sFlt-1 and CA 15.3 are indicators of endothelial damage and pulmonary fibrosis in SARS-CoV-2 infection

AbstractCOVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p < 0.001 Sens. 83.9% and Spec. 86.7%) with presence, extent and severity of the disease. Moreover, CA 15.3 appeared significantly increased in COVID-19 severe lung fibrosis (ICU vs NON-ICU patients 42.6 ± 3.3 vs 25.7 ± 1.5 U/mL, p < 0.0001) and was associated with lung damage severity grade (ROC AUC 0.958, decision threshold > 24.8 U/mL, p < 0.0001, Sens. 88.4% and Spec. 91.8%). In conclusion, serum levels of sFlt-1 and CA 15.3 appeared useful tools for categorizing COVID-19 clinical stage and may represent a valid aid for clinicians to better personalise treatment.

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SP-D Serum Levels Reveal Distinct Epithelial Damage in Direct Human ARDS

Journal of Clinical Medicine ◽

10.3390/jcm10040737 ◽

2021 ◽

Vol 10 (4) ◽

pp. 737

Author(s):

Konrad Peukert ◽

Benjamin Seeliger ◽

Mario Fox ◽

Caroline Feuerborn ◽

Andrea Sauer ◽

...

Keyword(s):

Bacterial Pneumonia ◽

Inflammatory Responses ◽

Serum Levels ◽

Endothelial Damage ◽

Lung Damage ◽

Surfactant Protein D ◽

Atypical Pneumonia ◽

Epithelial Damage ◽

Atypical Pathogen ◽

Atypical Pathogens

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome with multiple underlying diseases. Particularly epithelial damage results from direct (e.g., pneumonia) rather than indirect lung injury (e.g., nonpulmonary sepsis), which is more likely associated with endothelial damage. Hence, targeting ARDS patients based on their molecular phenotypes is a promising approach to improve outcome. With regard to distinct inflammatory responses and subsequent lung damage in direct ARDS due to the causing pathogen, we quantified markers of epithelial and endothelial damage and pro-inflammatory cytokines in patients with ARDS triggered by bacterial, viral, and atypical pathogen pneumonia or indirect ARDS. The serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8), lung epithelial injury markers surfactant protein D (SP-D), and soluble receptor for advanced glycation end-products (sRAGE) as well as endothelial injury marker angiopoietin-2 (Ang-2) from 49 patients with distinct types of ARDS were analyzed by multiplex immunoassay. Epithelial damage marker SP-D was significantly higher in direct ARDS caused by viral and atypical pathogens in contrast to ARDS caused by typical bacterial pneumonia and nonpulmonary sepsis. In contrast, sRAGE levels did not differ due to the causing pathogen. Patients with atypical pathogen pneumonia related ARDS showed significantly lower Ang-2 levels compared to patients with viral and indirect ARDS. Patients with viral and atypical pneumonia related ARDS possessed significantly lower serum IL-6 levels compared to bacterial pneumonia related ARDS and IL-6 levels in atypical pneumonia related ARDS were significantly lower than in indirect ARDS. Current findings report a potential difference in ARDS biomarkers due to the underlying disease and pathogen.

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MTHFR 677C>T (rs1801133) variant is associated with homocysteinemia but not with clinical severity in patients with peripheral arterial occlusive disease

10.21203/rs.3.rs-887964/v1 ◽

2021 ◽

Author(s):

Guilherme da Silva Silvestre ◽

Iriana Moratto Carrara ◽

Tamires Flauzino ◽

Marcell Alysson Batisti Lozovoy ◽

Rubens Cecchini ◽

...

Keyword(s):

Peripheral Arterial Occlusive Disease ◽

Clinical Stage ◽

Serum Levels ◽

Arterial Disease ◽

Recessive Model ◽

Arterial Occlusive Disease ◽

Occlusive Disease ◽

Clinical Severity ◽

University Hospital ◽

Peripheral Arterial

Abstract The aim of this study was to evaluate the association between the MTHFR 677C > T (rs1801133) genetic variant with susceptibility and severity of peripheral arterial occlusive disease (PAOD) and with serum levels of homocysteine (Hcy). This case-control study enrolled 157 patients with PAOD attended at University Hospital of Londrina, and unrelated 113 healthy individuals from Southern Brazil. The clinical severity of the PAOD patients was assessed by Fontaine classification and anatomoradiological categories by Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC). The MTHFR 677C > T was genotyped using real-time polymerase chain reaction. The PAOD patients showed higher Hcy than controls but the Hcy did not differ according to Fontaine and TASC categories. Patients carrying the TT genotype (recessive model) or CT + TT (dominant model) presented higher levels of Hcy than those carrying other genotypes. In conclusion, the T allele of MTHFR 677C > T variant was associated with hyperhomocysteinemia in PAOD patients, but not in controls. Moreover, this variant was not associated with the clinical stage and the anatomoradiological categories of PAOD. Our data suggested a possible interaction between MTHFR 677C > T variant and the presence of other genetic, epigenetic and environment factors associated with PAOD on modulation the metabolism of Hcy.

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Protective Effect of Vitamin E on Immune Triggered, Granulocyte Mediated Endothelial Injury

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661027 ◽

1984 ◽

Vol 51 (01) ◽

pp. 089-092 ◽

Cited By ~ 24

Author(s):

M A Boogaerts ◽

J Van de Broeck ◽

H Deckmyn ◽

C Roelant ◽

J Vermylen ◽

...

Keyword(s):

Vitamin E ◽

Protective Effect ◽

Umbilical Vein ◽

Endothelial Damage ◽

Endothelial Injury ◽

Mediated Effects ◽

Anti Oxidant ◽

Endothelial Cell Cultures ◽

Vitro Model

SummaryThe effect of alfa-tocopherol on the cell-cell interactions at the vessel wall were studied, using an in vitro model of human umbilical vein endothelial cell cultures (HUEC). Immune triggered granulocytes (PMN) will adhere to and damage HUEC and platelets enhance this PMN mediated endothelial injury. When HUEC are cultured in the presence of vitamin E, 51Cr-leakage induced by complement stimulated PMN is significantly decreased and the enhanced cytotoxicity by platelets is completely abolished (p <0.001).The inhibition of PMN induced endothelial injury is directly correlated to a diminished adherence of PMN to vitamin E- cultured HUEC (p <0.001), which may be mediated by an increase of both basal and stimulated endogenous prostacyclin (PGI2) from alfa-tocopherol-treated HUEC (p <0.025). The vitamin E-effect is abolished by incubation of HUEC with the irreversible cyclo-oxygenase inhibitor, acetylsalicylic acid, but the addition of exogenous PGI2 could not reproduce the vitamin E-mediated effects.We conclude that vitamin E exerts a protective effect on immune triggered endothelial damage, partly by increasing the endogenous anti-oxidant potential, partly by modulating intrinsic endothelial prostaglandin production. The failure to reproduce vitamin E-protection by exogenously added PGI2 may suggest additional, not yet elucidated vitamin E-effects on endothelial metabolism.

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Pathological Roles and Clinical Usefulness of Periostin in Type 2 Inflammation and Pulmonary Fibrosis

Biomolecules ◽

10.3390/biom11081084 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1084

Author(s):

Junya Ono ◽

Masayuki Takai ◽

Ayami Kamei ◽

Yoshinori Azuma ◽

Kenji Izuhara

Keyword(s):

Pulmonary Fibrosis ◽

Transforming Growth Factor ◽

Biological Fluids ◽

Allergic Inflammation ◽

Transforming Growth Factor Β ◽

Serum Levels ◽

Vital Role ◽

Interleukin 4 ◽

Type 2 Inflammation

Periostin is known to be a useful biomarker for various diseases. In this article, we focus on allergic diseases and pulmonary fibrosis, for which we and others are now developing detection systems for periostin as a biomarker. Biomarker-based precision medicine in the management of type 2 inflammation and fibrotic diseases since heterogeneity is of utmost importance. Periostin expression is induced by type 2 cytokines (interleukin-4/-13) or transforming growth factor-β, and plays a vital role in the pathogenesis of allergic inflammation or interstitial lung disease, respectively, andits serum levels are correlated disease severity, prognosis and responsiveness to the treatment. We first summarise the importance of type 2 biomarker and then describe the pathological role of periostin in the development and progression of type 2 allergic inflammation and pulmonary fibrosis. In addition, then, we summarise the recent development of assay methods for periostin detection, and analyse the diseases in which periostin concentration is elevated in serum and local biological fluids and its usefulness as a biomarker. Furthermore, we describe recent findings of periostin as a biomarker in the use of biologics or anti-fibrotic therapy. Finally, we describe the factors that influence the change in periostin concentration under the healthy conditions.

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Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD

Journal of Clinical Medicine ◽

10.3390/jcm10112285 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2285

Author(s):

John N. Shumar ◽

Abhimanyu Chandel ◽

Christopher S. King

Keyword(s):

Interstitial Lung Disease ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

Lung Diseases ◽

Interstitial Lung Diseases ◽

Treatment Pathway ◽

Antifibrotic Therapy ◽

New Treatment ◽

Fibrotic Lung Diseases

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.

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Prognostic role of neoplastic markers in Takotsubo syndrome

Scientific Reports ◽

10.1038/s41598-021-95990-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Francesco Santoro ◽

Tecla Zimotti ◽

Adriana Mallardi ◽

Alessandra Leopizzi ◽

Enrica Vitale ◽

...

Keyword(s):

Serum Levels ◽

Takotsubo Syndrome ◽

Ca 15.3 ◽

Risk Of Death ◽

Increased Risk ◽

Ca 19.9 ◽

Long Term Follow Up

AbstractTakotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9–14.8, HR = 7.8 95% CI 2.4–25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6–52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.

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Serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Procalcitonin Can Reflect Sepsis Severity and Predict Prognosis: A Prospective Cohort Study

Mediators of Inflammation ◽

10.1155/2014/641039 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Zhenyu Li ◽

Hongxia Wang ◽

Jian Liu ◽

Bing Chen ◽

Guangping Li

Keyword(s):

Sofa Score ◽

Prognostic Significance ◽

Elevated Serum ◽

Myeloid Cells ◽

Serum Levels ◽

Clinical Severity ◽

Apache Ii ◽

Apache Ii Score ◽

Survival Group ◽

Severity Scores

Objective. To investigate the prognostic significance of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), N-terminal probrain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cytokines, and clinical severity scores in patients with sepsis.Methods. A total of 102 patients with sepsis were divided into survival group (n=60) and nonsurvival group (n=42) based on 28-day mortality. Serum levels of biomarkers and cytokines were measured on days 1, 3, and 5 after admission to an ICU, meanwhile the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated.Results. Serum sTREM-1, PCT, and IL-6 levels of patients in the nonsurvival group were significantly higher than those in the survival group on day 1 (P<0.01). The area under a ROC curve for the prediction of 28 day mortality was 0.792 for PCT, 0.856 for sTREM-1, 0.953 for SOFA score, and 0.923 for APACHE II score. Multivariate logistic analysis showed that serum baseline sTREM-1 PCT levels and SOFA score were the independent predictors of 28-day mortality. Serum PCT, sTREM-1, and IL-6 levels showed a decrease trend over time in the survival group (P<0.05). Serum NT-pro-BNP levels showed the predictive utility from days 3 and 5 (P<0.05).Conclusion. In summary, elevated serum sTREM-1 and PCT levels provide superior prognostic accuracy to other biomarkers. Combination of serum sTREM-1 and PCT levels and SOFA score can offer the best powerful prognostic utility for sepsis mortality.

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CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats

Experimental Biology and Medicine ◽

10.1177/15353702211047183 ◽

2021 ◽

pp. 153537022110471

Author(s):

Junxia Zhang ◽

Xue Lin ◽

Jinxiu Xu ◽

Feng Tang ◽

Lupin Tan

Keyword(s):

Oxidative Stress ◽

Uric Acid ◽

Inflammatory Responses ◽

Umbilical Vein ◽

Specific Inhibitor ◽

Endothelial Damage ◽

Endothelial Injury ◽

Sprague Dawley ◽

Protein Levels ◽

And Oxidative Stress

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.

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The prognostic impact of combined pulmonary fibrosis and emphysema in patients with clinical stage IA non-small cell lung cancer

Surgery Today ◽

10.1007/s00595-017-1577-8 ◽

2017 ◽

Vol 48 (2) ◽

pp. 229-235 ◽

Cited By ~ 1

Author(s):

Tomoyoshi Takenaka ◽

Kiyomi Furuya ◽

Koji Yamazaki ◽

Naoko Miura ◽

Kana Tsutsui ◽

...

Keyword(s):

Lung Cancer ◽

Pulmonary Fibrosis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Clinical Stage ◽

Small Cell ◽

Prognostic Impact ◽

Small Cell Lung ◽

Clinical Stage Ia ◽

Stage Ia

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Evaluation of Osteoporosis in Hemophilic Arthropathy Patients: Correlation with Disease Severity and Serum Trace Minerals

Journal of Osteoporosis ◽

10.4061/2011/106380 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Eiman Mahmoud Ghaniema ◽

Sahar Fathi Ahmed ◽

Irene Raouf Amin ◽

Maryse Soliman Ayoub

Keyword(s):

Functional Assessment ◽

Serum Magnesium ◽

Serum Levels ◽

Clinical Severity ◽

Z Score ◽

Neck Of Femur ◽

Assessment Score ◽

Hemophilic Arthropathy ◽

Copper And Zinc ◽

Z Scores

Objective. To find out the presence of osteoporosis in hemophilic arthropathy patients and its correlation with clinical severity and serum levels of magnesium, copper, and zinc.Methods. Joint score, functional assessment score, bone densitometry, and serum magnesium, copper and zinc were done in twenty male hemophilic arthropathy patients and twenty controls.Results. There was highly significant lower Z scores of lumbar spine and neck of femur in patients versus controls (P<0.011). Z score of neck of femur correlated negatively with total joint score (P=0.013) and functional assessment score (P=0.011). Serum levels of copper and zinc correlated positively with Z score of neck of femur (P=0.004,P=0.001, resp.).Conclusion. Osteoporosis represents a frequent concomitant observation in hemophiliacs. Screening of young hemophiliacs for osteoporosis is recommended with measuring serum levels of magnesium, copper, and zinc for better management of the disease.

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