Serum Inflammatory Biomarkers Research Articles

Biomarker Value in the Diagnosis of Community-Acquired Pneumonia with Concomitant Chronic Heart Failure.

The diagnosis of community-acquired pneumonia (CAP) with chronic heart failure (CHF) is associated with objective difficulties. Our case–control study aims to establish whether established serum inflammatory biomarkers are relevant to the diagnosis of CAP in patients with CHF. Seventy inpatients with previously diagnosed CHF and suspected non-severe CAP were recruited and then stratified into two subgroups with confirmed and rejected diagnosis of CAP. C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and brain natriuretic peptide (BNP) were measured. The value of biomarkers was determined using logistic regression, and their discriminatory efficacy was assessed by analyzing receiver operating characteristic (ROC) curves. Significantly higher levels of CRP 50.0 (35.5–98.5) mg/L, PCT 0.10 (0.05–0.54) ng/mL and IL-6 46.1(21.4–150.3) pg/mL in cases were identified as compared to the control group—15.0 (9.5–25.0) mg/L, 0.05 (0.05–0.05) ng/mL and 13.6 (9.5; 25.0) pg/mL, respectively. The Area Under the ROC Curve (95% CI) was the highest for CRP—0.91 (0.83–0.98), followed by PCT—0.81 (0.72–0.90) and IL-6—0.81 (0.71–0.91). A CRP value of >28.5 mg/L had an optimal sensitivity and specificity ratio (85.7/91.4%). In conclusion, the measurement of serum CRP, PCT and IL-6 levels can be useful for the diagnosis of CAP in patients with CHF. CRP showed optimal diagnostic utility in this population.

Changes in serum biomarkers of inflammation in bovine besnoitiosis

BackgroundAcute and chronic besnoitiosis in extensive natural-service herds can have relevant effects in the health of bulls and negative consequences in their productive performance. Recent progress has been made in order to elucidate the pathogenesis of this disease. In this context, the study of biomarkers of inflammation in serum would contribute to gaining knowledge about the physiopathology of bovine besnoitiosis. Serological biomarkers could help in early diagnosis and prognosis, as seropositive bulls may have mild or severe testicular lesions.MethodsHerein, we have investigated the diagnostic and/or prognostic value of a panel of serum (serological) biomarkers related to inflammation, including total protein, globulin and albumin, haptoglobin (Hp), adenosine deaminase (ADA) paraoxonase-1 (PON-1) and acetylcholinesterase (AChE) in naturally and experimentally B. besnoiti-infected males classified according to different clinical phases of the disease (acute, chronic and subclinical besnoitiosis).ResultsResults showed a similar response pattern in these biomarkers for naturally and experimentally infected cattle, with a few relevant variations. Most significant changes occurred during the acute phase of infection, although significant changes in a few biomarkers were also observed during the chronic infection. Haptoglobin, albumin, PON-1 and ADA were identified as the biomarkers that showed changes of higher magnitude in the acute phase of the infection, whereas high total protein and globulin values were found in chronically infected cattle. We have described the changes of a panel of inflammatory biomarkers of acute and chronic bovine besnoitiosis.ConclusionsIn summary, several biomarkers with promising diagnostic value have been identified. The biomarkers associated with acute infection are related to previously reported molecular biomarkers in testicular parenchyma of infected bulls and could help in the diagnosis of early infections and complement results from specific immunoglobulin M (IgM) detection.Graphical abstract

P13.22 Menglia: an innovative approach to liquid biopsies in glioma patients

Abstract BACKGROUND Gliomas are the second most frequent primary brain tumor. Since 2016 gliomas are classified according to histological, and molecular features such as IDH status and 1p19q codeletion. Recently oncological research has focused on liquid biopsies to reduce the need for invasive diagnostic tests. Cerebrospinal fluid (CSF) is the principal source of brain tumor biomarkers. Modern technologies currently allow us to analyze proteomic and metabolomic tumor profiles, in order to find new biomarkers without being constrained by a priori hypothesis. Several data from the literature also suggests that inflammatory cells and cytokines in tumors contribute to tumor growth, progression and immunosuppression. The possibility of simultaneously testing different inflammatory molecules on the biological fluids could lead to the identification of new biological markers with prognostic and predictive value for treatment response. STUDY OBJECTIVES - Identification of protein and/or lipid biomarkers specific to the glioma subgroup among those under analysis. - Identification of tumor group- and subgroup-specific CSF and/or serum inflammatory biomarkers among those tested. - Correlation of biomarkers with Progression Free Survival (PFS), Overall Survival (OS). ELIGIBILITY CRITERIA - Patients with a radiological suspected diagnosis of glioma eligible for surgery. - Age ≥ 18 years. - Availability of histological samples, CSF, blood and urine. - Patients with unconfirmed histological diagnosis of glioma will be excluded. - Patients who have never received any systemic or local treatment for CNS diseases. STUDY DESIGN This is a prospective monocentric study involving mass spectrometry analysis for characterization of proteins and metabolites and ELISA analysis for the characterization of different cytokines in parallel anonymized biological samples consisting of tumor tissue, CSF, blood and urine from glioma patients, divided into three different molecular subtypes: 1p19q codelet/IDH mutated, 1p19q non-codelet/IDH mutated and 1p19q non-codelet/IDH wt. Biological samples will be taken at surgery, at 24–48 h after surgery and every 3 months up to 1 year. The control group will include patients with subarachnoid hemorrhage or hydrocephalus, either undergoing external ventricular shunting or undergoing ventricular catheter placement/revision surgery. STUDY ANALYSIS Data interpretation will be based on a statistical analysis of the data, applying tools such as Principal Component Analysis (PCA) Weighted Correlation Network Analysis (WGNCA), Multiple Venn Diagram, T-Test, ANOVA, Clustering and Gene Ontology Enrichment, non-parametric Mann-Whitney test. For the assessment of clinical outcome, survival curves will be compared between different groups of patients who share a similar protein/metabolomic/inflammatory profile.

Inflammatory biomarkers in very preterm infants during early intravenous paracetamol administration

BackgroundParacetamol promotes early closure of patent ductus arteriosus (PDA), and it may affect inflammation after preterm birth. ObjectiveThe aim of this study was to evaluate the association between paracetamol treatment and serum inflammatory biomarkers in very preterm infants with respiratory distress. Study designThe infants were randomly assigned to intravenous paracetamol or placebo during the first 4 days of life, and others received a lower dose of paracetamol unblinded. Serum samples were used for the analysis of 10 cytokines, C-reactive protein (CRP) and malondialdehyde (MDA). The impact of paracetamol on the biomarkers was evaluated, based on the levels during the early (<60 h) and the later (60–120 h) postnatal age. ResultsAltogether, 296 serum samples from 31 paracetamol and 25 placebo group infants were analysed. Paracetamol had no effect on cytokine levels during the first 60 h when most induced PDA contractions took place. Later paracetamol treatment was associated with lower serum levels of several cytokines, including interleukin (IL-) 10, interferon gamma-induced protein (IP-) 10, and monocyte chemoattractant protein-1. CRP levels were lower in the paracetamol group during the early treatment. Amongst the infants who had severe morbidities, MDA was higher (p = .045), regardless of paracetamol treatment. ConclusionNo significant differences in the cytokine levels were evident between the treatment and placebo groups. However, during early treatment, CRP levels were lower in the paracetamol group. To clarify whether this was due to a decrease in cardiopulmonary distress, or a distinct anti-inflammatory effect, requires further studies.

Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections

Accurate preoperative diagnosis of periprosthetic joint infections (PJIs) can be very challenging, especially in patients with chronic PJI caused by low-virulence microorganisms. Serum parameters, such as serum C-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR), are—among other diagnostic test methods—widely used to distinguish septic from aseptic failure after total hip or knee arthroplasty and are recommended by the AAOS in the preoperative setting. However, they are systemic parameters, and therefore, unspecific. Nevertheless, they may be the first and occasionally the only preoperative indication, especially when clinical symptoms are lacking. They are easy to obtain, cheap, and are available worldwide. In the last decade, different novel serum biomarkers (percentage of neutrophils, neutrophils to lymphocytes ratio, platelet count to mean platelet volume ratio, fibrinogen, D-Dimer, Il-6, PCT) were investigated to find a more specific and accurate serum parameter in the diagnosis of PJI. This article reviews the diagnostic value of established (serum CRP, ESR, WBC) and ‘novel’ serum inflammatory biomarkers (fibrinogen, D-dimer, interleukin-6 (IL-6), procalcitonin, percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), platelet count to mean platelet volume ratio (PC/mPV)) for the preoperative diagnosis of periprosthetic joint infections.

Poly- and perfluoroalkyl substances (PFASs) and lipidomics and inflammatory proteomics in the human EuroMix study

BACKGROUND AND AIM: Exposure to PFASs has been associated with high cholesterol levels, lower vaccination response and higher childhood infections, in epidemiological studies. The mechanistic pathways involved are often unknown. Biomarkers of effect can provide insight in the biological implications of PFAS exposure. We explored the association between serum PFAS concentrations, lipoprotein particle subclasses and inflammatory biomarkers. METHODS: In 127 adult participants of the EuroMix human biomonitoring study (mean age: 40 years, 70% women) we determined the concentrations and lipid content of the major lipoproteins in two plasma samples by nuclear magnetic resonance and the serum concentrations of five perfluoroalkyl sulfonates (PFSAs) and six perfluoroalkyl carboxylates (PFCAs), and analysed their association by linear mixed-effect regression models. Further, we used an OLINK high-throughput proteomic assay to analyze plasma inflammatory proteins and explored the association with PFAS by linear regression analysis. RESULTS:Most PFCAs, and PFOS were positively associated with HDL and LDL cholesterol concentrations and negatively associated with VLDL cholesterol and triglyceride concentrations in all lipoproteins. One interquartile range (IQR) increase in PFNA, PFDoDA and PFOS was associated with 11%-12% higher HDL cholesterol, independent of HDL particle size. One IQR increase in PFTrDA, PFHpS and PFOS was associated with 9%-14% higher cholesterol concentrations in the small-size LDL. Long-chain PFCAs were negatively associated with the cholesterol and triglyceride concentrations in the large- and mid-sized VLDL subfractions. We found mostly negative associations between PFAS and inflammatory biomarkers. One IQR increase in PFOS, PFNA, PFDA, PFUnDA and PFDoDA was associated with 2-3% lower anti-inflammatory factors, HGF and IL-10RB. CONCLUSIONS:In this exploratory study, we aimed to identify serum lipoprotein and inflammatory biomarkers as markers of exposure to PFAS. We observed that PFAS exposure may influence the distribution and lipid composition of major lipoprotein subclasses, as well as modulation of inflammatory responses. KEYWORDS: Proteomics, PFAS, Cardiovascular diseases, Toxicology

Omega-7 Mixed Fatty Acid Supplementation Fails to Reduce Serum Inflammatory Biomarkers: A Placebo-Controlled, Double-Blind Randomized Crossover Trial

We report the effects of mixed omega-7 fatty acid supplementation on changes in serum hsCRP, TNFα, and IL-6 levels and self-reported outcomes in people with non-specific chronic musculoskeletal discomfort. Design: A double-blind, placebo-controlled, 1:1 randomized single crossover trial composed of 688 mg/day palmiteolate for the verum and an equivalent amount of medium-chain triglycerides for the placebo. Method: Data were analyzed in two independent groups and as a crossover group. Results: From 211 screened participants in 2017–2019, 56 were randomized. Six participants dropped out and fifty completers contributed to the statistical analyses. At baseline, none of the investigated biomarkers were significantly correlated to subjectively assessed musculoskeletal discomfort levels. For the two-group analysis (n = 26 and n = 24), none of the serum biomarkers reached statistical significance; however, a statistically significant placebo effect was found in the subjective outcomes. Conclusion: For the crossover analysis (n = 50), three weeks of supplementation with n7FA containing 688 mg per day of palmiteolate did not reduce serum inflammatory biomarkers nor did it improve subjectively measured quality of life (QoL) compared to placebo. Future studies should explore appropriate biomarkers, sufficient power, length of dosing, inclusion criteria for volunteers with higher BMI, and the verification of cis-palmiteolate versus trans-palmiteolate.

Evaluation of Anti-inflammatory Activity after Treatment with the Biofield Energy Treated Proprietary Test Formulation on Combination of Cecal Slurry, LPS and E. Coli Induced Systemic Inflammatory Response Syndrome (SIRS) in Sprague Dawley Rats

The aim of this study was to evaluate the anti-inflammatory response of the Biofield Energy Treated Proprietary Test Formulation and Biofield Energy Treatment per se to the animals on Cecal Slurry, LPS and E. coli-induced systemic inflammatory response syndrome (SIRS) model in Sprague Dawley rats using serum inflammatory biomarkers. In this experiment, various inflammatory biomarkers such as monokine induced by gamma interferon (MIG), regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein-2 (MIP-2), matrix metallopeptidase 9 (MMP-9), troponin-1, procalcitonin, fibrinogen degradation product (FDP) were analysed using ELISA assay. A test formulation was formulated including minerals (magnesium, zinc, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, vitamin E, cyanocobalamin, and cholecalciferol), Panax ginseng extract, β-carotene, and cannabidiol isolate. The constituents of the test formulation were divided into two parts; one section was defined as the untreated test formulation, while the other portion of the test formulation and three group of animals received Biofield Energy Healing Treatment remotely for about 3 minutes by a renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The results showed that the level of MIG was significantly (p≤0.01) reduced by 48.57%, 56.14%, 47.95%, 51.92%, and 47.83% in the G5 (Cecal Slurry, LPS and E. coli along with the Biofield Energy Treated test formulation); G6 (Cecal Slurry, LPS and E. coli along with Biofield Energy Treatment per se to animals from day -15); G7 (Cecal Slurry, LPS and E. coli along with the Biofield Energy Treated test formulation from day -15); G8 (Cecal Slurry, LPS and E. coli along with Biofield Energy Treatment per se plus the Biofield Energy Treated test formulation from day -15), and G9 (Cecal Slurry, LPS and E. coli along with Biofield Energy Treatment per se animals plus the untreated test formulation) groups, respectively as compared to the disease control (G2) group. Additionally, the level of regulated on activation, normal T cell expressed and secreted (RANTES) was significantly (p≤0.001) decreased by 47.35%, 46.32%, 40.73%, 50.47%, and 39.96% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. The level of macrophage inflammatory protein-2 (MIP-2) was significantly (p≤0.001) decreased by 91.74%, 93.54%, 92.70%, 94.46%, and 93.80% in the G5, G6, G7, G8, and G9 groups, as compared to the G2 group. The level of MMP-9 was significantly (p≤0.001) decreased by 18.74%, 35.54%, 26.48%, 38.16%, and 22.52% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Moreover, the level of troponin-1 was decreased by 28.53%, 28.50%, 14.14%, 30.68%, and 36.34% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the untreated test formulation (G4) group. Additionally, the level of procalcitonin was significantly (p≤0.001) decreased by 27.27%, 51.73%, 46.40%, 54.65%, and 39.08% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Further, the level of fibrinogen degradation product (FDP) was significantly (p≤0.001) decreased by 66.7%, 62.5%, 31.5%, 51.6% and 40.1% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Overall, the data suggested anti-inflammatory potentials of the Biofield Energy Treated test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various inflammatory conditions that might be beneficial various types of systemic inflammatory disorders specially sepsis, trauma, septic shock or any types of injuries. Therefore, the results showed the significant slowdown the inflammation-related disease progression and its complications/symptoms in the preventive Biofield Energy Treatment group per se and/or Biofield Energy Treated Test formulation groups (viz. G6, G7, G8, and G9) comparatively with the disease control group.

The prognostic value of the serum inflammatory biomarkers in patients with carotid atherosclerosis

20 % of ischemic stroke appear to originate from carotid artery atherosclerotic disease. Serum biomarkers reflecting the activity of atherosclerotic process and may help for estimate risk of acute cerebrovascular events. Several serum inflammatory markers have been proposed for risk assessment, but their prognostic role less known.&#x0D; The aim of this study is to clarify the prognostic value of biomarkers of atherosclerosis lipoprotein-associated phospholipase A2 (Lp-PLA2) and E-selectin in patients with symptomatic and asymptomatic carotid stenosis.&#x0D; Materials and methods. The study involved 106 patients with atherosclerotic carotid stenosis &gt;50 % (74 men and 32 women, mean age 62.6±0.9) from which 76 symptomatic (35 with acute ipsilateral atherothrombotic stroke and 41 after carotid endarterectomy) and 30 asymptomatic patients. The control group consisted of age- and sex-matched 20 healthy subjects. The level of serum Lp-PLA2 and E-selectin was determined using a commercially available enzyme-linked immunosorbent assay kit.&#x0D; Results. The level of Lp-PLA 2 was in general significantly higher (p&lt;0.05) in patients groups than in the control group and most high Lp-PLA2 concentration was in groups of symptomatic patients who underwent carotid endarterectomy. The level of E-selectin in the study patients was significantly higher than in the control group (p&lt;0.05). The correlation of Lp-PLA 2 with E-selectin was significant for total patients (R=0.365664, p=0.00085) and group after carotid endarterectomy (R=0.429143, p=0.01796), but not for asymptomatic group (p&gt;0.05). Receiver Operating Characteristics curves of logistic regression models which takes into joint both indicators was specificity and sensitive for predicting the occurrence of ischemic stroke.&#x0D; Conclusion. Conducted study show that the levels of Lp-PLA 2 and E-selectin have a significant impact on the development of stroke in patients with atherosclerotic carotid stenosis and can be used to predict it. A multidimensional model of the dependence of the probability of stroke on a linear combination of Lp-PLA 2 and E-selectin allows to obtaining significantly higher characteristics of the accuracy of stroke prediction than models with each factor alone.

MRI contributes to accurate and early diagnosis of non-radiographic HLA-B27 negative axial spondyloarthritis

BackgroundNonradiographic axial spondyloarthropathies (nr-axSpA) are diagnosed by the absence of radiographic sacroiliitis and the presence of bone marrow edema (BME) on magnetic resonance imaging (MRI). According to the classification criteria of the international Assessment of Spondyloarthritis Society (ASAS), structural changes to sacroiliac joints (SIJs) on MRI cannot be used as criteria in the absence of BME. However, less than half the Asian patients with clinically active axSpA show BME. The incidence of human leukocyte antigen (HLA)-B27 is low in Asian populations, which makes it more difficult to identify nr-axSpA. We used MRI to evaluate the structural damage to SIJs in patients with nr-axSpA with and without BME with the aim of identifying the best methodology for accurate diagnosis, especially in populations with less common BME and HLA-B27.MethodsOne hundred three patients with inflammatory back pain were included in this prospective study. No patient’s radiograph met the definition of positive modified New York criteria. BME and structural damage to SIJ including sclerosis and erosion were assessed independently on coronal and axial short-tau inversion recovery and T1-weighted spin echo MRI scans by two well-trained musculoskeletal radiologists using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Demographics of patients were collected. Disease characteristics and structural damage were analyzed in patients with and without BME on SIJ MRI. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of structural damage.ResultsAll individuals in the cohort had at least one abnormal finding on SIJ MRI, including BME or structural damage; 36 of 103 patients had BME. We identified a significant positive correlation between SPARCC scores and severe erosion assessed by focal joint space widening (fJSW) (p = 0.001) in these 36 patients. Fifty-eight of the 103 enrolled patients fulfilled the ASAS criteria for nr-axSpA in the either absence or presence of BME. Of these 58 patients, 57 and 19 had erosions or fJSW, respectively, and the presence of BME was significantly correlated with fJSW (phi score of 0.319 and p = 0.015). We demonstrated a significant positive correlation between fJSW and either the presence or the severity of BME in patients with nr-axSpA who met the ASAS definition. There was a positive correlation between BME and fJSW across the whole study cohort (phi score of 0.389; p < 0.001). The area under the ROC curve (AUC) for fJSW on SIJ MRI was 0.736, p < 0.001. In both HLA-B27-positive and -negative groups, BME was more common in the presence of fJSW (phi scores of 0.370 and 0.377, p = 0.018 and 0.003, respectively) and SPARCC scores were higher in patients with fJSW (p < 0.001 and p = 0.005). We also identified a positive correlation between fJSW and BME in patients with nr-axSpA and normal serum levels of C-reactive protein (phi score of 0.362 and p = 0.001).ConclusionStructural damage detected on SIJ MRI, sclerosis, erosions and fJSW may be present in patients without detectable inflammation on SIJ MRI. However, fJSW is significantly correlated with the severity of inflammation seen on SIJ MRI, which contributes to the accurate diagnosis of nr-axSpA, and it could be used as an alternative diagnostic test for nr-axSpA in the general population, especially for those who do not carry the HLA-B27 gene, Asian patients without BME, or patients with normal serum inflammatory biomarkers.

Dietary Antioxidant Capacity and Serum Inflammatory Biomarkers Levels in Cancer Survivors

This study aimed to compare the dietary intake of carotenoids, tocopherols, ascorbic acid, flavonoids, and dietary total antioxidant capacity (dTAC) and to evaluate relationship of dTAC with serum inflammatory biomarkers in patients with gastrointestinal system (GIS) and non-GIS cancer. In total, 104 adult cancer survivors (52 GIS and 52 non-GIS cancer cases) were included. 24-hour dietary recalls were obtained and dTAC was calculated on the basis of oxygen radical absorption capacity (ORAC), Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), ferric reducing antioxidant potential (FRAP), and vitamin C equivalents (VCE). Serum C-reactive protein (CRP) level, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were used as inflammatory biomarkers. Routinely analyzed serum CRP, neutrophil, lymphocyte, and platelet levels every day in hospital biochemistry laboratory were obtained from patients’ file. There was no significant difference between patients with GIS and non-GIS cancer in terms of dietary intake of carotenoids, tocopherols, and flavonoids. While there was no significant difference between groups in terms of the mean dietary ORAC, TEAC, and FRAP, the mean TRAP of patients with GIS cancer was significantly higher than patients with non-GIS cancer. Serum inflammatory markers (CRP and NLR) were found to have an inverse relationship with dTAC.

Impact of iron status and inflammatory indices on atherosclerotic burden of patients with helicobacter pylori infection and coronary arterial disease

Objective: Both inflammation and iron deficiency are suggested to be associated with coronary arterial diseases (CAD) and H. Pylori infection. The explanatory interaction depending on serum iron status and inflammatory biomarkers for the extent of atherosclerosis in H. Pylori infection is obscure. Therefore, we aimed to analyze the impact of iron Status and inflammatory indices on atherosclerotic burden of seropositive CAD patients with CagA (cytotoxin-associated gene A) strains of H. Pylori.&#x0D; Materials and Methods: This was an observational study of patients' undergone elective and urgent coronary angiography due to CAD. Serologic H. pylori infection status and iron status was determined in all of 293 subjects. Further seropositive patients were divided into groups to evaluate the extent of coronary atherosclerosis according to Syntax scoring system. Propensity score matching and covariate- adjusted multivariate logistic regression were used to adjust for baseline differences between study groups.&#x0D; Results: The odds ratio of positive serology for the presence of iron deficiency and acute coronary syndromes were 2.5 (95% CI (1.1-5.4); p = 0.02) and 3.0 (95% CI (1.3-7.0); p = 0.007) respectively. After controlling for diabetes mellitus, smoking, MPV, RDW and haemoglobin levels; Tsat ≤ 24.5 remained negatively associated with advanced atherosclerosis (OR:9.9, 95% CI (4.1-24.3); p &lt; 0.0001). In our matched sample, multivariable linear regression analysis showed that association of syntax score with Tsat was independent of hs-CRP (p=0.001).&#x0D; Conclusions: Irrespective of inflammatory status, transferrin saturation can be the decisive mirror indicator of advanced atherosclerosis in seropositive CAD patients with CagA strains of H. Pylori.

Effects of a Home-Based Lifestyle Intervention Program on Cardiometabolic Health in Breast Cancer Survivors during the COVID-19 Lockdown.

This study aimed to evaluate the cardiometabolic effects of a home-based lifestyle intervention (LI) in breast cancer survivors (BCSs) during the COVID-19 lockdown. In total, 30 BCSs (women; stages 0–II; non-metastatic; aged 53.5 ± 7.6 years; non-physically active; normal left ventricular systolic function) with a risk factor for recurrence underwent a 3-month LI based on nutrition and exercise. Anthropometrics, Mediterranean diet adherence, physical activity level (PAL), cardiorespiratory fitness (VO2max), echocardiographic parameters, heart rate variability (average standard deviation of NN intervals (ASDNN/5 min) and 24 h very- (24 hVLF) and low-frequency (24 hLF)), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein (hs-CRP)) were evaluated before (T0) and after (T1) the LI. After the LI, there were improvements in: body mass index (kg/m2: T0 = 26.0 ± 5.0, T1 = 25.5 ± 4.7; p = 0.035); diet (Mediet score: T0 = 6.9 ± 2.3, T1 = 8.8 ± 2.2; p < 0.001); PAL (MET-min/week: T0 = 647 ± 547, T1 = 1043 ± 564; p < 0.001); VO2max (mL·min−1·kg−1: T0 = 30.5 ± 5.8, T1 = 33.4 ± 6.8; p < 0.001); signs of diastolic dysfunction (participants: T0 = 15, T1 = 10; p = 0.007); AS-DNN/5 min (ms: T0 = 50.6 ± 14.4, T1 = 55.3 ± 16.7; p = 0.032); 24 hLF (ms2: T0 = 589 ± 391, T1 = 732 ± 542; p = 0.014); glycemia (mg/dL: T0 = 100.8 ± 11.4, T1 = 91.7 ± 11.0; p < 0.001); insulin resistance (HOMA-IR score: T0 = 2.07 ± 1.54, T1 = 1.53 ± 1.11; p = 0.005); testosterone (ng/mL: T0 = 0.34 ± 0.27, T1 = 0.24 ± 0.20; p = 0.003); hs-CRP (mg/L: T0 = 2.18 ± 2.14, T1 = 1.75 ± 1.74; p = 0.027). The other parameters did not change. Despite the home-confinement, LI based on exercise and nutrition improved cardiometabolic health in BCSs.

Interactions via α2β1 Cell Integrin May Protect against the Progression of Airway Structural Changes in Asthma.

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.

233-OR: Circulating Inflammatory Biomarkers Are Not Improved with Combined Low-Volume High-Intensity Interval Training and Progressive Resistance Training in Prediabetes

In prediabetes (PD), circulating inflammatory biomarkers are associated with increased CVD1 risk. Exercise (Ex) has a positive effect on cardiovascular fitness and metabolic outcomes in PD but Ex effects on inflammation markers in PD are not fully known and were investigated in this study. Adults with PD (n=34) and normal fasting glucose (NG) (n=34) were randomised into one of four groups: NG control (NGC, n=16), NG Ex (NGE, n=18), PD control (PC, n=16) and PD Ex (PE, n=18). NGE/PE completed 12 weeks of supervised HIIT and progressive resistance training (PRT) 2 times/week, and NGC/PC unsupervised stretching 3 times/week. Baseline, age and weight were similar in PD and NG. Compared with NG, FPG and HbA1c were higher and VO2peak was significantly lower in PD (29±7 vs. 33±8 mL/kg/min, p=0.03). Comparing NG and PD at baseline, serum IL-1β was higher in NG (11.4±9.0 vs. 7.9±2.8 pg/mL, p=0.04), IL-12p70 and IL-22 were higher in PD (respectively, 5.7±3.6 vs. 4.4±2.2 pg/mL; 164.6±90.3 vs. 122.2±83.2 pg/mL, both p&amp;lt;0.05) and IL-1α, IL-6, IL-8, IL-15, M-CSF and TNFα were similar. At follow-up, HbA1c was reduced by -0.07±0.11% in NGE and -0.09±0.17% in PC (both p&amp;lt;0.05) and not changed in PE or NGC. PE had an increase in VO2peak (5.5±7.5mL/kg/min, p=0.01). Inflammatory biomarkers were unchanged in PE but NGE had reduced IL-12p70 (4.3±1.9 to 3.5±0.8 pg/mL, p=0.05) and M-CSF (124.5±58.2 to 93.8±36.2 pg/mL, p=0.02). Analysis of Ex with &amp;gt;80% adherence revealed that IL-1α, IL-1β, IL-8 and IL-15 were reduced in NGE, however no change was seen in PE despite a reduction in HbA1c of -0.14±0.17% (p=0.02). PD is associated with reduced cardiorespiratory fitness and increased IL-12p70 and IL-22. Ex reduced IL-12p70 and M-CSF in those with NG but not PD, even after stratifying by adherence and despite improvements in clinical markers. This study indicates low volume HIIT with PRT may not be adequate to reduce serum inflammatory biomarkers in prediabetes. Disclosure C. J. Baker: None. D. Min: None. J. Gerofi: None. X. Wang: None. S. L. Hocking: Advisory Panel; Self; Eli Lilly and Company, Inova, Novo Nordisk, Pfizer Inc. S. Colagiuri: None. N. A. Johnson: None. S. M. Twigg: Advisory Panel; Self; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis, Consultant; Self; Aktivo Labs, Sanofi-Aventis, Research Support; Self; Abbott Diabetes, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca. Funding National Health and Medical Research Council (APP1113612)

P196 Colon-involving versus non-colon-involving Crohn’s disease classification: is the Montreal classification outdated?

Abstract Background An appropriate disease classification is essential for the management of Crohn’s disease (CD) patients. Recently, a new classification of colon-involving versus non-colon-involving disease extension was considered to be more predictive of adverse outcomes than the Montreal classification (MRC). We aimed to investigate the association of a colon-based classification with clinically relevant outcomes in patients with CD compared with the MRC. Methods Retrospective cohort-study which consecutively included adult CD patients with at least 1 year of follow-up. Patients were categorized into colon-involving and non-colon-involving disease and according to the MRC. Patients’ demographic, clinical, biochemical, and imaging data were recorded and compared between the two classifications. The primary outcome was the need for treatment with steroids or biologics, hospitalization and major abdominal surgery. Results Of 327 patients, 52.3% were female with a mean age of 43.3±13.1 years. The most common disease location according to MRC was L1 (48.9%), followed by L3 (41.3%) and L2 (9.8%). Overall, 51.1% of patients had colon-involving disease. Although patients with colon-involvement at diagnosis had higher frequency of perianal lesions (27.5% vs 16.9%, P&amp;lt;0.05) and serum inflammatory biomarkers (lower hemoglobin, and higher leucocyte and platelet counts, c-reactive protein and erythrocyte sedimentation rate), this classification was not predictive of relevant outcomes. Considering the two types of colon-involving disease (L2, L3), patients with L2 disease had higher extraintestinal manifestations (43.8% vs 20.7%, respectively, P&amp;lt;0.05), higher B1 disease behavior (87.5% vs 58.5%, respectively, P&amp;lt;0.05) and lower B2 disease behavior (6.25% vs 22.2%, respectively, P&amp;lt;0.05). Disease location according to MRC was predictive of the need for treatment with biologics, hospitalization and major abdominal surgery in univariate analysis, but not in multivariate analysis. Conclusion Although simpler, defining Crohn’s disease extension by colon-involving versus non-colon-involving is not more predictive of adverse outcomes than the Montreal classification. Therefore, the use of Montreal Classification should still be considered essential in the adequate management of IBD patients.

Abstract 032: Uninterrupted Sitting Induces Unfavorable Changes In Resting Hemodynamics And Inflammatory And Vascular Biomarkers In Physically Inactive And Active Adults

Introduction: A single bout of uninterrupted sitting impairs vascular function in the legs, which may be due to reductions in blood flow and shear stress. Participating in regular moderate-to-vigorous physical activity (MVPA) has been identified as an effective approach for improving vascular function, and recent evidence suggests meeting the physical activity (PA) guidelines may attenuate some of the negative health outcomes associated with excessive sedentary behavior; however, it is not well understood how meeting the PA guidelines may influence the acute response to sitting. Our aim was to investigate the effects of 3 h of uninterrupted sitting on hemodynamics and vascular and inflammatory biomarkers in physically inactive and active adults. Hypothesis: We hypothesized active adults would experience less detrimental physiological changes after sitting compared to inactive adults. Methods: Eleven inactive (mean±SD, age: 47.1±8.9 y, body fat: 33.1±8.5%; 78.5% women) and 16 active adults (age: 46.1±8.9 y, body fat: 25.2±7.2%; 31.1% women) completed 3 h of uninterrupted sitting. Adults self-reported their PA with the International PA Questionnaire. Adults engaging in ≥150 min·wk -1 were classified as active and &lt;150 min·wk -1 , inactive. Hemodynamic variables, and superficial femoral artery (SFA) diameter and blood velocity were measured each hour over 3 h of sitting. Mean arterial pressure, blood flow and shear rate were calculated. Serum vascular and inflammatory biomarkers were measured pre and post sitting. Linear mixed-effects modeling was used to assess changes in dependent variables over time and between inactive and active adults, controlling for sex. Results: Inactive and active adults self-reported 7.3±7.1 and 93.3±64.8 min·d -1 of MVPA, respectively. Endothelin-1 (baseline: 8.3±13.4 pg/mL, post: 81.1±103.0 pg/mL; p&lt;0.001) and interleukin-6 (baseline: 0.08±0.06 pg/mL, post: 0.11±0.11 pg/mL; p=0.03) increased post sitting compared to baseline in all adults, regardless of PA status. Systolic blood pressure, mean arterial pressure, calf circumference, and SFA diameter, blood velocity, and mean blood flow decreased over time in both groups (p&lt;0.05 for all). There was an interaction effect for mean shear rate (p=0.008); inactive adults experienced a decline over 3 h of sitting (baseline: 76.1±48.2 s -1 ; 1 h: 55.0±27.4 s -1 ; 2 h: 45.3±24.2 s -1 ; 3 h: 40.8±25.5 s -1 ) while active participants demonstrated no change (baseline: 36.6±21.4 s -1 ; 1 h: 28.1±21.4 s -1 ; 2 h: 26.1±20.9 s -1 ; 3 h: 23.8±19.5 s -1 ). Inactive adults also had a higher oscillatory shear index compared to active adults (p&lt;0.001). Conclusion: Uninterrupted sitting induced unfavorable changes regardless of PA status; however, active adults demonstrated a more favorable shear profile. Meeting PA guidelines may attenuate some unfavorable changes within the vasculature associated with prolonged sitting.

Inflammatory Biomarkers Correlate with Time Evolution in Cerebral Venous Thrombosis

ObjectivesWe aimed to analyse the relationship between specific inflammatory biomarkers’ levels and the temporal pattern of cerebral venous thrombosis (CVT) symptoms. Materials and methodsWe performed a retrospective study of adult CVT patients admitted between Jan 01 2006 and Dec 31 2019. We excluded patients with infection at admission, autoimmune, inflammatory or haematological disorders.We evaluated serum inflammatory biomarkers at admission: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), absolute neutrophil count, absolute lymphocyte count, platelet count, monocyte count, neutrophile-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), bilirubin and monocyte-to-HDL ratio (M-HDLR). These were evaluated according to the time from symptom onset (acute, subacute or chronic). ResultsWe included 78 patients with CVT (mean age 41 ± 13 years). Neutrophil count (p = 0.017), monocyte (p = 0.024), CRP (p = 0.004), NLR (p<0.001) and LMR (p = 0.004) showed significant variation with CVT duration. Acute onset CVT exhibited higher absolute neutrophil count and NLR but lower LMR. The subacute group had higher monocyte values, and the chronic phase patients displayed higher LMR, but lower CRP. ESR, PLR and M-HDLR showed a tendency to decrease in the chronic phase. We did not observe any statistical difference between the duration of symptoms and levels of bilirubin. ConclusionsCVT patients present a differential inflammatory pattern along the time course of the disease: higher NLR and lower LMR in acute phase, and higher LMR and lower CRP level during the chronic phase. These differences may help to ascertain the onset of poorly defined symptoms and provide input regarding anticoagulation management.

Early Warning of Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation Using Heart Rate Variability and Serum Biomarkers

Early warning of infection is critical to reduce the risk of deterioration and mortality, especially in neutropenic patients following hematopoietic stem cell transplantation (HCT). Given that heart rate variability (HRV) is a sensitive and early marker for infection, and that serum inflammatory biomarkers can have high specificity for infection, we hypothesized their combination may be useful for accurate early warning of infection. In this study, we developed and evaluated a composite predictive model using continuous HRV with daily serum biomarker measurements to provide risk stratification of future deterioration in HCT recipients. A total of 116 ambulatory outpatients about to undergo HCT consented to collection of prospective demographic, clinical (daily vital signs), HRV (continuous electrocardiography [ECG] monitoring, laboratory [daily serum samples frozen at -80 °C]), and infection outcome variables (defined as the time of escalation of antibiotics), all from 24 hours pre-HCT to the onset of infection or 14 days post-HCT. Indications for antibiotic escalation were adjudicated as "true infection" or not by 2 blinded HCT clinicians. A composite time series of 8 HRV metrics was created for each patient, and the probability of deterioration within the next 72 hours was estimated using logistic regression modeling of composite HRV and serum biomarkers using a rule-based naïve Bayes model if the HRV-based probability exceeded a median threshold. Thirty-five patients (30%) withdrew within <24 hours owing to intolerability of ECG monitoring, leaving 81 patients, of whom 48 (59%) had antibiotic escalation adjudicated as true infection. The combined HRV and biomarker (TNF-α, IL-6, and IL-7) predictive model began increasing at ~48 hours on average before the diagnosis of infection, could distinguish between high risk of impending infection (>90% incidence of subsequent infection within 72 hours), average risk (~50%), and low risk (<10%), with an area under the receiver operating characteristic curve of 0.87. However, given that prophylactic predictive ECG monitoring and daily serum collection proved challenging for many patients, further refinement in measurement is necessary for further study.

Preeclamptic Programming Unevenly Modifies Hemodynamic and Renovascular Outcomes of Endotoxemia in Rat Offspring: Modulation by Sex and Antenatal Therapies

Preeclampsia (PE) enhances the vulnerability of adult offspring to serious illnesses. The current study investigated whether preeclamptic fetal programming impacts hemodynamic and renovascular responsiveness to endotoxemia in adult male and female offspring and whether antenatal reprogramming therapy with pioglitazone and/or losartan favorably modulates these interactions. PE was induced by oral administration of L-NAME (50 mg/kg/day) to pregnant dams for seven days starting from gestational day 14. Adult offspring of either sex was treated with lipopolysaccharides (LPS, 5 mg/kg) followed 4 hr later by hemodynamic and renovascular studies. Tail-cuff measurements showed that while LPS produced no hemodynamic changes in female offspring, it significantly decreased blood pressure and increased heart rate in age-matched male counterparts. In isolated perfused kidneys of male offspring, PE or LPS reduced renal vasodilations elicited by acetylcholine (0.01-7.29 nmol) or N-ethylcarboxamidoadenosine (NECA, 1.6-100 nmol), effects that disappeared in PE/LPS kidney preparations. Likewise, elevations caused by LPS in serum inflammatory cytokines (TNFα and IL-1β) and renal biomarkers (BUN and creatinine) were attenuated in PE/LPS males. Contrary to males, NECA, but not acetylcholine, vasodilation was facilitated by LPS in female preparations, an effect that was comprised in PE/LPS kidneys. Gestational administration of pioglitazone or losartan reversed the attenuated acetylcholine/NECA vasodilations but failed to modify LPS hypotension or inflammation. Gestational treatment with combined pioglitazone/losartan therapy improved acetylcholine renal vasodilations and partly attenuated the inflammatory response. Our data suggest that preeclamptic fetal programming of endotoxic manifestations in adult offspring depends on animal sex and targeted biological activity and are partly improved by pharmacologic antenatal reprogramming with pioglitazone or losartan.