Background: Acute pulmonary embolism (APE) is a common clinical condition. Its severity ranges from asymptomatic radiological findings to fatal obstructive shock. The potential circulating biomarkers have been studied to predict APE outcomes. This study aimed to explore their predictive power on prognosis in APE. Material and Method: It was a prospective observational study between March 2008 and April 2010. All consecutive patients diagnosed with APE were categorized as massive/high-risk, submassive/moderate-risk, and non-massive/low-risk. Cardiac troponin T (cTnT), myoglobin, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), growth differentiation factor-15 (GDF-15), and D-dimer levels were measured. Results: Of these patients, 14 (29.8%), 16 (34.0%), and 17 (36.2%) patients were categorized as low-risk, moderate-risk, and high risk-patients, respectively. There was no significant difference between the patient groups categorized based on the risk stratification in terms of demographic and clinical characteristics. The cTnT, myoglobin, HFABP, and D-dimer levels have also not differed significantly between the groups. There was a significant difference between the groups in respect of NT-proBNP and GDF-15 levels (p=0.009 and p=0.037, respectively). Nine (19.1%) patients had died by the 3rd-month follow-up. Adverse events were seen in 26 (55.3%) patients. GDF-15 had the highest area under the curve (AUC) value for predicting any adverse event (cut-off value=9.3 ng/mL, AUC=0.796, CI (confidence interval) 95%: 0.653– 0.899). NT-ProBNP was determined as the best predictor for mortality (cut-off value=229.2 pg/mL, AUC=0.889, CI 95%: 0.756– 0.964). Conclusion: Higher levels of NT-proBNP and GDF-15 were found to be associated with more severe APE, worse outcomes, and mortality.

Background: Pulmonary embolism (PE) is a common and potentially life-threatening disorder. Our study was aimed to investigate whether oxidative stress markers can be used as clinical markers in the evaluation of acute PE (APE) severity. Methods: 47 patients with objectively documented diagnosis of APE were recorded. Of these patients, 14 had low-risk PE, 16 had moderate-risk PE, and 17 had high-risk PE. 21 healthy subjects were also enrolled in this study. Ischemia-modified albumin (IMA), prooxidants-antioxidants balance (PAB), advanced protein oxidation products (AOPPs), and ferric reducing antioxidant power (FRAP) were measured as oxidative stress parameters to evaluate the role of oxidative stress. Results: In the low-risk and moderate-risk APE groups, AOPPs and PAB levels were significantly higher and FRAP levels were significantly lower than those in the control group. AOPPs and IMA levels in the patients with high-risk PE were significantly higher than those in both the low-risk and moderate-risk APE patients. There was a significant correlation between levels of AOPPs and the levels of both IMA (r: 0.462, p < 0.001) and PAB (r:0.378, p < 0.005). Serum FRAP levels were negatively correlated with PAB (r:− 0.683, p < 0.001) and AOPPs levels (r:− 0,384, p < 0.001). There was also a significant positive correlation between the serum IMA and PAB levels. Conclusions: We clearly demonstrated that reactive oxygen species formation is significantly enhanced in APE. IMA and AOPPs may be used as clinical markers in the evaluation of APE severity in clinical practice. However, further studies with larger patient populations and longer follow-up periods are required to confirm the mechanisms underlying these findings.

The multisystemic effects of COVID-19 may continue for a longer time period following the acute phase, depending on the severity of the disease. However, long-term systemic transcriptomic changes associated with COVID-19 disease and the impact of disease severity are not fully understood. We aimed to investigate the impact of COVID-19 and its severity on transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) following 1 year of the disease. PBMCs were isolated from the peripheral blood of healthy control donors who did not have COVID-19 (C; n = 13), from COVID-19 patients without pneumonia (NP; n = 11), and from COVID-19 patients with severe pneumonia (SP; n = 10) after 1-year of follow-up. Following RNA isolation from PBMCs, high-quality RNAs were sequenced after creating a library. Differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified using Benjamini–Hochberg correction and they were analysed for hierarchical clustering and principal component analysis (PCA). Intergroup comparisons (C vs. NP, C vs. SP, and NP vs. SP) of DEGs and DElncRNAs were performed and hub genes were determined. Functional enrichment analyses of DEGs and DElncRNAs were made using Metascape (v3.5.20240101) and the first version of NCPATH. The RNA sequencing analysis revealed 4843 DEGs and 1056 DElncRNAs in “C vs. NP”, 1651 DEGs and 577 DElncRNAs in “C vs. SP”, and 954 DEGs and 148 DElncRNAs in “NP vs. SP”, with 291 DEGs and 70 DElncRNAs shared across all groups, respectively. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation and downregulated DEGs to viral infections and immune responses. The analysis showed that 291 common and 14 hub genes were associated with pneumonia and that these genes could be regulated by the transcription factors JUN and NFκB1 carrying the NFκB binding site. We also revealed unique immune cell signatures across DEG categories indicating that the upregulated DEGs were associated with neutrophils and monocytes, while downregulated DEGs were associated with CD4 memory effector T cells. The comparative transcriptomic analysis of NP and SP groups with 52 gene signatures suggestive of IPF risk showed a lower risk of IPF in the SP group than the NP patients. Our findings suggest that COVID-19 may cause long term pathologies by modulating the expression of various DEGs, DeLncRNAs, and hub genes at the cellular level.

This study examined the long-term transcriptomic reprogramming in peripheral blood mononuclear cells (PBMCs) of severe COVID-19 patients and its effects for cancer development. RNA sequencing was conducted on PBMCs obtained from healthy controls, COVID-19 patients without pneumonia, and COVID-19 patients exhibiting severe pneumonia one year post-infection. Differential gene expression analysis identified a sustained pro-oncogenic molecular signature, especially among severe COVID-19 patients. Functional enrichment analysis revealed a substantial enrichment of cancer-associated pathways, encompassing apoptosis, viral carcinogenesis, and transcriptional dysregulation. Notably, the autophagy-related gene SQSTM1/P62 was recognized as a distinctive hub gene within the severe COVID-19 patients, interacting with pivotal genes associated with inflammation, apoptosis, and cancer advancement. Survival analysis demonstrated that elevated expression of COVID-19-associated hub genes correlated with unfavorable prognosis in various cancer types, including adrenocortical carcinoma, bladder urothelial carcinoma, and brain lower-grade glioma. These findings indicate that severe COVID-19 infection may establish a systemic milieu favorable to cancer development or recurrence, highlighting the necessity of prolonged oncological monitoring in these patients. Finding specific molecular targets and pathways can help us understand how COVID-19 might be linked to a higher risk of cancer.