Efficacy and safety of corticosteroid therapy in patients with cardiac arrest: A meta-analysis of randomized controlled trials.

BACKGROUND: The clinical benefits of steroid therapy during cardiac arrest (CA) are unclear. Several recent clinical trials have shown that administering corticosteroid therapy during CA may improve patient outcomes. The purpose of the present study was to determine whether providing corticosteroids improves outcomes for patients following CA. METHODS: We searched the PubMed, Embase, Cochrane Library, Web of Science and CNKI databases for randomized controlled trials comparing corticosteroid therapy to placebo during CA. RESULTS: Eleven relevant studies involving a total of 2273 patients were included in the meta-analysis. The statistical analysis showed that corticosteroid treatment during CA was significantly associated with an increased rate of sustained return of spontaneous circulation (ROSC) (OR: 2.05, 95% CI: 1.24 to 3.37, P < 0.01). Corticosteroid treatment during CA did not show a significant benefit in favorable neurological outcomes (OR: 1.13, 95% CI: 0.81 to 1.58, P = 0.49) or overall survival rate at hospital discharge (OR: 1.29, 95% CI: 0.74 to 2.26, P = 0.38). However, in the subgroup analysis, we found that patients had a significantly increased survival rate and ROSC if the dose of corticosteroid therapy above 100 mg methylprednisolone. The statistical analysis revealed no significant differences in adverse events. CONCLUSION: High-dose corticosteroid treatment (above 100 mg methylprednisolone) is associated with better overall survival rate at hospital discharge and ROSC outcomes. However, there is uncertainty regarding whether this treatment results in a benefit or harm to the favorable neurological outcomes at hospital discharge.

Inhibition of STEAP1 ameliorates inflammation and ferroptosis of acute lung injury caused by sepsis in LPS-induced human pulmonary microvascular endothelial cells.

BACKGROUND: Ferroptosis plays an important part in Acute lung injury (ALI) caused by sepsis. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) has potential effects on iron metabolism and inflammation but reports on its function in ferroptosis and sepsis-caused ALI are lacking. Here we explored the role of STEAP1 in sepsis-caused ALI and the possible mechanisms. METHODS AND RESULTS: Lipopolysaccharide (LPS) was added to human pulmonary microvascular endothelial cells (HPMECs) to form the sepsis-caused ALI model in vitro. The Cecal ligation and puncture (CLP) experiment was performed on C57/B6J mice to form the sepsis-caused ALI model in vivo. The effect of STEAP1 on inflammation was investigated by PCR, ELISA, and Western blot for the inflammatory factors and adhesion molecular. The reactive oxygen species (ROS) levels were detected by immunofluorescence. The effect of STEAP1 on ferroptosis was investigated by detecting malondialdehyde (MDA) levels, glutathione (GSH) levels, Fe2+ levels, cell viability, and mitochondrial morphology. Our findings suggested that STEAP1 expression was increased in the sepsis-induced ALI models. Inhibition of STEAP1 decreased the inflammatory response and ROS production as well as MDA levels but increased the levels of Nrf2 and GSH. Meanwhile, inhibition of STEAP1 improved cell viability and restored mitochondrial morphology. Western Blot results showed that inhibition of STEAP1 could affect the SLC7A11/GPX4 axis. CONCLUSION: Inhibition of STEAP1 may be valuable for pulmonary endothelial protection in lung injury caused by sepsis.

Clinical characteristics of Gram-negative and Gram-positive bacterial infection in acute cholangitis: a retrospective observational study.

BACKGROUND: To investigate the difference in the severity of illness, organ dysfunction, and prognosis of acute cholangitis due to different pathogenic bacterial infection types. METHODS: A retrospective observational study was performed. Patients who met the selection criteria according to blood culture and bile culture results of different pathogenic bacterial were divided into groups. The severity of illness, organ dysfunction, and prognosis of the groups were analyzed and compared comprehensively. RESULTS: A total of 424 patients were included, and no bacterial growth developed in 111 patients (26.2%). Among the 313 patients (73.8%) with bacterial growth, 155 patients had only Gram-negative bacteria cultured (49.5%), 48 patients had only Gram-positive bacteria cultured (15.3%), and 110 patients had both Gram-negative and Gram-positive bacteria cultured (35.1%). The proportion of Grade III patients and the APACHE II and SOFA scores of the mixed Gram-negative and positive group were the highest (p < 0.05); the intensive care unit admission day and hospital stay were longer, and the mortality rate were also higher 20/110 (18.2%) than the other two groups. Regression analysis showed that bacterial growth was an independent risk factor for organ dysfunction. The risks of an increased septic shock, neurological dysfunction, hepatic dysfunction, hematological dysfunction, and respiratory dysfunction in the mixed Gram-negative and positive group were higher than the Gram-negative group (P < 0.05). The Cox proportional hazards regression prompt showed that different culture results were independent risk factors for death. The mixed Gram-negative and positive group had increased hazard ratios and 95% CI of 7.30 (95% CI 1.55 to 34.38) compared with the Gram-negative group. There was no difference between the Gram-negative group and the Gram-positive group in the severity of illness, organ dysfunction, intensive care unit admission day, hospital stay, mortality rate, and risk of death (P > 0.05). CONCLUSIONS: In acute cholangitis, mixed infection with Gram-negative and Gram-positive bacteria was more severe and was associated with a higher risk of death. There were no apparent differences between Gram-negative and Gram-positive bacterial infections.

Utilizing reclassification to explore characteristics and prognosis of KDIGOSCr AKI subgroups: a retrospective analysis of a multicenter prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is widespread in the intensive care unit (ICU) and affects patient prognosis. According to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, the absolute and relative increases of serum creatinine (Scr) are classified into the same stage. Whether the prognosis of the two types of patients is similar in the ICU remains unclear. METHODS: According to the absolute and relative increase of Scr, AKI stage 1 and stage 3 patients were divided into stage 1a and 1b, stage 3a and 3b groups, respectively. Their demographics, laboratory results, clinical characteristics, and outcomes were analyzed retrospectively. RESULTS: Of the 345 eligible cases, we analyzed stage 1 because stage 3a group had only one patient. Using 53 or 61.88 µmol/L as the reference Scr (Scrref), no significant differences were observed in ICU mortality (P53=0.076, P61.88=0.070) or renal replacement therapy (RRT) ratio, (P53=0.356, P61.88=0.471) between stage 1a and 1b, but stage 1b had longer ICU length of stay (LOS) than stage 1a (P53<0.001, P61.88=0.032). In the Kaplan-Meier survival analysis, no differences were observed in ICU mortality between stage 1a and 1b (P53=0.378, P61.88=0.255). In a multivariate analysis, respiratory failure [HR = 4.462 (95% CI 1.144-17.401), p = 0.031] and vasoactive drug therapy [HR = 4.023 (95% CI 1.584-10.216), p = 0.003] were found to be independently associated with increased risk of death. CONCLUSION: ICU LOS benefit was more prominent in KDIGOSCr AKI stage 1a patients than in stage 1 b. Further prospective studies with a larger sample size are necessary to confirm the effectiveness of reclassification.

A Peptide-Based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. METHODS: In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. RESULTS: To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. CONCLUSIONS: Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.

Practice of Extracorporeal Therapies for Septic Acute Kidney Injury Patients in Intensive Care Units in Mainland China.

BACKGROUND: Continuous renal replacement therapy (CRRT) and other extracorporeal therapies for acute kidney injury (AKI) and other organ dysfunction syndromes in critically ill patients are common in the intensive care unit (ICU). Many studies have focused on clinical practice for managing these conditions. However, there are few studies that describe the utilization of extracorporeal therapies, especially CRRT, in patients with sepsis-associated AKI. SUMMARY: Two hundred ICU physicians were included in a survey from February 28, 2017, to March 20, 2017, on the current status of septic AKI and clinical practice in CRRT. According to the responses, 40% of sepsis patients in the ICU had AKI, and 25% required extracorporeal therapies. However, 29% of candidates gave up therapy for medical or nonmedical reasons. Overall survival for sepsis was 60%; among survivors, 80% were dialysis free at discharge. CRRT was the most common modality of extracorporeal therapy in the ICU, and 82% of physicians chose convection as the major clearance mode. The survey showed 30% of physicians saw the removal of inflammatory mediators as the major objective of extracorporeal therapies; however, only 18.5% of physicians considered inflammation as a measure to trigger CRRT. The median treatment duration of CRRT in China was 12 h per day for 5 days. Key Messages: There were some similarities and differences in CRRT practice for septic AKI patients in China and globally. The differences reveal some insights into improving the outcomes of these patients.

Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study.

BACKGROUND: Poor inter-rater reliability in chest radiograph interpretation has been reported in the context of acute respiratory distress syndrome (ARDS), although not for the Berlin definition of ARDS. We sought to examine the effect of training material on the accuracy and consistency of intensivists' chest radiograph interpretations for ARDS diagnosis. METHODS: We conducted a rater agreement study in which 286 intensivists (residents 41.3%, junior attending physicians 35.3%, and senior attending physician 23.4%) independently reviewed the same 12 chest radiographs developed by the ARDS Definition Task Force ("the panel") before and after training. Radiographic diagnoses by the panel were classified into the consistent (n = 4), equivocal (n = 4), and inconsistent (n = 4) categories and were used as a reference. The 1.5-hour training course attended by all 286 intensivists included introduction of the diagnostic rationale, and a subsequent in-depth discussion to reach consensus for all 12 radiographs. RESULTS: Overall diagnostic accuracy, which was defined as the percentage of chest radiographs that were interpreted correctly, improved but remained poor after training (42.0 ± 14.8% before training vs. 55.3 ± 23.4% after training, p < 0.001). Diagnostic sensitivity and specificity improved after training for all diagnostic categories (p < 0.001), with the exception of specificity for the equivocal category (p = 0.883). Diagnostic accuracy was higher for the consistent category than for the inconsistent and equivocal categories (p < 0.001). Comparisons of pre-training and post-training results revealed that inter-rater agreement was poor and did not improve after training, as assessed by overall agreement (0.450 ± 0.406 vs. 0.461 ± 0.575, p = 0.792), Fleiss's kappa (0.133 ± 0.575 vs. 0.178 ± 0.710, p = 0.405), and intraclass correlation coefficient (ICC; 0.219 vs. 0.276, p = 0.470). CONCLUSIONS: The radiographic diagnostic accuracy and inter-rater agreement were poor when the Berlin radiographic definition was used, and were not significantly improved by the training set of chest radiographs developed by the ARDS Definition Task Force. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (registration number NCT01704066 ) on 6 October 2012.

Characteristics of critically ill patients in ICUs in mainland China.

OBJECTIVES: We sought to describe the demographics, case mix, interventions, and clinical outcome of critically ill patients admitted to ICUs in Mainland China. DESIGN: A 2-month (July 1, 2009, to August 31, 2009) prospective, observational cohort study. SETTING: Twenty-two ICUs in Mainland China. PATIENTS: Adult patients admitted to participating ICUs during the study period with an ICU length of stay >24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, including demographics, underlying diseases, severity of illness, admission status, complications, intervention and treatment during ICU stay, and clinical outcome were recorded in case report form. The primary outcome measure was all-cause hospital mortality. Independent predictors for hospital mortality were determined with multivariate logistic regression analysis. One thousand two hundred ninety-seven patients met the inclusion criteria for the study, 821 (63.3%) were male, and mean age was 58.5 ± 19.2 yrs. Mean Acute Physiology and Chronic Health Evaluation II score was 18.0 ± 8.1, and mean Sequential Organ Failure Assessment score was 6.5 ± 3.8. One third of the patients were postoperative ICU admissions. Seven hundred sixty-five patients (59.0%) developed infections, followed by severe sepsis or septic shock (484, 37.3%), acute kidney injury (398, 30.7%), and acute lung injury/acute respiratory distress syndrome (351, 27.1%). Mechanical ventilation was used in almost three fourths of the patients, whereas any type of renal replacement therapy was used in 173 patients (13.3%). Hospital mortality was 20.3%. Multivariate logistic regression analysis found that Acute Physiology and Chronic Health Evaluation II score, solid tumor, severe sepsis/septic shock, acute lung injury/acute respiratory distress syndrome, and acute kidney injury were independent risk factors for hospital mortality. CONCLUSIONS: Critically ill patients in ICUs in Mainland China exhibited a case mix similar to those of Western countries, although there are significant differences in intensive care unit admission rates and disease severity between Western and Chinese ICUs.

Analysis of Pathogenic Bacteria Distribution and Related Factors in Recurrent Acute Cholangitis.

Background: To evaluate the risk factors and prognosis of patients with acute cholangitis recurrence. Methods: A total of 503 patients with acute cholangitis admitted to the First Affiliated Hospital of Chongqing Medical University between July 2013 and January 2022 were included in this retrospective observational study, who were followed up for 360 days and divided into relapse group and non-recurrence group according to the recurrence of acute cholangitis. Risk factors and prognosis of patients with acute cholangitis recurrence were analyzed by univariate, multivariate analyses and proportional hazards model. Results: A total of 161 patients with recurrent acute cholangitis were identified. Recurrent acute cholangitis usually occurred within 125 days; Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, and Enterococcus faecium was the most common positive record both in blood and bile culture. In the multivariate analysis, abdominal pain (OR = 2.448, 95% CI = 1.196-5.010, P = 0.014), bile stones (OR = 2.429, 95% CI = 1.024-5.762, P = 0.044), diabetes (OR = 1.790, 95% CI = 1.007-3.182, P = 0.047), pathogen (OR = 3.305, 95% CI = 1.932-5.654, P<0.001), and chronic kidney disease (OR = 2.500, 95% CI = 1.197-5.221, P = 0.015) may be ascertained as the risk factors of acute cholangitis recurrence. The recurrence of acute cholangitis was identified as an independent risk factor for patient death (HR = 4.524, 95% CI = 1.426-14.357, P = 0.010) by Cox proportional-hazards regression. Conclusion: Abdominal pain, bile stones, diabetes and chronic kidney disease may be risk factors of acute cholangitis recurrence. Patients with recurrent acute cholangitis have poor prognosis and high mortality. Early control of recurrent risk factors and active intervention are beneficial to high-risk patients.

Transcriptomic analysis of human pulmonary microvascular endothelial cells treated with LPS.

Acute respiratory distress syndrome (ARDS) has a rapid onset and progression, which lead to the severity and complexity of the primary disease and significantly increase the fatality rate of patients. Transcriptomics provides some ideas for clarifying the mechanism of ARDS, exploring prevention and treatment targets, and searching for related specific markers. In this study, RNA-Seq technology was used to observe the gene expression of human pulmonary microvascular endothelial cells (PMVECs) induced by LPS, and to excavate the key genes and signaling pathways in ARDS process. A total of 2300 up-regulated genes were detected, and a corresponding 1696 down-regulated genes were screened. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) were also used for functional annotation of key genes. TFDP1 was identified as a cell cycle-dependent differentially expressed gene, and its reduced expression was verified in LPS-treated PMVECs and lung tissues of CLP-induced mice. In addition, the inhibition of TFDP1 on inflammation and apoptosis, and the promotion of proliferation were confirmed. The decreased expression of E2F1, Rb, CDK1 and the activation of MAPK signaling pathway were substantiated in the in vivo and in vitro models of ARDS. Moreover, SREBF1 has been demonstrated to be involved in cell cycle arrest in PMVECs by inhibiting CDK1. Our study shows that transcriptomics combined with basic research can broaden the investigation of ARDS mechanisms and may provide a basis for future mechanistic innovations.

Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

Risk Factors and Prognosis of Carbapenem-Resistant Organism Colonization and Infection in Acute Cholangitis.

Background: To identify the risk factors and prognosis of carbapenem-resistant organisms (CRO) in patients with acute cholangitis. Methods: This retrospective observational study was conducted to explore the risk factors and prognosis of CRO infection in 503 acute cholangitis patients diagnosed between July 2013 and January 2022 at the First Affiliated Hospital of Chongqing Medical University, who were divided into a CRO group and non-CRO group based on the presence or absence of CRO. Univariate, multivariate analyses, and the proportional hazards model were used to compare the risk factors and prognosis of CRO suffering in patients with acute cholangitis. Results: We identified 35 patients colonized with CRO from 503 acute cholangitis patients. In the multivariate analysis, tumor (OR=7.09, 95% CI=1.11-45.30, P=0.038) and chronic kidney disease (OR=8.70, 95% CI=2.11-35.88, P=0.003) were ascertained as the risk factors of the occurrence on CRO infection under the background of acute cholangitis. CRO infection was identified as an independent risk factor for acute cholangitis patient death (HR=5.147, 95% CI=1.475-17.595, P=0.01) by Cox proportional-hazards regression. Conclusion: Tumor and chronic kidney disease may be risk factors for CRO infection. Patients diagnosed with acute cholangitis further infected with CRO had a poor prognosis and a more severe mortality. Active screening for CRO is expected to facilitate early prevention, diagnosis, and treatment of high-risk patients.

FAM49B, restrained by miR-22, relieved hepatic ischemia/reperfusion injury by inhibiting TRAF6/IKK signaling pathway in a Rac1-dependent manner.

Hepatic ischemia/reperfusion (I/R) injury plays a pivotal pathogenic role in trauma, hepatectomy, and liver transplantation. However, the whole mechanism remains undescribed. The objective of this study is to investigate the internal mechanism by which microRNA-22 (miR-22) targets family with sequence similarity 49 member B (FAM49B), thus aggravating hepatic I/R injury. Here, we found that miR-22 was upregulated while FAM49B was reduced in hepatic I/R injury. Inhibition of miR-22 in vitro was able to intensify expression of FAM49B, thus reducing phosphorylation of inhibitors of nuclear factor kappa-B kinase (IKK) and downstream pro-inflammatory proteins. A dual luciferase reporter assay indicated that miR-22 directly targeted FAM49B. Remission of hepatic pathologic alterations, apoptosis, and release of cytokines derived from constraints of miR-22 were abolished in vivo by repressing FAM49B. Further interference of Ras-related C3 botulinum toxin substrate 1 (Rac1) reversed the function of FAM49B inhibition, thus achieving anti-inflammatory consequences.

Knowledge and attitudes of healthcare workers in Chinese intensive care units regarding 2009 H1N1 influenza pandemic.

BACKGROUND: To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic. METHODS: A survey conducted in 21 intensive care units in 17 provinces in China. RESULTS: Out of 733 questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001). CONCLUSION: Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.

[Difference between single hole exhalation valve and plateau exhalation valve when used in patients treated with BiPAP Vision ventilator for chronic obstructive pulmonary disease with hypercapnia].

OBJECTIVE: To observe difference in clinical effect between single hole exhalation valve and plateau exhalation valve when used in patients treated with BiPAP Vision ventilator for chronic obstructive pulmonary disease (COPD) with hypercapnia. METHODS: Forty seven patients with hypercapnia due to COPD, who were admitted to the central intensive care unit (ICU) in the First Affiliated Hospital of Chongqing Medical University from October 2008 to July 2010, treated with noninvasive positive pressure ventilation (NIPPV) by BiPAP Vision ventilator, were enrolled in the study. The patients were divided randomly into NIPPV with application of single hole exhalation valve group (n=22) and plateau exhalation valve group (n=25). In each group, parameters of the arterial blood gas, including arterial partial pressure of oxygen (PaO(2)) and arterial partial pressure of carbon dioxide (PaCO2), were measured at the time points of 0, 2, 4, 8, 24, 48 hours of NIPPV and 24 hours post NIPPV. RESULTS: The general conditions were similar in both groups at 0 hour. Compared with that of 0 hour, marked improvement in PaO(2) (mm Hg, 1 mm Hg=0.133 kPa, single hole exhalation valve group: 70.4±10.2, 78.7± 10.4, 82.6±9.2, 86.5±9.6, 90.4±9.0, 91.3±8.9 vs. 57.2±16.4; plateau exhalation valve group: 71.1±12.3, 77.9±11.6, 83.3±8.9, 85.9±8.2, 89.4±8.2, 92.1±8.5 vs. 56.9±17.2) and obvious lowering of PaCO(2) (mm Hg, single hole exhalation valve group: 76.3±11.9, 74.1±12.7, 71.3±11.2, 67.4±10.5, 65.4±8.2, 61.4±7.9 vs. 85.7±19.2; plateau exhalation valve group: 72.6±10.5, 70.1±11.5, 67.4±10.1, 63.9±9.7, 62.8±7.7, 59.1±7.3 vs. 86.3±17.9) were observed at the time points of 2, 4, 8, 24, 48 hours of NIPPV and 24 hours post NIPPV in both groups (all P<0.05). Comparing single hole exhalation valve group with plateau exhalation valve group, PaO2 showed no statistical significance at the same time point (all P>0.05). However, PaCO(2) was significantly lower in plateau exhalation valve group than that in single hole exhalation valve group at the time points of 2, 4, 8 and 24 hours (all P<0.05). CONCLUSION: During BiPAP Vision ventilator in NIPPV treatment of patients with COPD complicated with CO2 retention , single hole exhalation valve and plateau exhalation valve both resulted in marked improvement in PaO2 and obvious decrease in PaCO2. Plateau exhalation valve corrected CO2 retention more quickly and effectively than side hole exhalation valve probably by preventing CO2 rebreathing by the patients.

MicroRNA-877-5p alleviates ARDS via enhancing PI3K/Akt path by targeting CDKN1B both in vivo and in vitro.

Acute respiratory distress syndrome (ARDS) is a public health problem with high morbidity and mortality worldwide due to lacking known characteristic biomarkers and timely intervention. Pulmonary edema caused by inflammation and pulmonary microvascular endothelial cell disfunction is the main pathophysiological change of ARDS. Circulating microRNAs (miRNAs) are differentially expressed between subjects who did and did not develop ARDS. Many miRNAs have been exemplified to be involved in ARDS and could represent the novel therapeutic targets, but the role of microRNA-877-5p (miR-877-5p) in ARDS and its regulatory mechanisms are still unknown. Herein, we explore the underlying function of miR-877-5p toward anesis of ARDS and addressed that miRNA-877 can reduce the release of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 thus attenuating the damage of pulmonary microvascular endothelial cells (HPMECs). Have further evaluated the protein expression, we detected that miR-877-5p contributed to the relief of ARDS by suppressing Cyclin-dependent kinase inhibitor 1B (CDKN1B), which serves as a regulator of endothelial cell polarization and migration through phosphatidylinositol-3-kinase and AKT (PI3K/Akt) signaling pathway. Besides, we noticed that CDKN1B restrains cell differentiation by inhibiting Cdk2 (cyclin-dependent kinase 2), instead of Cdk4 (cyclin-dependent kinase 4), during which the nuclear translocation of CDKN1B may participate. Together, our works testified that miR-877-5p might suppress inflammatory responses and promote HPMECs regeneration via targeting CDKN1B by modulation of Cdk2 and PI3K/Akt path. These molecules likely modulating ARDS progression may inform biomarkers and therapeutic development.

Inhibition of microRNA-92a ameliorates lipopolysaccharide-induced endothelial barrier dysfunction by targeting ITGA5 through the PI3K/Akt signaling pathway in human pulmonary microvascular endothelial cells.

Overwhelming inflammation and extensive alveolar-endothelial injury are characteristic pathological features of acute respiratory distress syndrome (ARDS)). MicroRNAs are involved in the regulation of a variety of cellular processes including endothelial damage and inflammatory responses. However, little is known about their function and the molecules regulating lung microvascular endothelial injury. Here, we determined the levels of microRNA-92a (miR-92a) in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMECs). We found that miR-92a expression was greater in HPMECs treated with LPS than in control cells. Inhibition of miR-92a through transfection with a miR-92a inhibitor significantly increased HPMECs migration, enhanced tube formation, and improved endothelial cell barrier dysfunction. Inhibition of miR-92a ameliorated the inflammatory response by decreasing the release of the proinflammatory factors IL-6 and TNF-α. In addition, integrin α5 (ITGA5) was found to be a target gene of miR-92a in LPS-induced endothelial barrier dysfunction. Western blot analysis showed that inhibition of miR-92a may ameliorate endothelial barrier dysfunction by activating the PI3K/Akt signaling pathway. Together, these results reveal an important role of miR-92a in LPS-induced endothelial barrier dysfunction, and suggest that miR-92a may have potential as a prognostic indicator and a future target for the treatment of acute lung injury (ALI)/ARDS.

MicroRNA-92a serves as a risk factor in sepsis-induced ARDS and regulates apoptosis and cell migration in lipopolysaccharide-induced HPMEC and A549 cell injury.

AIMS: Sepsis-induced acute respiratory distress syndrome (ARDS) is a common, high mortality complication in intensive care unit (ICU) patients. MicroRNA-92a (miR-92a) plays a role in many diseases, but its association with sepsis-induced ARDS is unclear. MATERIALS AND METHODS: We enrolled 53 patients, including 17 with sepsis only, and 36 with sepsis-induced ARDS. Lipopolysaccharide (LPS) was used to stimulate pulmonary microvascular endothelial cells (HPMEC) and alveolar epithelial A549 cells, which were used to investigate the miR-92a roles in ARDS. MiR-92a expression levels in patient serum and cells were quantified using quantitative reverse transcription-polymerase chain reaction (RT-PCR), and protein expression was examined using Western blotting. The effect of miR-92a on apoptosis was examined using flow cytometry. Wound healing and transwell migration assays were used to evaluate cell migration. KEY FINDINGS: Serum miR-92a expression was higher in patients with sepsis-induced ARDS, when compared to patients with sepsis only. After LPS treatment in cells, miR-92a expression was higher when compared with control group, cell apoptosis and inflammatory responses were increased and cell migration was inhibited. However, cell apoptosis and inflammatory responses were decreased and cell migration was enhanced after miR-92a downregulation, when compared with inhibitor negative control (NC) group. Moreover, phosphorylated-Akt and phosphorylated-mTOR expression were increased after miR-92a inhibition. SIGNIFICANCE: Our study provides evidence that circulating serum miR-92a could act as a risk factor for sepsis-induced ARDS. MiR-92a inhibition attenuated the adverse effects of LPS on ARDS through the Akt/mTOR signaling pathway.

Coronavirus disease 2019 (COVID-19): cytokine storms, hyper-inflammatory phenotypes, and acute respiratory distress syndrome.

Coronavirus Disease 2019 (COVID-19) was first identified in China at the end of 2019. Acute respiratory distress syndrome (ARDS) represents the most common and serious complication of COVID-19. Cytokine storms are a pathophysiological feature of COVID-19 and play an important role in distinguishing hyper-inflammatory subphenotypes of ARDS. Accordingly, in this review, we focus on hyper-inflammatory host responses in ARDS that play a critical role in the differentiated development of COVID-19. Furthermore, we discuss inflammation-related indicators that have the potential to identify hyper-inflammatory subphenotypes of COVID-19, especially for those with a high risk of ARDS. Finally, we explore the possibility of improving the quality of monitoring and treatment of COVID-19 patients and in reducing the incidence of critical illness and mortality via better distinguishing hyper- and hypo-inflammatory subphenotypes of COVID-19.

[Stratified outcomes of "Kidney Disease: Improving Global Outcomes" serum creatinine criteria in critical ill patients: a secondary analysis of a multicenter prospective study].

OBJECTIVE: To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China. METHODS: A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKISCr) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL×min-1×1.73 m-2, and AoCKD was defined as meeting the KDIGO-AKISCr standard and baseline eGFR was 15-59 mL×min-1×1.73 m-2. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis. RESULTS: Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients (n = 322), AoCKD patients (n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation II (APACHE II) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL×min-1×1.73 m-2): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (µmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ 2 = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio (HR) = 4.458, 95% confidence interval (95%CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU (HR = 5.181, 95%CI was 2.033-13.199, P = 0.001), and AoCKD (HR = 5.377, 95%CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days. CONCLUSIONS: Further detailed classification (PAKI, AoCKD) based on KDIGO-AKISCr standard combined with eGFR is related to ICU mortality in critical patients within 28 days.