Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Serum ß2-microglobulin as an independent risk factor for mortality in patients with acute respiratory distress syndrome caused by bacterial infection.

Acute respiratory distress syndrome (ARDS) is a heterogeneous disease with extremely high mortality. We hypothesized that the serum ß2-microglobulin (ß2MG) level would be elevated and be an independent risk factor for 28-day mortality in patients with ARDS caused by bacterial infection. We retrospectively enrolled 257 patients with ARDS caused by bacterial infection from January 1, 2015 to February 28, 2021. Patients were followed for up to 28 days and were divided into a survival group and non-survival group according to their clinical outcomes. The serum ß2MG levels and other clinical data were collected. The relationship between ß2MG levels and 28-day mortality was explored by performing a Cox regression analysis adjusted for age, updated Charlson comorbidity index, disorders of consciousness, septic shock, albumin level, cardiac troponin I level, procalcitonin level, lactic acid level, prothrombin time, partial pressure of arterial oxygen/fraction of inspired oxygen ratio, estimated glomerular filtration rate and Sequential Organ Failure Assessment. In this cohort, 96 patients died in 28 days, yielding a 28-day mortality of 37.4%. The median level of serum ß2MG for all enrolled patients was 4.7 (interquartile range [IQR]: 2.9-8.5) mg/L. Higher ß2MG levels were significantly associated with 28-day mortality when the ß2MG level was analysed as a continuous variable (hazard ratio [HR]: 1.053; 95% confidence interval [CI] 1.004-1.104; P = 0.032) and when it was categorized into tertiles (HR: 3.241; 95% CI 1.180-8.905; P = 0.023). The ß2MG level exhibited a high diagnostic accuracy for predicting 28-day mortality (area under the curve [AUC] = 0.732; 95% CI 0.673-0.785; sensitivity: 74.0%; specificity: 64.0%; P < 0.001). The level of serum ß2MG is elevated and is an independent risk factor of 28-day mortality in patients with ARDS caused by bacterial infection.

Extracorporeal membrane oxygenation for tuberculosis-related acute respiratory distress syndrome: An international multicentre retrospective cohort study.

OBJECTIVE: To report the outcomes of patients with severe tuberculosis (TB)-related acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO), including predictors of 90-day mortality and associated complications. METHODS: An international multicenter retrospective study was conducted in 20 ECMO centers across 13 countries between 2002 and 2022. RESULTS: We collected demographic data, clinical details, ECMO-related complications, and 90-day survival status for 79 patients (median APACHE II score of 20 [25th to 75th percentile, 16 to 28], median age 39 [28 to 48] years, PaO2/FiO2 ratio of 69 [55 to 82] mmHg before ECMO) who met the inclusion criteria. Thoracic computed tomography showed that 61 patients (77%) had cavitary TB, while 18 patients (23%) had miliary TB. ECMO-related complications included major bleeding (23%), ventilator-associated pneumonia (41%), and bloodstream infections (32%). The overall 90-day survival rate was 51%, with a median ECMO duration of 20 days [10 to 34] and a median ICU stay of 42 days [24 to 65]. Among patients on VV ECMO, those with miliary TB had a higher 90-day survival rate than those with cavitary TB (90-day survival rates of 81% vs. 46%, respectively; log-rank P = 0.02). Multivariable analyses identified older age, drug-resistant TB, and pre-ECMO SOFA scores as independent predictors of 90-day mortality. CONCLUSION: The use of ECMO for TB-related ARDS appears to be justifiable. Patients with miliary TB have a much better prognosis compared to those with cavitary TB on VV ECMO.

Is there still a place for ECCO2R?

The therapeutic target of extracorporeal carbon dioxide removal (ECCO2R) is the elimination of carbon dioxide (CO2) from the blood across a gas exchange membrane without influencing oxygenation to a clinically relevant extent. In acute respiratory distress syndrome (ARDS), ECCO2R has been used to reduce tidal volume, plateau pressure, and driving pressure ("ultraprotective ventilation"). Despite achieving these goals, no benefits in outcome could be shown. Thus, in ARDS, the use of ECCO2R to achieve ultraprotective ventilation can no longer be recommended. Furthermore, ECCO2R has also been used to avoid intubation or facilitate weaning in obstructive lung failure as well as to avoid mechanical ventilation in patients during bridging to lung transplantation. Although these goals can be achieved in many patients, the effects on outcome still remain unclear due to lack of evidence. Despite involving less blood flow, smaller cannulas, and smaller gas exchange membranes compared with extracorporeal membrane oxygenation, ECCO2R bears a comparable risk of complications, especially bleeding. Trials to define indications and analyze the risk-benefit balance are needed prior to implementation of ECCO2R as a standard therapy. Consequently, until then, ECCO2R should be used in clinical studies and experienced centers only. This article is freely available.

Transpulmonary Pressure as a Predictor of Successful Lung Recruitment: Reanalysis of a Multicenter International Randomized Clinical Trial.

BACKGROUND: Recruitment maneuvers are used in patients with ARDS to enhance oxygenation and lung mechanics. Heterogeneous lung and chest-wall mechanics lead to unpredictable transpulmonary pressures and could impact recruitment maneuver success. Tailoring care based on individualized transpulmonary pressure might optimize recruitment, preventing overdistention. This study aimed to identify the optimal transpulmonary pressure for effective recruitment and to explore its association with baseline characteristics. METHODS: We performed post hoc analysis on the Esophageal Pressure Guided Ventilation (EpVent2) trial. We estimated the dose-response relationship between end-recruitment end-inspiratory transpulmonary pressure and the change in lung elastance after a recruitment maneuver by using logistic regression weighted by a generalized propensity score. A positive change in lung elastance was indicative of overdistention. We examined how patient characteristics, disease severity markers, and respiratory parameters predict transpulmonary pressure by using multivariate linear regression models and dominance analyses. RESULTS: Of 121 subjects, 43.8% had a positive change in lung elastance. Subjects with a positive change in lung elastance had a mean ± SD transpulmonary pressure of 15.1 ± 4.9 cm H2O, compared with 13.9 ± 3.9 cm H2O in those with a negative change in lung elastance. Higher transpulmonary pressure was associated with increased probability of a positive change in lung elastance (adjusted odds ratio 1.35 per 1 cm H2O of transpulmonary pressure, 95% CI 1.13-1.61; P = .001), which indicated an S-shaped dose-response curve, with overdistention probability > 50% at transpulmonary pressure values > 18.3 cm H2O. The volume of recruitment was transpulmonary pressure-dependent (P < .001; R2 = 0.49) and inversely related to a change in lung elastance after adjusting for baseline lung elastance (P < .001; R2= 0.43). Negative correlations were observed between transpulmonary pressure and body mass index, PEEP, Sequential Organ Failure Assessment score, and PaO2 /FIO2 , whereas baseline lung elastance showed a positive correlation. The body mass index emerged as the dominant negative predictor of transpulmonary pressure (ranking 1; contribution to R2 = 0.08), whereas pre-recruitment elastance was the sole positive predictor (contribution to R2 = 0.06). CONCLUSIONS: Higher end-recruitment transpulmonary pressure increases the volume of recruitment but raises the risk of overdistention, providing the rationale for transpulmonary pressure to be used as a clinical target. Predictors, for example, body mass index, could guide recruitment maneuver individualization to balance adequate volume gain with overdistention.

A bibliometric analysis of respiratory mechanics research related to acute respiratory distress syndrome from 1985 to 2023.

Background: Acute respiratory distress syndrome (ARDS) is a severe condition characterized by lung stiffness and compromised gas exchange, often requiring mechanical ventilation for treatment. In addition to its clinical significance, understanding the publication trends and research patterns in respiratory mechanics related to ARDS can provide insights into the evolution of this field from a bibliometric perspective, aiding in strategic planning and resource allocation for future research endeavors. Objective: This study aimed to explore the trends and identify the hotspots in respiratory mechanics research related to ARDS. Methods: All relevant studies on respiratory mechanics of ARDS published between 1985 and 2023 were retrieved from the Web of Science Core Collection (WoSCC), and the retrieval strategy was topic search "TS = respiratory mechanics OR lung mechanics AND TS = ARDS OR acute respiratory distress syndrome." Annual trends, citation patterns, and contributions from countries, institutions, authors, and journals were analyzed using Bibliometrix Biblioshiny. Networks and overlay of authors, institutions, countries, journals, co-citations, and keywords were analyzed and visualized using VOSviewer. Results: Our analysis included 1,248 articles published between 1985 and 2023, revealing fluctuations in publication output over time. The United States emerged as the leading contributor, with Critical Care Medicine being the most prominent journal. Key research themes included mechanical ventilation, acute lung injury, and protective ventilation strategies. International collaboration was evident, facilitating knowledge exchange and interdisciplinary cooperation. Conclusion: Our study sheds light on the evolving landscape of respiratory mechanics research in ARDS. International collaboration is pivotal in advancing the field, while researchers increasingly focus on personalized approaches to address the complexities of ARDS respiratory mechanics.

Mapping a Decade (2014-2024) of Research on Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A Visual Analysis with CiteSpace and VOSviewer.

Background: Acute Respiratory Distress Syndrome (ARDS) stands as a primary cause of mortality among critically ill patients. Extracorporeal Membrane Oxygenation (ECMO) is increasingly employed in the rescue therapy of ARDS patients. However, the current status of research in the field of ECMO-assisted ARDS remains unclear. Objective: This research aims to categorize and evaluate the literature regarding Extracorporeal Membrane Oxygenation (ECMO) support for Acute Respiratory Distress Syndrome (ARDS), offering a comprehensive analysis of bibliometric properties, research hotspots, and developmental trends within the domain of ECMO-assisted ARDS. Methods: A literature search was conducted for ECMO-assisted support for patients with ARDS in the Web of Science Core Collection (WoSCC) database from 2014 to 2024. We employed visualization tools such as CiteSpace and VOSviewer to explore and assess connections among nations, institutions, researchers, and co-cited journals, authors, references, and keywords. Results: This study included 1739 publications. The United States leads in publication volume with Columbia University at the forefront of ECMO research. Intensive Care Medicine has been identified as the most cited journal in this field. Alain Combes from France stands out as a key contributor, particularly in his 2018 publication in the New England Journal of Medicine, which is the most cited work in the discipline. Furthermore, keyword analysis identified three distinct research phases: examining complications associated with ECMO therapy, exploring optimal strategies for mechanical ventilation under ECMO support, and compiling insights into the application of ECMO in treating COVID-19 patients and in the development of predictive models for patient outcomes. Conclusion: Using bibliometric visualization techniques, this study revealed significant progress in the use of ECMO for treating ARDS respiratory support, evaluated the impact of these findings, and outlined potential areas for future studies.

Effect of Thoracic Squeezing Technique and Expiratory Flow Increase Technique on Neonates With Neonatal Respiratory Distress Syndrome: A Case Report.

Neonatal respiratory distress syndrome (NRDS) is a major cause of morbidity and death in premature newborns due to inadequate surfactant synthesis in the lungs. Preterm birth carries a higher risk of respiratory problems. Clinically cyanosis, grunting, retractions, and tachypnea are signs of early respiratory distress associated with RDS Should therapeutic measures not be implemented, the infant may suffer respiratory failure and increasing hypoxia. This case study investigates how physical therapy affects a preterm newborn with NRDS regarding thoracic squeeze, percussion, and vibration with expiratory flow increase technique The patient's prenatal, natal, and postnatal history is included in depth in the report, along with information on the mother's health, pregnancy difficulties, birth details, first clinical presentation, and care that followed. Despite advancements in treatment through the use of surfactants, prenatal corticosteroids, and advanced respiratory care for the newborn, RDS continues to be the leading cause of morbidity and mortality in premature newborns. The significance of interdisciplinary methods in improving the care and prognosis of newborns with NRDS is shown by this instance.

Anti MDA-5 associated rapidly progressive interstitial lung disease complicated by viral pneumonia - a fatal outcome.

Dermatomyositis is a heterogeneous systemic disease, with 7% to 10% of the individuals presenting the Anti MDA-5 antibody. This subset of patients has clinically amyotropic dermatomyositis, presenting with cutaneous ulcer and rapidly progressive interstitial lung disease. We report the case of a 22-year-old male with a six-month history of low-grade fever associated with myalgia, polyarthralgia, and marked weight loss. He had a history of shortness of breath and high-grade fever 15 days before admission. His clinical features and imaging workup were consistent with acute respiratory distress syndrome. A nasal swab was positive for H1N1 influenza virus infection. During the disease investigation, he succumbed after nine days of admission. The autopsy examination showed diffuse alveolar damage on a background of non-specific interstitial pattern of injury in the lungs. His postmortem muscle biopsy revealed subtle changes of inflammatory myopathy. The brain showed diffuse subarachnoid hemorrhage. Evaluation of postmortem serum sample revealed positivity for Anti MDA-5 and Ro-52 antibodies. This was a case of Anti MDA-5 and Ro-52 associated dermatomyositis with non-specific interstitial pneumonia pattern of lung injury complicated with H1N1 influenza pneumonia, leading to diffuse alveolar damage and subsequent respiratory failure and death. Serum Anti MDA-5 antibodies represent an important biomarker for diagnosing and predicting prognosis for patients with idiopathic inflammatory myopathies, especially clinically amyopathic dermatomyositis. Anti-Ro-52 has been reported in a wide variety of autoimmune diseases, particularly in myositis, scleroderma, and autoimmune liver diseases. Ro-52 autoantibodies are associated with interstitial lung disease (ILD), and their presence should encourage the clinician's curiosity to search for ILD.

Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

BACKGROUND: Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100 ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. METHODS: Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. RESULTS: We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). CONCLUSIONS: In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. TRIAL REGISTRATION: NCT03266016; August 23, 2017.

Impact of early continuous positive airway pressure in the delivery room (DR-CPAP) on neonates < 1500 g in a low-resource setting: a protocol for a pilot feasibility and acceptability randomized controlled trial.

BACKGROUND: Preterm birth is the leading cause of childhood mortality, and respiratory distress syndrome is the predominant cause of these deaths. Early continuous positive airway pressure is effective in high-resource settings, reducing the rate of continuous positive airway pressure failure, and the need for mechanical ventilation and surfactant. However, most deaths in preterm infants occur in low-resource settings without access to mechanical ventilation or surfactant. We hypothesize that in such settings, early continuous positive airway pressure will reduce the rate of failure and therefore preterm mortality. METHODS: This is a mixed methods feasibility and acceptability, single-center pilot randomized control trial of early continuous positive airway pressure among infants with birthweight 800-1500 g. There are two parallel arms: (i) application of continuous positive airway pressure; with optional oxygen when indicated; applied in the delivery room within 15 min of birth; transitioning to bubble continuous positive airway pressure after admission to the neonatal unit if Downes Score ≥ 4 (intervention), (ii) supplementary oxygen at delivery when indicated; transitioning to bubble continuous positive airways pressure after admission to the neonatal unit if Downes Score ≥ 4 (control). A two-stage consent process (verbal consent during labor, followed by full written consent within 24 h of birth) and a low-cost third-party allocation process for randomization will be piloted. We will use focus group discussions and key informant interviews to explore the acceptability of the intervention, two-stage consent process, and trial design. We will interview healthcare workers, mothers, and caregivers of preterm infants. Feasibility will be assessed by the proportion of infants randomized within 15 min of delivery; the proportion of infants in the intervention arm receiving CPAP within 15 min of delivery; and the proportion of infants with primary and secondary outcomes measured successfully. DISCUSSION: This pilot trial will enhance our understanding of methods and techniques that can enable emergency neonatal research to be carried out effectively, affordably, and acceptably in low-resource settings. This mixed-methods approach will allow a comprehensive exploration of parental and healthcare worker perceptions, experiences, and acceptance of the intervention and trial design. TRIAL REGISTRATION: The study is registered on the Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08 August 2022.  https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23888 .

Guillain-Barré Syndrome Complicated by Severe Acute Respiratory Distress Syndrome: A Case Report.

Guillain-Barré syndrome (GBS) stands out as the most prevalent and severe acute immune-mediated paralytic neuropathy. Approximately 30% of patients experience respiratory failure necessitating admission to the intensive care unit (ICU) and invasive mechanical ventilation. The management of diseases concomitant with acute respiratory distress syndrome (ARDS) poses significant challenges. This case report illustrates the swift development of ARDS in a patient with GBS, explores the utility of the biomarker neurofilament light chain, and highlights the unexpected advantages of proactive ARDS intervention.

Management of severe acute respiratory distress syndrome in Australia and New Zealand (SAGE-ANZ): An observational study.

Objective: Acute respiratory distress syndrome (ARDS) is associated with significant mortality, morbidity, and cost. We aimed to describe characteristics and management of adult patients admitted to intensive care units (ICUs) in Australia and New Zealand with moderate-severe ARDS, to better understand contemporary practice. Design: Bi-national, prospective, observational, multi-centre study. Setting: 19 ICUs in Australia and New Zealand. Participants: Mechanically ventilated patients with moderate-severe ARDS. Main outcome measures: Baseline demographic characteristics, ventilation characteristics, use of adjunctive support therapy and all-cause mortality to day 28. Data were summarised using descriptive statistics. Results: 200 participants were enrolled, mean (±SD) age 55.5 (±15.9) years, 40% (n = 80) female. Around half (51.5%) had no baseline comorbidities and 45 (31%) tested positive for COVID-19. On day 1, mean SOFA score was 9 ± 3; median (IQR) PaO2/FiO2 ratio 119 (89, 142), median (IQR) FiO2 70% (50%, 99%) and mean (±SD) positive end expiratory pressure (PEEP) 11 (±3) cmH2O. On day one, 10.5% (n = 21) received lung protective ventilation (LPV) (tidal volume ≤6.5 mL/kg predicted body weight and plateau pressure or peak pressure ≤30 cm H2O). Adjunctive therapies were received by 86% (n = 172) of patients at some stage from enrolment to day 28. Systemic steroids were most used (n = 127) followed by neuromuscular blockers (n = 122) and prone positioning (n = 27). Median ventilator-free days (IQR) to day 28 was 5 (0, 20). In-hospital mortality, censored at day 28, was 30.5% (n = 61). Conclusions: In Australia and New Zealand, compliance with evidence-based practices including LPV and prone positioning was low in this cohort. Therapies with proven benefit in the treatment of patients with moderate-severe ARDS, such as lung protective ventilation and prone positioning, were not routinely employed.

Influence of catheter thickness on respiratory physiology during less invasive surfactant administration in extremely preterm infants.

Introduction: Delivering surfactant via thin catheters (minimal-invasive surfactant therapy (MIST); less invasive surfactant administration (LISA)) has become a common procedure. However, the effect of tracheal obstruction caused by catheters of different sizes on tracheal resistance in extremely low gestational age newborns (ELGANs) is unknown. Methods: To investigate the effect of catheters size 3.5, 5 and 6 French on airway resistance in ELGANs of 23-28 weeks gestational age during LISA, we performed calculations based on Hagen-Poiseuille's law and compared these with a clinically and physically more accurate method: computational fluid dynamics (CFD) simulations of respiratory airflow, performed in 3D virtual airway models derived from MRI. Results: The presence of the above catheters decreased the cross-sectional area of the infants' tracheal entrance (the cricoid ring) by 13-53%. Hagen-Poiseuille's law predicted an increase in resistance by 1.5-4.5 times and 1.3-2.6 times in ELGANs born at 23 and 28 weeks, respectively. However, CFD simulations demonstrated an even higher increase in resistance of 3.4-85.1 and 1.1-3.5 times, respectively. The higher calculated resistances were due to the extremely narrow remaining lumen at the glottis and cricoid with the catheter inserted, resulting in a stronger glottal jet and turbulent airflow, which was not predicted by Hagen-Poiseuille. Conclusion: Catheter thickness can greatly increase tracheal resistance during LISA-procedures in ELGANs. Based on these models, it is recommended to use the thinnest catheter possible during LISA in ELGANs to avoid unnecessary increases in airway resistance in infants already experiencing dyspnea due to respiratory distress syndrome.

Oxygenation Indices in Adult COVID ARDS Patients.

How to cite this article: Palanidurai S, Phua J, Mukhopadhyay A. Oxygenation Indices in Adult COVID ARDS Patients. Indian J Crit Care Med 2024;28(9):887-888.

Author Response: Oxygenation Indices in Adult COVID ARDS Patients.

How to cite this article: Vadi SMR, Sanwalka N, Suthar D. Author Response: Oxygenation Indices in Adult COVID ARDS Patients. Indian J Crit Care Med 2024;28(9):889.

Baicalein ameliorates SEB-induced acute respiratory distress syndrome in a microbiota-dependent manner.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by sudden and extensive pulmonary inflammation, with a mortality rate of approximately 40 %. Presently, there is no effective treatment to prevent or reverse its severe consequences. Baicalein (BAI) is a natural vicinal trihydroxyflavone and has been identified as the core quality marker of Scutellariae baicalensis for its effect on lung inflammation. However, its oral bioavailability is limited. The majority of studies that investigate BAI's in vivo mechanisms use injection techniques. Currently, there is no clear understanding of the mechanisms by which low-bioavailable BAI functions orally. PURPOSE: This study aimed to evaluate the efficiency of BAI in ARDS mice and its underlying mechanisms. STUDY DESIGN AND METHODS: Behavioral experiments, histological analysis, immunofluorescence staining, flow cytometry of immune cells, qRT-PCR, and ELISA analysis were performed to evaluate the efficiency of BAI in ARDS mice. Lung tissues transcriptomic-based analyses were performed to detect the differentially expressed genes and biological pathways. Fecal samples were subjected to microbial 16S rRNA analysis and untargeted metabolomics analysis in order to identify the specific flora and metabolites associated with BAI. Furthermore, antibiotic cocktail treatment and fecal microbiota transplantation were used to elucidate the gut microbiota-mediated effects on ARDS. RESULTS: In our study, we first find that oral administration of BAI effectively mitigates staphylococcal enterotoxin B-induced ARDS. BAI can alleviate gut dysbiosis and regulate the Toll-like signaling pathway and amino acid metabolism. The protective effects of BAI against ARDS are gut microbiota dependent. Modulation of gut microbiota increases the production of short-chain fatty acids and enhances lung barrier function, which is consistent with the therapeutic interventions with BAI. Notably, BAI greatly enriches the abundance of Prevotellaceae, a butyrate-producing bacterial family, exhibiting a positive correlation with key differentially expressed genes in the TLR4/MyD88 signaling cascades. CONCLUSION: BAI emerges as a potential prebiotic agent to attenuate ARDS, and targeting specific microbial species may offer an innovative therapeutic approach to investigate other flavonoids with limited bioavailability.

Association between lactate-to-albumin ratio and short-time mortality in patients with acute respiratory distress syndrome.

STUDY OBJECTIVE: The lactate-to-albumin ratio (LAR) has been confirmed to be an effective prognostic marker in sepsis, heart failure, and acute respiratory failure. However, the relationship between LAR and mortality in patients with acute respiratory distress syndrome (ARDS) remains unclear. We aim to evaluate the predictive value of LAR for ARDS patients. DESIGN: A retrospective cohort study. SETTING: Medical Information Mart for Intensive Care IV (v2.2) database. PATIENTS: 769 patients with acute respiratory distress syndrome(ARDS). INTERVENTIONS: We divided the patients into two subgroups according to the primary study endpoint (28-days all-cause mortality): the 28-day survivors and the 28-day non-survivors. MEASURES: Multivariate Cox Regression, Receiver Operator Characteristic (ROC) and Kaplan-Meier survival analysis were used to investigate the relationship between LAR and short-time mortality in patients with ARDS. MAIN RESULTS: The 28-day mortality was 38 % in this study. Multivariable Cox regression analysis showed that LAR was an independent predictive factor for 28-day mortality (HR 1.11, 95 %CI: 1.06-1.16, P < 0.001). The area under curve (AUC) of LAR in the ROC was 70.34 % (95 %CI: 66.53 % - 74.15 %) that provided significantly higher discrimination compared with lactate (AUC = 68.00 %, P = 0.0007) or albumin (AUC = 63.17 %, P = 0.002) alone. LAR was also not inferior to SAPSII with the AUC of 73.44 % (95 %CI: 69.84 % - 77.04 %, P = 0.21). Additionally, Kaplan-Meier survival analysis displayed that ARDS patients with high LAR (> the cut-off value 0.9055) had a significantly higher 28-day overall mortality rate (P < 0.001) and in-hospital mortality rate (P < 0.001). However, patients in high LAR group had shorter length of hospital stay (P < 0.001), which might be caused by higher in-hospital mortality. CONCLUSIONS: We confirmed that there was a positive correlation between LAR and 28-day mortality. This could provide anesthesiologists and critical care physicians with a more convenient tool than SAPSII without being superior for detecting ARDS patients with poor prognosis timely.

A tidal volume of 7 mL/kg PBW or higher may be safe for COVID-19 patients.

PURPOSE: The novel coronavirus disease (COVID-19) has revived the debate on the optimal tidal volume during acute respiratory distress syndrome (ARDS). Some experts recommend 6 mL/kg of predicted body weight (PBW) for all patients, while others suggest 7-9 mL/kg PBW for those with compliance >50 mL/cmH2O. We investigated whether a tidal volume ≥ 7 ml/kg PBW may be safe in COVID-19 patients, particularly those with compliance >50 mL/cmH2O. MATERIALS AND METHODS: This secondary analysis of a multicenter study compares the Intensive Care Unit (ICU) mortality among 600 patients ventilated with <7 or ≥ 7 mL/kg PBW. Compliance was categorized as <40, 40-50, or > 50 mL/cmH2O. RESULTS: 346 patients were ventilated with <7 (6.2 ± 0.5) mL/kg PBW and 254 with ≥7 (7.9 ± 0.9) mL/kg PBW. ICU mortality was 33 % and 29 % in the two groups (p = 0.272). At multivariable regression analysis, tidal volume ≥ 7 mL/kg PBW was associated with lower ICU mortality in the overall population (odds ratio: 0.62 [95 %-confidence interval: 0.40-0.95]) and in each compliance category. CONCLUSIONS: A tidal volume ≥ 7 (up to 9) mL/kg PBW was associated with lower ICU mortality in these COVID-19 patients, including those with compliance <40 mL/cmH2O. This finding should be interpreted cautiously due to the retrospective study design. TRIAL REGISTRATION: ClinicalTrails.govNCT04388670.

Risk factors for acute respiratory distress syndrome in sepsis patients: A meta-analysis.

Background: Acute Respiratory Distress Syndrome (ARDS) is a critical complication of sepsis, associated with high morbidity and mortality. Identifying risk factors for ARDS among sepsis patients is essential for early intervention and improving outcomes. Methods: We conducted a comprehensive meta-analysis, reviewing studies that examined the association between various risk factors and ARDS development in sepsis patients. Databases such as PubMed, EMBASE, Cochrane Library, Medline, CINAHL, and Web of Science were searched up to January 2024, without language restrictions. Eligible studies included observational cohorts and case-control studies. Pooled odds ratios (ORs) and standardized mean differences (SMDs) were calculated using a random-effects model. Heterogeneity was assessed through I2 statistics, and publication bias was evaluated via the Luis Furuya-Kanamori (LFK) index. Results: 15 studies with more than 40,000 participants were analyzed. Significant risk factors for ARDS included pulmonary infection (OR: 2.696, 95 % CI: 1.655 to 4.390), septic shock (OR: 2.627, 95 % CI: 1.850 to 3.731), and pancreatitis (OR: 3.734, 95 % CI: 2.958 to 4.712). No significant associations were found between the development of ARDS in septic patients and the following risk factors: sex (OR: 1.106, 95%CI: 0.957-1.279), smoking status (OR: 1.214, 95%CI: 0.835-1.765), or steroid use (OR: 0.901, 95%CI: 0.617-1.314). APACHE-II and SOFA scores were predictive of ARDS development, emphasizing their utility in clinical assessments. Conclusion: Pulmonary infection, septic shock, and pancreatitis significantly increase ARDS risk in sepsis patients. Our findings advocate for targeted management of these risk factors to mitigate ARDS development, emphasizing the importance of personalized care in sepsis management.