Prognostic value of red blood cell distribution width to albumin ratio for predicting mortality in adult patients meeting sepsis-3 criteria in intensive care units.

BACKGROUND: Patients with sepsis with low albumin levels and high red blood cell distribution width levels have poor prognoses. Red blood cell distribution width to albumin ratio (RAR) has recently attracted attention as an innovative inflammation biomarker. We aimed to explore the association between RAR and the prognosis of patients with sepsis. METHODS: This retrospective observational study included 402 patients meeting the sepsis-3 standards admitted to Yantai Yuhuangding Hospital's intensive care units (ICUs) between January 2020 and December 2022. The relationship between RAR and mortality in patients with sepsis was examined using regression analysis, Kaplan-Meier analyses, and a receiver operating characteristic curve. Subgroup and sensitivity analyses were conducted to assess the results' robustness. RESULTS: RAR, when considered as a continuous variable, was a significant independent in-hospital mortality risk factor (adjusted odds ratio [OR]: 1.383; 95% confidence interval [CI]: 1.164-1.645; P < 0.001). When considering RAR as a categorical variable, the ORs (95% CIs) of hospital mortality for quartile 2 (Q2), Q3, and Q4 compared with Q1 were 1.027 (0.413-2.551), 3.632 (1.579-8.354), and 4.175 (1.625-10.729), respectively, P < 0.001. Similar outcomes were observed for 28- and 90-day mortalities. CONCLUSIONS: RAR may indicate clinical prognosis for patients with sepsis in the ICU, potentially providing a low-cost, easily repeatable, and accessible biomarker for risk categorization for these patients.

LGK974 suppresses the formation of deep vein thrombosis in mice with sepsis.

BACKGROUND: Sepsis is a disorder characterized by host inflammation and is caused by systemic infection. The inflammatory cytokine storm results in platelet overactivation, leading to coagulation dysfunction and thrombosis, but the underlying mechanism remains poorly understood. Recent evidence has shown that the Wnt/ß-catenin signaling pathway is related to sepsis, but its role and mechanism in sepsis complicated with deep vein thrombosis (DVT) are unclear. METHODS: In this study, a cecal ligation and puncture (CLP)-induced sepsis model and DVT mouse model were constructed by inferior vena cava ligation. The levels of serum inflammatory factors and adhesion molecules were measured in each group, and the thrombus weight and size, hematoxylin-eosin staining, collagen fiber tissue, and transcriptome of the venous wall were analyzed. The activation of the Wnt/ß-catenin signal was evaluated by quantitative real-time polymerase chain reaction, Western blotting, ELISA, and immunohistochemical and immunofluorescence methods. RESULTS: Sepsis significantly promoted the formation of venous wall collagen fibers and DVT. In addition, Porcn significantly upregulated and activated the Wnt/ß-catenin signaling pathway in sepsis mouse models with DVT. In contrast, the Wnt signaling inhibitor LGK974 was found to improve the survival rate, decrease thrombosis, and inhibit the expression of inflammation and adhesion molecules in sepsis mice with DVT. Therefore, activation of the Wnt/ß-catenin signal may promote the formation of DVT in sepsis mice. CONCLUSIONS: LGK974 protects against DVT formation in sepsis mice by inhibiting the activation of the Wnt/ß-catenin signal and down-regulating the production of proinflammatory cytokines, PAI-1, and adhesion molecules. LGK974 may be a new candidate for the treatment of sepsis complicated with DVT.

miR-346 regulates the development of ARDS by regulating the function of pulmonary microvascular endothelial cells.

In recent years, many studies have reported that microRNAs play an important role in the pathogenesis of a variety of diseases, and the aim of this paper is to explore the role and mechanism of miR-346 in acute respiratory distress syndrome (ARDS). A mouse model of ARDS was constructed by LPS induction, and RT-qPCR assay was used to verify that the expression level of miR-346 in lung tissue was significantly increased, and was negatively correlated with oxygenation index. Inhibiting the expression of miR-346 in mice and HPMECs by miR-346 inhibitor confirmed that decreased miR-346 expression could lead to increased oxygenation index, decreased lung index, lung water content and NO content to reduce lung injury in mice, while lung inflammation was alleviated and apoptosis was reduced in mice. The same results were obtained in cells. BCL6 was predicted to be a target of miR-346 by targetscan and miRDB; when miR-346 was inhibited, BCL6 expression was increased, and if miR-346 and BCL6 expression were inhibited at the same time, it could aggravate lung injury and reduce the proliferation of HPMECs and increase their apoptosis and inflammation in mice. This shows that miR-346 inhibits the migration of HPMECs by regulating BCL6 expression, which in turn promotes the apoptosis of HPMECs, leading to inflammation and inducing ARDS.

Human epididymis protein 4 as a new diagnostic biomarker for rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: This study aimed to evaluate the role of human epididymis protein 4 (HE4) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: HE4 levels in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) samples were determined via electrochemiluminescence immunoassays in 102 RA patients (46 patients with ILD and 56 patients without ILD) and 51 healthy controls (HCs). RESULTS: Serum HE4 levels were significantly higher in RA-ILD patients (141.8±65.92 pmol/l) than those in the RA-no ILD patients (82.67±26.17 pmol/l) and healthy controls (35.72±7.6 pmol/l) (p<0.0001). Consistent with serum HE4 levels, BALF HE4 levels were significantly higher in RA-ILD patients (637.6±154.9 pmol/l) than those in the RA-no ILD patients (427.3±111.2 pmol/l) and healthy controls (206.9±30.46 pmol/l) (p<0.0001). In RA-ILD patients, HE4 levels were positively correlated with HRCT (high-resolution computed tomography) fibrosis scores, whereas a significant inverse relationship was found between HE4 levels and lung function parameters (such as, diffusion capacity of the lung for carbon monoxide (DLCO)). The logistic regression analysis showed that high levels of BALF HE4 (≥595 pmol/l) were associated with RA-ILD (odds ratio [OR] =8.09; 95% confidence interval [CI] =1.317-49.682; p=0.024). CONCLUSIONS: Serum and BALF HE4 levels were elevated in RA-ILD patients and strongly associated with the severity of ILD, thus supporting their potential clinical value as a new diagnostic aid for patients with RA-ILD.

Prognostic role of heart-type fatty acid binding protein in pulmonary embolism: a meta-analysis.

INTRODUCTION: Pulmonary embolism (PE) has a high morbidity and mortality. Hence it is important to recognize factors associated with higher risk of adverse outcomes in hemodynamically stable patients. Heart-type fatty acid binding protein (H-FABP) is a novel marker evaluated in recent years for prognosis in acute PE. Our aim was to evaluate the available evidence on the accuracy of H-FABP for predicting the prognosis of adverse clinical outcomes (defined as the occurrence of any of the following: death, cardiopulmonary resuscitation, endotracheal intubation, use of vasopressors, thrombolysis, surgical embolectomy, or admission to the intensive care unit) or mortality in patients with acute PE. METHODS: Unrestricted searches of PubMed, the Cochrane Library, Web of Science and Science Direct were performed using the terms of "H-FABP" or "heart-type fatty acid binding protein" and ("pulmonary embolism" or "pulmonary thromboembolism"). A random-effect model was used to pool study results; χ(2) and I(2) testing was used to test for heterogeneity. Data of six studies were included in this analysis. RESULTS: 34 of 119(28.57%; 95%CI, 20.42%-36.72%) patients with elevated H-FABP levels had adverse events during follow-up compared with 24 of 475 (5.05%; 95%CI, 3.08%-7.02%) patients with normal levels. High H-FABP levels were associated with a high risk of occurrence of adverse clinical outcome (pooled OR, 10.81; 95%CI, 3.92-29.83). CONCLUSION: The results of this meta-analysis indicate that H-FABP is a good predictor for adverse outcomes in patients with acute PE.

Diagnostic utility of N-terminal-proBNP in differentiating acute pulmonary embolism from heart failure in patients with acute dyspnea.

BACKGROUND: The plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level is frequently elevated in dyspnoeic patients and increasingly used in emergency departments to assess the cause of acute dyspnea. In this study we prospectively tested NT-proBNP levels in patients with congestive heart failure (CHF) and/or acute pulmonary embolism (APE) and determined the utility of NT-proBNP for discriminating APE from CHF. METHODS: A cohort of 177 dyspnoeic patients with a diagnosis of APE and/or CHF was prospectively studied between June 2010 and March 2013. NT-proBNP was measured by the electrochemiluminescence immunoassay (ECLIA). All patients were evaluated with transthoracic echocardiography (TTE). APE was diagnosed in the presence of thrombi signs in the pulmonary arteries with computed tomographic pulmonary angiography (CTPA) or a high-probability lung ventilation/perfusion scan. Risk stratification was based on the evaluation on admission according to the ESC guidelines from 2008. The diagnosis of CHF was based on the guidelines of the American College of Cardiology/American Heart Association and the European Society of Cardiology. Two physicians independently reviewed the records to determine the final diagnosis. RESULTS: Fifty-nine patients met the criteria for dyspnea caused by APE, and 113 patients were diagnosed with CHF. Most of the APE patients (41, 69.5%) were intermediate-risk. The symptoms and signs, such as orthopnea, paroxysmal nocturnal dyspnea and rales in the lungs, were more common in patients with CHF than in patients with APE (P < 0.01). Median NT-proBNP was significantly lower in patients with APE compared to those in patients with CHF (2 855.9 pg/ml vs. 6 911.4 pg/ml, P < 0.01). We constructed the receiver operating characteristics (ROC) curve in predicting the diagnosis of APE. At a cut point = 1 582.750 pg/ml, NT-proBNP provided a specificity of 93% and a true positive rate (sensitivity) of 17% for the diagnosis. At a cut point = 3 390.000 pg/ml, NT-proBNP had a specificity of 83% and a sensitivity of 84% for the diagnosis of APE. At a cut point = 6 486.500 pg/ml, they were 54% and 93% respectively. CONCLUSIONS: NT-proBNP can assist in excluding CHF patients from those admitted to the emergency department with acute dyspnea and identifying patients with a high probability of APE, which would reduce the missed diagnosis of APE. Larger studies are necessary to validate these findings.