Clinical significance of platelet mononuclear cell aggregates in patients with sepsis and acute respiratory distress syndrome

BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.

Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

Outcomes of combined mitochondria and mesenchymal stem cellsderived 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)-1β/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/β-catenin/zonula occludens(ZO)-1/E-cadherin]exhibited an opposite pattern of inflam-mation(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 inflam-matory 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-1β/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.

Outpatient insulin use in type 2 diabetes mellitus and acute respiratory distress syndrome outcomes:A retrospective cohort study

BACKGROUND The impact of type 2 diabetes mellitus(T2DM)on acute respiratory distress syndrome(ARDS)is debatable.T2DM was suspected to reduce the risk and complications of ARDS.However,during coronavirus disease 2019(COVID-19),T2DM predisposed patients to ARDS,especially those who were on insulin at home.AIMTo evaluate the impact of outpatient insulin use in T2DM patients on non-COVID-19 ARDS outcomes.METHODS We conducted a retrospective cohort analysis using the Nationwide Inpatient Sample database.Adult patients diagnosed with ARDS were stratified into insulin-dependent diabetes mellitus(DM)(IDDM)and non-insulindependent DM(NIDDM)groups.After applying exclusion criteria and matching over 20 variables,we compared cohorts for mortality,duration of mechanical ventilation,incidence of acute kidney injury(AKI),length of stay(LOS),hospitalization costs,and other clinical outcomes.RESULTS Following 1:1 propensity score matching,the analysis included 274 patients in each group.Notably,no statistically significant differences emerged between the IDDM and NIDDM groups in terms of mortality rates(32.8%vs 31.0%,P=0.520),median hospital LOS(10 d,P=0.537),requirement for mechanical ventilation,incidence rates of sepsis,pneumonia or AKI,median total hospitalization costs,or patient disposition upon discharge.CONCLUSION Compared to alternative anti-diabetic medications,outpatient insulin treatment does not appear to exert an independent influence on in-hospital morbidity or mortality in diabetic patients with non-COVID-19 ARDS.

Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor

BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)patients.Mesenchymal stromal cell-derived microvesicles(MSC-MVs)have been shown to exert antifibrotic effects in lung diseases.AIM To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.METHODS MSC-MVs with low hepatocyte growth factor(HGF)expression(siHGF-MSC-MVs)were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model.Following intubation,respiratory mechanics-related indicators were measured via an experimental small animal lung function tester.Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging.Immunohistochemical,western blotting,ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.RESULTS The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice.Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores.However,low expression of HGF(siHGF-MSC-MVs)significantly inhibited the effects of MSC-MVs(P<0.05).Compared with the ARDS pulmonary fibrosis group,the MSC-MVs group exhibited suppressed expression of type I collagen antigen,type III collagen antigen,and the proteins transforming growth factor-βandα-smooth muscle actin,whereas the siHGF-MVs group exhibited significantly increased expression of these proteins.In addition,pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group,and the effects of the MSC-MVs were significantly inhibited by low HGF expression(all P<0.05).CONCLUSION MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

Mechanisms and Research Progress of Traditional Chinese Medicine Regulating NF-κB in the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring the relevance of NF-κB and the pathogenesis of this disease,it was found that this disease was mainly associated with inflammation,dysfunction of the endothelial barrier,oxidative stress,impaired clearance of alveolar fluid,and coagulation disorders.Traditional Chinese medicine(TCM)has the characteristics of multitargeting,multipathway effects,and high safety,which can directly or indirectly affect the treatment of ALI/ARDS.This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS.It provides an overview from the perspectives of Chinese herbal monomers,TCM couplet medicines,TCM injections,Chinese herbal compounds,and Chinese herbal preparations,offering insights into the prevention and treatment of ALI/ARDS with TCM.

Steroids in acute respiratory distress syndrome:A panacea or still a puzzle?

Acute respiratory distress syndrome(ARDS)is a unique entity marked by various etiologies and heterogenous pathophysiologies.There remain concerns regarding the efficacy of particular medications for each severity level apart from respiratory support.Among several pharmacotherapies which have been examined in the treatment of ARDS,corticosteroids,in particular,have demonstrated potential for improving the resolution of ARDS.Nevertheless,it is imperative to consider the potential adverse effects of hyperglycemia,susceptibility to hospital-acquired infections,and the development of intensive care unit acquired weakness when administering corticosteroids.Thus far,a multitude of trials spanning several decades have investigated the role of corticosteroids in ARDS.Further stringent trials are necessary to identify particular subgroups before implementing corticosteroids more widely in the treatment of ARDS.This review article provides a concise overview of the most recent evidence regarding the role and impact of corticosteroids in the management of ARDS.

Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review

Acute respiratory distress syndrome(ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the "sponge lung"- and the "shape matching"-model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients' response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort.

Lung recruitment maneuver effects on respiratory mechanics and extravascular lung water index in patients with acute respiratory distress syndrome

BACKGROUND：Animal experiments showed that recruitment maneuver （RM） and protective ventilation strategy of the lung could improve oxygenation and reduce extravascular lung water. This study was to investigate the effects of RM on respiratory mechanics and extravascular lung water index （EVLWI） in patients with acute respiratory distress syndrome （ARDS）. METHODS：Thirty patients with ARDS were randomized into a RM group and a non-RM group. In the RM group, after basic mechanical ventilation stabilized for 30 minutes, RM was performed and repeated once every 12 hours for 3 days. In the non-RM group, lung protective strategy was conducted without RM. Oxygenation index （PaO2/FiO2）, peak inspiratory pressure （PIP）, Plateau pressure （Pplat）, static pulmonary compliance （Cst） and EVLWI of patients before treatment and at 12, 24, 48, 72 hours after the treatment were measured and compared between the groups. Hemodynamic changes were observed before and after RM. One-way ANOVA, Student＇s t test and Fisher＇s exact test were used to process the data. RESULTS：The levels of PaO2/FiO2 and Cst increased after treatment in the two groups, but they were higher in the RM group than in the non-RM group （P〈0.05）. The PIP and Pplat decreased after treatment in the two groups, but they were lower in the RM group than in the non-RM group （P〈0.05）. The EVLWI in the two groups showed downward trend after treatment （P〈0.05）, and the differences were signifcant at all time points （P〈0.01）; the EVLWI in the RM group was lower than that in the non-RM group at 12, 24, 48 and 72 hours （P〈0.05 or P〈0.01）. Compared with pre-RM, hemodynamics changes during RM were significantly different （P〈0.01）; compared with pre-RM, the changes were not significantly different at 120 seconds after the end of RM （P〉0.05）. CONCLUSIONS： RM could reduce EVLWI, increase oxygenation and lung compliance. The effect of RM on hemodynamics was transient.

Blood eosinophils and mortality in patients with acute respiratory distress syndrome: A propensity score matching analysis

BACKGROUND: The effect of blood eosinophils(EOSs) on mortality in acute respiratory distress syndrome(ARDS) patients and whether corticosteroids affect this effect are unclear.METHODS: The Medical Information Mart for Intensive Care III database(version 1.4) was used to extract data. Patients with ARDS were selected for inclusion. Cox regression models using the backward stepwise method and propensity score matching(PSM) were used to assess the relationship between blood EOS counts and 28-day mortality. RESULTS: A total of 2,567 patients with ARDS were included, and the 28-day mortality rate was 24.19%. The crude 28-day mortality was significantly lower in patients with EOS counts ≥2%(18.60% [85/457] vs. 25.40% [536/2,110], P=0.002) than in those with EOS counts <2%. In the Cox regression model, the EOS counts ≥2% showed a significant association with the decreased 28-day mortality(hazard ratio [HR] 0.731;95% confidence interval [95% CI] 0.581–0.921, P=0.008). In the corticosteroid non-use subgroup, EOS counts ≥2% was significantly related to decreased 28-day mortality(HR 0.697, 95% CI 0.535–0.909, P=0.008), but the result was not significant in the corticosteroid non-use subgroup model(P=0.860). A total of 457 well-matched pairs were obtained by a 1:1 matching algorithm after PSM. The 28-day mortality remained significantly lower in the EOS counts ≥2% group(18.60% [85/457] vs. 26.70% [122/457], P=0.003).CONCLUSIONS Higher EOS counts are related to lower 28-day mortality in ARDS patients, and this relationship can be counteracted by using corticosteroids.

VASCULAR ENDOTHELIAL INJURIES AND CHANGES OF BLOOD COAGULATION AND FIBRINOLYSIS INDEXES IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME

Objective To study endothelial damage by observing changes of circulating endothelial cells (CECs) in blood, coagula-tion and fibrinolysis index in patients with acute respiratory distress syndrome. Methods CECs were separated by isopycnic centrifugation method in 14 patients with acute lung injury (ALI), 7 patients with acute respiratory distress syndrome (ARDS), 10 intensive care unit (ICU) controls, and 15 healthy controls. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FG), fibrin degradation products (FDP), and D-dimer were examined simultaneously. Acute physiology and chronic health evaluation (APACHE)Ⅱand lung injury score (LIS) were recorded to evaluate severity of illness and lung injury. Results (1) The number of CECs in ALI (10.4 ±2.3) and ARDS groups (16.1 ±2.7) was higher than that in the healthy (1.9 ±0.5) (P< 0.01). In both ALI and ARDS, the number of CECs correlated with APACHEⅡ(r=0.55, P< 0.05 and r=0.62, P< 0.05, respectively)and LIS (r=0.60, P< 0.05 and r=0.53, P< 0.05, respectively). CEC number was negatively correlated with PaO 2 in ALI and ARDS (r=-0.49, P< 0.05 and r=-0.64, P< 0.05, respectively). (2) The level of FDP and D-dimer were higher in ALI and ARDS patients than that in ICU and healthy control groups (P< 0.05). The level of FG in ARDS group was significantly higher than in the ICU and healthy control groups (P< 0.05). But in ALI group, the level of FG was significantly higher than only healthy control group (P< 0.05). Conclusions Endothelial cell damage occurs in ARDS patients, which may play a major role in the pathophysiology of ARDS. Changes of endothelial cell activation and damage markers, such as CECs, plasma coagulation and fibrinolysis index, to some extent reflect severity of illness and lung injury in ARDS.

Effect of protective lung ventilation strategy combined with lung recruitment maneuver in patients with acute respiratory distress syndrome (ARDS)

Objective:To evaluate the efficacy and safety of protective lung ventilation strategy combined with lung recruitment maneuver (RM) in the treatment patients with acute respiratory distress syndrome (ARDS).Methods:Totally 74 patients with ARDS admitted to the Department of Intensive Care Unit, Changshu Second People's Hospital in Jiangsu Province between September 2010 and June 2013 were selected and randomly divided into lung recruitment group and non-lung recruitment group, and the initial ventilation solution for both groups was synchronized intermittent mandatory ventilation (SIMV). For RM, SIMV mode (pressure control and pressure support) was adopted. Positive end expiratory pressure (PEEP) was increased by 5 cm H2O every time and maintained for 40-50 s before entering the next increasing period, and the peak airway pressure was kept below 45 cm H2O. After PEEP reached the maximum value, it was gradually reduced by 5 cm H2O every time and finally maintained at 15 cm H2O for 10 min.Results:A total of 74 patients with mean age of (49.0±18.6) years old were enrolled, 36 patients were enrolled in lung recruitment maneuver (RM) group and 38 patients were enrolled into non-lung recruitment maneuver (non-RM) group. 44 were male and accounted for 59.5% of all the patients. For the indicators such as PEEP, pressure support (PS), plateau airway pressure (Pplat), peak airway pressure (Ppeak), vital capacity (VC) and fraction of inspired oxygen (FiO2), no statistical differences in the indicators were found between the RM group and non-RM group on D1, D3 and D7 (P>0.05), except that only FiO2 of RM group on D7 was significantly lower than that of non-RM group (47.2±10.0) vs. (52.2±10.5),P<0.05]. For the indicators of blood gas analysis, including pH, arterial oxygen pressure (PaO2), arterial carbon dioxide pressure (PaCO2) and oxygenation index (PaO2/FiO2), PaO2 and PaO2/FiO2 of RM group were significantly higher than those of non-RM group on D7, and the values were [(90.2±16.1) mmHg vs. (76.4±11.3) mmHg,P<0.05] and [(196.5±40.7) mmHg vs. (151.7±37.3) mmHg,P<0.05] respectively. There was no statistical difference in heart rate (HR), cardiac index (CI), central venous pressure (CVP) or mean arterial pressure (MAP) between RM group and non-RM group on D1, D3 and D7 (P>0.05). 28-day mortality, ICU mortality and in-hospital mortality were 25% vs. 28.9%, 25% vs. 26.3% and 36.1% vs. 39.5% respectively between RM group and non-RM group (allP>0.05).Conclusion:Protective lung ventilation strategy combined with lung recruitment maneuver can improve the indicators such as PaO2, FiO2 and PaO2/FiO2 on D7, but failed to improve the final outcomes such as 28-day mortality, ICU mortality and in-hospital mortality.

Risk factors associated with acute respiratory distress syndrome in COVID-19 patients outside Wuhan: A double-center retrospective cohort study of 197 cases in Hunan, China

BACKGROUND There have been few reports on the risk factors for acute respiratory distress syndrome(ARDS)in coronavirus disease 2019(COVID-19),and there were obvious differences regarding the incidence of ADRS between Wuhan and outside Wuhan in China.AIM To investigate the risk factors associated with ARDS in COVID-19,and compare the characteristics of ARDS between Wuhan and outside Wuhan in China.METHODS Patients were enrolled from two medical centers in Hunan Province.A total of 197 patients with confirmed COVID-19,who had either been discharged or had died by March 15,2020,were included in this study.We retrospectively collected the patients’clinical data,and the factors associated with ARDS were compared by theχ²test,Fisher’s exact test,and Mann-Whitney U test.Significant variables were chosen for the univariate and multivariate logistic regression analyses.In addition,literature in the PubMed database was reviewed,and the characteristics of ARDS,mortality,and biomarkers of COVID-19 severity were compared between Wuhan and outside Wuhan in China.RESULTS Compared with the non-ARDS group,patients in the ARDS group were significantly older,had more coexisting diseases,dyspnea,higher D-dimer,lactate dehydrogenase(LDH),and C-reactive protein.In univariate logistic analysis,risk factors associated with the development of ARDS included older age[odds ratio(OR)=1.04),coexisting diseases(OR=3.94),dyspnea(OR=17.82),dry/moist rales(OR=9.06),consolidative/mixed opacities(OR=2.93),lymphocytes(OR=0.68 for high lymphocytes compared to low lymphocytes),D-dimer(OR=1.41),albumin(OR=0.69 for high albumin compared to low albumin),alanine aminotransferase(OR=1.03),aspartate aminotransferase(OR=1.02),LDH(OR=1.02),C-reactive protein(OR=1.04)and procalcitonin(OR=17.01).In logistic multivariate analysis,dyspnea(adjusted OR=27.10),dry/moist rales(adjusted OR=9.46),and higher LDH(adjusted OR=1.02)were independent risk factors.The literature review showed that patients in Wuhan had a higher incidence of ARDS,higher mortality rate,and higher levels of biomarkers associated with COVID-19 severity than those outside Wuhan in China.CONCLUSION Dyspnea,dry/moist rales and higher LDH are independent risk factors for ARDS in COVID-19.The incidence of ARDS in Wuhan seems to be overestimated compared with outside Wuhan in China.

A nomogram for predicting acute respiratory distress syndrome in COVID-19 patients

Objective: To predict the in-hospital incidence of acute respiratory distress syndrome(ARDS) in COVID-19 patients by developing a predictive nomogram.Methods: Patients with COVID-19 admitted to Changsha Public Health Centre between 30 January 2020, and 22 February 2020 were enrolled in this study. Clinical characteristics and laboratory variables were analyzed and compared between patients with or without ARDS. Clinical characteristics and laboratory variables that were risk factors of ARDS were screened by the least absolute shrinkage and selection operator binary logistic regression. Based on risk factors, a prediction model was established by logistic regression and the final nomogram prognostic model was performed. The calibration curve was applied to evaluate the consistency between the nomogram and the ideal observation.Results: A total of 113 patients, including 99 non-ARDS patients and 14 ARDS patients were included in this study. Eight variables including hypertension, chronic obstructive pulmonary disease, cough, lactate dehydrogenase, creatine kinase, white blood count, body temperature, and heart rate were included in the model. The area under receiver operating characteristic curve, specificity, sensitivity, and accuracy of the full model were 0.969, 1.000, 0.857, and 0.875, respectively. The calibration curve also showed good agreement between the predicted and observed values in the model.Conclusions: The nomogram can be used to predict the in-hospital incidence of ARDS in COVID-19 patients.

Correlation between circulating endothelial cell level and acute respiratory distress syndrome in postoperative patients

BACKGROUND Acute respiratory distress syndrome(ARDS)is injury of alveolar epithelial cells and capillary endothelial cells caused by various factors,including endogenous and exogenous lung factors,leading to diffuse pulmonary interstitial and alveolar edema,and acute respiratory failure.ARDS involves alveolar epithelial cells and pulmonary interstitial capillary endothelial cells.Circulating endothelial cells(CECs)are the only marker that directly reflects vascular endothelial injury in vivo.There have been few studies on the correlation between peripheral blood CECs and ARDS at home and abroad.The lungs are the organs with the highest capillary density and the most endothelial cells,thus,it is speculated that when ARDS occurs,CECs are stimulated and damaged,and released into the circulatory system.AIM To explore the correlation between CEC level and severity of ARDS in patients postoperatively.METHODS Blood samples were collected from all patients on day 2(d2)and day 5(d5)after surgery.The control group comprised 32 healthy volunteers.Number of CECs was measured by flow cytometry,and operation time was recorded.Changes in various indexes of patients were monitored,and diagnosis of ARDS was determined based on ARDS Berlin definition.We comprised d2 CECs in different groups,correlation between operation time and d2 CECs,ARDS of different severity by d2 CECs,and predictive value of d2 CECs for ARDS in postoperative patients.RESULTS The number of d2 CECs in the ARDS group was significantly higher than that in the healthy control group(P<0.001).The number of d2 CECs in the ARDS group was significantly higher than that in the non-ARDS group(P<0.001).The number of d2 CECs in the non-ARDS group was significantly higher than that in the healthy control group(P<0.001).Operation time was positively correlated with number of CECs on d2(rs=0.302,P=0.001).The number of d2 CECs in the deceased group was significantly higher than that in the improved group(P<0.001).There was no significant difference in number of d2 CECs between patients with mild and moderate ARDS.The number of d2 CECs in patients with severe ARDS was significantly higher than that in patients with mild and moderate ARDS(P=0.041,P=0.037).There was no significant difference in number of d5 and d2 CECs in the non-ARDS group after admission to intensive care.The number of d5 CECs was higher than the number of d2 CECs in the ARDS improved group(P<0.001).The number of d5 CECs was higher than the number of d2 CECs in the ARDS deceased group(P=0.002).If the number of CECs was>1351/mL,sensitivity and specificity of predicting ARDS were 80.8%and 78.1%,respectively.CONCLUSION Changes in number of CECs might predict occurrence and adverse outcome of ARDS after surgery,and higher numbers of CECs indicate worse prognosis of ARDS.

Effect of pulsed corticosteroids and tocilizumab on hyperinflammation in COVID-19 patients with acute respiratory distress syndrome

Objective:To compare the efficacy of pulsed-dose corticosteroids(≥250 mg methylprednisolone,3 days)and tocilizumab in treating COVID-19-related hyperinflammation.Methods:This prospective observational study included RT-PCR positive COVID-19 patients with acute respiratory distress syndrome,who were admitted to the COVID-19 Adult Intensive Care Unit of Prof Dr.Murat Dilmener Emergency Hospital(Istanbul,Turkey)between December 1,2020 and February 28,2021.Clinical,laboratory and radiological examinations were used to diagnose COVID-19 associated hyperinflammation.Three cohort groups were formed:the pulsed-dose corticosteroids group(250 mg methylprednisolone for 3 days),the tocilizumab group(8 mg/day single dose or 400 mg/day for 2 days),and the combined group(pulsed-dose corticosteroid+tocilizumab).The difference in mortality rates among the groups was compared primarily.The most common cause(s)of death was determined.Furthermore,adverse events(secondary infection,acute kidney injury,arrhythmia,gastrointestinal system bleeding)for 28 days were recorded.Results:A total of 60 patients were included in this study,with 20 patients in each group.There was no statistically significant difference between the 3 groups in mortality rates(55%in the pulsed corticosteroid group,60%in the tocilizumab group,50%in the combined group,χ2=0.404,P=0.817).Infectious causes were found to be the most common cause of mortality in all the three groups,and no difference was found between them(χ2=0.404,P=0.817).There was also no difference in the development of adverse events such as secondary infection,acute kidney injury,arrhythmia,and gastrointestinal bleeding among the groups(P>0.05).Conclusions:Corticosteroids can be used instead of tocilizumab to treat hyperinflammation in COVID-19 patients with acute respiratory distress syndrome.

Right ventricle dysfunction does not predict mortality in patients with SARS-CoV-2-related acute respiratory distress syndrome on extracorporeal membrane oxygenation support

BACKGROUND The prognostic role of right ventricle dilatation and dysfunction(RVDD)has not been elucidated in patients with coronavirus disease(COVID)-related respiratory failure refractory to standard treatment needing extracorporeal membrane oxygenation(ECMO)support.AIM To assess whether pre veno-venous(VV)ECMO RVDD were related to inintensive care unit(ICU)mortality.METHODS We enrolled 61 patients with COVID-related acute respiratory distress syndrome refractory to conventional treatment submitted to VV ECMO and consecutively admitted to our ICU(an ECMO referral center)from 31th March 2020 to 31th August 2021.An echocardiographic exam was performed immediately before VV ECMO implantation.RESULTS Males were prevalent(73.8%)and patients with a body mass index>30 kg/m^(2) were the majority(46/61,75%).The overall in-ICU mortality rate was 54.1%(33/61).RVDD was detectable in more than half of the population(34/61,55.7%)and associated with higher simplified organ functional assessment(SOFA)values(P=0.029)and a longer mechanical ventilation duration prior to ECMO support(P=0.046).Renal replacement therapy was more frequently needed in RVDD patients(P=0.002).A higher in-ICU mortality(P=0.024)was observed in RVDD patients.No echo variables were independent predictors of in-ICU death.CONCLUSION In patients with COVID-related respiratory failure on ECMO support,RVDD(dilatation and dysfunction)is a common finding and identifies a subset of patients characterized by a more severe disease(as indicated by higher SOFA values and need of renal replacement therapy)and by a higher in-ICU mortality.RVDD(also when considered separately)did not result independently associated with in-ICU mortality in these patients.

The Concept Study of Recombinant Human Soluble Thrombomodulin in Patients with Acute Respiratory Distress Syndrome

Background: Recombinant human soluble thrombomodulin (rhTM) was approved for the treatment of disseminated intravascular coagulation in Japan, and rhTM has anti-inflammatory effects. Disordered coagulation is a part of the acute respiratory distress syndrome (ARDS) pathophysiology and thus we hypothesize that anticoagulant therapy may help. This preliminary study was to observe the safety of rhTM administration and the improvement on biomarker levels after the therapy for ARDS-patients. Objectives: Case series of ARDS-patients. Methods: Seventeen ARDS-patients that required ventilatory management were treated with rhTM and clinical and laboratory data were collected including platelets, thrombin-antithrombin complex (TAT), fibrinogen degradation products, oxygen saturation/the fraction of inspired oxygen (SpO2/FIO2), and high-mobility group-1 (HMG-1). The administration of rhTM was started during 6 days at a bolus dose of 0.06 mg/kg/day immediately after the diagnosis of ARDS. Results: Eleven of the 17 ARDS-patients were alive at 28 days after the beginning of the administration of rhTM. The serial pattern of the SpO2/FIO2 showed remarkable differences between the survivors and nonsurvivors from day 5 to day 7. The TAT in the survivors significantly decreased after treatment, and there were significantly lower levels in the TAT on day 7 in comparison to that of the nonsurvivors. The serial changes of HMG-1 showed increased levels in the nonsurvivors until day 5 after the administration of rhTM. Conclusions: Additional rhTM administration can safely improve the parameters in survival ARDS-patients, as demonstrated by significant improvements in the SpO2/FIO2, HMG-1 and TAT.

Effect of ulinastatin combined with CRRT therapy on the endothelial oxidative damage and inflammatory injury in patients with acute respiratory distress syndrome

Objective:To study the effect of ulinastatin combined with CRRT therapy on the endothelial oxidative damage and inflammatory injury in patients with acute respiratory distress syndrome (ARDS).Methods: A total of 60 patients with ARDS who were treated in our hospital between April 2011 and April 2016 were collected and divided into the control group (n=29) who received pure CRRT therapy and the combined treatment group (n=31) who received ulinastatin combined with CRRT therapy after the therapy and related laboratory examination were reviewed. Before treatment and after 5d of treatment, enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of endothelial function indexes and inflammation indexes in serum and exhaled breath condensate;RIA method was used to detect the levels of oxidative stress indexes in serum and exhaled breath condensate.Results: Before treatment, the differences in the endothelial function, oxidative stress and inflammation indexes in serum and exhaled breath condensate were not statistically significant between two groups of patients. After treatment, endothelial function index NO levels in serum and exhaled breath condensate of observation group were higher than those of control group while ET-1 levels were lower than those of control group;oxidative stress indexes CAT and SOD levels in serum and exhaled breath condensate of observation group were higher than those of control group while MAO levels were lower than those of control group;inflammation indexes PCT, IL-1β and HMGB1 levels in serum and exhaled breath condensate of observation group were lower than those of control group.Conclusion: Ulinastatin combined with CRRT therapy can improve the endothelial function and reduce the oxidative stress and inflammatory injury in patients with ARDS.

Suppression of miR-17 Alleviates Acute Respiratory Distress-associated Lung Fibrosis by Regulating Mfn2

Objective Acute respiratory distress syndrome(ARDS)patients currently have relatively high mortality,which is associated with early lung fibrosis.This study aimed to investigate whether miR-17 suppression could alleviate ARDS-associated lung fibrosis by regulating Mfn2.Methods A mouse model of ARDS-related lung fibrosis was constructed via intratracheal instillation of bleomycin.The expression level of miR-17 in lung tissues was detected via quantitative real time polymerase chain reaction(qRT-PCR).In the ARDS mouse model of lung fibrosis,the mitigating effects of miR-17 interference were evaluated via tail vein injection of the miR negative control or the miR-17 antagomir.The pathological changes in the lung tissue were examined via HE staining and Masson’s trichrome staining,and the underlying molecular mechanism was investigated via ELISA,qRT-PCR and Western blotting.Results Bleomycin-induced pulmonary fibrosis significantly increased collagen deposition and the levels of hydroxyproline(HYP)and miR-17.Interfering with miR-17 significantly reduced the levels of HYP and miR-17 and upregulated the expression of Mfn2.The intravenous injection of the miR-17 antagomir alleviated lung inflammation and reduced collagen deposition.In addition,interference with miR-17 could upregulate LC3B expression,downregulate p62 expression,and improve mitochondrial structure.Conclusion Interfering with miR-17 can improve pulmonary fibrosis in mice by promoting mitochondrial autophagy via Mfn2.