Preventive Effects of Melatonin on Delirium in Intensive Care Unit Patients: A Meta-Analysis of Randomized Controlled Trials.

Aims: To investigate the preventive efficacy of melatonin on the incidence of delirium and other clinical outcomes of subjects in the intensive care unit (ICU). Methods: Randomized controlled trials concerning the effects of melatonin on delirium published from inception to July 2022 were identified from PubMed, Embase, and the Cochrane Library. The primary outcome was delirium incidence. The secondary outcome was the length of ICU stay, the duration of mechanical ventilation, and the mortality in ICU. A meta-analysis was performed. Estimates were presented as risk ratio (RR) or standard mean difference (SMD) with 95% confidence interval (CI). Results: Eleven RCTs with 2002 patients were included. The forest plots showed that the delirium incidence did not significantly decrease after melatonin administration (RR 0.85; 95% CI, 0.61~1.18, P = .32, I2=60%, P for heterogeneity = .01). The subgroup analyses confirmed that melatonin significantly reduced the incidence of delirium (RR 0.70; 95% CI, 0.56~0.89, P = .003, I2 = 32%, P for heterogeneity = .22) for the special ICU patients. Also, for ICU patients, the length of ICU stays, duration of mechanical ventilation, and mortality were not significantly decreased after melatonin treatment (all P > .05). Conclusion: Melatonin may decrease the incidence of delirium for special ICU patients. PROSPERO registration number: CRD42022354874.

Prognostic Value of Neutrophils-to-Lymphocytes Ratio and Platelets-to-Lymphocytes Ratio in Sepsis Patients With Lymphopenia.

Background: Inflammation plays a critical role in sepsis. The integration of neutrophil-to-lymphocyte ratio (NLR) and platelets-to-lymphocytes ratio (PLR) from multiple cell types offers a novel approach to rapidly assess inflammation status. However, the predictive role of NLR and PLR in sepsis with lymphopenia remains uncertain. Objectives: The purpose of this study was to explore the prognostic value of NLR and PLR in sepsis patients with lymphopenia. Design and methods: In this observational retrospective study, we included 172 sepsis patients with lymphopenia and collected clinical characteristics for analysis. Through binary logistic regression analysis, we identified independent factors. Receiver-operating characteristic curves (ROC) and areas under the curves (AUC) were employed to assess the ability to predict hospital mortality risk. Results: Our results showed a total hospital mortality rate of 53.49%. Multivariate analysis demonstrated that NLR (OR = 1.11, P < .001) and PLR (OR = 1.01, P = .003) were independent predictors associated with hospital mortality in sepsis patients with lymphopenia. The AUCs of NLR and PLR were 0.750 (95% CI: 0.634-0.788, P < .001) and 0.662 (95% CI: 0.580-0.743, P < .001), respectively. Notably, an optimal cut-off value of 18.93 for NLR displayed a sensitivity of 75.0% and specificity of 63.0% in discriminating hospital mortality in sepsis patients with lymphopenia, while the optimal cut-off value for PLR was 377.50, with a sensitivity of 67.5% and specificity of 64.1%. Conclusion: NLR and PLR serve as independent predictors of hospital mortality in sepsis patients with lymphopenia.

Intensify Standardized Anticoagulation for Cancer-associated Pulmonary Embolism: From Single-center Real-world Data.

PURPOSE: Pulmonary embolism (PE) is a significant contributor to mortality in patients with cancer. Although anticoagulation serves as the cornerstone of treatment for cancer-associated PE, it has not been emphasized in real-world settings. The aim of this study was to examine the impact of suboptimal anticoagulant treatment on the prognosis of cancer-associated PE. METHODS: A cohort of 356 individuals newly diagnosed with acute PE were enrolled. The primary outcome of the study was recurrent venous thromboembolism (VTE), and the secondary outcomes were all-cause mortality and major bleeding (consisting of a reduction in the hemoglobin level by at least 20 g/L, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ or fatal bleeding). FINDINGS: Of the total participants, 156 (43.8%) were diagnosed with cancer. A comparison between the cancer and noncancer groups revealed that patients with cancer were more frequently asymptomatic (41.0% vs 4.5%; P < 0.001), less likely to have right ventricular dysfunction (4.5% vs 14.0%; P = 0.001), received less anticoagulant treatment during hospitalization (85.3% vs 98.5%; P < 0.001), and had a shorter duration of anticoagulation (5.02 [7.40] months vs 14.19 [10.65] months; P < 0.001). In addition, patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%; P < 0.001) and all-cause mortality (23.7% vs 10.5%; P = 0.001). Multiple Cox regression analysis indicated that discontinuation of anticoagulation at 3 months was a significant risk factor for recurrent VTE in the cancer group (HR, 15.815; 95% CI, 3.047-82.079; P = 0.001). IMPLICATIONS: The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE. The ultimate goal is to enhance patient prognosis and quality of life.

Cathelicidin induces epithelial-mesenchymal transition to promote airway remodeling in smoking-related chronic obstructive pulmonary disease.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is an important characteristic in the remodeling of airways that occurs in chronic obstructive pulmonary disease (COPD). Cigarette smoke is a potential driving factor of this EMT in COPD. However, the mechanisms by which cigarette smoke induce EMT remain uncertain. Cathelicidin has been implicated as a causal factor of airway inflammation and mucus hypersecretion in smoking-related COPD. This study aimed to investigate whether cathelicidin induces EMT to promote airway remodeling in this disease. METHODS: Human lung tissue was collected from smokers with COPD and smokers without COPD. The EMT markers E-cadherin and vimentin were examined by immunohistochemistry. Mouse models of COPD were established by taking mice with airway cathelin-related antimicrobial peptide (CRAMP), the murine homologue of cathelicidin, either upregulated or downregulated by intranasal introduction of lentiviral vectors and then exposing them to cigarette smoke. E-cadherin and vimentin expression in the airways of the model mice was examined using immunofluorescence. Tumor necrosis factor alpha (TNF-α) converting enzyme (TACE), transforming growth factor alpha (TGF-α), and epidermal growth factor receptor (EGFR) expression was analyzed by Western blot. Additionally, NCI-H292 human airway epithelial cells, both with and without cathelicidin downregulation, were stimulated with cigarette smoke extract (CSE) and LL-37 synthetic peptide, a bioactive fragment of cathelicidin. This was done to confirm that the TACE/TGF-α/EGFR signaling pathway is activated in humans exposed to cigarette smoke. RESULTS: Significant EMT was found in the small airways of smokers both with and without COPD, as well as in the airways of COPD model mice. Downregulation of CRAMP in COPD mice, however, ameliorated airway EMT induced by cigarette smoke. Conversely, upregulation of CRAMP enhanced airway EMT in vivo; TACE, TGF-α, and EGFR were found to be involved in this process. In vitro, EMT induced by CSE and LL-37 was inhibited by blocking TACE, TGF-α, and EGFR expression. CONCLUSIONS: Cathelicidin promotes airway EMT by activating the TACE/TGF-α/EGFR signaling pathway. This mediates smoking-induced airway remodeling in the pathogenesis of COPD.

Lentivirus-mediated angiopoietin-2 gene silencing decreases TNF-α induced apoptosis of alveolar epithelium cells.

OBJECTIVE: To investigate the role of angiopoietin-2 (Ang-2) in tumor necrosis factor-α (TNF-α) induced apoptosis of alveolar epithelium cells (AECs). METHODS: TNF-α was used to induce human alveolar epithelial HPAEpiC cells, and Ang-2 siRNA vector was transfected to the HPAEpiC cells. RT-PCR and Western blot were used. TUNEL staining was applied to observe apoptosis, and annexin V-FITC-PI staining was used to calculate apoptosis rate. RESULTS: mRNA and protein expressions of Ang-2, activated Bax, and cleaved caspase-3 in HPAEpiC cells were up-regulated, but the expression level of Bcl-2 decreased (P < 0.05). After transfection of Ang-2 siRNA, mRNA and protein expressions of Ang-2, activated Bax, and cleaved caspase-3 in HPAEpiC cells were down-regulated, but the expression level of Bcl-2 increased (P < 0.05). The number of apoptotic cells increased after TNF-α treatment; however, the number decreased after Ang-2 siRNA transfection. Annexin V-FITC-PI staining verified that the total number of apoptotic cells was elevated with TNF-α treatment, but declined after transfection of Ang-2 siRNA. CONCLUSIONS: The expression level of Ang-2 increased during TNF-α-induced apoptosis. Inhibiting Ang-2 expression may suppress the early stages of cell apoptosis and the degree of TNF-α-induced apoptosis.

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.