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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.
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Antibacterianos , Infecciones Comunitarias Adquiridas , Levofloxacino , Quinolonas , Humanos , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Levofloxacino/uso terapéutico , Levofloxacino/efectos adversos , Levofloxacino/administración & dosificación , Método Doble Ciego , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Adulto , Anciano , Resultado del Tratamiento , Quinolonas/uso terapéutico , Quinolonas/administración & dosificación , Quinolonas/efectos adversos , Administración Intravenosa , Infusiones Intravenosas , Adulto Joven , Neumonía/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Anciano de 80 o más AñosRESUMEN
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.
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Procedimientos Quirúrgicos Cardíacos , Síndrome de Dificultad Respiratoria , Humanos , Puente Cardiopulmonar/efectos adversos , Estudios Retrospectivos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/etiología , PronósticoRESUMEN
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.
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COVID-19 , Microbiota , Neumonía , Humanos , COVID-19/genética , COVID-19/metabolismo , SARS-CoV-2/genética , Respiración Artificial , Pulmón , Neumonía/metabolismo , BacteriasRESUMEN
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 = 1.056â½1.427, P = 0.008), secondary operation (OR = 1.910, 95%CI = 1.131â½3.425, P = 0.015) and pre-infection exposure to linezolid (OR = 3.704, 95%CI = 1.291â½10.629, 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.
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Infecciones Bacterianas , Procedimientos Quirúrgicos Cardíacos , Humanos , Adulto , Farmacorresistencia Bacteriana Múltiple , Linezolid , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Pacientes Internos , Factores de Riesgo , Antibacterianos/uso terapéuticoRESUMEN
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.
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Antiinfecciosos , Neumonía , Humanos , Adolescente , Adulto , Estudios Prospectivos , Evaluación in Situ Rápida , Método Simple Ciego , Hospitales Generales , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
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.
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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.
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MicroARNs , ARN Largo no Codificante , Síndrome de Dificultad Respiratoria , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Interleucina-17/genética , MicroARNs/genética , MicroARNs/metabolismo , Síndrome de Dificultad Respiratoria/genética , Redes Reguladoras de GenesRESUMEN
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.
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Pueblos del Este de Asia , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Embolia Pulmonar , Humanos , China/epidemiología , Pueblos del Este de Asia/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Polimorfismo de Nucleótido Simple/genética , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etnología , Embolia Pulmonar/genética , Factores de RiesgoRESUMEN
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.
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Pulmonary arterial hypertension (PAH) is a progressive and complex pulmonary vascular disease with poor prognosis. The aim of this study was to provide a new understanding of the pathogenesis of disease and potential treatment targets for patients with PAH based on multiple-microarray analysis.Two microarray datasets (GSE53408 and GSE113439) downloaded from the Gene Expression Omnibus (GEO) database were analysed. All the raw data were processed by R, and differentially expressed genes (DEGs) were screened out by the "limma" package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed and visualized by R and Cytoscape software. Protein-protein interactions (PPI) of DEGs were analysed based on the NetworkAnalyst online tool. A total of 442 upregulated DEGs and 84 downregulated DEGs were identified. GO enrichment analysis showed that these DEGs were mainly enriched in mitotic nuclear division, organelle fission, chromosome segregation, nuclear division, and sister chromatid segregation. Significant KEGG pathway enrichment included ribosome biogenesis in eukaryotes, RNA transport, proteoglycans in cancer, dilated cardiomyopathy, rheumatoid arthritis, vascular smooth muscle contraction, focal adhesion, regulation of the actin cytoskeleton, and hypertrophic cardiomyopathy. The PPI network identified 10 hub genes including HSP90AA1, CDC5L, MDM2, LRRK2, CFTR, IQGAP1, CAND1, TOP2A, DDX21, and HIF1A. We elucidated potential biomarkers and therapeutic targets for PAH by bioinformatic analysis, which provides a theoretical basis for future study.
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Biología Computacional , Hipertensión Arterial Pulmonar , Proteínas de Ciclo Celular/genética , ARN Helicasas DEAD-box/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Hipertensión Arterial Pulmonar/genética , Proteínas de Unión al ARN/genética , Transducción de Señal/genéticaRESUMEN
INTRODUCTION: Combined forceps and cryoprobe biopsy during bronchoscopy are increasingly used. However, the adult standard cuffed endotracheal tube (SCETT) is can be limited by general anaesthesia and neuromuscular blockade. An adult uncuffed endotracheal tube (UCETT) might provide simple and safe airway support in stable patients during forceps and cryoprobe biopsy under spontaneous respiration. METHODS: A retrospective review of stable patients undergoing forceps and cryoprobe biopsy was performed. They were divided into a UCETT group (N = 33) and a SCETT group (N = 27). The primary technical outcome was the successful intubation and completion of bronchoscopy. The primary safety outcome was the incidence of desaturation events. Recovery time and side effects were also recorded. RESULTS: UCETTs and SCETTs were successfully inserted, and bronchoscopic procedures were completed in all patients. Only 3/33 (9.1%) patients in the UCETT group exhibited a drop of SPO2 < 90% during the bronchoscopy, compared to 2/27 (7.4%) patients in the SCETT group (P = 0.545). Patients recovered faster in the UCETT group than those in the SCETT group. Major bleeding, laryngospasm and major arrhythmias did not occur in either group. Incidences of sinus tachycardia, incidences of vomiting, minor and moderate bleeding and premature atrial contractions were not significantly different between the two groups. Nausea occurred in 5/33 (15.2%) patients in the UCETT group, compared to 11/27 (40.7%) in the SCETT group. CONCLUSION: This study suggests that UCETT under spontaneous respiration can provide satisfactory airway support and a shorter recovery time in stable patients; thus, it may be an option to assist forceps and cryoprobe biopsy.
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Broncoscopía , Instrumentos Quirúrgicos , Adulto , Anestesia General , Biopsia/efectos adversos , Biopsia/métodos , Broncoscopía/efectos adversos , Broncoscopía/métodos , Hemorragia/epidemiología , Hemorragia/etiología , Humanos , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/métodos , Instrumentos Quirúrgicos/efectos adversosRESUMEN
Acute respiratory distress syndrome (ARDS) is a leading cause of death in critically ill patients due to hypoxemic respiratory failure. The specific pathogenesis underlying ARDS has not been fully elucidated. In this study, we constructed a triple regulatory network involving competing endogenous RNA (ceRNA) to investigate the potential mechanism of ARDS and evaluated the immune cell infiltration patterns in ARDS patients. Overall, we downloaded three microarray datasets that included 60 patients with sepsis-induced ARDS and 79 patients with sepsis alone from the public Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs, including 9 DElncRNAs, 9 DEmiRNAs, and 269 DEmRNAs) by R software. The DEGs were subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional enrichment analysis, and a protein-protein interaction (PPI) network was generated for uncovering interactive relationships among DEmRNAs. Then, a ceRNA network that contained 5 DElncRNAs, 7 DEmiRNAs, and 71 DEmRNAs was established according to the overlapping genes in both DEGs and predicted genes by public databases. Finally, we identified the TUG1/miR-140-5p/NFE2L2 pathway as the hub pathway in the whole network through Cytoscape. In addition, we evaluated the distribution of 22 subtypes of immune cells and recognized three differentially expressed immune cells in patients with sepsis-induced ARDS by "Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)" algorithm, namely, naive B cells, regulatory T cells, and eosinophils. Correlations between differentially expressed immune cells and hub genes in the ceRNA network were also performed. In conclusion, we demonstrated a new potential regulatory mechanism underlying ARDS (the TUG1/miR-140-5p/NFE2L2 ceRNA regulatory pathway), which may help in further exploring the pathogenesis of ARDS.
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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.
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Aneurisma de la Aorta/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Hipoxia/epidemiología , Unidades de Cuidados Intensivos , Tiempo de Internación , Complicaciones Posoperatorias/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Adulto , Disección Aórtica/diagnóstico , Disección Aórtica/epidemiología , Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/epidemiología , China/epidemiología , Femenino , Humanos , Hipoxia/diagnóstico , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/terapia , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Apnea Obstructiva del Sueño/diagnóstico , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
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Proteína C-Reactiva/metabolismo , Polipéptido alfa Relacionado con Calcitonina/sangre , Infecciones del Sistema Respiratorio/microbiología , Rinorrea/complicaciones , Virosis/diagnóstico , Anciano , Área Bajo la Curva , Infecciones Bacterianas/diagnóstico , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Infecciones del Sistema Respiratorio/sangre , Estudios Retrospectivos , Virosis/sangreRESUMEN
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.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Obesidad/complicaciones , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/etiología , Adulto , Anciano , Índice de Masa Corporal , Procedimientos Quirúrgicos Cardíacos/métodos , Estudios de Casos y Controles , Susceptibilidad a Enfermedades , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mortalidad , Obesidad/epidemiología , Obesidad/cirugía , Síndrome de Dificultad Respiratoria/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
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.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , Nomogramas , Síndrome de Dificultad Respiratoria/diagnóstico , Medición de Riesgo/métodos , Beijing/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Síndrome de Dificultad Respiratoria/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Despite advances in treatment strategies, acute respiratory distress syndrome (ARDS) after cardiac surgery remains associated with high morbidity and mortality. A method of screening patients for risk of ARDS after cardiac surgery is needed. OBJECTIVES: To develop and validate an ARDS prediction score designed to identify patients at high risk of ARDS after cardiac or aortic surgery. METHODS: An ARDS prediction score was derived from a retrospective derivation cohort and validated in a prospective cohort. Discrimination and calibration of the score were assessed with area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test, respectively. A sensitivity analysis was conducted to assess model performance at different cutoff points. RESULTS: The retrospective derivation cohort consisted of 201 patients with and 602 patients without ARDS who had undergone cardiac or aortic surgery. Nine routinely available clinical variables were included in the ARDS prediction score. In the derivation cohort, the score distinguished patients with versus without ARDS with area under the curve of 0.84 (95% CI, 0.81-0.88; Hosmer-Lemeshow P = .55). In the validation cohort, 46 of 1834 patients (2.5%) had ARDS develop within 7 days after cardiac or aortic surgery. Area under the curve was 0.78 (95% CI, 0.71-0.85), and the score was well calibrated (Hosmer-Lemeshow P = .53). CONCLUSIONS: The ARDS prediction score can be used to identify high-risk patients from the first day after cardiac or aortic surgery. Patients with a score of 3 or greater should be closely monitored. The score requires external validation before clinical use.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Síndrome de Dificultad Respiratoria , Humanos , Estudios Prospectivos , Curva ROC , Síndrome de Dificultad Respiratoria/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Takayasu's arteritis (TA) may involve the pulmonary artery, which signifies a poor prognosis. This study investigated the features of TA patients with pulmonary artery involvement. METHODS: One hundred and twenty-six inpatients diagnosed with TA were retrospectively studied. The clinical data of TA patients with and without pulmonary artery involvement were compared. The imaging features of pulmonary artery lesions in TA patients were evaluated. The treatment responses of pulmonary artery lesions were described, and the drug regimens in different treatment response groups were compared. RESULTS: Among the patients with TA, 15.9% showed associated pulmonary artery involvement. The disease durations were significantly longer in patients with pulmonary artery involvement than in those without (108.0 months (53.5, 222.0) vs. 36.0 months (12.0, 120.0); p = 0.038). Hemoptysis was more common in TA patients with pulmonary artery involvement than in those without (15.0%, 3 cases vs. 0.0%; p < 0.001). TA patients with disease duration longer than 5 years showed a 3.42-fold higher odds of pulmonary artery involvement than those with a disease duration of less than 5 years (adjusted odds ratio, 3.42 (95% confidence interval, 1.20-9.76); p = 0.02). The most common imaging manifestations of pulmonary artery involvement were stenosis and occlusion. Among the six patients who had good response to treatment of pulmonary artery lesions, five were treated with the interleukin-6 receptor antagonist tocilizumab. CONCLUSIONS: TA patients with pulmonary artery involvement have a longer course of disease and more symptoms of hemoptysis. TA-related pulmonary artery lesions more commonly manifested as stenosis and occlusion. Tocilizumab may be effective for TA-related pulmonary vascular disease. Key Points ⢠Disease duration longer than 5 years is associated with pulmonary artery involvement in TA. ⢠Hemoptysis is a characteristic clinical symptom of TA with pulmonary artery involvement. ⢠Tocilizumab may be more effective for pulmonary artery lesions of TA.
Asunto(s)
Arteritis de Takayasu , China , Humanos , Arteria Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/diagnóstico por imagen , Arteritis de Takayasu/tratamiento farmacológicoRESUMEN
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.