Applicability of mouse models for induction of severe acute lung injury.

Acute lung injury (ALI) is a significant clinical challenge associated with high morbidity and mortality. Worldwide, it affects approximately 200.000 individuals annually, with a staggering 40% mortality rate in hospitalized cases and persistent complications in out-of-hospital cases. This review focuses on the key immunological pathways underlying bacterial ALI and the exploration of mouse models as tools for its induction. These models serve as indispensable platforms for unraveling the inflammatory cascades and biological responses inherent to ALI, while also facilitating the evaluation of novel therapeutic agents. However, their utility is not without challenges, mainly due to the stringent biosafety protocols required by the diverse bacterial virulence profiles. Simple and reproducible models of pulmonary bacterial infection are currently available, including intratracheal, intranasal, pleural and, intraperitoneal approaches. These models use endotoxins such as commercially available lipopolysaccharide (LPS) or live pathogens such as Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Streptococcus pneumoniae, all of which are implicated in the pathogenesis of ALI. Combining murine models of bacterial lung infection with in-depth studies of the underlying immunological mechanisms is a cornerstone in advancing the therapeutic landscape for acute bacterial lung injury.

The impact of diabetes mellitus on blood-tissue barrier regulation and vascular complications: Is the lung different from other organs?

Diabetes Mellitus presents a formidable challenge as one of the most prevalent and complex chronic diseases, exerting significant strain on both patients and the world economy. It is recognized as a common comorbidity among severely ill individuals, often leading to a myriad of micro- and macro-vascular complications. Despite extensive research dissecting the pathophysiology and molecular mechanisms underlying vascular complications of diabetes, relatively little attention has been paid to potential lung-related complications. This review aims to illuminate the impact of diabetes on prevalent respiratory diseases, including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), tuberculosis (TB), pneumonia infections, and asthma, and compare the vascular complications with other vascular beds. Additionally, we explore the primary mechanistic pathways contributing to these complications, such as the expression modulation of blood-tissue-barrier proteins, resulting in increased paracellular and transcellular permeability, and compromised immune responses rendering diabetes patients more susceptible to infections. The activation of inflammatory pathways leading to cellular injury and hastening the onset of these respiratory complications is also discussed.

A Review of Current Evidence for the Use of Steroids in the Medical Intensive Care Unit.

Systemic steroids are frequently used in critically ill patients for their anti-inflammatory properties. Potential benefits of these agents should be balanced against their known side effects. In this paper, we review trials assessing the use of systemic steroids in common conditions requiring admission to the intensive care unit. These include septic shock, the acute respiratory distress syndrome, severe pneumonia, COVID-19, and hypercapnic respiratory failure due to chronic obstructive pulmonary disease. We will mainly focus on well-conducted randomized controlled trials to determine whether steroids should be administered to critically ill patients presenting with these conditions.

Prone-position decreases airway closure in a patient with ARDS undergoing venovenous extracorporeal membrane oxygenation.

PURPOSE: Airway closure is a interruption of communication between larger and smaller airways. The presence of airway closure during mechanical ventilation may lead to the overestimation of driving pressure (DP), introducing errors in the assessment of respiratory mechanics and in positive end-expiratory pressure (PEEP) setting on the ventilator. Patients with severe acute respiratory distress syndrome (ARDS) may exhibit the airway closure phenomenon, which can be easily diagnosed with a low-flow inflation. Prone positioning is a therapeutic manoeuver proven to reduce mortality in ARDS patients, and has been widely implemented also in patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). To date, the impact of prone positioning on changes in airway closure has not been described. METHODS: We present an image analysis of the pressure waveform during volume-controlled ventilation and low-flow inflations before and after prone positioning in an ARDS patient on VV ECMO. RESULTS: A high airway opening pressure level (23 cmH2O) was detected in the supine position during tidal ventilation. Airway closure was confirmed by using a low-flow inflation. Prone positioning significantly attenuated airway closure, with the airway opening pressure decreasing to 13 cmH2O. After re-supination, airway closure was lower as compared with supine position at baseline (17 cmH2O). CONCLUSION: Prone positioning reduced airway closure in an ARDS patient on VV ECMO support.

Five sessions of Hyperbaric Oxygen for critically ill patients with COVID-19-induced ARDS: a randomised, open label, phase II trial.

BACKGROUND: Few treatment options exist for patients with COVID-19-induced acute respiratory distress syndrome (ARDS). Data on the benefits and harms of hyperbaric oxygen treatment (HBOT) for this condition is limited. OBJECTIVE: To evaluate benefits and harms of HBOT in patients with COVID-19 induced ARDS. METHODS: In this open-label trial conducted at three hospitals in Sweden and Germany, patients with moderate to severe ARDS and at least two risk factors for unfavourable outcome, were randomly assigned (1:1) to medical oxygen 100%, 2·4 Atmospheres absolute (ATA), 80 minutes (HBOT) adjuvant to best practice or to best practice alone (Control). Randomisation was stratified by sex and site. The primary endpoint was ICU admission by Day 30. RESULTS: Between June 4, 2020, and Dec 1, 2021, 34 subjects were randomised to HBOT (N=18) or Control (N=16). The trial was prematurely terminated for futility. There was no statistically significant difference in ICU admission, 5 (50%) in Control vs 13 (72%) in HBOT. OR 2·54 [95% CI 0·62-10·39], p=0·19. HARMS: 102 adverse events (AEs) were recorded. 16 (94%) subjects in the HBOT group and 14 (93%) in the control group had at least one AE. Three serious adverse events (SAEs), were at least, possibly related to HBOT. All deaths were unlikely related to HBOT. CONCLUSIONS: HBOT did not reduce ICU admission or mortality in patients with COVID-19-induced ARDS. The trial cannot conclude definitive benefits or harms. Treating COVID-19-induced ARDS with HBOT is feasible with a favourable harms profile. FUNDING: Swedish Research Council, grant number KBF 2019-00446.

Bidirectional pressure: a mini review of ventilator-lung-kidney interactions.

Acute kidney injury and respiratory failure that requires mechanical ventilation are both common complications of critical illnesses. Failure of either of these organ systems also increases the risk of failure to the other. As a result, there is a high incidence of patients with concomitant acute kidney injury and the need for mechanical ventilation, which has a devasting impact on intensive care unit outcomes, including mortality. Despite decades of research into the mechanisms of ventilator-lung-kidney interactions, several gaps in knowledge remain and current treatment strategies are primarily supportive. In this review, we outline our current understanding of the mechanisms of acute kidney injury due to mechanical ventilation including a discussion of; 1) The impact of mechanical ventilation on renal perfusion, 2) activation of neurohormonal pathways by positive pressure ventilation, and 3) the role of inflammatory mediators released during ventilator induced lung injury. We also provide a review of the mechanisms by which acute kidney injury increases the risk of respiratory failure. Next, we outline a summary of the current therapeutic approach to preventing lung and kidney injury in the critically ill, including fluid and vasopressor management, ventilator strategies, and treatment of acute kidney injury. Finally, we conclude with a discussion outlining opportunities for novel investigations that may provide a rationale for new treatment approaches.

Outcomes of combined mitochondria and mesenchymal stem cells-derived exosome therapy in rat acute respiratory distress syndrome and sepsis.

BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging. AIM: To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EXAD) and exogenous mitochondria (mitoEx) protect the lung from ARDS complicated by SS. METHODS: In vitro study, including L2 cells treated with lipopolysaccharide (LPS) and in vivo study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EXAD), 4 (ARDS-SS + mitoEx), and 5 (ARDS-SS + EXAD + mitoEx), were included in the present study. RESULTS: In vitro study showed an abundance of mitoEx found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels (P < 0.001). The protein levels of inflammation [interleukin (IL)-1ß/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EXAD treatment than without EXAD treatment, whereas the protein expressions of cellular junctions [occluding/ß-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all P < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all P < 0.0001), whereas arterial oxygen-saturation (SaO2%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO2% among the groups (all P < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1ß/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all P < 0.0001). CONCLUSION: Combined EXAD-mitoEx therapy was better than merely one for protecting the lung against ARDS-SS induced injury.

Unmasking Negative Pressure Pulmonary Edema Following Hanging: A Case Series.

Pulmonary edema is a rare mechanism of death that develops after partial hanging, a potential complication that physicians should consider early in the management of these patients. This case series discusses the presentation, evaluation, and treatment course of three patients who had attempted suicide by hanging and were admitted to the hospital. These patients were admitted to the intensive care unit after being stabilized and supportive treatment was provided. In all the cases, a radiological scan of the chest revealed diffuse infiltrates consistent with pulmonary edema on both sides, features of which were also noted during a diagnostic bronchoscopy. After providing the best intensive care in the hospital, two patients clinically improved, and one patient succumbed to cardiac arrest. As most patients will be brought dead to the hospital following hanging, negative pressure pulmonary edema remains underdiagnosed. Thus, this case series enumerates the possible etiologies of negative pressure pulmonary edema and its contribution to death following suicidal hanging.

Was there a weekend effect on mortality rates for hospitalized patients with COVID-19 and acute myocardial infarction? Insights from the National Inpatient Sample, 2020.

Our study aimed to assess the effect of weekend versus weekday hospital admissions on all-cause mortality in patients with acute myocardial infarction (AMI) and COVID-19 during the COVID-19 pandemic. We analyzed data from the National Inpatient Sample (NIS) 2020, identifying patients with co-existing AMI and COVID-19 admitted on weekdays and weekends. Baseline demographics, comorbidities, and outcomes were assessed. A multivariable regression analysis was conducted, adjusting for confounders to determine the odds of all-cause mortality. Among 74,820 patients, 55,145 (73.7%) were admitted on weekdays, while 19,675 (26.3%) were admitted on weekends. Weekend admissions showed slightly higher proportions of men (61.3% vs. 60%) and whites (56.3% vs. 54.9%) with a median age of 73 years (range: 62-82). The overall all-cause mortality had an odds ratio (OR) of 1.00 (95% CI, 0.92-1.09; P = 0.934). After adjusting for covariates, there was no significant associations between mortality and hospital type (rural: OR = 1.04; 95% CI, 0.78-1.39; P = 0.789; urban teaching: OR = 1.04; 95% CI, 0.94-1.14; P = 0.450) or geographic region (Northeast: OR = 1.16; 95% CI, 0.96-1.39; P = 0.12; Midwest: OR = 0.99; 95% CI, 0.83-1.17; P = 0.871; South: OR = 0.97; 95% CI, 0.85-1.12; P = 0.697; West: OR = 0.94; 95% CI, 0.77-1.15; P = 0.554). There was no significant difference in the rate of all-cause mortality among patients admitted for AMI and COVID-19 between weekdays and weekends.

Clinical characteristics and risk factors for mortality in pneumonia-associated acute respiratory distress syndrome patients: a single center retrospective cohort study.

Background: Pathogenic diversity may have contributed to the high mortality of pneumonia-associated acute respiratory distress syndrome (p-ARDS). Metagenomics next-generation sequencing (mNGS) serves as a valuable diagnostic tool for early pathogen identification. However, its clinical utility in p-ARDS remains understudied. There are still limited researches on the etiology, clinical characteristics and risk factors for 28-day mortality in p-ARDS patients. Methods: A single center retrospective cohort study of 75 p-ARDS patients was conducted. Patients were categorized into survival and deceased groups based on their 28-day outcomes. A comprehensive clinical evaluation was conducted, including baseline characteristics, laboratory indicators, outcomes and pathogen identification by mNGS and traditional microbiological testing. We then evaluated the diagnostic value of mNGS and identified clinical characteristics and risk factors for 28-day mortality in p-ARDS. Result: The overall ICU mortality was 26.67%, and the 28-day mortality was 57.33%, with 32 cases (42.67%) in the survival group, and 43 cases (57.33%) in the deceased group. Patients in the deceased group were older than those in the survival group (68(59,73) years vs. 59(44,67) years, P=0.04). The average lengths of ICU and hospital stay were 9(5,13) days and 14(7,21) days, respectively. The survival group had longer lengths of ICU and hospital stay (ICU: 11(7,17) days and hospital: 17(9,27) days) compared to the deceased group (ICU: 8(4,11) days and hospital: 12(6,19) days) (P<0.05). Survival patients exhibited lower Acute Physiology and Chronic Health Evaluation (APACHE) II score on the 3rd and 7th days, higher lymphocyte counts, higher CD3+ and CD8+ T cell counts compared to deceased patients (P<0.05). Multivariate logistic regression analysis identified age, APACHE II scores on 3rd and 7th days, CD8+ T cell count and length of ICU as independent risk factors for 28-day mortality in p-ARDS patients. mNGS demonstrated a significantly higher overall pathogen detection rate (70/75, 93.33%) compared to the traditional method (50/75, 66.67%, P=0.022). The average turnaround time (TAT) for mNGS was significantly shorter at 1(1,1) day compared to 4(3,5) days for the traditional method (P<0.001). Conclusion: Metagenome next-generation sequencing can be used as a valuable tool for identifying pathogens in p-ARDS, reducing diagnostic time and improving accuracy. Early application of mNGS alongside traditional methods is recommended for p-ARDS. Furthermore, older age, higher APACHE II scores, lower lymphocyte counts and lymphocyte subset counts were associated with increased mortality in p-ARDS patients, highlighting the importance of timely assessment of immune status and disease severity, especially in elderly.

Physiological and clinical effects of trunk inclination adjustment in patients with respiratory failure: a scoping review and narrative synthesis.

BACKGROUND: Adjusting trunk inclination from a semi-recumbent position to a supine-flat position or vice versa in patients with respiratory failure significantly affects numerous aspects of respiratory physiology including respiratory mechanics, oxygenation, end-expiratory lung volume, and ventilatory efficiency. Despite these observed effects, the current clinical evidence regarding this positioning manoeuvre is limited. This study undertakes a scoping review of patients with respiratory failure undergoing mechanical ventilation to assess the effect of trunk inclination on physiological lung parameters. METHODS: The PubMed, Cochrane, and Scopus databases were systematically searched from 2003 to 2023. INTERVENTIONS: Changes in trunk inclination. MEASUREMENTS: Four domains were evaluated in this study: 1) respiratory mechanics, 2) ventilation distribution, 3) oxygenation, and 4) ventilatory efficiency. RESULTS: After searching the three databases and removing duplicates, 220 studies were screened. Of these, 37 were assessed in detail, and 13 were included in the final analysis, comprising 274 patients. All selected studies were experimental, and assessed respiratory mechanics, ventilation distribution, oxygenation, and ventilatory efficiency, primarily within 60 min post postural change. CONCLUSION: In patients with acute respiratory failure, transitioning from a supine to a semi-recumbent position leads to decreased respiratory system compliance and increased airway driving pressure. Additionally, C-ARDS patients experienced an improvement in ventilatory efficiency, which resulted in lower PaCO2 levels. Improvements in oxygenation were observed in a few patients and only in those who exhibited an increase in EELV upon moving to a semi-recumbent position. Therefore, the trunk inclination angle must be accurately reported in patients with respiratory failure under mechanical ventilation.

Changing clinical practice and prognosis for severe respiratory failure over time: A nationwide inpatient database study.

BACKGROUND: Severe respiratory failure requires numerous interventions and its clinical implementation changes over time. We aimed to clarify the clinical practice and prognosis of severe respiratory failure and its changes over time. METHODS: In a nationwide Japanese administrative database from 2016 to 2019, we identified nonoperative patients with severe respiratory failure without congestive heart failure as the main diagnosis who received mechanical ventilation (MV) for more than four days. We examined trends in patient characteristics, adjunctive interventions, and prognosis. RESULTS: Among 66,905 patients included in this study, patients received antibiotics (90%), high-dose corticosteroids (14%), low-dose corticosteroids (18%), and 51% were admitted to the critical care unit. Hospital mortality was 35%. Median mechanical ventilation lasted 10 days. Tracheostomy occurred in 23% of cases. Median critical care and hospital stays were 10 and 25 days, respectively. Among survivors, 23% had mechanical ventilation dependency at hospital discharge. Large relative changes in adjunctive therapies included fentanyl (30%-38%), rocuronium (4.4%-6.7%), vasopressin (3.8%-6.0%), early rehabilitation (27%-38%), extracorporeal membrane oxygenation (0.7%-1.2%), dopamine (15%-10%), and sivelestat (8.6%-3.5%). No notable changes were seen in mechanical ventilation duration, tracheostomy, critical care unit stay, hospital stay, or ventilator dependency at discharge, except for a slight reduction in hospital mortality (36%-34%). CONCLUSIONS: Several adjunctive therapies for severe respiratory failure changed from 2016 to 2019, with an increase in evidence-based practices and a slight decrease in hospital mortality.

Association of Red Blood Cell Transfusion Thresholds and Outcomes in Medical Patients with Acute Respiratory Failure Supported with Extra Corporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study.

BACKGROUND: The hemoglobin value to trigger red blood cell (RBC) transfusion for patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) is controversial. Previous guidelines recommended transfusing to a normal hemoglobin, but recent studies suggest more RBC transfusions are associated with increased adverse outcomes. RESEARCH QUESTION: Is implementation of different institutional RBC transfusion thresholds for patients receiving VV-ECMO associated with changes in RBC utilization and patient outcomes? STUDY DESIGN AND METHODS: Single-center retrospective study of patients receiving VV-ECMO using segmented regression to test associations between implementation of institutional transfusion thresholds and trends in RBC utilization. Associations with secondary outcomes, including in-hospital survival, were also assessed. RESULTS: The study included 229 patients: 91 in the "no threshold (NT)" cohort, 48 in the "hemoglobin <8 g/dL (<8 g/dL)" cohort and 90 in the "hemoglobin <7 g/dL (<7 g/dL)" cohort. Despite a decrease in RBC/ECMO day following implementation of different thresholds, (mean +/- SD; 0.6 +/- 1.0 in the NT cohort, 0.3 +/- 0.8 in the <8 g/dL cohort, and 0.3 +/- 1.1 in the <7 g/dL cohort, p < 0.001), segmented regression showed no association between implementation of transfusion thresholds and changes in trends in RBC/ECMO day. We observed an increased hazard of death in the NT cohort compared to the <8 g/dL cohort (aHR: 2.08, 95% CI: 1.12-3.88), and in the <7 g/dL cohort compared to the <8g/dL cohort (aHR: 1.93, 95% CI: 1.02-3.62). There was no difference in the hazard of death between the NT and <7 g/dL cohorts (aHR: 1.08, 95% CI: 0.69-1.69). INTERPRETATION: We observed a decrease in RBC/ECMO day over time, but changes were not associated temporally with implementation of transfusion thresholds. A transfusion threshold of hemoglobin <8 g/dL was associated with a lower hazard of death, but these findings are limited by study methodology. Further research is needed investigating optimal RBC transfusion practices for patients supported with VV-ECMO.

Leptospirosis-Associated Acute Respiratory Distress Syndrome (ARDS) in Pregnancy: A Rare Presentation.

Leptospirosis, a zoonotic disease caused by spirochetes of the genus Leptospira, poses unique challenges in pregnancy due to its varied clinical presentation and potential adverse outcomes for both mother and fetus. We present a case of a 24-year-old primigravida at 35 weeks of gestation who presented with fever, dyspnea, and abdominal pain, and was ultimately diagnosed with leptospirosis complicated by acute respiratory distress syndrome (ARDS). Prompt initiation of antibiotic therapy, supportive care, and timely delivery via emergency cesarean section led to favorable maternal and neonatal outcomes. This case report underscores the importance of considering leptospirosis in pregnant patients presenting with similar symptoms, particularly in endemic regions, and highlights the critical role of multidisciplinary management in optimizing outcomes.

Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

Using the sympathetic system, beta blockers and alpha-2 agonists, to address acute respiratory distress syndrome.

Acute Respiratory Distress Syndrome (ARDS) manifests as an acute inflammatory lung injury characterized by persistent hypoxemia, featuring a swift onset, high mortality, and predominantly supportive care as the current therapeutic approach, while effective treatments remain an area of active investigation. Adrenergic receptors (AR) play a pivotal role as stress hormone receptors, extensively participating in various inflammatory processes by initiating downstream signaling pathways. Advancements in molecular biology and pharmacology continually unveil the physiological significance of distinct AR subtypes. Interventions targeting these subtypes have the potential to induce specific alterations in cellular and organismal functions, presenting a promising avenue as a therapeutic target for managing ARDS. This article elucidates the pathogenesis of ARDS and the basic structure and function of AR. It also explores the relationship between AR and ARDS from the perspective of different AR subtypes, aiming to provide new insights for the improvement of ARDS.

Systemic Corticosteroid as an Adjunct for Acute Respiratory Distress Syndrome in Non-Fatal Fresh Water Drowning: An Evidence-based Case Report.

BACKGROUND: Acute lung injury or acute respiratory distress syndrome (ARDS) is one of the most common complications of non-fatal drowning. Although respiratory societies' guidelines endorse the role of systemic corticosteroids in ARDS, the evidence for systemic corticosteroid use in ARDS due to non-fatal drowning is limited. METHODS: A search was conducted on Pubmed, OVID, and EuropePMC, assessing the clinical question using inclusion and exclusion criteria. The selected studies were critically appraised, and the results were summarized. RESULTS: A total of six retrospective studies were selected and assessed, all studies showed poor validity and a high risk of bias. Out of six studies, only four informed us of steroid administration's effect on outcomes. In two studies, mortality associated with corticosteroid administration seemed to be higher. On the contrary, one study found no mortality in the corticosteroid group, but 100% mortality was observed in the control group. In another study, steroid therapy seemed to not affect hospital length of stay or mechanical ventilation rates. CONCLUSION: Corticosteroid administration for non-fatal drowning and its impact on clinical outcomes remains equivocal. Routine administration of corticosteroids is not indicated and should be done on a case-by-case basis.

Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome.

Endothelial cells (ECs) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. Pulmonary endothelial barrier integrity is maintained through coordinated cellular processes involving receptors, signaling molecules, junctional complexes, and protein-regulated cytoskeletal reorganization. In acute lung injury (ALI) or its more severe form acute respiratory distress syndrome (ARDS), the loss of endothelial barrier integrity secondary to endothelial dysfunction caused by severe pulmonary inflammation and/or infection leads to pulmonary edema and hypoxemia. Pro-inflammatory agonists such as histamine, thrombin, bradykinin, interleukin 1ß, tumor necrosis factor α, vascular endothelial growth factor, angiopoietin-2, and platelet-activating factor, as well as bacterial toxins and reactive oxygen species, cause dynamic changes in cytoskeletal structure, adherens junction disorganization, and detachment of vascular endothelial cadherin (VE-cadherin) from the actin cytoskeleton, leading to an increase in endothelial permeability. Endothelial interactions with leukocytes, platelets, and coagulation enhance the inflammatory response. Moreover, inflammatory infiltration and the associated generation of pro-inflammatory cytokines during infection cause EC death, resulting in further compromise of the structural integrity of lung endothelial barrier. Despite the use of potent antibiotics and aggressive intensive care support, the mortality of ALI is still high, because the mechanisms of pulmonary EC barrier disruption are not fully understood. In this review, we summarized recent advances in the studies of endothelial cytoskeletal reorganization, inter-endothelial junctions, endothelial inflammation, EC death, and endothelial repair in ALI and ARDS, intending to shed some light on the potential diagnostic and therapeutic targets in the clinical management of the disease.

Effect of caspase inhibitors on hemodynamics and inflammatory factors in ARDS model rats.

To study the effects of caspase inhibitors on hemodynamics and inflammatory factors in acute respiratory distress syndrome (ARDS) model rats. Sixty healthy male Wistar rats were randomly divided into three groups, namely, the control group, ARDS group and ARDS + Caspase inhibitor group, with 20 rats in each group. The control group was intraperitoneally injected with 2 mL/kg saline, and the ARDS model group was established by intraperitoneally injecting 4 mg/kg Lipopolysaccharide (LPS), ARDS + Caspase inhibitor group was adminstered 20 mg/kg caspase inhibitor after intraperitoneal LPS injection. Changes in pulmonary arterial pressure (PAP) and mean arterial pressure (MAP) at 6 and 12 h before and after administration were recorded. Moreover, arterial blood gas was evaluated with a blood gas analyzer and changes in the partial pressure of O2 (PaO2), partial pressure of CO2 (PaCO2), partial pressure of O2/fraction of inspired O2 (PaO2/FiO2) were evaluated. In addition, the lung wet/dry weight (W/D) ratio and inflammatory factor levels in lung tissue were determined. Finally, pathological sections were used to determine the pulmonary artery media thickness (MT), MT percentage (MT%), and the degree of muscle vascularization. The pulmonary arterial pressure of rats was determined at several time points. Compared with the control group, the model group had a significantly increased pulmonary arterial pressure at each time point (P < 0.01), and the mean arterial pressure significantly increased at 6 h (P < 0.05). Compared with that of rats in the model group, the pulmonary arterial pressure of rats in drug administration group was significantly reduced at each time point after administration (P < 0.01), and the mean arterial pressure was significantly reduced at 6 h (P < 0.05). The arterial blood gas analysis showed that compared with those in the control group, PaO2, PaCO2 and PaO2/FiO2 in the model group were significantly reduced (P < 0.01), and PaO2, PaCO2 and PaO2/FiO2 were significantly increased after caspase inhibitor treatment (P < 0.05 or 0.01). The levels of the inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the model group were significantly higher than those in the control group (P < 0.01), and they were significantly decreased after caspase inhibitor treatment (P < 0.01). In the model group, pulmonary artery MT, MT% and the degree of muscle vascularization were significantly increased (P < 0.05 or 0.01), and pulmonary artery MT and the degree of muscle vascularization were significantly reduced after caspase inhibitor treatment (P < 0.05 or 0.01). Apoptosis Repressor with a Caspase Recuitment Domain (ARC) can alleviate the occurrence and development of pulmonary hypertension (PH) by affecting hemodynamics and reducing inflammation.