccines' effectiveness in reducing COVID-19 infection rates and disease severity, their impact on critical patients presenting with acute respiratory failure is elusive. The aim of this study was to further investigate the influence of vaccination on mortality rates among severely ill COVID-19 patients experiencing acute respiratory failure. METHODS: This retrospective cohort study was carried out at a tertiary medical center in Taiwan. From April to September 2022, patients who tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through reverse transcription polymerase chain reaction (RT-PCR) and subsequently experienced acute respiratory failure were included in the study. Baseline characteristics, including vaccination history, along with information regarding critical illness and clinical outcomes, were gathered and compared between patients who received the vaccine and those who did not. RESULTS: A total of 215 patients with COVID-19 exhibiting acute respiratory failure, as confirmed via RT‒PCR, were included in the analysis. Of this cohort, sixty-six (30.7%) patients died within 28 days. Neither administration of the vaccine nor achievement of primary series vaccination status had a significantly different effect on 28 day mortality, number of viral shedding events, acute respiratory distress syndrome (ARDS) incidence or other clinical outcomes. Patients who received the booster vaccine and completed the primary series showed a tendency of increased 28 days of ventilator-free status, though this difference was not statistically significant (p = 0.815). CONCLUSIONS: Vaccination status did not significantly influence mortality rates, the occurrence of ARDS, or the viral shedding duration in COVID-19 patients with acute respiratory failure.

Clinical characteristics and outcomes among critically ill patients with cancer and COVID-19-related acute respiratory failure.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected individuals worldwide, and patients with cancer are particularly vulnerable to COVID-19-related severe illness, respiratory failure, and mortality. The relationship between COVID-19 and cancer remains a critical concern, and a comprehensive investigation of the factors affecting survival among patients with cancer who develop COVID-19-related respiratory failure is warranted. We aim to compare the characteristics and outcomes of COVID-19-related acute respiratory failure in patients with and without underlying cancer, while analyzing factors affecting in-hospital survival among cancer patients. METHODS: We conducted a retrospective observational study at Taipei Veterans General Hospital in Taiwan from May to September 2022, a period during which the omicron variant of the severe acute respiratory syndrome coronavirus 2 was circulating. Eligible patients had COVID-19 and acute respiratory failure. Clinical data, demographic information, disease severity markers, treatment details, and outcomes were collected and analyzed. RESULTS: Of the 215 enrolled critically ill patients with COVID-19, 65 had cancer. The patients with cancer were younger and had lower absolute lymphocyte counts, higher ferritin and lactate dehydrogenase (LDH) concentrations, and increased vasopressor use compared with those without cancer. The patients with cancer also received more COVID-19 specific treatments but had higher in-hospital mortality rate (61.5% vs 36%, P = 0.002) and longer viral shedding (13 vs 10 days, P = 0.007) than those without cancer did. Smoking [odds ratio (OR): 5.804, 95% confidence interval (CI): 1.847-39.746], elevated LDH (OR: 1.004, 95% CI: 1.001-1.012), vasopressor use (OR: 5.437, 95% CI: 1.202-24.593), and new renal replacement therapy (OR: 3.523, 95% CI: 1.203-61.108) were independent predictors of in-hospital mortality among patients with cancer and respiratory failure. CONCLUSION: Critically ill patients with cancer experiencing COVID-19-related acute respiratory failure present unique clinical features and worse clinical outcomes compared with those without cancer. Smoking, elevated LDH, vasopressor use, and new renal replacement therapy were risk factors for in-hospital mortality in these patients.

Risk factors for prolonged mechanical ventilation in critically ill patients with influenza-related acute respiratory distress syndrome.

BACKGROUND: Patients with influenza-related acute respiratory distress syndrome (ARDS) are critically ill and require mechanical ventilation (MV) support. Prolonged mechanical ventilation (PMV) is often seen in these cases and the optimal management strategy is not established. This study aimed to investigate risk factors for PMV and factors related to weaning failure in these patients. METHODS: This retrospective cohort study was conducted by eight medical centers in Taiwan. All patients in the intensive care unit with virology-proven influenza-related ARDS requiring invasive MV from January 1 to March 31, 2016, were included. Demographic data, critical illness data and clinical outcomes were collected and analyzed. PMV is defined as mechanical ventilation use for more than 21 days. RESULTS: There were 263 patients with influenza-related ARDS requiring invasive MV enrolled during the study period. Seventy-eight patients had PMV. The final weaning rate was 68.8% during 60 days of observation. The mortality rate in PMV group was 39.7%. Risk factors for PMV were body mass index (BMI) > 25 (kg/m2) [odds ratio (OR) 2.087; 95% confidence interval (CI) 1.006-4.329], extracorporeal membrane oxygenation (ECMO) use (OR 6.181; 95% CI 2.338-16.336), combined bacterial pneumonia (OR 4.115; 95% CI 2.002-8.456) and neuromuscular blockade use over 48 h (OR 2.8; 95% CI 1.334-5.879). In addition, risk factors for weaning failure in PMV patients were ECMO (OR 5.05; 95% CI 1.75-14.58) use and bacteremia (OR 3.91; 95% CI 1.20-12.69). CONCLUSIONS: Patients with influenza-related ARDS and PMV have a high mortality rate. Risk factors for PMV include BMI > 25, ECMO use, combined bacterial pneumonia and neuromuscular blockade use over 48 h. In addition, ECMO use and bacteremia predict unsuccessful weaning in PMV patients.

Critical care response during the COVID-19 pandemic.

Since the coronavirus disease 2019 (COVID-19) pandemic, millions of people worldwide have passed away due to critical illness. Intensive care for severe COVID-19 infection remains one of the most important ways to save patients' lives. In Taiwan, the government-led critical care model and COVID-19 clinical rounds, grand rounds, and chief rounds by experts; critical care guidelines established by the Taiwan Centers for Disease Control and major professional societies; consensus and management recommendations among medical institutes; and research works in the field of critical care constitute the concrete basis of intensive care. This review article briefly summarizes the current achievements of critical care for COVID-19 in Taiwan and recommendations on future directions.

Efficacy of combination therapy with standard-dose carbapenem for treating nosocomial pneumonia caused by carbapenem-resistant Acinetobacter baumannii in intensive care units: A multicentre retrospective propensity score-matched study.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is common worldwide. Despite carbapenem resistance, standard-dose carbapenems are still used in clinical practice. Hence in this study, we aimed to compare the efficacy and outcomes of a regimen containing standard-dose carbapenems with those of a regimen lacking carbapenems during the treatment of critically ill patients with CRAB nosocomial pneumonia in the intensive care unit (ICU). Initially, 735 patients were recruited for this multicentre retrospective cohort study. After exclusion, time-window bias adjustment, and propensity score matching, multiple clinical outcomes were compared between the carbapenem-containing (CC) (n = 166) and no carbapenem-containing (NCC) (n = 166) groups. The CC group showed a higher risk of clinical failure on day 7 than the NCC group (44.6% vs. 33.1%, P = 0.043). The lengths of ICU stay (21 and 16 days, P = 0.024) and hospital stay (61 and 44 days, P = 0.003) were longer in the CC group than in the NCC group. Multivariate analysis showed that the CC regimen was associated with higher clinical failure (adjusted odds ratio (aOR) = 1.64, 95% CI = 1.05-2.56, P = 0.031) and lower microbiological eradication (aOR = 0.48, 95% CI = 0.23-1.00, P = 0.049) at day 7 than the NCC group. Thus, a regimen containing a standard dose of carbapenem should be prescribed with caution for treating CRAB nosocomial pneumonia in the ICU.

A combination of oxygenation and driving pressure can provide valuable information in predicting the risk of mortality in ARDS patients.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common life-threatening condition in critically ill patients. Itis also an important public health issue because it can cause substantial mortality and health care burden worldwide. The objective of this study was to investigate therisk factors that impact ARDS mortality in a medical center in Taiwan. METHODS: This was a single center, observational study thatretrospectively analyzed data from adults in 6 intensive care units (ICUs) at Taichung Veterans General Hospital in Taiwan from 1st October, 2018to30th September, 2019. Patients needing invasive mechanical ventilation and meeting the Berlin definition criteria were included for analysis. RESULTS: A total of 1,778 subjects were screened in 6 adult ICUs and 370 patients fulfilled the criteria of ARDS in the first 24 hours of the ICU admission. Among these patients, the prevalenceof ARDS was 20.8% and the overall hospital mortality rate was 42.2%. The mortality rates of mild, moderate and severe ARDS were 35.9%, 43.9% and 46.5%, respectively. In a multivariate logistic regression model, combination of driving pressure (DP) > 14cmH2O and oxygenation (P/F ratio)≤150 was an independent predictor of mortality (OR2.497, 95% CI 1.201-5.191, p = 0.014). Patients with worse oxygenation and a higher driving pressure had the highest hospital mortality rate(p<0.0001). CONCLUSIONS: ARDS is common in ICUs and the mortality rate remains high. Combining oxygenation and respiratory mechanics may better predict the outcomes of these ARDS patients.

Association of Late Radiographic Assessment of Lung Edema Score with Clinical Outcome in Patients with Influenza-Associated Acute Respiratory Distress Syndrome.

Background: Influenza virus infection leads to acute pulmonary injury and acute respiratory distress syndrome (ARDS). The Radiographic Assessment of Lung Edema (RALE) score has been proposed as a reliable tool for the evaluation of the opacity of chest X-rays (CXRs). This study aimed to examine the RALE scores and outcomes in patients with influenza-associated ARDS. Methods: Patients who were newly diagnosed with influenza-associated ARDS from December 2015 to March 2016 were enrolled. Two independent reviewers scored the CXRs obtained on the day of ICU admission and on days 2 and 7 after intensive care unit (ICU) admission. Results: During the study, 47 patients had influenza-associated ARDS. Five died within 7 days of ICU admission. Of the remaining 42, non-survivors (N = 12) had higher Sequential Organ Failure Assessment scores (SOFA) at ICU admission and higher day 7 RALE scores than survivors (N = 30). The day 7 RALE score independently related to late in-hospital mortality (aOR = 1.121, 95% CI: 1.014-1.240, p = 0.025). Conclusions: The RALE score for the evaluation of opacity on CXRs is a highly reproducible tool. Moreover, RALE score on day 7 was an independent predictor of late in-hospital mortality in patients with influenza-associated ARDS.

NLRP3 Inflammasome Activates Endothelial-to-Mesenchymal Transition via Focal Adhesion Kinase Pathway in Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis has poor clinical outcomes despite antifibrotic treatment. The nucleotide-binding domain leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome and endothelial-to-mesenchymal transition (EndoMT) were shown to be involved in the pathogenesis of pulmonary fibrosis. However, the detailed mechanism is unknown. Our study aimed to investigate the role of the NLRP3 inflammasome in the regulation of EndoMT in pulmonary fibrosis. The inhibition of the NLRP3 inflammasome via a caspase-1 inhibitor, Ac-YVAD-cmk (YVAD), was intraperitoneally administered to male C57BL/6 mice (8-12 weeks old) one hour before bleomycin intratracheal injection (1.5 U/kg). Immunohistochemical staining, Masson's trichrome staining, enzyme-linked immunosorbent assay, immunofluorescence, and Western blotting were used to assess the activity of the NLRP3 inflammasome and EndoMT in lung samples from mice. Human pulmonary microvascular endothelial cells (HPMECs) were used as a model of EndoMT in vitro with YVAD and bleomycin stimulation. We observed the activation of the NLRP3 inflammasome and EndoMT (decreased vascular endothelial cadherin with increased alpha-smooth muscle actin and vimentin) in the lung samples after bleomycin. However, inhibition of the NLRP3 inflammasome significantly reduces EndoMT via inhibiting focal adhesion kinase (FAK). In vitro studies also confirmed these findings. In conclusion, NLRP3 inflammasome inhibition could reduce lung inflammation and fibrosis via the regulation of EndoMT by the FAK pathway.

Analysis of the effect of cytomegalovirus infection in clinical outcomes and prolonged duration of SARS-CoV-2 shedding in intensive care unit patients with COVID-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global outbreak disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cytomegalovirus (CMV) infection can occur in critical COVID-19 patients and is associated with adverse clinical outcomes. OBJECTIVE: The aim of this study was to explore the clinical characteristics and outcome of CMV infection in critical COVID-19 patients. DESIGN: This was a retrospective cohort study. METHODS: From May to September 2021, SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients with intensive care unit (ICU) admission were enrolled. CMV infection was confirmed by PCR. Baseline characteristics, critical illness data and clinical outcomes were recorded and analyzed. RESULTS: Seventy-two RT-PCR-confirmed COVID-19 patients with ICU admission were included during the study period and 48 (66.7%) patients required mechanical ventilation (MV). Overall, in-hospital mortality was 19.4%. Twenty-one (29.2%) patients developed CMV infection. Patients with CMV infection had a higher likelihood of diabetes, higher lactate dehydrogenase and lactate levels, and higher proportions of MV, anticoagulant, and steroid use. Patients with CMV infection were associated with longer duration of SARS-CoV-2 shedding, longer ICU and hospital stay, and fewer ventilator-free days. The independent risk factor for development of CMV infection was a higher accumulative steroid dose. CONCLUSION: CMV infection adversely impacted the outcomes of critical COVID-19 patients, resulting in longer ICU stays, longer mechanical ventilation uses and prolonged shedding of SARS-CoV-2.

Comparison of clinical outcomes in critically ill COVID-19 patients on mechanical ventilation with nosocomial pneumonia between Alpha and Omicron variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pandemic that has resulted in millions of deaths worldwide. Critically ill COVID-19 patients who require intubation and develop nosocomial pneumonia, commonly caused by gram-negative bacilli, have a higher mortality rate than those without nosocomial pneumonia. OBJECTIVES: The aim of this study is to compare the clinical characteristics and outcomes and associated risk factors of Alpha and Omicron SARS-CoV-2 variants in critically ill patients on mechanical ventilation (MV) with nosocomial pneumonia. DESIGN: This is a retrospective single-center cohort study. METHODS: This observational study was conducted at Taipei Veterans General Hospital, Taiwan from May 2021 to September 2022. Critically ill patients who had confirmed SARS-CoV-2 infection and intubated on a MV with bacterial pneumonia were enrolled. Demographic data, laboratory results, and treatment information were collected and analyzed. In addition, clinical outcomes among different SARS-CoV-2 variants were examined. RESULTS: This study included 94 critically ill COVID-19 patients who required intubation and intensive care unit (ICU) admission. The Alpha group had a longer duration of SARS-CoV-2 viral shedding, MV days, and ICU stay, while the Omicron group had older age, more comorbidities, higher APACHE II scores, and higher in-hospital mortality (47.0% versus 25.0%, p = 0.047). However, independent risk factors for in-hospital mortality included malignancy, lower serum albumin levels, and lack of Remdesivir treatment, except for the SARS-CoV-2 variant. CONCLUSION: Our study discovered a higher in-hospital mortality rate in severe COVID-19 patients with MV and secondary pneumonia infected with the Omicron variant compared to the Alpha variant; however, real independent risk factors for in-hospital mortality are malignancy, lower serum albumin level, and lack of Remdesivir treatment.

Mortality and ventilator dependence in critically ill patients with ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a key pathogen associated with ventilator-associated pneumonia (VAP). Research on treatment outcomes, especially ventilator dependence, in patients with VAP caused by CRAB remains limited. METHODS: This retrospective multicenter study included ICU-admitted patients with VAP caused by CRAB. The original cohort was included as the mortality evaluation cohort. The ventilator dependence evaluation cohort included cases that survived more than 21 days after VAP and without prolonged ventilation before VAP onset. The mortality rate, ventilator dependence rate, clinical factors associated with treatment outcomes, and treatment outcome differences with various VAP onset times were investigated. RESULTS: In total, 401 patients with VAP caused by CRAB were analyzed. The 21-day all-cause mortality rate was 25.2%, and the 21-day ventilator dependence rate was 48.8%. Clinical factors associated with 21-day mortality included lower body mass index, higher sequential organ failure assessment score, vasopressors usage, CRAB persistence, and VAP onset time > seven days. Clinical factors associated with 21-day ventilator dependence included older age, vasopressors usage, and VAP onset time > seven days. CONCLUSIONS: ICU-admitted patients with CRAB-related VAP had high mortality and ventilator dependence rates. Older age, vasopressor usage, and longer VAP onset time were independent factors associated with ventilator dependence.

The prevalence, presentation and outcome of colistin susceptible-only Acinetobacter Baumannii-associated pneumonia in intensive care unit: a multicenter observational study.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.

The main e-cigarette component vegetable glycerin enhances neutrophil migration and fibrosis in endotoxin-induced lung injury via p38 MAPK activation.

We investigated the effects of vegetable glycerin (VG), a main e-cigarette constituent, on endotoxin-induced acute lung injury (ALI). Mice received intratracheal administration of 30% VG in phosphate buffered saline (PBS) vehicle or only PBS (control) for 4 days. On Day 5, mice received an intratracheal instillation of lipopolysaccharide (LPS) (LPS group and VG + LPS group) or PBS (VG group and control group). Lung histopathology, expression of chemokine receptors, and regulatory signaling were analyzed 24 h after the Day 5 treatment. VG significantly increased ALI-associated histopathological and fibrotic changes in both the VG group and LPS-induced ALI mice (VG + LPS group). Immunohistochemistry (IHC) and western blot analyses revealed that VG administration resulted in upregulation of neutrophil markers [lymphocyte antigen 6 complex locus G6D (Ly6G) and myeloperoxidase (MPO)] as well as upregulation of the expression of transforming growth factor-ß (TGF-ß), a central mediator of fibrogenesis, in the lungs of both VG and VG + LPS groups. VG enhanced the expression of adhesion molecules [very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1)] and increased activation of p38 mitogen-activated protein kinase (p38 MAPK) to prompt neutrophil recruitment in the lungs of mice with ALI. Intraperitoneal administration of a p38 inhibitor attenuated these histopathological changes significantly as well as VG-induced upregulation in expression of Ly6G, MPO, VLA-4, VCAM-1, TGF-ß, and collagen-1 in mice with ALI. In conclusion, VG enhances neutrophil chemotaxis and fibrosis and it amplifies the inflammatory response associated with LPS-induced ALI in the lungs via enhancement of p38 MAPK activity.

Role of nebulized colistin as a substitutive strategy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective cohort study.

BACKGROUND: Adverse reactions, especially nephrotoxicity, are great concerns of intravenous colistin treatment. The role of substitutive nebulized colistin in treating nosocomial pneumonia caused by carbapenem-resistant Gram-negative bacterial (CR-GNB) in critically ill patients remains unknown. METHODS: This retrospective study enrolled patients with nosocomial pneumonia caused by colistin-susceptible CRGNB in the intensive care unit (ICU) without intravenous colistin treatment. Patients were categorized based on whether substitutive nebulized colistin was used alongside other intravenous antibiotics. Clinical responses and mortality rates were compared between the two groups in the original and propensity score (PS)-matched cohorts. This study aimed to investigate the clinical effectiveness of substitutive nebulized colistin in treatment outcomes of nosocomial pneumonia caused by CR-GNB. The impact of dosing strategy of nebulized colistin was also explored. RESULTS: In total, 343 and 214 patients with and without substitutive nebulized colistin, respectively, were enrolled for analysis. In the PS-matched cohort, clinical failure rates on day 7 (22.6 vs. 42.6%, p = 0.001), day 14 (27.0 vs. 42.6%, p = 0.013), and day 28 (27.8 vs. 41.7%, p = 0.027) were significantly lower in patients with nebulized colistin. In multivariate analysis, nebulized colistin was an independent factor associated with lower day 14 clinical failure (Original cohort: adjusted odds ratio (aOR) 0.45, 95% confidence interval (CI) 0.30-0.67; PS-matched cohort: aOR 0.48, 95% CI 0.27-0.87). There were no differences in clinical failure rate and mortality rate between patients receiving high (> 6 MIU/day) and low (≤ 6 MIU/day) dose nebulized colistin in the PS-matched cohort. CONCLUSIONS: In ICU-admitted patients with nosocomial pneumonia caused by colistin-susceptible CRGNB, substitutive nebulized colistin was associated with better clinical outcomes.

Clinical effectiveness of tigecycline in combination therapy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective multi-centre observational study.

BACKGROUND: Tigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU). METHODS: This multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents. RESULTS: We analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p < 0.001) on day 28. In multivariate analysis, tigecycline treatment was a protective factor against clinical failure (PS-matched cohort: aOR 0.52, 95% CI 0.28-0.95) and all-cause mortality (original cohort: aHR 0.69, 95% CI 0.47-0.99; PS-matched cohort: aHR 0.47, 95% CI 0.30-0.74) at 28 days. Kaplan-Meier survival analysis in subgroups of patients suggested significant clinical benefits of tigecycline when added to a colistin-included (log rank p value 0.005) and carbapenem-included (log rank p value 0.007) combination regimen. CONCLUSIONS: In this retrospective observational study that included ICU-admitted patients with nosocomial pneumonia caused by tigecycline-susceptible CR-GNB, mostly CRAB, tigecycline as part of a combination treatment regimen was associated with lower clinical failure and all-cause mortality rates.

Clinical Outcomes and Prolonged SARS-CoV-2 Viral Shedding in ICU Patients with Severe COVID-19 Infection and Nosocomial Bacterial Pneumonia: A Retrospective Cohort Study.

OBJECTIVES: This study explored the clinical outcomes and association of prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding in patients with severe coronavirus disease 2019 (COVID-19) infection who developed nosocomial pneumonia. METHODS: This was a retrospective study conducted in a medical center in Taiwan. From May to September 2021, patients from four intensive care units were enrolled after SARS-CoV-2 was confirmed through quantitative polymerase chain reaction and all cases were compatible with the definitions of severe COVID-19 infection. Baseline characteristics, disease severity, clinical outcomes, and times of viral shedding were recorded. RESULTS: A total of 72 patients were diagnosed as having severe COVID-19 infection and 30 developed nosocomial pneumonia, comprising hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). The patients with severe COVID-19 infection and concomitant HAP/VAP had longer intensive care unit (ICU) stays and fewer ventilator-free days at Day 28. An independent risk factor for nosocomial pneumonia was a greater SOFA score at admission. Furthermore, the patients with severe COVID-19 infection who developed HAP/VAP had a significantly longer duration of SARS-CoV-2 shedding (19.50 days vs. 15.00 days, p = 0.006). CONCLUSIONS: Patients with severe COVID-19 infection who developed nosocomial pneumonia had longer SARS-CoV-2 shedding days, more complications, and worse outcomes.

COVID-19-associated pulmonary aspergillosis is associated with increased in-hospital mortality and prolonged SARS-CoV-2 viral shedding.

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is common in critically ill patients with COVID-19 and is associated with worse outcomes. However, reports on CAPA and its impact on treatment outcomes in Asian populations are limited. METHODS: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction-confirmed COVID-19 admitted to intensive care units (ICUs) were retrospectively enrolled in this observational study. The incidence rate of CAPA during ICU admission was investigated. The clinical factors associated with CAPA, including corticosteroid exposure, were analyzed. The impact of CAPA on the treatment outcomes and SARS-CoV-2 viral shedding were explored. RESULTS: A total of 72 ICU-admitted patients with COVID-19 were included in the analysis. The incidence rate of CAPA was 15.3% (11/72) in all patients and 23% (11/48) in the mechanically ventilated patients. The median time from ICU admission to CAPA diagnosis was 15 days. A lower fibrinogen level (adjusted odds ratio [aOR], 0.983; 95% confidence interval [CI], 0.967-0.999) was independently associated with CAPA. The patients with CAPA had a higher in-hospital mortality rate (55% vs. 13%, p = 0.001) and a longer SARS-CoV-2 viral shedding time (22 days vs. 16 days, p = 0.037) than those without CAPA. CONCLUSION: Lower serum fibrinogen levels was independently associated with CAPA among the ICU-admitted patients with COVID-19. The patients with CAPA had a higher in-hospital mortality rate and a longer SARS-CoV-2 viral shedding time than those without CAPA.