Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population.

BACKGROUND: A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. METHODS: We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. RESULTS: After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10-14), ABO rs582094 (p-value = 1.16 × 10-10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10-17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. CONCLUSIONS: We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development.

Association between cardiopulmonary bypass time and mortality among patients with acute respiratory distress syndrome after cardiac surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) can lead to lung injury and even acute respiratory distress syndrome (ARDS) through triggering systemic inflammatory response. The objective of this study was to investigate the impact of CPB time on clinical outcomes in patients with ARDS after cardiac surgery. METHODS: Totally, patients with ARDS after cardiac surgery in Beijing Anzhen Hospital from January 2005 to December 2015 were retrospectively included and were further divided into three groups according to the median time of CPB. The primary endpoints were the ICU mortality and in-hospital mortality, and ICU and hospital stay. Restricted cubic spline (RCS), logistic regression, cox regression model, and receiver operating characteristic (ROC) curve were adopted to explore the relationship between CPB time and clinical endpoints. RESULTS: A total of 54,217 patients underwent cardiac surgery during the above period, of whom 210 patients developed ARDS after surgery and were finally included. The ICU mortality and in-hospital mortality were 21.0% and 41.9% in all ARDS patients after cardiac surgery respectively. Patients with long CPB time (CPB time ≥ 173 min) had longer length of ICU stay (P = 0.011), higher ICU (P < 0.001) mortality and in-hospital(P = 0.002) mortality compared with non-CPB patients (CPB = 0). For each ten minutes increment in CPB time, the hazards of a worse outcome increased by 13.3% for ICU mortality and 9.3% for in-hospital mortality after adjusting for potential factors. ROC curves showed CPB time presented more satisfactory power to predict mortality compared with APCHEII score. The optimal cut-off value of CPB time were 160.5 min for ICU mortality and in-hospital mortality. CONCLUSIONS: Our findings demonstrated the significant prognostic value of CPB time in patients with ARDS after cardiac surgery. Longer time of CPB was associated with poorer clinical outcomes, and could be served as an indicator to predict short-term mortality in patients with ARDS after cardiac surgery.

Multidrug-resistant bacterial infection in adult patients following cardiac surgery: clinical characteristics and risk factors.

BACKGROUND: The prevalence of infections with multidrug-resistant organism (MDRO) pose great challenges for anti-infective therapy. Previous research on MDRO infections after cardiac surgery was limited. Therefore, understanding and mastering the clinical characteristics and risk predictors of MDRO infection after cardiac surgery is of great significance for standardized management of perioperative patients. METHODS: The medical records of adult patients with MDRO infection after cardiac surgery from January 2018 to October 2021 were collected, and patients were divided into MDR infection group (n = 176) and non-MDR infection group (n = 233). Univariate and multivariate regression analysis of variables was performed to determine the risk predictors of MDRO infection. RESULTS: The incidence of MDRO infection was 8.6%. Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common, accounting for 37.3%, 23.5% and 18.0%, respectively. The main infection type were lower respiratory tract infection (LTRI = 29.0%). Univariate analysis showed that underwent coronary artery bypass graft (CABG) (P = 0.001) and secondary operation (P = 0.008), pre-infection exposure to vancomycin (P < 0.001) and linezolid (P = 0.002), combination antibiotics (P < 0.001), four antibiotics in combination (P = 0.005), glucocorticoid use (P = 0.029), preoperative hypoalbuminemia (P = 0.003) were risk factors for post-operative MDRO infection. Multivariate regression analysis showed that underwent CABG (OR = 1.228, 95%CI = 1.056∽1.427, P = 0.008), secondary operation (OR = 1.910, 95%CI = 1.131∽3.425, P = 0.015) and pre-infection exposure to linezolid (OR = 3.704, 95%CI = 1.291∽10.629, P = 0.005) were independent risk predictors for MDRO infection. The risk of MDRO infection increased with the length of stay in the ICU (P < 0.001) and the length of stay before diagnosis of infection (P = 0.003), and the difference was statistically significant. Meanwhile, the length of stay after infection (P = 0.005) and the total length of hospital stay (P < 0.001) were significantly longer in the MDRO infection group, and the all-cause mortality was numerically higher in the MDRO infection group (31.3% versus 23.2%). CONCLUSIONS: The morbidity and mortality of MDRO infection was high in adult cardiac surgery, and many risk factors influence the occurrence of MDRO infection. In the future, clinicians should focus on high-risk patients, strengthen multidisciplinary collaboration on infection prevention and control measures, reduce the morbidity and mortality of MDRO infection, and improve the prognosis of in-hospital patients.

Detection of aortic prosthetic graft infection with 18F-FDG PET/CT imaging, concordance with consensus MAGIC graft infection criteria.

OBJECTIVES: The aim of this study was to investigate the diagnostic yield of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for detecting thoracic aortic graft infection (AGI) in comparison to expert consensus MAGIC criteria. METHODS: Patients suspected clinically of having thoracic-AGI were prospectively recruited. Consensus MAGIC criteria for AGI were compared to findings on FDG PET imaging. MAGIC criteria were verified against clinical/surgical, radiological, and microbiological/laboratory predefined major and minor parameters. FDG images were interpreted using a semiquantitative visual grading score (VGS, abnormal ≥ 3), focal uptake and quantitative maximum standard FDG uptake value (SUVmax, abnormal ≥ 7.3), and target-to-background FDG ratio (TBRmax, abnormal ≥ 4.2). RESULTS: Of 35 patients suspected of having thoracic-AGI, MAGIC diagnostic criteria were positive for AGI in 25 patients (71%) and negative in 10 (29%). FDG PET imaging was abnormal in 27 patients (77%). Abnormal and normal FDG imaging findings were concordant with MAGIC criteria in 31 patients (88.6%). In 4 patients, FDG imaging results were discordant with MAGIC criteria. By ROC analysis, optimal FDG cut-off values for detecting AGI by MAGIC were ≥ 3 for VGS, ≥ 7.3 for SUVmax and ≥ 4.2 for TBRmax, with concordance with MAGIC criteria in 88.6%, 85.7%, and 88.6% of patients, respectively. Two or more FDG imaging parameters (VGS, focal uptake, SUVmax, and TBRmax) yielded highest diagnostic concordance of 91.4%. VGS inverse odds ratio for AGI was 7.14. In 4 of 6 selective patients who had repeat FDG PET imaging during antibiotic treatment, quantitative FDG imaging values improved over time with associated improvement of laboratory markers of inflammation. CONCLUSIONS: FDG PET/CT imaging, using (semi-)quantitative imaging parameters, showed high concordance with expert consensus MAGIC criteria for AGI. These data suggest a potential complementary role of quantitative FDG/CT imaging, not only to detect AGI, but also to monitor response to antibiotic treatment.

Is obstructive sleep apnoea associated with hypoxaemia and prolonged ICU stay after type A aortic dissection repair? A retrospective study in Chinese population.

BACKGROUND: Although obstructive sleep apnoea (OSA) is prevalent among patients with aortic dissection, its prognostic impact is not yet determined in patients undergoing major vascular surgery. We aimed to investigate the association of OSA with hypoxaemia and with prolonged intensive care unit (ICU) stay after type A aortic dissection (TAAD) repair. METHODS: This retrospective study continuously enrolled 83 patients who underwent TAAD repair from January 1 to December 31, 2018. OSA was diagnosed by sleep test and defined as an apnoea hypopnea index (AHI) of ≥ 15/h, while an AHI of > 30/h was defined severe OSA. Hypoxaemia was defined as an oxygenation index (OI) of < 200 mmHg. Prolonged ICU stay referred to an ICU stay of > 72 h. Receiver operating characteristic curve analysis was performed to evaluate the predictive value of postoperative OI for prolonged ICU stay. Multivariate logistic regression was performed to assess the association of OSA with hypoxaemia and prolonged ICU stay. RESULTS: A total of 41 (49.4%) patients were diagnosed with OSA using the sleep test. Hypoxaemia occurred postoperatively in 56 patients (67.5%). Postoperatively hypoxaemia developed mostly in patients with OSA (52.4% vs. 83.0%, p = 0.003), and particularly in those with severe OSA (52.4% vs. 90.5%, p = 0.003). The postoperative OI could fairly predict a prolonged ICU stay (area under the receiver-operating characteristic curve, 0.72; 95% confidence intervals [CI] 0.60-0.84; p = 0.002). Severe OSA was associated with both postoperative hypoxaemia (odds ratio [OR] 6.65; 95% CI 1.56-46.26, p = 0.008) and prolonged ICU stay (OR 5.58; 95% CI 1.54-20.24, p = 0.009). CONCLUSIONS: OSA was common in patients with TAAD. Severe OSA was associated with postoperative hypoxaemia and prolonged ICU stay following TAAD repair.

"Obesity Paradox" in Acute Respiratory Distress Syndrome Among Patients Undergoing Cardiac Surgery: A Retrospective Study.

BACKGROUND The "obesity paradox" exists in many diseases. It is unclear whether it also exists in acute respiratory distress syndrome (ARDS). The purpose of our study was to clarify the relationship between obesity and the development of and hospital mortality from ARDS among patients who underwent cardiac surgery. MATERIAL AND METHODS This retrospective case-control study included 202 patients with ARDS and 808 matching patients without ARDS. We clarified the relationship between obesity and the development of ARDS after adjusting for confounding factors by multiple logistic regression analysis. A total of 202 ARDS patients were divided into survival and mortality groups. After all confounding factors were adjusted by multiple logistic regression analysis, we demonstrated the relationship between obesity and mortality from ARDS. RESULTS We found a significant association between body mass index (BMI) and the development of ARDS; the cutoff point of BMI was 24.78 kg/m² by adjusting for confounding factors for the development of ARDS. When the BMI was lower than 24.78 kg/m², the higher BMI was a protective factor (odds ratio [OR] 0.68, P=0.000, 95% confidence interval [CI] 0.55-0.84). When the BMI was higher than 24.78 kg/m², the higher BMI was a risk factor (OR 1.07, P=0.050, 95% CI 1.00-1.14). However, obesity was found to be associated with decreased ARDS mortality by adjusting for confounding factors (OR 0.91, P=0.039, 95% CI 0.83-1.00). CONCLUSIONS An "obesity paradox" may exist in ARDS among patients with obesity who undergo cardiac surgery.

C-reactive protein or procalcitonin combined with rhinorrhea for discrimination of viral from bacterial infections in hospitalized adults in non-intensive care units with lower respiratory tract infections.

BACKGROUND: Whether procalcitonin (PCT) or C-reactive protein (CRP) combined with certain clinical characteristics can better distinguish viral from bacterial infections remains unclear. The aim of the study was to assess the ability of PCT or CRP combined with clinical characteristics to distinguish between viral and bacterial infections in hospitalized non-intensive care unit (ICU) adults with lower respiratory tract infection (LRTI). METHODS: This was a post-hoc analysis of a randomized clinical trial previously conducted among LRTI patients. The ability of PCT, CRP and PCT or CRP combined with clinical symptoms to discriminate between viral and bacterial infection were assessed by portraying receiver operating characteristic (ROC) curves among patients with only a viral or a typical bacterial infection. RESULTS: In total, 209 infected patients (viral 69%, bacterial 31%) were included in the study. When using CRP or PCT to discriminate between viral and bacterial LRTI, the optimal cut-off points were 22 mg/L and 0.18 ng/mL, respectively. When the optimal cut-off for CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) combined with rhinorrhea was used to discriminate viral from bacterial LRTI, the AUCs were 0.81 (95% CI: 0.75-0.87) and 0.80 (95% CI: 0.74-0.86), which was statistically significantly better than when CRP or PCT used alone (p < 0.001). When CRP ≤ 22 mg/L, PCT ≤ 0.18 ng/mL and rhinorrhea were combined, the AUC was 0.86 (95% CI: 0.80-0.91), which was statistically significantly higher than when CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) was combined with rhinorrhea (p = 0.011 and p = 0.021). CONCLUSIONS: Either CRP ≤ 22 mg/L or PCT ≤ 0.18 ng/mL combined with rhinorrhea could help distinguish viral from bacterial infections in hospitalized non-ICU adults with LRTI. When rhinorrhea was combined together, discrimination ability was further improved.

A Nomogram to Predict Acute Respiratory Distress Syndrome After Cardiac Surgery.

PURPOSE: To establish a model to predict the risk of acute respiratory distress syndrome (ARDS) after cardiac surgery. METHODS: Data were collected on 132 ARDS patients, who received valvular or coronary artery bypass grafting surgery from January 2009 to December 2019. We developed the prediction model by multivariable logistic regression. Then, we used the coefficients for developing a nomogram that predicts ARDS occurrence. Internal validation was performed using resampling techniques to evaluate and optimize the model. RESULTS: All variables fit into the model, including albumin level before surgery (odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.92, 0.99; P = .01), cardiopulmonary bypass time (OR: 1.01; 95% CI: 1.00, 1.02; P = .02), APACHE II after surgery (OR: 1.21; 95% CI: 1.13, 1.29; P < .001), and history of diabetes (OR: 2.31; 95% CI: 1.88, 3.87; P < .001); these were considered to build the nomogram. The score distinguished ARDS patients from non-ARDS patients with an AUC of 0.785 (95% CI: 0.740, 0.830) and was well calibrated (Hosmer-Lemeshow P = .53). CONCLUSIONS: Our developed model predicted ARDS in patients undergoing cardiac surgery and may serve as a tool for identifying patients at high risk for ARDS after cardiac surgery.

Downregulated microRNA-27b attenuates lipopolysaccharide-induced acute lung injury via activation of NF-E2-related factor 2 and inhibition of nuclear factor κB signaling pathway.

Acute lung injury (ALI) is a life-threatening, diffuse heterogeneous lung injury characterized by acute onset, pulmonary edema, and respiratory failure. Lipopolysaccharide (LPS) is a leading cause for ALI and when administered to a mouse it induces a lung phenotype exhibiting some of the clinical characteristics of human ALI. This study focused on investigating whether microRNA-27b (miR-27b) affects ALI in a mouse model established by LPS-induction and to further explore the underlying mechanism. After model establishment, the mice were treated with miR-27b agomir, miR-27b antagomir, or D-ribofuranosylbenzimidazole (an inhibitor of nuclear factor-E2-related factor 2 [Nrf2]) to determine levels of miR-27b, Nrf2, nuclear factor kappa-light-chain-enhancer of activated B cells nuclear factor κB (NF-κB), p-NF-κB, and heme oxygenase-1 (HO-1). The levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) were determined. The results of luciferase activity suggested that Nrf2 was a target gene of miR-27b. It was indicated that the Nrf2 level decreased in lung tissues from ALI mice. The downregulation of miR-27b decreased the levels of IL-1ß, IL-6, and TNF-α in BALF of ALI mice. Downregulated miR-27b increased Nrf2 level, thus enhancing HO-1 level along with reduction of NF-κB level as well as the extent of NF-κB phosphorylation in the lung tissues of the transfected mice. Pathological changes were ameliorated in LPS-reduced mice elicited by miR-27b inhibition. The results of this study demonstrate that downregulated miR-27b couldenhance Nrf2 and HO-1 expressions, inhibit NF-κB signaling pathway, which exerts a protective effect on LPS-induced ALI in mice.

LL-37 and its analog FF/CAP18 attenuate neutrophil migration in sepsis-induced acute lung injury.

INTRODUCTION: Sepsis can result in acute lung injury. LL-37 is a small cationic host defense peptide involved in anti-inflammatory. In the current study, it was hypothesized that antimicrobial peptide LL-37 could play a protective role in attenuating the progression of sepsis-induced acute lung injury. METHODS: Forty male C57BL/6 mice were induced into sepsis using cecal ligation and puncture, and subsequently administered with recombinant mouse osteopontin. Peptides LL-37, the LL-37 analog (FF/CAP18, called sLL-37), or normal saline was intravenously administered into septic mice for 20 hours. Then, proinflammatory cytokines (IL-6 and IL-1ß), acute lung injury markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]), the neutrophil infiltration marker (myeloperoxidase [MPO]), and neutrophil infiltration were detected. Furthermore, the neutrophil migration and expression of migration-related factors (focal adhesion kinase [FAK], ERK, and P38) in differentiated HL-60 cells were detected. RESULTS: Septic mice had upregulated IL-6, IL-1ß, ALT, AST, LDH, MPO, p-FAK, p-ERK, and p-P38, infiltrated neutrophils, and migrated neutrophil-like HL-60 cells. In contrast, the administration of peptide LL-37 and sLL-37 inhibited all these changes. Compared with septic mice, it was found that proinflammatory cytokines, lung injury markers, MPO, and infiltrated neutrophils decreased in mice treated with LL-37 and sLL-37. In addition, the migrated neutrophil-like HL-60 cells and activated p-FAK, p-ERK, and p-P38 proteins were suppressed by LL-37 and sLL-37 treatments. CONCLUSIONS: Peptide LL-37 and its analog sLL-37 attenuated the progression of sepsis-induced acute lung injury by inhibiting neutrophil infiltration and migration through the FAK, ERK, and P38 pathways.

[Efficacy and safety of delayed thrombolytic therapy for acute massive pulmonary throboembolism].

OBJECTIVE: To observe the efficacy and safety of delayed thrombolytic therapy on acute massive pulmonary thromboembolism (PTE) and discuss the influence factors. METHODS: From 2009 to 2013, the clinical data of patients with acute massive pulmonary thromboembolism were analyzed retrospectively. Patients with over 14-day duration and treated with thrombolytic therapy (delayed thrombolytic group) were compared with those within 14-day duration and treated with thrombolytic therapy (normal thrombolytic group) in the same period. General conditions before treatment, case history, efficacy and the incidence of bleeding after one-week treatment were collected. The influence factors of delayed thrombolytic therapy were analyzed. RESULTS: Sixty two cases were collected and divided into the normal thrombolytic group with 32 cases and the delayed thrombolytic group with 30 cases. Compared with the normal thrombolytic group, the delayed thrombolytic group had a longer duration [(24.8 ± 0.9) vs.(7.2 ± 0.6)d, P<0.001], an aggravation time of (5.3 ± 0.8) d, and higher systolic pulmonary arterial pressure (SPAP) [(69 ± 4)vs. (55 ± 4)mmHg, 1 mmHg= 0.133 kPa, P= 0.016]. Ages, genders, D-Dimmer, CT subpulmonic obstruction index (CTI), brain natriuretic peptide (BNP), cardiactroponinI (TnI), PaCO2values and PaO2values had no statistical difference between two groups. After one-week treatment, the efficacy and the incidence of bleeding was 78% and 25% respectively in normal thrombolytic group, while they were 77% and 30% respectively in delayed thrombolytic group, and there was no significant difference between two groups (P>0.05). The single factor analysis showed that the delayed thrombolytic group had more patients with hypertension, were older and had a lower PaO2(P<0.05 or 0.01). Multivariate logistic regression analysis did not find the predictors of delayed thrombolytic therapy (P>0.05). CONCLUSIONS: For acute massive PTE patients with duration over 14 days, increased D-D and new exacerbation of symptoms,delayed thrombolytic therapy had the same efficacy with the normal thrombolytic therapy. The factors for predicting efficacy need further research.

[Diagnosis and surgical treatment of pulmonary artery sarcoma].

OBJECTIVE: To characterize the differential diagnostic characteristics and the surgical treatment efficacy of pulmonary artery sarcoma (PAS). METHODS: From November 2001 to January 2014, 19 PAS patients were diagnosed and 14 of them underwent surgery at Beijing Anzhen Hospital. And their data were retrospectively reviewed. RESULTS: All 19 patients underwent pulmonary artery computed tomography angiography (CTA) scan. All showed a filling defect within the lumen of pulmonary artery with a sign of wall eclipsing. And 14 of them had pulmonary artery sarcoma confirmed through postoperative histopathological examination while another 5 patients were confirmed to have FDG abnormal high intake mass shadow on Positron emission tomography-computed tomography (PET-CT) scan. Fourteen patients underwent surgery, including pulmonary endarterectomy (n = 12) and pneumonectomy (n = 2), and another five had no indication for operation and died shortly. No perioperative death occurred for surgical patients. Five non-surgical patients survived (20.3 ± 11.2) days after discharge. And 14 postoperative patients survived (16.8 ± 3.8) months. The difference between two groups reached statistical significance (P = 0.000). The survival difference between two surgical procedures and between two pathological classifications did not reach statistical significance. Nine patients did not while another 5 received adjuvant radiotherapy and chemotherapy. Their average survivals were (12.3 ± 3.2) and (22.8 ± 4.3) months respectively. And the inter-group difference reached statistical significance (P = 0.000). CONCLUSIONS: The sign of wall eclipsing on pulmonary artery CTA scan is pathognomonic for PAS. Radical surgical resection provides a longer survival than non-surgery and adjuvant chemotherapy may further extend survival.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Association between coagulation disorder scores and in-hospital mortality in ARF patients: a retrospective analysis from the MIMIC-IV database.

Introduction: Acute respiratory failure (ARF) has a high mortality rate, and currently, there is no convenient risk predictor. The coagulation disorder score was proven to be a promising metric for predicting in-hospital mortality, but its role in ARF patients remains unknown. Methods: In this retrospective study, data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients diagnosed with ARF and hospitalized for more than 2 days at their first admission were included. The coagulation disorder score was defined based on the sepsis-induced coagulopathy score and was calculated by parameters, namely, additive platelet count (PLT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), based on which the participants were divided into six groups. Results: Overall, 5,284 ARF patients were enrolled. The in-hospital mortality rate was 27.9%. High levels of additive platelet score, INR score, and APTT score were significantly associated with increased mortality in ARF patients (P < 0.001). Binary logistic regression analysis showed that a higher coagulation disorder score was significantly related to the increased risk of in-hospital mortality in ARF patients (Model 2: coagulation disorder score = 6 vs. coagulation disorder score = 0: OR, 95% CI: 7.09, 4.07-12.34, P < 0.001). The AUC of the coagulation disorder score was 0.611 (P < 0.001), which was smaller than that of sequential organ failure assessment (SOFA) (De-long test P = 0.014) and simplified acute physiology score II (SAPS II) (De-long test P < 0.001) but larger than that of additive platelet count (De-long test P < 0.001), INR (De-long test P < 0.001), and APTT (De-long test P < 0.001), respectively. In subgroup analysis, we found that in-hospital mortality was markedly elevated with an increased coagulation disorder score in ARF patients. No significant interactions were observed in most subgroups. Of note, patients who did not administrate oral anticoagulant had a higher risk of in-hospital mortality than those who administrated oral anticoagulant (P for interaction = 0.024). Conclusion: This study found a significant positive association between coagulation disorder scores and in-hospital mortality. The coagulation disorder score was superior to the single indicators (additive platelet count, INR, or APTT) and inferior to SAPS II and SOFA for predicting in-hospital mortality in ARF patients.

LncRNA NEAT1: A novel regulator associated with the inflammatory response in acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition with an unfavorable prognosis. As the pathogenesis of ARDS remains unclear, we aimed to identify the core genes associated with ARDS and the mechanisms by which competing endogenous RNAs (ceRNAs) regulate the disease's progression. METHODS: Three mRNA microarray datasets (GSE17355, GSE48787, and GSE130936), derived from the Gene Expression Omnibus (GEO) database, were selected. Common differentially expressed genes (DEGs) related to acute lung injury (ALI) were identified and subjected to enrichment analysis. Then, hub genes were figured out through the protein-protein interaction (PPI) network and functional analysis, and targeted miRNAs and lncRNAs were predicted. Finally, the ceRNA networks associated with ALI were constructed and validated experimentally. RESULTS: A total of 155 upregulated and 93 downregulated DEGs were identified in the three datasets. The TNF signaling pathway and IL-17 signaling pathway were the most enriched pathways. Then, eleven DEGs enriched in the IL-17 signaling pathway were selected as the hub genes. Three miRNAs (mmu-mir-155-5p, mmu-mir-21a-5p, and mmu-mir-122-5p), which were located in the lung tissue and predicted to bind the hub genes at the same time, and two lncRNAs (Neat1 and Tug1), which have binding sites for the aforementioned miRNAs, were filtered. With qPCR verification, we identified a ceRNA network composed of NEAT1, miR-21-5p, MMP9, and CXCL5. NEAT1 knockdown promoted the migration and reduced the expression of pro-inflammatory factor and reactive oxygen species (ROS) in lung epithelial cells. We eventually confirmed that NEAT1/miR-21-5p/CXCL5/MMP9 played a pivotal role in regulating the inflammatory response in ALI. CONCLUSION: The IL-17 signaling pathway is of great importance in the pathogenesis of ARDS. NEAT1/miR-21-5p is involved in the inflammation of ALI by regulating CXCL5 and MMP9.

Protocol of a multicenter, single-blind, randomized, parallel controlled trial evaluating the effect of microbiological rapid on-site evaluation (M-ROSE) guiding anti-infection treatment in patients with severe hospital-acquired pneumonia.

INTRODUCTION: The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. METHODS/DESIGN: This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria. ETHICS AND DISSEMINATION: This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). TRIAL REGISTRATION: ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

[Obstructive sleep apnea-hypopnea syndrome in patients with pulmonary thromboembolism: clinical features and management].

OBJECTIVE: To describe the clinical features of obstructive sleep apnea-hypopnea syndrome (OSAHS) in hospitalized pulmonary thromboembolism (PTE) patients, and to explore its impact on the severity of disease and management among patients with PTE. METHODS: Demographic and clinical characteristics of 28 PTE patients complicated with OSAHS admitted to this hospital from January 2002 to December 2010 were analyzed. A total of 30 PTE patients without OSAHS served as a control group. RESULTS: PTE patients with OSAHS had a significantly lower age of onset of disease [(55 ± 11) yr vs (66 ± 11) yr, t = 3.230, P < 0.01], an increased body mass index (BMI) [(30.1 ± 2.8) kg/m(2) vs (26.1 ± 3.1) kg/m(2), t = -4.161, P < 0.001] and a higher smoking index [(19 ± 6) packs/yr vs (8 ± 4) packs/yr, t = -1.713, P < 0.05] when compared with PTE patients without OSAHS. PaO2 [(70 ± 8) mm Hg vs (79 ± 6) mm Hg, 1 mm Hg = 0.133 kPa, t = 4.233, P < 0.05] and involved lung segments [(8 ± 4) vs (5 ± 3), t = -2.496, P < 0.05] in PTE patients with OSAHS were more severe than those in PTE patients without OSAHS. All patients received anticoagulation and/or thrombolysis treatment, and continuous positive airway pressure (CPAP) ventilation was used in some PTE patients with OSAHS. CONCLUSION: PTE patients with OSAHS had a significantly earlier age of onset of disease and more severe conditions than PTE patients without OSAHS. Treatments including anticoagulation and CPAP should be used in these patients.

A novel pyroptosis related genes signature for predicting prognosis and estimating tumor immune microenvironment in lung adenocarcinoma.

Background: Pyroptosis is a newly found form of programmed cell death, accompanied by inflammatory response as well as immune response. Here, the specific function and prognosis predictive of pyroptosis-related genes (PRGs) were systematically explored in lung adenocarcinoma (LUAD). Methods: The gene expression data and corresponding clinical information of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), and the expression level of PRGs was identified between normal and tumor tissues. Furthermore, univariate Cox proportional hazards regression was conducted to filter the PRGs related to overall survival, and least absolute shrinkage and selection operator (LASSO) regression was subsequent employed to establish the PRGs risk model. Besides, the correlation of risk score with patients' clinical features, tumor mutational burden (TMB) as well as tumor microenvironment (TME) was also investigated. Results: A total of 5 PRGs (NLRC4, NLRP1, NLRP3, NOD1, PLCG1, and BAK1) was used to establish the risk prognostic model. According the median value of risk score, all the patients were classified into low- and high-risk score group. Kaplan-Meier analysis indicted that the LUAD patients in low-risk group exhibited a better survival outcome compared the patients in high-risk group (P<0.001). After adjusting for age, gender, and clinical stage, the risk score was also considered as and independent risk factor affecting the overall survival of LUAD patients (HR =2.949, 95% CI: 1.762-4.937). Moreover, low-risk score group exhibited a higher Immune score and lower Tumor purity compared with high-risk score group. ssGSEA results proved that the enrichment scores of most immune cells and immune related signal pathway in low-risk score group was significant higher than that in high-risk score group. In addition, the PRGs risk score was also positive correlated with TMB in LUAD tissues. Conclusions: In this study, a novel prognostic model based on PRGs was constructed and used to predict the survival outcome of LUAD patients. In addition, the PRGs risk signature was also associated with TMB and anti-tumor immune environment. The induction of pyroptosis inside tumors might be considered a potential strategy in cancer treatments.