Association Of Systemic Inflammation Research Articles

Perioperative Levels of IL8 and IL18, but not IL6, are Associated with Nucleus Basalis Magnocellularis Atrophy Three Months after Surgery

Past studies have observed that brain atrophy may accelerate after surgical procedures. Furthermore, an association of systemic inflammation with neurodegeneration has been described. We hypothesize that postoperative interleukin (IL) levels in circulation as well as the perioperative change in interleukin levels are associated with increased postoperative atrophy in the Nucleus basalis magnocellularis (of Meynert, NBM) which is the major source of cortical acetylcholine. We analyzed data from the BioCog cohort which included patients ≥ 65 years presenting for elective major surgery (≥ 60min). Blood samples were taken before surgery and on the first postoperative day. Magnetic resonance imaging of the brain and neuropsychological assessments were conducted before surgery and after three months follow-up. We used linear regression analysis to determine the association of three interleukins (IL6, IL8 and IL18) with NBM atrophy (in % volume change from baseline before surgery to follow-up), as well as to examine the associations of NBM atrophy and volume with postoperative cognitive ability and perioperative cognitive change. Receiver-operating curves were used to determine the prognostic value of preoperative interleukin levels. For IL8 (N = 97) and IL18 (N = 217), but not IL6 (N = 240), we observed significant associations of higher postoperative IL levels at the first postoperative day with higher NBM atrophy at three months after surgery. Subsequent analyses suggested that in both IL8 and IL18, this association was driven by a more general association of chronically elevated IL levels and NBM atrophy, reflected by preoperative IL concentrations, rather than IL response to surgery, measured as the difference between pre- and postoperative IL concentrations. At follow-up, NBM volume was positively associated with the level of cognitive performance, but NBM atrophy was not significantly related to perioperative cognitive change. Prognostic value of preoperative IL concentrations for NBM atrophy was low. Our results suggest that an association of postoperative interleukin levels with NBM atrophy is driven by preoperatively elevated interleukins due to pre-existing inflammation, rather than perioperative change in interleukin levels in response to surgery and anesthesia. The BioCog study has been registered at clinicaltrials.gov on Oct 15, 2014 (NCT02265263).Graphical

Association of systemic inflammation with the obesity paradox in cancer: results from multi-cohort studies.

This study aimed to explore whether the obesity paradox exists in overall and specific cancers and to investigate the role of systemic inflammation in the obesity paradox. The Cox proportional hazard model was used to explore the relationship between body mass index (BMI) and all-cause mortality. The mediated effect was used to investigate the proportion of systemic inflammation mediating the relationship between BMI and cancer survival risk. The survival probability showed a step-like increase with an increase in BMI regardless of pathological stage. Approximately 10.8%-24.0% of the overall association between BMI and all-cause mortality in cancer was mediated by inflammation. In the internal validation, we found evidence of the obesity paradox in all body composition obtained using BIA, with inflammation remaining an important mediating factor. Furthermore, we also validated the existence of the obesity paradox of cancer in NHANES. Systemic inflammation remains an important factor in mediating the association between BMI and prognosis in cancer patients. The obesity paradox is prevalent in most cancers, except for hepatic biliary cancer and breast cancer. Inflammation may be one of the true features of the obesity paradox in cancer.

Association of systemic inflammation with shock severity, 30-day mortality, and therapy response in patients with cardiogenic shock

BackgroundMortality in cardiogenic shock (CS) remains high even when mechanical circulatory support (MCS) restores adequate circulation. To detect a potential contribution of systemic inflammation to shock severity, this study determined associations between C-reactive protein (CRP) concentrations and outcomes in patients with CS.MethodsUnselected, consecutive patients with CS and CRP measurements treated at a single large cardiovascular center between 2009 and 2019 were analyzed. Adjusted regression models were fitted to evaluate the association of CRP with shock severity, 30-day in-hospital mortality and treatment response to MCS.ResultsThe analysis included 1116 patients [median age: 70 (IQR 58–79) years, 795 (71.3%) male, lactate 4.6 (IQR 2.2–9.5) mmol/l, CRP 17 (IQR 5–71) mg/l]. The cause of CS was acute myocardial infarction in 530 (48%) patients, 648 (58%) patients presented with cardiac arrest. Plasma CRP concentrations were equally distributed across shock severities (SCAI stage B–E). Higher CRP concentrations were associated with 30-day in-hospital mortality (8% relative risk increase per 50 mg/l increase in CRP, range 3–13%; p < 0.001), even after adjustment for CS severity and other potential confounders. Higher CRP concentrations were only associated with higher mortality in patients not treated with MCS [hazard ratio (HR) for CRP > median 1.50; 95%-CI 1.21–1.86; p < 0.001], but not in those treated with MCS (HR for CRP > median 0.92; 95%-CI 0.67–1.26; p = 0.59; p-interaction = 0.01).ConclusionElevated CRP concentrations are associated with increased 30-day in-hospital mortality in unselected patients with cardiogenic shock. The use of mechanical circulatory support attenuates this association.Graphical abstract

Association of systemic inflammation with posttraumatic stress disorder after a myocardial infarction

BackgroundAdverse mental health conditions including depression, posttraumatic stress disorder (PTSD), and anxiety are prevalent among patients who survive myocardial infarctions (MI) and are associated with adverse outcomes. The mechanisms underlying these associations, however, are not well understood. Inflammatory pathways may mediate the cardiovascular outcomes of patients with mental health disorders. We examined the bidirectional association between PTSD symptoms and inflammatory biomarkers in a young/middle-aged post MI population. We further examined how this association may differ between women and men as well as between Black and non-Black individuals. MethodsParticipants included individuals with early onset MI between the ages 25 and 60. Mental health scores for depression, PTSD, perceived stress, and anxiety as well as inflammatory biomarkers, interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), were collected at baseline and at six-month follow up. We examined the bidirectional changes in mental health symptoms and inflammatory biomarkers between baseline and follow-up. ResultsAmong 244 patients in the study (mean age: 50.8, 48.4% female, 64.3% Black), the geometric means for IL-6 level and hsCRP at rest were 1.7 pg/mL and 2.76 mg/L, respectively. Mental health scores at baseline did not consistently predict changes in inflammatory biomarkers at follow-up. However, baseline levels of both IL-6 and hsCRP were robustly associated with an increase in re-experiencing PTSD symptoms at 6 months: in adjusted linear mixed models, there was a 1.58-point increase in re-experiencing PTSD symptoms per unit of baseline hsCRP (p = 0.01) and 2.59-point increase per unit of baseline IL-6 (p = 0.02). Once the analysis was stratified by race, the association was only noted in Black individuals. Baseline inflammation was not associated with change in any of the other mental health symptom scores. ConclusionMarkers of inflammation are associated with an increase in post-event PTSD symptoms in younger or middle-aged patients who experienced an MI, especially Black patients. These results suggest a mechanistic link between inflammation and the development of PTSD among individuals with cardiovascular disease.

The association of systemic inflammation and cognitive functions of pre-school aged children residing in a Schistosoma haematobium endemic area in Zimbabwe.

Cognitive function is negatively impacted by schistosomiasis and might be caused by systemic inflammation which has been hypothesized to be one of the mechanisms driving cognitive decline, This study explored the association of systemic inflammatory biomarkers; interleukin (IL)-10, IL-6, IL-17, transforming growth factor (TGF-β), tumor necrosis factor (TNF-α), C-reactive protein (CRP) and hematological parameters with cognitive performance of preschool-aged children (PSAC) from an Schistosoma haematobium endemic area. The Griffith III tool was used to measure the cognitive performance of 136 PSAC. Whole blood and sera were collected and used to quantify levels of IL-10, TNF-α, IL-6, TGF-β, IL-17 A and CRP using the enzyme-linked immunosorbent assay and hematological parameters using the hematology analyzer. Spearman correlation analysis was used to determine the relationship between each inflammatory biomarker and cognitive performance. Multivariate logistic regression analysis was used to determine whether systemic inflammation due to S. haematobium infection affected cognitive performance in PSAC. Higher levels of TNF-α and IL-6, were correlated with lower performance in the Foundations of Learning domain (r = -0.30; p < 0.001 and r = -0.26; p < 0.001), respectively. Low cognitive performance in the Eye-Hand-Coordination Domain was observed in PSAC with high levels of the following inflammatory biomarkers that showed negative correlations to performance; TNF-α (r = -0.26; p < 0.001), IL-6 (r = -0.29; p < 0.001), IL-10 (r = -0.18; p < 0.04), WBC (r = -0.29; p < 0.001), neutrophils (r = -0.21; p = 0.01) and lymphocytes (r = -0.25; p = 0.003) The General Development Domain correlated with TNF-α (r = -0.28; p < 0.001) and IL-6 (r = -0.30; p < 0.001). TGF-β, L-17A and MXD had no significant correlations to performance in any of the cognitive domains. The overall general development of PSAC was negatively impacted by S. haematobium infections (OR = 7.6; p = 0.008) and (OR = 5.6; p = 0.03) where the PSAC had higher levels of TNF-α and IL-6 respectively. Systemic inflammation and S. haematobium infections are negatively associated with cognitive function. We recommend the inclusion of PSAC into mass drug treatment programs.

Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer

Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). We included 1767 older adults with cancer (66.2% males, 70.97±5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p<0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p<0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

Correlation between hematological parameters and PET/CT metabolic parameters in patients with head and neck cancer

BackgroundSystemic inflammation is predictive of the overall survival in cancer patients and is related to the density of immune cells in the tumor microenvironment of cancer, which in turn correlates with 18F -fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) metabolic parameters (MPs). The density of tumor-infiltrating lymphocytes (TILs) in the microenvironment has the potential to be a biomarker that can be used clinically to optimize patient selection in oropharyngeal head and neck squamous cell carcinoma (HNSCC). There is little to no data regarding the association of systemic inflammation with PET/CT-MPs, especially in HNSCC. This study aimed to evaluate the correlation between markers of host inflammation, namely blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), with the PET/CT-MPs standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor, derived from FDG-PET/CT in patients with nonmetastatic (cM0) HNSCC before treatment. We hypothesized that NLR and PLR at baseline are positively correlated with PET/CT-MPs.MethodsA retrospective review of consecutive patients with HNSCC with a pretreatment PET/CT was performed. NLR and PLR were computed using complete blood counts measured within 10 days before the start of any treatment. The correlation between NLR and PLR with PET/CT-MPs was evaluated with Spearman's rho test.ResultsSeventy-one patients were analyzed. Overall survival (OS) at 1, 2, and 3 years was 86%, 76%, and 68%. PLR was found to be correlated with MTV (rho = 0.26, P = .03) and TLG (rho = 0.28, P = .02) but not with maximum SUV or mean SUV. There was no correlation between NLR and the analyzed PET/CT-MPs. TLG was associated with worse survival in uni- and multivariable analysis, but no other PET/CT-MPs were associated with either OS or disease-specific survival (DSS). NLR and PLR were associated with OS and DSS on uni- and multivariable analysis.ConclusionsIn patients with HNSCC before any treatment such as definitive radio (chemo)therapy or oncologic surgery followed by adjuvant RT, baseline PLR correlated with MTV and TLG but not with SUV. NLR was not correlated with any PET/CT-MPs analyzed in our study. Confirmatory studies are needed, and a potential interaction between tumor microenvironment, host inflammation, and FDG-PET/CT measures warrants further investigation.

Association of Systemic Inflammation with Lipid Profiles and Management in Patients with Rheumatoid Arthritis

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis Cardiovascular disease (CVD) is a leading cause of premature mortality among patients with rheumatoid arthritis (RA). The use of lipid-lowering therapies in this population has been associated with not only improved CVD outcomes and lipid profiles but also decreased systemic inflammation. Furthermore, increased inflammation has been associated with low total cholesterol, LDL and HDL levels, referred to as the 'lipid paradox,' adding complexity to optimal management and therapeutic interventions. Objective/Purpose This study sought to demonstrate a correlation between systemic inflammation as by erythrocyte sedimentation rate (ESR) and lipid markers in RA patients while characterizing lipid monitoring and management practices in this population. Methods This was a retrospective cross-sectional study of RA patients seen ≥ 2 times in an outpatient rheumatology clinic from October 2015 to October 2020 at a minority-serving metropolitan academic medical center. Patients were excluded if they did not have a reported ESR in the electronic medical record (EMR). Clinical variables for each patient were defined by the first reported value during the study period. Elevated ESR was defined as ≥ 20 mm/hr. Statistical methods included t-test and chi-square test as appropriate. Results Among 756 patients with RA, the mean age was 54.1 years, 80.7% were female and 43.4% were non-Hispanic Black. 200 (26.5%) patients had a lipid panel reported in the EMR. Patients with elevated ESR were not significantly more likely to have been evaluated with a lipid panel than those with normal ESR (29.5% versus 23.5%, P=0.06). Patients with an elevated ESR had a significantly lower LDL than those with a normal ESR (94.6 mg/dl versus 105.4 mg/dL, P=0.03). When comparing patients with elevated and normal ESR, the following lipid components were not significantly different: total cholesterol (P=0.09), HDL cholesterol (P=0.87) or triglycerides (P=0.67). A significant difference in the prescription of lipid-lowering medications between patients with elevated and normal ESR was not detected (9.9% versus 8.1%, P=0.38). Conclusions Among patients with elevated ESR, only 29.5% of patients were evaluated with a lipid profile and 9.9% patients were prescribed a lipid-lowering medication despite evidence that these therapies decrease both CVD risk and inflammation. The study findings contribute to the existing evidence behind the 'lipid paradox,' as LDL is inversely correlated with inflammation among patients with RA. Thus, due to the 'lipid paradox' and RA-associated inflammation, patients with elevated ESR and RA may benefit from specialized risk evaluation and rigorous management of atherosclerotic CVD with a lipid specialist or preventive cardiologist. Nothing to disclose.

MO680: Association of Systemic Inflammation with Changing Peritoneal Membrane Characteristics

Abstract BACKGROUND AND AIMS Increasing transport status with ultrafiltration (UF) and solute-removal inadequacy is among the most challenging issues in peritoneal dialysis (PD) continuity. Decreased transport status is less frequent but also results in solute clearance. Although the current incidence of peritonitis has reduced considerably, defined membrane disruptions are still frequently observed. Our study examines the relationship between different types of membrane disruptions and the course of systemic inflammation in incident PD patients. METHOD This is a retrospective, single-site, cohort study of incident adult PD patients (n = 202) sampled between January 2000 and January 2020. An increase or decrease in transport status is defined as two or more categories of a rise or decline in peritoneal equilibration test (PET) from their baseline during follow-up. The 4-h dialysate/plasma creatinine ratio was used to classify PET categories. C-reactive protein (CRP) values were obtained from the annual tests in the routine controls of the patients. RESULTS Baseline demographics, diabetes frequency, residual renal function, baseline laboratory, frequency of renin–angiotensin–aldosterone system blockers, high glucose–containing dialysate and icodextrin use were similar among the groups. Total episodes of peritonitis and peritonitis rates within the first 5 years of follow-up was higher in patients with stable transport status with a median rate of 0 (min:0 to max:5) than patients with increased transport status [median rate of 0 (min:0 to max:3)] and decreased transport status [median rate of 0 (min:0 to max:1)] (P = 0.009). The main time-dependent effect of CRP was statistically significant [Wilks’ λ = 0.76, F (5, 127) = 7.75, P &amp;lt; 0.001]. The joint effect of the mean CRP value depending on time and group was also significant [Wilks’ λ = 0.91, F (10, 254) = 1.10, P = 0.36]. The effect of CRP and time was significantly different between the groups [F (2, 131) = 3.49, P = 0.03; partial η2 = 0.05]. While there was a significant difference between stable and increased transporters in the post-hoc analysis, no similar significance was found between stable and decreased transporters (P = 0.03 and P = 0.99, respectively). CONCLUSION Our study shows that the peritoneal membrane kinetics may change into different characteristics in many patients over time, despite the very low frequency of peritonitis episodes and similar baseline characteristics, and may be significantly affected by systemic inflammation. Systemic inflammation, in particular, appears to be related to increased transport status, which is most often responsible for the deterioration of UF and solute clearance over time.

Association of Systemic Inflammation and Overall Survival in Elderly Patients with Cancer Cachexia - Results from a Multicenter Study.

BackgroundSystemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality.Patients and MethodsThis multicenter cohort study included 746 EPCC (age >65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria.ResultsThe C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet–lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (<25.03) had a worse overall survival (OS) than patients with high ALI (≥25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590–2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups.ConclusionThe prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.

Association of Systemic Inflammation with Depressive Symptoms in Individuals with COPD.

RationaleDepression is a prevalent comorbidity of chronic obstructive pulmonary disease (COPD) that, along with COPD, has been associated with inflammation. An association between inflammation and depression in COPD has not been validated in a large COPD cohort.MethodsIndividuals from the University of Pittsburgh SCCOR cohort and the COPDGene cohort with tobacco use history and airway obstruction (FEV1/FVC <0.7) were evaluated using the Beck Depression Inventory II (BDI-II) and the Hospital Anxiety and Depression Scale (HADS), respectively. Participants completed symptom-related questionnaires and plasma IL-6 measurements. T-test, Fisher’s Exact tests and logistic regression were used for statistical analysis.ResultsThe SCCOR cohort included 220 obstructed participants: 44% female and 21.4% with elevated depressive symptoms. GOLD staging distribution was predominantly stage I and II. The COPDGene cohort included 745 obstructed participants: 44% female and 13.0% with elevated depressive symptoms. GOLD distribution was predominantly stage II and III. In the SCCOR cohort, correlation between IL-6 and depressive symptoms trended toward significance (p= 0.08). Multivariable modeling adjusted for FEV1, age, gender and medical comorbidities showed a significant association (OR = 1.70, 95% CI = 1.08–2.69). IL-6 was significantly associated with elevated depressive symptoms in COPDGene in both univariate (p=0.001) and multivariable modeling (OR = 1.52, 95% CI =1.13–2.04).ConclusionElevated plasma IL-6 levels are associated with depressive symptoms in individuals with COPD independent of airflow limitation and comorbid risk factors for depression. Our results suggest that systemic inflammation may play a significant and possibly bidirectional role in depression associated with COPD.

Association of systemic inflammation with survival in patients with cancer cachexia: results from a multicentre cohort study.

BackgroundAlthough systemic inflammation is an important feature of the cancer cachexia, studies on the association between systemic inflammation and prognostic of cancer cachexia are limited. The objective of this study is to evaluate whether the neutrophil‐to‐lymphocyte ratio (NLR) is associated with outcome and quality of life for patients with cancer cachexia and investigated any interaction between NLR and the clinical parameters.MethodsThis is a multicentre cohort study of 2612 cancer patients suffering from cachexia diagnosed between June 2012 and December 2019. The main parameters measured were overall survival (OS) time and all‐cause mortality. The association between NLR and all‐cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two‐sided P‐value. Optimal stratification was used to solve threshold points. We also evaluated the cross‐classification of NLR for each variable of survival.ResultsOf the 2612 participants diagnosed with cancer cachexia, 1533 (58.7%) were male, and the mean (SD) age was 58.7 (11.7) years. Over a median follow‐up of 4.5 years, we observed 1189 deaths. The overall mortality rate for patients with cancer cachexia during the first 12 months was 30.2% (95%CI: 28.4%–32.0%), resulting in a rate of 226.07 events per 1000 patient‐years. An increase in NLR had an inverted L‐shaped dose–response association with all‐cause mortality. The optimal cut‐off point for NLR as a predictor of mortality in cancer patients with cachexia was 3.5. An NLR of 3.5 or greater could independently predict OS (HR, 1.51, 95%CI: 1.33–1.71). These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified including gender, BMI, tumour type, KPS score and albumin in content. Increasing NLRs were independently associated with a worsening in the majority of EORTC QLQ‐C30 domains. Elevated baseline NLR was associated with low response and poor survival in patients treated with immunotherapy.ConclusionsThe baseline NLR status was found to be a significant negative prognostic biomarker for patients with cachexia; this effect was independent of other known prognostic factors.

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Objective:The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.MethodsA total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m2.ResultsAmong 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069–1.430; and HR: 1.600, 95% CI: 1.350–1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054–1.434; and HR: 1.658, 95% CI: 1.389–1.979, respectively). Patients with both NLR ≥ 3 and underweight (vs. neither) had much worse OS (HR: 2.445, 95% CI: 1.853–3.225) and RFS (HR: 2.405, 95% CI: 1.802–3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy.ConclusionsOur results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

Association of systemic inflammation and coagulation biomarkers with source-specific PM2.5 mass concentrations among young and elderly subjects in central Tehran

ABSTRACT In this study, we investigated the association between short-term exposure to different sources of fine particulate matter (PM2.5) and biomarkers of coagulation and inflammation in two different panels of elderly and healthy young individuals in central Tehran. Five biomarkers, including white blood cells (WBC), high sensitive C-reactive protein (hsCRP), tumor necrosis factor-soluble receptor-II (sTNF-RII), interleukin-6 (IL-6), and von Willebrand factor (vWF) were analyzed in the blood samples drawn every 8 weeks from the subjects between May 2012 and May 2013. The studied populations consisted of 44 elderly individuals at a retirement home as well as 40 young adults residing at a school dormitory. Positive Matrix Factorization (PMF)-resolved source-specific PM2.5 mass concentrations and biomarker levels were used as the input to the linear mixed-effects regression model to evaluate the impact of exposure to previously identified PM sources at retirement home and school dormitory in two time lag configurations: lag 1–3 (1–3 days before the blood sampling), and lag 4–6 (4–6 days before the blood sampling). Our analysis of the elderly revealed positive associations of all biomarkers (except hsCRP) with particles of secondary origin in both time lags, further corroborating the toxicity of secondary aerosols formed by photochemical processing in central Tehran. Moreover, industrial emissions, and road dust particles were positively associated with WBC, sTNF-RII, and IL-6 among seniors, while vehicular emissions exhibited positive associations with all biomarkers in either first- or second-time lag. In contrast, most of the PM2.5 sources showed insignificant associations with biomarkers of inflammation in the panel of healthy young subjects. Therefore, findings from this study indicated that various PM2.5 sources increase the levels of inflammation and coagulation biomarkers, although the strength and significance of these associations vary depending on the type of PM sources, demographic characteristics, and differ across the different time lags. Implications: Tehran, the capital of Iran with a population of more than 9 million people, has been facing serious air pollution challenges as a result of extensive vehicular, and industrial activities in the previous years. Among various air pollutants in Tehran, fine particulate matters (PM2.5, particles with aerodynamic diameters < 2.5 µm) are known as one of the most important critical pollutants, causing several adverse health impacts including lung cancer, respiratory, cardiovascular, and cardiopulmonary diseases. Therefore, a number of studies in the area have tried to investigate the adverse health impacts of exposure to PM2.5. However, no studies have ever been conducted in Tehran to examine the association between specific PM2.5 sources and biomarkers of coagulation and systemic inflammation as indicators of cardiovascular disorders. Indeed, this is the first study in the area investigating the association of source-specific PM2.5 with biomarkers of inflammation including white blood cells (WBC), high sensitive C-reactive protein (hsCRP), tumor necrosis factor-soluble receptor-II (sTNF-RII), interleukin-6 (IL-6), and von Willebrand factor (vWF). Our results have important implications for policy makers in identifying the most toxic sources of PM2.5, and in turn designing schemes for mitigating adverse health impacts of air pollution in Tehran.

Abstract 482: Beta-catenin Activation in Cardiac Fibroblasts Modulates the Immune Micro-environment to Promote Fibrosis and Heart Failure Following Chronic Injury

Almost 6.5 million people in United States suffer from heart failure (HF). Diastolic HF following non-ischemic cardiac insult is a progressive condition with limited effective therapies underscoring the urgency to invest in identifying novel therapeutic targets for treatment. Reactive fibrosis in response to pathological stress is one of the major causes of diastolic HF. Emerging data suggest an association of systemic inflammation with reactive fibrosis and HF. Canonical Wnt/beta-catenin signaling has been linked to HF and fibrosis with limited understanding of the precise cellular and molecular mechanism. We utilized thoracic aortic constriction (TAC), a well-defined model of HF, to study Wnt signaling mediated reactive fibrosis. TAC was induced in a transgenic mouse model with stabilized beta-catenin (Wnt signaling) in fibroblasts (Bcat/Postn). Wnt activation following TAC resulted in increased maladaptive reactive fibrosis, HF marker ANP, and cardiac hypertrophy with preserved Ejection Fraction (pEF) suggesting Wnt-mediated progression of diastolic heart failure with pEF. TAC also resulted in increased macrophage activation and recruitment of CD8+ cytotoxic T-cells. In vitro co-culture of Wnt3a-overexpressing fibroblasts with activated myeloid cells promoted fibroblast proliferation and collagen synthesis. Therefore, we hypothesize that Wnt signaling activation promotes interstitial fibrosis via recruitment of specific inflammatory cells. Genomic analysis further supports this by demonstrating distinct chemokine gene expression patterns in fibroblasts resulting from Wnt activation in these injury models. Our future goal is to elucidate the role of Wnt signaling in modulating the fibroblast-immune cell crosstalk in modulating interstitial fibrosis induced diastolic HFpEF. Currently, there is no approved therapy to specifically target reactive fibrosis to avert diastolic dysfunction. Our study is aiming to identify targetable cellular and molecular players that improve, prevent or avert reactive fibrosis mediated HFpEF in order to reduce the incidence and severity of pathology resulting from HF.

399PD - Association of systemic inflammation with local tumour characteristics and survival in glioma patients

BackgroundImmunotherapy has yield only modest clinical efficacy in glioma so far. However, gliomas are characterized by a range of immune suppressive features. Here, we aimed to analyze the correlation of systemic inflammation with local tumor characteristics and overall survival in glioma patients. MethodsGlioma patients were recruited at time of diagnosis or recurrence within the Vienna Cancer and Thrombosis Study (CATS). At study inclusion, a blood draw was performed. IDH1 mutation, PD-L1 and podoplanin in glioma were assessed via immunohistochemistry. Results193 glioma patients (4.7% diffuse glioma, 19.7% anaplastic glioma, 75.6% glioblastoma) were included. IDH1 mutation was present in 40/193 (20.7%) patients, PD-L1 expression was observed in 20/193 (10.4%) patients, and podoplanin positivity was found in 134/193 (69.4%) patients. IDH1 mutation was associated with higher platelet count (median: 303 vs. 232G/L, p=0.001) and lower neutrophil count (4.71 vs 6.55G/L, p=0.021) as well as lower neutrophil/lymphocyte (N/L) ratio (3.34 vs. 5.13, p=0.016). PD-L1 was associated with higher monocyte count (0.657 vs. 0.450G/L, p=0.008), higher C-reactive protein (CRP) (0.43 vs. 0.1mg/dL, p=0.005) and higher fibrinogen (379 vs. 303mg/dL, p=0.001). Podoplanin was associated with higher leukocyte count (8.88 vs 7.22G/L, p=0.040), higher neutrophil count (6.44 vs 5.03G/L, p=0.048), higher N/L ratio (5.4 vs. 3.2, p=0.006) and lower platelet count (227 vs 289G/L, p<0.0001). Upon multivariable adjustment for sex and age, platelet count (hazard ratio per 1 unit increase: 0.997, 95% CI [0.995-0.999], p=0.006), leukocyte count (1.040 [1.004-1.077], p=0.030), neutrophil count (1.043 [1.000-1-087], p=0.049) and CRP levels (1.095 [1.010-1-187], p=0.027) correlated with overall survival. ConclusionsSystemic inflammation correlated with overall survival in the present glioma cohort. Furthermore, molecular glioma characteristics (IDH1 mutation, PD-L1, podoplanin) were linked to distinct systemic inflammation patterns. Clinical trials on immune modulating therapies should consider these different glioma-immune system interactions in order to potentially select patients with the highest benefit. Legal entity responsible for the studyMedial University of Vienna. FundingAustrian National Bank. DisclosureP. Mir Seyed Nazari: Travel / Accommodation / Expenses: Bayer. M. Preusser: Research grant / Funding (self): Böhringer-Ingelheim; Research grant / Funding (self): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Gerson Lehrman Group (GLG); Honoraria (self), Advisory / Consultancy: CMC Contrast; Honoraria (self), Advisory / Consultancy: GlaxoSmithKline,; Honoraria (self), Advisory / Consultancy: Mundipharma; Honoraria (self), Advisory / Consultancy: Astra; Honoraria (self), Advisory / Consultancy: Zeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medahead; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. A.S. Berghoff: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Meyers Squibb; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.

Association of Systemic Inflammation and Fatigue in Osteoarthritis: 2007-2010 National Health and Nutrition Examination Survey.

Mechanistic insight into osteoarthritis fatigue is needed as clinical management of this condition is nonspecific. Systemic inflammation is associated with fatigue in other chronic diseases. The purpose of this study was to explore the relationship between systemic inflammation and fatigue in osteoarthritis, while controlling for covariates. This secondary analysis with a cross-sectional, multiyear retrospective design used data from the 2007-2010 National Health and Nutrition Examination Survey. Adults with self-reported osteoarthritis who participated in an examination at a mobile center and had no comorbidities associated with fatigue or systemic inflammation were included (n = 296). Complex sample analysis, independent samples t tests, and χ2 tests of independence were used to explore differences between nonfatigued and fatigued adults with osteoarthritis. Adjusted hierarchical logistic regression models were used to calculate odds of fatigue as a function of two systemic inflammatory markers, C-reactive protein (CRP), and white blood cell (WBC) count. Fatigued adults with osteoarthritis had significantly higher CRP levels and WBC counts compared to nonfatigued adults with osteoarthritis. In adjusted logistic regression models, increased CRP was associated with higher odds of fatigue when controlling for age, days affected by pain, depressive symptoms, sleep quantity, and body mass index (Odds ratio [OR] = 3.38, 95% CI [1.18, 9.69]). WBC count was not associated with higher odds of fatigue when controlling for these variables (OR = 1.10, 95% CI [0.92, 1.32]). Systemic inflammation may have a relationship with fatigue in osteoarthritis. Future work is necessary to replicate these findings in more robust studies.

Association of Systemic Inflammation With Retinal Vascular Caliber in Patients With AIDS.

PurposeTo evaluate relationships among retinal vascular caliber and biomarkers of systemic inflammation in patients with AIDS.MethodsA total of 454 participants with AIDS had retinal vascular caliber (central retinal artery equivalent and central retinal vein equivalent) determined from enrollment retinal photographs by reading center graders masked to clinical and biomarker information. Cryopreserved plasma specimens were assayed for inflammatory biomarkers, including C-reactive protein (CRP), IL-6, interferon-γ inducible protein (IP)-10, kynurenine/tryptophan (KT) ratio, and intestinal fatty acid binding protein (I-FABP).ResultsIn the simple linear regression of retinal vascular caliber on plasma biomarkers, elevated CRP, IL-6, and IP-10 were associated with retinal venular dilation, and elevated KT ratio with retinal arteriolar narrowing. In the multiple linear regression, including baseline characteristics and plasma biomarkers, AMD was associated with dilation of retinal arterioles (mean difference: 9.1 μm; 95% confidence interval [CI] 5.2, 12.9; P < 0.001) and venules (mean difference, 10.9 μm; 95% CI, 5.3, 16.6; P < 0.001), as was black race (P < 0.001). Hyperlipidemia was associated with retinal venular narrowing (mean difference, −7.5 μm; 95% CI, −13.7, −1.2; P = 0.02); cardiovascular disease with arteriolar narrowing (mean difference, −5.2 μm; 95% CI, −10.3, −0.1; P = 0.05); age with arteriolar narrowing (slope, −0.26 μm/year; 95% CI, −0.46, −0.06; P = 0.009); and IL-6 with venular dilation (slope, 5.3 μm/standard deviation log10[plasma IL-6 concentration]; 95% CI, 2.7, 8.0; P < 0.001).ConclusionsThese data suggest that retinal vascular caliber is associated with age, race, AMD, hyperlipidemia, cardiovascular disease, and selected biomarkers of systemic inflammation.

17 – Dynamic Association of Systemic Inflammation, Gut Microbial Dysbiosis and Gut Barrier Integrity in Acute Pancreatitis (AP): Lessons Learnt from Animal Model

17 – Dynamic Association of Systemic Inflammation, Gut Microbial Dysbiosis and Gut Barrier Integrity in Acute Pancreatitis (AP): Lessons Learnt from Animal Model

Systemic inflammation in patients of chronic obstructive pulmonary disease with metabolic syndrome.

Context:India has 18% of the global population and an increasing burden of chronic respiratory diseases. The prevalence of Metabolic syndrome (MS) was found to be as high as 39.7% among Indian population. Metabolic syndrome is found to be more common in Chronic Obstructive Pulmonary Disease (COPD) when compared to the general population. This study was done to assess the prevalence of metabolic syndrome in COPD and the association of systemic inflammation in COPD patients with metabolic syndrome.Methodology:This study enrolled 150 consecutive consenting patients of stable COPD attending the outpatient pulmonology department. Detailed history, clinical examination, spirometry, and relevant routine laboratory investigations including complete blood count, fasting blood sugar, and lipid profile were done. In addition, hsCRP, Serum lactate and Vitamin D level was assessed in all patients. Diagnosis of COPD and Metabolic syndrome was done according to GOLD guidelines, 2018 and the International Diabetes Federation criteria respectively.Result:The prevalence of metabolic syndrome was found to be 27.3% in our COPD patients. The frequency of metabolic syndrome in GOLD stage I, II, III, and IV was 75%, 32%, 17%, and 13.5%, respectively. Logistic regression analysis showed a significant relationship of blood leucocyte count (OR = 0.342, CI = 0.171-0.686), hs-CRP (OR = 0.020, CI = 0.003-0.122), pack years (OR = 1.083, CI = 1.026-1.14) and vitamin D levels (OR = 1.219, CI = 1.093-1.359) with metabolic syndrome in COPD patients.Conclusion:Metabolic syndrome is a co-morbidity that is very often overlooked in patients of COPD. Systemic inflammation which is a common characteristic of both COPD and Metabolic syndrome has been found to be an important contributor towards cardiovascular morbidity and mortality.