Soluble Adhesion Research Articles

Systemic and central nervous system neuroinflammatory signatures of neuropsychiatric symptoms and related cognitive decline in older people

BackgroundNeuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer’s disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical disease progression.MethodsWe quantified a panel of 38 neuroinflammation and vascular injury markers in paired serum and cerebrospinal fluid (CSF) samples in a cohort of cognitively normal and impaired older subjects. We performed neuropsychiatric and cognitive evaluations and measured CSF biomarkers of AD pathology. Multivariate analysis determined serum and CSF neuroinflammatory alterations associated with NPS, considering cognitive status, AD pathology, and cognitive decline at follow-up visits.ResultsNPS were associated with distinct inflammatory profiles in serum, involving eotaxin-3, interleukin (IL)-6 and C-reactive protein (CRP); and in CSF, including soluble intracellular cell adhesion molecule-1 (sICAM-1), IL-8, 10-kDa interferon-γ-induced protein, and CRP. AD pathology interacted with CSF sICAM-1 in association with NPS. Presenting NPS was associated with subsequent cognitive decline which was mediated by CSF sICAM-1.ConclusionsDistinct systemic and CNS inflammatory processes are involved in the pathophysiology of NPS in older people. Neuroinflammation may explain the link between NPS and more rapid clinical disease progression.

Changes of Cell Adhesion Molecules and T Cell Subset Populations in Acute Myeloid Leukemia Patients Undergoing Intravenous Administration of Cytarabine Supplemented with Idarubicin

Objective. The present study aimed at investigating the efficacy and safety of intravenous administration of cytarabine supplemented with idarubicin in treating acute myeloid leukemia (AML) patients undergoing first attack and its effects on serum levels of cell adhesion molecules, cytokines in response to inflammation, and T cell subset populations in acute myeloid leukemia (AML) patients undergoing first attack. Methods. A total of 88 AML patients eligible for inclusion and exclusion criteria participated in the study and were randomly assigned into the control group (n = 44) in which the patients received intravenous administration of cytarabine and daunorubicin and the study group (n = 44) in which the patients received intravenous administration of cytarabine and idarubicin. Clinical response, incidence of adverse reactions, and quality of life 3 months after therapy were evaluated. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), IL-10, and IL-35 were measured by ELISA methods. Phenotypic characteristics of T cell subsets including CD4+, CD8+, CD4+IL-10 Tregs, and CD4+CD25+CD127−Foxp3+ Tregs were analyzed by flow cytometry. Results. The clinical response rate of the study group was better than that of the control group (65.91% vs. 45.45%) ( P < 0.05 ). After treatment, the study group revealed significantly lower levels of sICAM-1, sVCAM-1, IL-10, and IL-35, a lower proportion of Tregs, a higher rate of CD4+/CD8+ T cells, along with increased scores of the Karnofsky Performance Scale (KPS) compared with the control group ( P < 0.05 ). The incidence rate of adverse reactions in the study group was lower than that in the control group (34.09% vs. 61.36%) ( P < 0.05 ). Conclusion. These findings demonstrate that intravenous administration of cytarabine supplemented with idarubicin can improve the immune function and quality of life of AML patients, and this combination drug therapy is effective and safe for AML.

Abstract WP198: Hematological And Embolic Biomarkers And Clinical Outcomes In Patients With Cancer And Ischemic Stroke

Introduction: We previously showed that patients with cancer and acute ischemic stroke (AIS) have higher markers of coagulation, platelet, and endothelial activation, and more circulating microemboli than patients with AIS and no cancer. Herein, we evaluate whether these markers are associated with clinical outcomes in patients with cancer and AIS. Methods: In the MOST-Cancer prospective study, we enrolled 50 adults with active solid-tumor cancer and AIS at 2 New York hospitals from 2016-2020. We collected blood from participants 72-120 hours after stroke onset. We performed a 30-minute transcranial Doppler (TCD) microemboli detection study a median of 4 days after stroke onset. The exposure variables were hematological markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of microemboli on TCD. The primary outcome was a composite of recurrent arterial or venous thromboembolism or death. The secondary outcome was recurrent AIS. We used Cox regression to evaluate individual associations between biomarkers and subsequent outcomes. Results: Median age was 69 years (IQR, 60-76) and 24 participants (48%) were women. The most common cancers were lung (28%) and pancreatic (22%); 86% of participants had distant metastases. During a mean follow-up of 278 days (SD, 367), 43 (86%) participants had the primary outcome of recurrent thromboembolism or death, including 28 (56%) who had recurrent thromboembolism, 13 who had recurrent AIS (26%), and 30 (60%) who died. D-dimer, P-selectin, sICAM-1, sVCAM-1, and microemboli were associated with the composite outcome (Table). Similar results were seen for recurrent AIS. Conclusion: Markers of hypercoagulability and embolic disease were associated with adverse clinical outcomes in cancer-related stroke.

Rrelationship between endothelial function, thickness of "intima media" with some clinical and metabolic parameters in hypertensive patients depending on genetic predictors

Objective. Тo study the relationship between endothelial function, "intima-media" thickness (IMT) of carotid arteries, some anthropometric, clinical and metabolic parameters in patients with essential arterial hypertension (EAH) depending on the genes polymorphism NOS3 (rs2070744) and GNB3 (rs5443).Material and methods. 100 patients with EAH and 48 practically healthy subjects (control group) participated in the study. All participants underwent clinical and laboratory examinations. The correlation values of Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery (FMD BA), total nitric oxide metabolites (NO), Soluble Vascular Cell Adhesion Molecule (sVCAM-1), the transcriptional activity of NOS3 gene, and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping were performed by Real-Time PCR. Results. In EAH patients with dominant T-allele carriers of the NOS3 gene (rs2070744) and/or C-allele of the GNB3 gene (rs5443) FMD BA inversely correlates with the triglycerides level (r =-0.45; p=0.042) and carotid IMT (r=-0.88-/-0.44/; P≤0.006-0.001). In the carriers of mutation C-allele of the NOS3 gene and TT-genotype of the GNB3 gene – with sVCAM-1 (r=-0.41; p=0.009), atherogenic index (r=-0.69; p=0.013) and diastolic arterial pressure (r=-0.84; p=0.036).Conclusion. Matrix correlations of endothelial function, IMT with clinical and metabolic parameters in EAH patients showed the dependence of connections on the allelic state of the genes NOS3 (rs2070744) and GNB3 (rs5443).

Dietary Strawberries Improve Biomarkers of Antioxidant Status and Endothelial Function in Adults with Cardiometabolic Risks in a Randomized Controlled Crossover Trial.

Strawberries, a popularly consumed berry fruit, are rich in bioactive compounds with antioxidant effects. In this study, we examined the effects of two dietary achievable doses of strawberries on the antioxidant status and biomarkers of endothelial function in adults with features of metabolic syndrome and a confirmed low baseline of fruit and vegetable intake. In a 14-week randomized controlled crossover study, participants were assigned to one of three groups for four weeks separated by a one-week washout period: control powder, one serving (low dose: 13 g strawberry powder/day), or 2.5 servings (high dose: 32 g strawberry powder/day). Blood samples and health data were collected at baseline and at the end of each four-week phase of intervention. Thirty-three participants completed all three phases of the trial. Significant increases were observed in serum antioxidant capacity and superoxide dismutase activity as well as decreases in lipid peroxidation after both low and high dose strawberry phases when compared with the control phase. Significant decreases were also observed in soluble vascular cell adhesion molecule-1 and tumor necrosis factor-α with the high dose strawberry phase. These data confirm that consuming strawberries for four weeks significantly improves antioxidant status, endothelial function, and inflammation in adults with cardiometabolic risks.

Effects of Hyperbaric Oxygen Therapy on Serum Adhesion Molecules, and Serum Oxidative Stress in Patients with Acute Traumatic Brain Injury.

Background: Serum concentrations of adhesion molecules and oxidative stress is thought to participate in the pathobiology of secondary brain injury after acute traumatic brain injury (TBI). We aimed to study the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the adhesion molecules levels and antioxidant capacity. Methods: Thirty blood samples from ten patients after acute TBI were obtained after injury and before and after HBOT. Four patients received early HBOT started two weeks after injury, four patients received late HBOT started ten weeks after injury and two patients did not receive HBOT and served as control in this study. The HBOT patients received total 30 times HBOT in six weeks period. Results: Those serum biomarkers in patients with TBI had not significantly difference in glutathione (GSH), thiobarbituric acid reactive substances (TBARS), soluble intercellular cell adhesion-molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentrations on admission between early HBOT, late HBOT, and control group (p = 0.916, p = 0.98, p = 0.306, and p = 0.548, respectively). Serum GSH levels were higher at 10 weeks after injury in the early HBOT group than in the late HBOT group and control group (mean, 1.40 μmol/L, 1.16 μmol/L, and 1.05 μmol/L, respectively). Then the serum GSH level was increased at 18 weeks after injury in the late HBOT group (mean, 1.49 μmol/L). However, there was only statistically significant difference at Weeks 18 (p = 0.916, p = 0.463, and p = 0.006, at Week 2, Week 10, and Week 18, respectively). Serum TBARS levels were decreased at 10 weeks after injury in the early HBOT group than in the late HBOT group and control group (mean, 11.21 μmol/L, 17.23 μmol/L, and 17.14 μmol/L, respectively). Then the serum TBARS level was decreased at 18 weeks after injury in the late HBOT group (mean, 12.06 μmol/L). There was statistically significant difference after HBOT (p = 0.98, p = 0.007, and p = 0.018, at Week 2, Week 10, and Week 18, respectively). There was no statistically significant difference between the three groups on sICAM-1 and sVCAM-1 levels from Week 2 to Week 18. Conclusions: HBOT can improve serum oxidative stress in patients after TBI. These molecules may be added as evaluation markers in clinical practice. Perhaps in the future it may also become part of the treatment of patients after acute traumatic brain injury. Further large-scale study may be warrant.

Resistin levels and inflammatory and endothelial dysfunction markers in obese postmenopausal women with type 2 diabetes mellitus

BackgroundObesity-associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk.AimsTo explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women.MethodsSerum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women.ResultsResistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P = 0.013); conversely hsCRP were ~ 2X higher in T2DM women than in controls (P = 0.0132) without any difference according to CHD history. At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independently associated to resistin levels at stepwise regression analysis.Resistin levels were independently associated to CHD, increasing the risk by 1.15 times (0.986–1.344 95% CI), together with age, tHcy, LDL-C and hypertension.ConclusionsCirculating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.

Psoriatic disease is associated with systemic inflammation, endothelial activation,\xa0and altered haemostatic function

Psoriasis is a chronic, immune-mediated inflammatory skin disease, affecting approximately 2% of the general population, which can be accompanied by psoriatic arthritis (PsA). The condition has been associated with an increased cardiovascular burden. Hypercoagulability is a potential underlying mechanism that may contribute to the increased risk of major cardiovascular events in psoriatic individuals. Whole blood samples were collected from 20 PsA patients and 20 healthy individuals. The concentrations of inflammatory molecules (C-reactive protein, serum amyloid A, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble P-selectin) were determined by enzyme-linked immunosorbent assays. In addition, clotting efficiency was evaluated by thromboelastography. The fibrin network architecture was also assessed by scanning electron microscopy. Elevated levels of circulating inflammatory molecules were significantly associated with the presence of psoriatic disease. Furthermore, an increased tendency towards thrombus formation was significantly predictive of disease presence. Scanning electron microscopy revealed that fibrin clots were denser in psoriatic individuals, compared to healthy controls, with an increased fibrin fibre diameter associated with psoriatic disease. Our results add to the accumulating evidence of the systemic nature of psoriasis and the subsequent risk of cardiovascular comorbidities, potentially due to an acquired hypercoagulability. We suggest that haemostatic function should be monitored carefully in psoriatic patients that present with severe disease, due to the pre-eminent risk of developing thrombotic complications.

894-P: Monophasic Glucose Response Curve Is Associated with Increased C-Reactive Protein in Obese Adolescents

Three distinct glucose response curves, biphasic, monophasic and incessant increase, have been demonstrated in adults and adolescents during OGTT. Individuals with incessant increase and monophasic curves have increased risk of type 2 diabetes and decreased insulin sensitivity and secretion and thus are likely at increased risk for other cardiometabolic diseases. We, therefore, examined differences in traditional, and nontraditional cardiometabolic risk factors between obese adolescents with biphasic (n=9; age=12.6±0.9 yr, BMI=31.8±5.9 kg/m2; mean±SD) and monophasic (n=6; age=13.1±0.9; BMI=35.3±6.9) glucose response curves. Traditional risk factors were blood pressure and lipids while non-traditional risk factors included reactive hyperemia (RH), inflammatory markers [c-reactive protein (CRP), interleukin-6 (IL-6)], adiponectin, soluble intracellular adhesion molecule 1 (SICAM1), and insulin sensitivity and secretion (OGTT, Matsuda and insulinogenic indices). Systolic and diastolic blood pressure, triglycerides, HDL and LDL did not differ between groups. RH, Il-6 and Matsuda index also did not differ. Subjects with monophasic curves tended to have increased SICAM1 (260±33 vs. 184±21; mean±SE; p=0.087) and had significantly increased CRP levels (4.40±1.03 vs. 1.66±0.28 ng/ml; p=0.009) compared to subjects with biphasic curves. Adiponection (3570±450 vs. 2350±440 ng/ml; p=0.089) and insulin secretion (4.31±0.52 vs. 2.89±0.53 µU dl/mg ml; p=0.089) tended to be lower in subjects with monophasic curves. The difference in CRP remained significant when BMI was included as a covariate (p=0.02). Obese adolescents with monophasic glucose response curves to OGTT have increased inflammation compared to subjects with biphasic curves. Longitudinal studies are needed to determine whether this early phase of glucose intolerance causes increased inflammation or whether early inflammation reduces insulin secretion and causes early glucose intolerance. Disclosure R. P. Hoffman: Consultant; Self; Provention Bio, Inc., Other Relationship; Self; Medscape, Research Support; Self; Provention Bio, Inc. R. Cazeau: None. L. Rauch: None. J. A. Bauer: None. Funding National Center for Research Resources (UL1RR05755)

Angiogenesis-related factors associated with nivolumab efficacy in patients with advanced gastric cancer after refractory or intolerant to ramucirumab-based therapy.

234 Background: Nivolumab (Nivo) is a standard therapy after ramucirumab (RAM)-based second-line chemotherapy in patients (pts) with advanced gastric cancer (AGC). However, the relationship between angiogenesis-related factors and the efficacies of immune-checkpoint inhibitors after anti-angiogenic chemotherapy is unclear. Methods: We retrospectively evaluated pts with AGCs who received Nivo after RAM-based second-line chemotherapy at a single institution from Nov 2017 to Aug 2019. Clinical benefit of Nivo was defined as CR, PR, or >4 months of SD and non-CR/non-PD. In addition, preserved serum samples at time points of pre-RAM, pre-Nivo, and post-Nivo (within 12 weeks from the start of Nivo) were analyzed by using the designated panel, containing vascular endothelial growth factor-A/D (VEGF-A/D), placental growth factor (PlGF), soluble vascular endothelial growth factor receptor-1/2/3 (sVEGFR-1/2/3), Interleukin-6/8 (IL-6/8), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), angiopoietin-2, hepatocyte growth factor (HGF), interferon gamma (INF-γ), osteopontin (OPN), soluble neuropilin-1, and thrombospondin-2 (TSP-2). We investigated the association between angiogenesis-related factors and clinical outcomes with Nivo. Results: We evaluated 167 samples from 58 pts, including 10 pts (17.2%) exhibiting clinical benefit. Characteristics of pts were as follows: median age, 68; male, 74%; PS, 0/1-2, 17/83%; HER2 positive, 16%; prior gastrectomy, 40%; histology, intestinal/diffuse, 16/84%; disease status, metastatic/recurrent, 69/31%; lung metasstasis, 14%; liver metasstasis, 26%; peritoneum metastasis, 67%; lymph node metastasis, 31%. The median progression-free survival (PFS) and overall survival (OS) of Nivo were 1.7 and 6.2 months, respectively, with a median follow-up of 5.0 months. There were no correlations between pre-Nivo levels of angiogenesis-related factors and clinical benefit; however, the median post-Nivo/pre-Nivo VEGF-A ratio was significantly lower in pts with clinical benefit than in those without clinical benefit (0.44 versus 0.94, p = 0.008). By multivariate analysis using characteristics of pts and data from pre-Nivo samples, VEGF-A above the median level of 1400 pg/mL and sVCAM-1 below the median level of 1640000 pg/mL were independent prognostic factors for poor PFS (hazard ratio, 1.90, p = 0.033) and OS (hazard ratio, 2.02, p = 0.037), respectively. Conclusions: Our study suggests that rapid decline of serum VEGF-A level after Nivo and higher VEGF-A before Nivo were respectively associated with the clinical benefit of Nivo and poor survival in pts with AGC treated with Nivo after RAM-based second-line chemotherapy.

0044 Association Between Chronotype and Circulating Levels of Interleukin-6 in Colorectal Cancer Patients: Preliminary Results from the ColoCare Study

Abstract Introduction Accumulating evidence suggests that chronotype, i.e., circadian topology of an individual indicating morning or evening type, is associated with inflammation. To date, no study has examined the relationship between chronotype and inflammation in colorectal cancer patients. We investigated the associations between chronotype and inflammatory and angiogenesis biomarkers in colorectal cancer patients. Methods We used pre-surgery serum samples from n=67 newly diagnosed colorectal cancer patients (stage I-IV) recruited at the ColoCare Study site in Heidelberg, Germany. The ColoCare Study is an ongoing, international, multisite, prospective cohort study in colorectal cancer patients. Inflammatory and angiogenesis biomarkers [c-reactive protein (CRP), interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1)] were measured at the Huntsman Cancer Institute, USA using the Meso Scale Discovery platform and were log transformed. Chronotype was assessed prior to surgery with the reduced Morningness-Eveningness Questionnaire (rMEQ; scale 4–25; a higher score indicates more morning-type). Patients were dichotomized, based on the median values for rMEQ, into 2 groups: rMEQ-low (score≤16.0; n=35; indicating more evening-type) or rMEQ-high (score>16.0; n=32; indicating more morning-type). Results Using Mann-Whitney U test, we observed that rMEQ-low group (i.e., more evening-type) compared to rMEQ-high group (i.e., more morning-type) had approx. two times significantly higher levels of log transformed IL-6 (mean=2.24 vs. 1.30; U=382.0; Z=-2.23; p=0.03), but not for other inflammatory or angiogenesis biomarkers. This association between chronotype and IL-6 was maintained even after adjusting for age, sex, tumor stage, tumor site, and sleep duration using a generalized estimating equations model (adjusted mean difference=1.10; 95% confidence interval=0.33, 1.88; p=0.01; effect size, Cohen’s d=0.69). Conclusion These preliminary findings suggest that the evening chronotype is associated with increased IL-6 inflammatory biomarker in colorectal cancer patients. Further research is needed to confirm and understand the mechanistic underpinnings of the observed results. Support Funding: NCI U01 CA206110, R01 CA189184, and R01 CA207371.

Prognostic Value of Soluble Vascular Cell Adhesion Molecule-1 (SVCAM-1) in Children with Sepsis

Prognostic Value of Soluble Vascular Cell Adhesion Molecule-1 (SVCAM-1) in Children with Sepsis

Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) improves diagnostic accuracy of D-Dimer in patients with suspected deep vein thrombosis (DVT)

D-Dimer has a high sensitivity but a low specificity for the diagnosis of deep vein thrombosis (DVT) which limits its implementation as a general screening parameter. There is a demand for additional biomarkers to improve its diagnostic accuracy. Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) is generated at the site of venous thrombosis, thus, represents a promising biomarker. Patients with clinically suspected DVT (N = 159) were prospectively recruited and underwent manual compression ultrasonography (CCUS) to confirm or exclude DVT. The diagnostic value of D-Dimer, sPECAM-1 and the combination of both was assessed. sPECAM-1 levels were significantly higher in patients with DVT (N = 44) compared to patients without DVT (N = 115) (85.9 [76.1/98.0] ng/mL versus 68.0 [50.1/86.0] ng/mL; p < 0.001) with a diagnostic sensitivity of 100% and a specificity of 28.7% at the cut point > 50.2 ng/mL. sPECAM-1 improved the diagnostic accuracy of D-Dimer: the combination of both biomarkers yielded a ROC-AUC of 0.925 compared to 0.905 for D-Dimer alone and 0.721 for sPECAM-1 alone with a reduction of false-positive D-Dimer cases 72- > 43 (Δ = − 31.9%). The discrimination mainly occurred in a subgroup of patients characterized by an inflammatory background (defined by c-reactive protein level > 1 mg/mL). sPECAM-1 represents a novel diagnostic biomarker for venous thrombosis. It does not qualify as a diagnostic biomarker alone but improves the diagnostic accuracy of D-Dimer in patients with suspected DVT.

Abstract C47: Plasma ANP and soluble cell adhesion molecule X are novel risk factors for pancreatic cancer-associated thrombosis

Abstract Cancer-associated thrombosis/thromboembolism (CAT) is a serious clinical complication and leads to occasional cause of death in patients with cancers, including pancreatic ductal adenocarcinoma (PDAC). However, diagnostic and inhibitory approach for CAT is still unestablished. We found that CAT with cardiomegaly and increase of plasma atrial natriuretic peptide (ANP) were frequently observed in the PDAC mice containing conditional KrasG12D mutation and knockout of TGF-β receptor type II (Tgfbr2) (PKF mice). Similar to usual thrombotic patients without cancer, high plasma level of cytokines including soluble cell adhesion molecule X was detected in the mice. Molecule-X was immunohistochemically observed in activated endothelium and thrombi. Injection of neutralized anti-molecule-X antibody reduced onset of CAT and cardiac weight in the PKF mice. Meanwhile, high plasma levels of ANP and/or molecule-X were detected in PDAC patients before and after diagnosis of CAT. Taken together, increase of ANP and/or molecule-X is a new risk factor of CAT in PDAC patients. Blocking molecule-X, at least in part, would be an inhibitory approach for CAT in PDAC. Citation Format: Makoto Sano, Hideaki Ijichi, Kazunaga Ishigaki, Ryota Takahashi, Koji Miyabayashi, Keisuke Tateishi, Hiroyuki Isayama, Kazuhiko Koike. Plasma ANP and soluble cell adhesion molecule X are novel risk factors for pancreatic cancer-associated thrombosis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C47.

Effect of Shuxuening combined with edaravone on neurological function, serum VEGF and serum sVCAM-1 in patients with cerebral infarction

Objective To investigate the effects of Shuxuening injection combined with edaravone on neurological function, serum vascular endothelial growth factor (VEGF) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with cerebral infarction. Methods A total of 112 patients with cerebral infarction admitted to Zhejiang Provincial Armed Police Hospital from August 2016 to August 2018 were enrolled in the study.They were divided into observation group and control group according to the digital table, with 56 patients in each group.The two groups were given routine symptomatic treatment.On the basis of this, the control group was given edaravone treatment, and the observation group was given Shuxuening injection combined with edaravone.The changes of NIHSS, GCS score, serum NSE, NGF, NTF, VEGF and sVCAM-1 levels before and after treatment were compared between the two groups, and the clinical efficacy was compared. Results After treatment, the effective rate of the observation group was 92.86%(52/56), which was higher than that of the control group 73.21%(41/56), the difference was statistically significant (χ2=7.669, P<0.05). After treatment, the NIHSS score, NSE, sVCAM-1 of the two groups were decreased, which of the observation group were lower than those of the control group[(3.27±1.16)points vs.(6.32±2.12)points, (13.15±1.14)μg/L vs.(17.64±1.89)μg/L, (648.56±134.67)ng/mL vs.(1 078.36±131.23)ng/mL], while the GCS score, NGF, NTF, VEGF levels of the two groups were elevated, which of the observation group were higher than those of the control group[(13.64±3.86)points vs.(11.89±3.41)points, (76.13±8.72)μg/L vs.(68.24±7.25)μg/L, (5.14±0.36)μg/L vs.(3.74±0.29)μg/L, (831.51±91.67)ng/L vs.(752.83±91.24)ng/L], the differences were statistically significant (t=9.414, 2.543, 15.223, 5.205, 22.663, 4.552, 15.672, all P<0.05). Conclusion Shuxuening injection combined with edaravone can improve the curative effect of patients with cerebral infarction, improve neurological function, effectively improve serum VEGF level and decrease sVCAM-1 level.It is worthy of clinical application. Key words: Infarction, middle cerebral artery; Central nervous system; Vascular endothelial growth factors; Shuxuening; Edaravone

P872Activity of nonspecific systemic inflammation and biochemical markers of endothelial dysfunction as the criteria of coronary heart disease destabilization

Abstract Introduction Nonspecific systemic inflammation (NSSI) as well as endothelial dysfunction (EDF) plays an important role in the development and progression of coronary heart disease (CHD). Its exacerbation can cause the atherosclerotic plaque damage and the CHD progression with development of atherothrombotic complications. Purpose To evaluate the activity of nonspecific systemic inflammation and biochemical markers of endothelial dysfunction and their diagnostic significance in CHD patients as the criteria of disease destabilization. Methods The study included 173 CHD patients (the average age was 57.24±5.12 years). 92 patients were with stable angina (45 with 2nd and 47 with 3rd functional classes) and 81 patients were with acute coronary syndromes (ACS) (43 with unstable (progressive) angina and 38 – with acute myocardial infarction). The study excluded patients with severe chronic heart failure, liver and kidney dysfunction, acute or chronic inflammatory diseases, diabetes mellitus, severe obesity, infectious diseases. The control group included 30 healthy subjects (average age was 55.37±4.82 years). Activity of NSSI was assessed by the concentration of high sensitive C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and pregnancy-associated plasma protein A (PAPP-A) as a marker of endogenic destruction, which were determined by ELISA. EDF was assessed by the concentration of endothelin-1 (ET-1) and soluble vascular cell adhesion molecules (sVCAM) using ELISA method. Results CHD patients were characterized by significant increasing of hsCRP, TNF-α, PAPP-A levels regarding to control group (5.29±0.19 and 0.87±0.04 mg/L for hsCRP, respectively, p&lt;0.001; 4.28±0.18 and 1.18±0.07 ng/mL for TNF-α, respectively, p&lt;0.001; 9.81±0.16 and 3.12±0.42 mIU/L for PAPP-A, respectively, p&lt;0.01), which was the evidence of NSSI activation. Levels of both ET-1 and sVCAM-1 in CHD patients were more than twice higher than in the control group (9.89±0.28 and 4.01±0.36 ng/mL for ET-1, respectively p&lt;0.001; 1442.9±25.3 and 626.0±34.1 ng/mL for sVCAM, respectively, p&lt;0.001). Levels of biochemical markers of both NSSI and EDF increased with an increase in disease severity (p&lt;0.01) and the most severe changes were in patients with ACS, especially in patients with acute myocardial infarction. Significant relationships were between levels of both ET-1 and sVCAM with both hsCRP and TNF-α. Significant relationships were between PAPP-A level with both hsCRP and TNF-α, but were absent with both ET-1 and sVCAM levels. Therefore, we believe that the endogenic destruction of plaque is more related with activation of NSSI than with progression of EDF. Conclusion The severity of the CHD is associated with the degree of both activation of nonspecific systemic inflammation and dysfunction of vascular endothelium. Elevated production of these markers can be considered as the indicator of both atherosclerotic plaque damage and the possibility of ACS development.

Relationship of mottling score, skin microcirculatory perfusion indices and biomarkers of endothelial dysfunction in patients with septic shock: an observational study

BackgroundIn patients with septic shock, the skin is often chosen for the evaluation of peripheral perfusion and oxygenation. Changes in skin microcirculatory vessel oxygen saturation and relative hemoglobin concentration can be described using a mottling score or captured with hyperspectral imaging. However, the effectiveness of the mottling score in assessing microcirculation remains to be shown. We hypothesize that the mottling score in patients with septic shock is related to skin microcirculatory perfusion indices quantified by hyperspectral imaging, biomarkers that reflect endothelium activation and damage, and clinical outcome.MethodsHyperspectral imaging of the knee area was performed in 95 intensive care patients with septic shock enrolled in a single-center observational study to obtain relative oxy/deoxyhemoglobin concentration values and construct anatomical maps of skin microcirculatory saturation. The blood was sampled to obtain concentrations of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-2, and syndecan-1. The spectrophotometrically obtained skin microvascular perfusion indices were compared to the mottling score and biomarker concentration. The association between mottling score, skin microcirculatory perfusion indices, and 28-day mortality was also analyzed.ResultsMicrocirculatory oxygen saturation was significantly lower and total hemoglobin concentration was significantly higher in patients with a mottling score of 2 compared to those with a score of 0 (p = 0.02), with no difference between other scores. We found an association between microcirculatory oxygen saturation and PAI-1 levels (rho = − 0.3; p = 0.007). Increased mottling score and decreased microcirculatory oxygen saturation were predictive of 28-day mortality (mottling score 2 vs 0: OR 15.31, 95% CI 4.12–68.11; microcirculatory oxygen saturation: OR 0.90, 95% CI 0.85–0.95). Endothelial biomarkers did not increase the predictive value of skin microcirculatory perfusion indices.ConclusionsHigher mottling scores are associated with lower microcirculatory oxygen saturation but with significant overlap between scores. Microcirculatory oxygen saturation is a quantitative measure of peripheral oxygenation and is more specific than the mottling score in predicting 28-day mortality.

Health effects of exposure to diesel exhaust in diesel-powered trains

BackgroundShort-term controlled exposure to diesel exhaust (DE) in chamber studies have shown mixed results on lung and systemic effects. There is a paucity of studies on well-characterized real-life DE exposure in humans. In the present study, 29 healthy volunteers were exposed to DE while sitting as passengers in diesel-powered trains. Exposure in electric trains was used as control scenario. Each train scenario consisted of three consecutive days (6 h/day) ending with biomarker samplings.ResultsCombustion-derived air pollutants were considerably higher in the passenger carriages of diesel trains compared with electric trains. The concentrations of black carbon and ultrafine particles were 8.5 μg/m3 and 1.2–1.8 × 105 particles/cm3 higher, respectively, in diesel as compared to electric trains. Net increases of NOx and NO2 concentrations were 317 μg/m3 and 36 μg/m3. Exposure to DE was associated with reduced lung function and increased levels of DNA strand breaks in peripheral blood mononuclear cells (PBMCs), whereas there were unaltered levels of oxidatively damaged DNA, soluble cell adhesion molecules, acute phase proteins in blood and urinary excretion of metabolites of polycyclic aromatic hydrocarbons. Also the microvascular function was unaltered. An increase in the low frequency of heart rate variability measures was observed, whereas time-domain measures were unaltered.ConclusionExposure to DE inside diesel-powered trains for 3 days was associated with reduced lung function and systemic effects in terms of altered heart rate variability and increased levels of DNA strand breaks in PBMCs compared with electric trains.Trial registrationClinicalTrials.Gov (NCT03104387). Registered on March 23rd 2017

P066 Validation of assay for detection of free soluble mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in human serum and cerebrospinal fluid

P066 Validation of assay for detection of free soluble mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in human serum and cerebrospinal fluid

Diagnostic and Prognostic Significance of Soluble Cell Adhesion Molecules in Typical Hemolytic Uremic Syndrome

Diagnostic and Prognostic Significance of Soluble Cell Adhesion Molecules in Typical Hemolytic Uremic Syndrome