scholarly journals When Cultures Fail: Postmortem Decoy Receptor 3 (DcR3) as a Marker of Antemortem Sepsis

2019 ◽  
Vol 9 (1-2) ◽  
pp. 15-23
Author(s):  
Katrina Thompson ◽  
Joseph Connor

Introduction: Decoy receptor 3 (DcR3) has shown utility as a reliable surrogate marker. Levels of DcR3 in the serum increase and remain elevated in several disease states including cancer and sepsis. In inflammatory conditions, DcR3 is upregulated in inflammatory cells to suppress exponential immune propagation. The use of DcR3 as an indication of sepsis has been documented in the antemortem setting, but its use in the postmortem setting is unknown. The purpose of this study is to evaluate postmortem DcR3 as a marker of antemortem sepsis. Methods: A retrospective investigation was performed to identify patients whose primary cause of death fell into one of four cohorts (control, cancer, culture-positive sepsis, and suspected culture-negative sepsis). Serum was obtained and tested by a commercially available enzyme-linked immunosorbent assay to quantify DcR3 levels. Results: Twenty-five of 47 samples contained detectable levels of DcR3 (average 0.75 ± 0.3 ng/mL). Comparing culture-positive sepsis to the control cohort at a cutoff value of 0.26 ng/mL, DcR3 positivity showed a sensitivity of 64% and a specificity of 73%. Compared to each other, patients with cancer had similar values to those with culture-positive sepsis (P = .90). Time of specimen collection had a negative role in detection and quantification (P = .038). Discussion: Several studies have shown DcR3 may be a viable antemortem biomarker of sepsis, but its use in postmortem sepsis testing has not been adequately investigated. This study shows that in postmortem testing, DcR3 shows less sensitivity and specificity with a relatively short window for proper testing.

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Su Lin ◽  
Bing Wu ◽  
Yehong Lin ◽  
Mingfang Wang ◽  
Yueyong Zhu ◽  
...  

Aims. To explore the expression level and clinical significance of decoy receptor 3 (DcR3) in patients with acute-on-chronic liver failure (ACLF).Methods. Serum DcR3 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 76 patients with ACLF and 41 non-ACLF patients with chronic liver disease. Blood routine and liver functions were accessed for their correlations with DcR3.Results. Serum DcR3 in ACLF patients was significantly higher than that in non-ACLF patients. It was positively correlated with neutrophilic granulocyte, aspartate aminotransferase, prothrombin time, and international standardized ratio, but negatively correlated with platelet and serum albumin. At the early stage, the level of DcR3 was not significantly different between the survival and nonsurvival group of ACLF. However, at the late stage, DcR3 increased in nonsurvival and gradually decreased in survivals. The baseline DcR3 could not sufficiently predict the outcome of ACLF, while the change of DcR3 within the first week displayed a better predictive value than model for end-stage liver disease (MELD) score.Conclusions. DcR3 was highly expressed in patients with ACLF and correlated with several clinical indices. Dynamic change of DcR3 might predict the prognosis of ACLF.


2020 ◽  
Vol 29 (3) ◽  
pp. 153-162
Author(s):  
Maha H Hassan ◽  
Manal M Yassin ◽  
Yahia M Hassan ◽  
Nagwa M Abo El Magd

Background: Sepsis is a leading cause of morbidity and mortality that has a global burden. Early recognition of sepsis and differentiating it from similar conditions is crucial. Objective: In the present study we aimed to measure the serum level of decoy receptor 3 (DcR3) in sepsis patients to study its role as a promising biomarker for bacterial sepsis. Methodology: The present study included 30 patients, divided into a sepsis group (n=15) and a systemic inflammatory response syndrome (SIRS) group (n=15), and 15 healthy controls. Sepsis patients were identified by positive blood culture or positive 16S ribosomal DNA (rDNA) polymerase chain reaction (PCR) results. SIRS patients were identified by negative blood culture or negative 16S rDNA PCR results. Serum DcR3 level was measured by quantitative enzyme-linked immunosorbent assay (ELISA). Receiver-operating characteristic (ROC) curve analysis was performed for DcR3 and C-reactive protein (CRP) alone and in combination. Results: The serum DcR3 level was significantly higher in sepsis than SIRS patients and healthy controls (5.21 ± 2.28 ng/mL, 1.96 ± 0.90 ng/mL, and 0.95 ± 0.79 ng/mL, respectively). The ROC area under the curve (AUC) of DcR3 for sepsis versus SIRS was 0.920 at a cut-off >2.4 ng/mL, with 93.33% sensitivity and 86.67% specificity. The AUC of combined positive DcR3 and positive CRP for sepsis versus SIRS was 0.967 with 93.33% sensitivity and 100% specificity. Conclusion: DcR3, alone or in combination with CRP, is a promising biomarker for distinguishing sepsis from SIRS patients and may efficiently guide physicians to identifying sepsis patients, for whom the further usage of new diagnostics can be cost-effective.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 784
Author(s):  
Sandra Minic ◽  
Marion Florimond ◽  
Jérémy Sadoine ◽  
Anne Valot-Salengro ◽  
Catherine Chaussain ◽  
...  

Dental pulp is a dynamic tissue able to heal after injury under moderate inflammatory conditions. Our study aimed to evaluate pulp repair under inflammatory conditions in rats. For this purpose, we developed a rat model of controlled pulpitis followed by pulpotomy with a tricalcium silicate-based cement. Fifty-four cavities were prepared on the occlusal face of the maxillary upper first molar of 27 eight-week-old male rats. E. coli lipopolysaccharides at 10 mg/mL or phosphate-buffered saline PBS was injected after pulp injury. Non-inflamed molars were used as controls. Levels of inflammation-related molecules were measured 6 and 24 h after induction by enzyme-linked immunosorbent assay of coronal pulp samples. Pulp capping and coronal obturation after pulpotomy were performed with tricalcium silicate-based cement. Four and fifteen days after pulpotomy, histological and immunohistochemical analysis was performed to assess pulp inflammation and repair processes. Our results showed significantly higher levels of innate inflammatory proteins (IL-1β, IL-6, TNF-α and CXCL-1) compared with those in controls. Moderate residual inflammation near the capping material was demonstrated by histology and immunohistochemistry, with the presence of few CD68-positive cells. We showed that, in this model of controlled pulpitis, pulpotomy with BiodentineTM allowed the synthesis at the injury site of a mineralized bridge formed from mineralized tissue secreted by cells displaying odontoblastic characteristics. Analysis of these data suggests overall that, with the limitations inherent to findings in animal models, pulpotomy with a silicate-based cement is a good treatment for controlling inflammation and enhancing repair in cases of controlled pulpitis.


2006 ◽  
Vol 282 (4) ◽  
pp. 2346-2354 ◽  
Author(s):  
Chih-Hsin Tang ◽  
Tsui-Ling Hsu ◽  
Wan-Wan Lin ◽  
Ming-Zong Lai ◽  
Rong-Sen Yang ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 460
Author(s):  
Saray Varona ◽  
Lídia Puertas ◽  
María Galán ◽  
Mar Orriols ◽  
Laia Cañes ◽  
...  

Abdominal aortic aneurysm (AAA) is a common life-threatening condition characterized by exacerbated inflammation and the generation of reactive oxygen species. Pharmacological treatments to slow AAA progression or to prevent its rupture remain a challenge. Targeting phosphodiesterase 4 (PDE4) has been verified as an effective therapeutic strategy for an array of inflammatory conditions; however, no studies have assessed yet PDE4 in AAA. Here, we used angiotensin II (AngII)-infused apolipoprotein E deficient mice to study the involvement of the PDE4 subfamily in aneurysmal disease. PDE4B but not PDE4D was upregulated in inflammatory cells from both experimental and human AAA. The administration of the PDE4 selective inhibitor rolipram (3 mg/kg/day) to AngII-challenged mice (1000 ng/kg bodyweight/min) protected against AAA formation, limiting the progressive increase in the aortic diameter without affecting the blood pressure. The drug strongly attenuated the rise in vascular oxidative stress (superoxide anion) induced by AngII, and decreased the expression of inflammatory markers, as well as the recruitment of macrophages (MAC3+), lymphocytes (CD3+), and neutrophils (ELANE+) into the vessel wall. Rolipram also normalized the vascular MMP2 expression and MMP activity, preserving the elastin integrity and improving the vascular remodelling. These results point to PDE4B as a new therapeutic target for AAA.


2018 ◽  
Vol 10 ◽  
pp. 117957351880358 ◽  
Author(s):  
Ashish Kumar Gupta ◽  
Komal Rani ◽  
Surabhi Swarnkar ◽  
Gaurav Khunger Kumar ◽  
Mohd Imran Khan ◽  
...  

Aim of the Study: Parkinson’s disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson’s disease and schizophrenia for optimum therapy. Methods: Naïve and treated, Parkinson’s disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson’s disease and schizophrenia. Results: Apolipoprotein E levels are higher in Parkinson’s disease patients as compared with schizophrenic samples ( P < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson’s disease and schizophrenia in the right perspective. Conclusion: Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson’s disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.


mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Sanjana R. Sen ◽  
Emily C. Sanders ◽  
Kristin N. Gabriel ◽  
Brian M. Miller ◽  
Hariny M. Isoda ◽  
...  

ABSTRACT Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention. IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.


2012 ◽  
Vol 13 (1) ◽  
pp. 28 ◽  
Author(s):  
Donghai Yang ◽  
Xin Fan ◽  
Ping Yin ◽  
Qiang Wen ◽  
Feng Yan ◽  
...  

2019 ◽  
Vol 33 (4) ◽  
pp. 395-402 ◽  
Author(s):  
Giuseppe Brescia ◽  
Franco Schiavon ◽  
Lorenzo Nicolè ◽  
Elisabetta Zanoletti ◽  
Claudia Zanotti ◽  
...  

Background An example of aggressive eosinophilic polyposis can be found in eosinophilic granulomatosis with polyangiitis (EGPA). Intercellular adhesion molecule-1 (iCAM-1) and vascular cell adhesion molecule-1 (vCAM-1) play a part in mediating the recruitment and adhesion of leukocytes to the vessel wall, and their blood-to-tissue migration under inflammatory conditions. Objective This prospective study compared 3 groups—patients with a definite diagnosis EGPA, non-EGPA patients with phenotypic features suggestive of EGPA, and patients with non-eosinophilic nasal polyposis (controls)—in terms of nasal tissue histology, iCAM-1 and vCAM-1 expression, and blood inflammatory cells. Methods A total of 58 adults underwent sinus surgery (13 patients with EGPA, 23 suspected of having EGPA, and 22 controls). Results Mean tissue eosinophil counts were significantly higher in EGPA patients and suspected cases of EGPA than in controls. Although iCAM-1 and vCAM-1 were diffusely expressed in sinonasal tissues, they did not differently stain EGPA, eosinophilic-type and non-eosinophilic polyposis. Blood basophil and eosinophil levels were high in both the EGPA and the suspected EGPA groups. Intergroup differences were found for eosinophils but not for basophils. Conclusions We do not have yet blood or tissue markers able to differentiate the early phase of EGPA from chronic rhinosinusitis with nasal polyps. Further investigations are mandatory considering EGPA patients at their initial diagnosis and before any treatment, in terms of nasal histology and blood inflammatory cells, to identify markers characterizing sinonasal mucosa inflammation and useful for an early diagnosis of EGPA.


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