Differences In Inflammatory Biomarkers Research Articles

Early diagnostic value of Presepsin in sepsis: a prospective study on a population with suspected sepsis in fever clinics

To analyze the early diagnostic value of plasma soluble cluster of differentiation 14 subtype (sCD14-ST, Presepsin) in sepsis in a population with suspected sepsis in fever clinic. A prospective observational study was conducted. The patients admitted to the fever clinic of Beijing Chaoyang Hospital from April to December 2022 were enrolled as the study objects. According to sequential organ failure assessment (SOFA) score, the patients were divided into low SOFA score group (SOFA score ≤3) and high SOFA score group (SOFA score > 3). Venous blood was collected at the time of admission. The level of plasma Presepsin was detected by chemiluminescence enzyme-linked immunoassay. The level of plasma procalcitonin (PCT) was detected by enzyme-linked immunofluorescence method. The level of C-reactive protein (CRP) was detected by scattering turbidimetry. White blood cell count (WBC) and neutrophil count (NEUT) were measured by automatic blood cell analyzer. For patients with fear of cold or chills, venous blood of upper limbs was taken for blood culture at the time of admission. The differences in inflammatory biomarkers were compared between the two groups. Binary multivariate Logistic regression analysis was used to screen the early risk factors of sepsis in fever outpatients with suspected sepsis. Receiver operator characteristic curve (ROC curve) was drawn to investigate the early diagnostic value of Presepsin and other inflammatory markers in sepsis, and to analyze the optimal cut-off value. A total of 149 fever outpatients with suspected sepsis were enrolled, including 92 patients with low SOFA score and 57 patients with high SOFA score. Plasma PCT and Presepsin levels in the high SOFA score group were significantly higher than those in the low SOFA score group [PCT (μg/L): 0.77 (0.18, 2.02) vs. 0.22 (0.09, 0.71), Presepsin (ng/L): 1 129.00 (785.50, 1 766.50) vs. 563.00 (460.50, 772.25), both P < 0.01]. There was no significant difference in WBC, NEUT, CRP or positive rate of blood culture between the high and low SOFA score groups [WBC (×109/L): 11.32±5.47 vs. 11.14±5.29, NEUT (×109/L): 9.88±4.89 vs. 9.60±5.10, CRP (mg/L): 54.05 (15.95, 128.90) vs. 46.11 (19.60, 104.60), blood culture positivity rate: 42.3% (11/26) vs. 29.4% (10/34), all P > 0.05]. Multivariate Logistic regression analysis showed that Presepsin was an early risk factor for sepsis in suspected sepsis patients in fever clinics [odds ratio (OR) = 16.96, 95% confidence interval (95%CI) was 6.35-45.29, P = 0.000]. ROC curve analysis showed that the early diagnostic value of Presepsin in sepsis was significantly better than WBC, NEUT, CRP, PCT, and blood culture [the area under the ROC curve (AUC) and 95%CI: 0.832 (0.771-0.899) vs. 0.522 (0.424-0.619), 0.532 (0.435-0.629), 0.533 (0.435-0.632), 0.664 (0.574-0.753), 0.554 (0.458-0.650)]. When the optimal cut-off value of Presepsin was 646.50 ng/L, its sensitivity and positive predictive value were higher than those of WBC, NEUT, CRP, and PCT (sensitivity: 89.5% vs. 38.6%, 68.4%, 38.6%, 57.9%; positive predictive value: 64.6% vs. 44.9%, 44.3%, 47.8%, 55.9%). Plasma PCT and Presepsin have early diagnostic value for sepsis in suspected sepsis patients in fever clinics, and Presepsin is more sensitive than PCT and can be used as an early marker of sepsis.

Systemic inflammation in relation to exceptional memory in the Long Life Family Study (LLFS)

Background and objectivesWe previously found a substantial familial aggregation of healthy aging phenotypes, including exceptional memory (EM) in long-lived persons. In the current study, we aim to assess whether long-lived families with EM and without EM (non-EM) differ in systemic inflammation status and trajectory. MethodsThe current study included 4333 participants of the multi-center Long Life Family Study (LLFS). LLFS families were classified as EM (556 individuals from 28 families) or non-EM (3777 individuals from 416 families), with 2 or more offspring exhibiting exceptional memory performance (i.e. having baseline composite z-score representing immediate and delayed story memory being 1.5 SD above the mean in the nondemented offspring sample) considered as EM. Blood samples from baseline were used to measure inflammatory biomarkers including total white blood cell (WBC) and its subtypes (neutrophils, lymphocytes, monocytes) count, platelet count, high sensitivity C-reactive protein, and interleukin-6. Generalized linear models were used to examine cross-sectional differences in inflammatory biomarkers at baseline. In a sub-sample of 2227 participants (338 subjects from 24 EM families and 1889 from 328 non-EM families) with repeated measures of immune cell counts, we examined whether the rate of biomarker change differed between EM and non-EM families. All models were adjusted for family size, relatedness, age, sex, education, field center, APOE genotype, and body mass index. ResultsLLFS participants from EM families had a marginally higher monocyte count at baseline (b = 0.028, SE = 0.0110, p = 0.010) after adjusting for age, sex, education, and field site, particularly in men (p < 0.0001) but not in women (p = 0.493) (p-interaction = 0.003). Over time, monocyte counts increased (p < 0.0001) in both EM and non-EM families, while lymphocytes and platelet counts decreased over time in the non-EM families (p < 0.0001) but not in the EM families. After adjusting for multiple variables, there was no significant difference in biomarker change over time between the EM and non-EM families. DiscussionCompared with non-EM families, EM families had significantly higher monocyte count at baseline but had similar change over time. Our study suggests that differences in monocyte counts may be a pathway through which EM emerges in some long-lived families, especially among men.

Abstract 18296: Insights From the LURIC Study: Decoding the Peripheral Immune Cell Composition in Atherosclerosis Through Single Cell RNA-Sequencing

Introduction: Atherosclerosis and its clinical sequelae, myocardial infarction and stroke, represent the main causes of death worldwide. Although preclinical evidence has suggested the existence of a sustained inflammatory and immune response driving disease and complications, the extend of cellular alterations in human atherosclerosis remains enigmatic. Hypothesis: Here, we employ single cell RNA-sequencing (scRNA-seq) on peripheral blood mononucleated cells (PBMCs) in a well-defined cardiovascular risk cohort from the Ludwigshafen Risk and Cardiovascular Health (LURIC) trial to define changes in the immune cell landscape in atherosclerotic patients Methods: Of 3317 patients enrolled in the LURIC trial, we selected individuals with stable coronary-artery disease (CAD) (n=31) and healthy patients (no CAD) (n=16) by propensity score matching, adjusted for CRP, NT-proBNP, Troponin T, LDL-C, and Cystatin-C, in a case-control design. scRNA-seq was performed by droplet sequencing on PBMCs stored in liquid nitrogen. Individual data sets were integrated and changes between healthy individuals and patients with CAD were evaluated on numeric and transcriptional levels. Results: We identified several regulated leukocyte populations that were differentially regulated between both conditions. Interestingly, small cell populations like Tregs (&gt;1.4-fold more), platelets (&gt;10-fold more), stem cells (&gt;3-fold more), and proliferating cells (&gt;2-fold-more) were significantly increased in PBMCs from patients suffering from CAD. On the contrary, naïve B cell and T cell populations were considerably overrepresented in healthy control patients (&gt;1.4-fold more). Pathway analyses of distinct clusters in patients with CAD revealed increased signalling for cellular exhaustion, response to stress, and leukocyte activation, which strikingly resembles the underlying pathology in atherosclerosis. Conclusions: Employing scRNAseq, we demonstrate that atherosclerosis is associated with a profound change in the circulating immune cell landscape even in the absence of measurable differences in inflammatory biomarkers. These findings propose the usage of scRNAseq for the discovery of outcome-relevant cellular biomarkers in the future.

A comparison of diet quality and cardiovascular and inflammatory responses between aerobically trained male adults following either a long-term vegan or omnivorous dietary pattern.

Vegan dietary patterns are increasingly being adopted by endurance athletes, yet research examining the influence of this dietary pattern on exercise-related physiology is limited. This pilot study, therefore, aimed to explore nutrient status, diet quality and cardiovascular and inflammatory responses in aerobically trained adult males following vegan and omnivorous dietary patterns during aerobic exercise. An incremental ramp running test was used to assess peak oxygen consumption (VO2peak ) in males aged 18-55 years, engaging in >4 h training/week. Exercise testing was performed during walking and steady-state running conditions (60% and 90% of VO2peak ). Participants were grouped by dietary pattern type and were equivalent for age, training volume and VO2peak . When compared to the omnivorous group (n = 8, age 35.6 years, VO2peak 55.7 mL/kg/min), the vegan group (n = 12, age 33.4 years, VO2peak 56.4 m/kg/min) consumed more energy from carbohydrates (p = 0.007), and less energy from protein (p = 0.001) while exhibiting a higher overall diet quality score (p = 0.008). No differences in inflammatory biomarkers were observed before or after running. Total red blood cell count, haemoglobin and haematocrit levels were lower in the vegan dietary group. In summary, aerobically trained males, following a long-term vegan diet, can tolerate a short bout of running broadly comparatively to their omnivore counterparts. More arduous endurance exercise conditions should be explored to further uncover potential outcomes of consuming a vegan dietary pattern and exercise-related physiology.

702 PROGNOSTIC ROLE OF MYOCARDIAL VIABILITY ASSESSMENT BY 18F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IN STEMI PATIENTS WITH LATE PRESENTATION

Abstract Background ST-segment elevation myocardial infarction (STEMI) is one of the world's leading causes of disability and death. The incidence of late-onset STEMI (i.e. after at least 12 hours from symptom onset to medical observation) accounts up to 10% of overall STEMI events and optimal management in this setting is still debated due to the lack of randomized data. The aim of the present study is to explore the usefulness of FDG-PET to improve late-onset STEMI treatment. Methods We conducted a single-center retrospective observational study that included patients admitted for late-onset STEMI who underwent coronary angiography and FDG-PET to evaluate myocardial viability (MV). Follow-up by telephone interview and / or clinical follow-up at 6, 12, 24, 36, 48 and 60 months was performed in all patients. The prevalence of myocardial viability (MV) related to infarct-related artery (IRA) by FDG-PET study (using a semi-quantitative visual scoring method), the study of clinical and angiographic predictors of viability and the association of myocardial viability evaluated with FDG-PET with the improvement of the left ventricular ejection fraction (LVEF) were investigated. Results A total of 27 patients with mean age 64.7 ± 11.1 years, predominantly men (n=25, 92,6%), were enrolled in the study. Compared to patients without MV (n=12), MV-patients (n=15) presented more frequently dyslipidemia (100.0% vs 66.7%, p=0.015) and diabetes (53.3% vs 16.5%, p=0.050) but showed no difference in inflammatory biomarkers and echocardiographic parameters. Multivessel disease (MVD 86.7% vs 33.3%, p=0.004) and high-grade collateral-connection (hg-CC 80.0% vs 33.3%, p=0.027) were more frequent in MV-patients compared to patients without MV. The presence of angiographically visible hg-CC (OR=8.00, 95%CI 1.40-45.76, p=0.019) and MVD (OR=13.00, 95%CI 1.92-88.00, p&amp;lt;0.001) were positive predictors of FDG-PET MV related to IRA and remained independent positive predictors of FDG-PET MV related to IRA at multivariable logistic regression analysis (p&amp;lt;0.05). No significant differences were recorded between patients without MV and MV-patients in the incidence of MACEs (20.0% vs 50.0%, p=0.100). Of note, as compared to patients without MV, MV-patients displayed a significant improvement in LVEF (86.7% vs 50.0%, p = 0.036), with a higher mean value of LVEF at follow-up (39.4 ± 10.9 vs 29.6 ± 8.0, p = 0.013) and of LVEF change from baseline to follow-up (6.1 ± 7.2 vs -1.1 ± 9.1, p = 0.027). Conclusions This study could be of great help in clinical practice in order to provide a personalized approach in patients with late-STEMI, suggesting the potential benefit of a routine assessment IRA-related viability by FDG-PET in all asymptomatic late-STEMI subjects and providing further evidence in favor of a revascularization of occluded IRA in those with documented myocardial viability.

Baseline Systemic Inflammatory Markers Interleukin 6 and Ferritin Are Associated with Toxicities and Progression-Free Survival in Multiple Myeloma Patients Treated with Idecabtagene Vicleucel

Introduction: A challenge of chimeric antigen receptor (CAR) T-cell therapy is the en-masse activation of tumor-reactive T-cells that can lead to cardiovascular, respiratory, and neurologic toxicities, including cytokine release syndrome (CRS) and neurotoxicity (NT). Recent studies found that elevated levels of cytokines and inflammatory markers pre-treatment are associated with severe toxicities in B cell lymphoma patients receiving axicabtagene ciloleucel. However, less is known about patients with relapsed/refractory multiple myeloma (RRMM) treated with commercial idecabtagene vicleucel (ide-cel). We evaluated the associations of serum cytokines and inflammatory biomarkers with immune-mediated toxicities and progression-free survival (PFS) in RRMM patients treated with commercial ide-cel. Methods: Serum samples were collected at baseline (within 45 days of lymphodepleting chemotherapy) and daily from infusion until hospital discharge. The Ella automated simple plex immunoassay system (ProteinSimple) was used to measure cytokines including GM-CSF, IL2, IL6, IL15, IFNγ, TNFα, and Angiopoietin 1&2. Standard clinical tests were used to measure ferritin and C-reactive protein at baseline (pre-lymphodepleting chemotherapy), infusion, and daily until hospital discharge. Treatment-related toxicities were graded based on ASTCT guidelines and managed according to institutional policies. Treatment responses were graded based on IMWG response criteria. Chi-square and Kruskal-Wallis tests were used to examine the distribution of each cytokine and inflammatory biomarker at baseline, infusion, and peak (highest level between day one post infusion and last day of hospitalization) by any grade and ≥ grade 2 CRS and NT. For cytokines or inflammatory biomarkers associated with CRS and NT, maximally selected rank statistics were used to determine optimal cut-points for PFS, and Kaplan-Meier survival curves and log-rank tests were used to examine PFS by optimal cut-points of selected cytokines and inflammatory biomarkers. Results: 28 patients who received ide-cel by May 1st, 2022 were included. Median age was 65 years. 38% of patients had high-risk cytogenetics and 54% had penta-refractory disease. Median number of prior lines of therapy was 6 (range 4-13). CRS was seen in 79% (≥ grade 2: 14%) and NT in 11% (≥ grade 2: 7%) of patients. Tocilizumab and steroids were used in 79% and 32% of patients, respectively. With a median follow up of 6.2 months, best overall response rate was 82%, with 57% of patients achieving a complete response or better. Of those, 69% were minimal residual disease negative. Four patients died of myeloma progression. Patients with any grade versus no CRS had higher levels of baseline ferritin (402 vs 133 ng/mL; P=0.045), peak ferritin (2804 vs 191 ng/mL; P<0.001), and peak IL6 (3681 vs 20 pg/mL; P<0.001). Patients with ≥ grade 2 vs < grade 2 CRS had higher levels of baseline IL6 (19 vs 5 pg/mL; P=0.04; Figure 1). A positive but not statistically significant association was observed for baseline IL6 with ≥ grade 2 vs < grade 2 NT (19 vs 6 pg/mL; P=0.12). There were positive correlations between baseline and peak ferritin (r=0.43; P=0.02) and baseline ferritin and IL6 (r=0.58; P=0.005), but no correlation between baseline and peak IL6 (r=-0.06; P=0.8). Using optimal cut-points for baseline ferritin (1700 ng/mL) and IL6 (10 pg/mL), patients with high (n=5) vs low (n=23) baseline ferritin had an inferior PFS (median PFS of 4.8 months vs not reached [NR]; P=0.0005), and patients with high (n=6) vs low (n=16) baseline IL6 had an inferior PFS (median PFS of 3 months vs NR; P=0.069). When combining baseline ferritin and IL6, patients with either high (n=8) vs low (n=20) ferritin or IL6 had an inferior PFS (median PFS of 4.8 months vs NR; P=0.021; Figure 1). No other differences in inflammatory biomarkers or cytokines by toxicities or PFS were identified. Conclusions: In our single center experience, we found associations between ferritin and IL6 with CRS and NT. Median PFS was inferior in patients with elevated baseline ferritin and IL6. This suggests that a pre-existing pro-inflammatory state puts ide-cel patients at risk for toxicities in addition to inferior PFS. Tailoring toxicity and additional therapeutic management to patient risk may mitigate morbidity and mortality. D.K.H. and L.C.P contributed equally; M.A. and M.L.D contributed equallyFigure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Elevated levels of serum CDCP1 in individuals recovering from severe COVID-19 disease.

Background: COVID-19 survivors report residual lung abnormalities after discharge from the hospital. The aim of this study was to identify biomarkers in serum and induced sputum samples from patients after hospitalization for COVID-19.Methods: Patients admitted to hospitals in Spain with laboratory-confirmed COVID-19 were recruited for this study. SARS-CoV-2-infected patients were divided into groups with mild/moderate and severe disease according to the severity of their symptoms during hospitalization. Levels of 92 biomarkers were measured in serum and induced sputum samples.Results: A total of 108 patients (46.2% severe cases) were included in this study. The median number of days after the onset of symptoms was 104. A significant difference was observed in diffusing capacity for carbon monoxide (DLCO), an indicator of lung function, whereby DLCO <80% was significantly lower in severe cases (p <0.001). Differences in inflammatory biomarkers were observed between patients with mild/moderate and severe disease. For some biomarkers, correlations in serum and induced sputum levels were detected. Independent predictors of severe disease were DLCO <80% and the serum CDCP1 value.Conclusions: Higher levels of CDCP1 remain after hospital discharge and are associated with the severity of COVID-19. The possible prognostic implications warrant further investigation.

Does previous stroke modify the relationship between inflammatory biomarkers and clinical endpoints in CKD patients?

BackgroundChronic kidney disease (CKD) is an independent risk factor for stroke. Stroke is also an independent risk factor for worse CKD outcomes and inflammation may contribute to this bidirectional relationship. This study aims to investigate inflammatory biomarkers in patients with non-dialysis CKD (ND-CKD) with and without stroke.MethodsA propensity matched sample from > 3000 Salford Kidney Study (SKS) patients, differentiated by previous stroke at study recruitment, had stored plasma analyzed for interleukin- 6 (IL-6), Von Willebrand Factor (VWF) and C-reactive protein (CRP). Multivariable cox regression analysis investigated associations between inflammation and death, end-stage renal disease (ESRD) and future non-fatal cardiovascular events (NFCVE).ResultsA total of 157 previous stroke patients were compared against 162 non-stroke patients. There were no significant differences in inflammatory biomarkers between the two groups. Previous stroke was associated with greater mortality risk, hazard ratio (HR) (95% CI) was 1.45 (1.07–1.97). Higher inflammatory biomarker concentrations were independently associated with death but not ESRD or NFCVE in the total population. For each 1 standard deviation (SD) increase in log IL-6, VWF and CRP, the HR for all-cause mortality were 1.35 (1.10–1.70), 1.26 (1.05–1.51) and 1.34 (1.12–1.61), respectively. CRP retained its independent association (HR 1.47 (1.15–1.87)) with death in the stroke population.ConclusionPrevious stroke is an important determinant of mortality. However, the adverse combination of stroke and ND-CKD does not seem to be driven by higher levels of inflammation detected after the stroke event. Biomarkers of inflammation were associated with worse outcome in both stroke and non-stroke ND-CKD patients.Trial registration15/NW/0818.

A Systematic Review and Meta-analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers.

Dysregulation of immune responses to surgical stress in older patients and those with frailty may manifest as differences in inflammatory biomarkers. We conducted a systematic review and meta-analysis to examine differences in perioperative inflammatory biomarkers between older and younger patients, and between patients with and without frailty. MEDLINE, Embase, Cochrane, and CINAHL databases were searched (Inception to June 23, 2020). Observational or experimental studies reporting the perioperative level or activity of biomarkers in surgical patients stratified by age or frailty status were included. The primary outcome was inflammatory biomarkers (grouped by window of ascertainment: pre-op; post-op: <12 hours, 12-24 hours, 1-3 days, 3 days to 1 week, and >1 week). Quality assessment was conducted using the Newcastle-Ottawa Scale. Inverse-variance, random-effects meta-analysis was conducted. Forty-five studies (4263 patients) were included in the review, of which 36 were pooled for meta-analysis (28 noncardiac and 8 cardiac studies). Two studies investigated frailty as the exposure, while the remaining investigated age. In noncardiac studies, older patients had higher preoperative levels of interleukin (IL)-6 and C-reactive protein (CRP), lower preoperative levels of lymphocytes, and higher postoperative levels of IL-6 (<12 hours) and CRP (12-24 hours) than younger patients. In cardiac studies, older patients had higher preoperative levels of IL-6 and CRP and higher postoperative levels of IL-6 (<12 hours and >1 week). Our findings demonstrate a paucity of frailty-specific studies; however, the presence of age-associated differences in the perioperative inflammatory response is consistent with age-associated states of chronic systemic inflammation and immunosenescence. Additional studies assessing frailty-specific changes in the systemic biologic response to surgery may inform the development of targeted interventions.

Inflammatory profiles in Chilean Mapuche and non-Mapuche women with gallstones at risk of developing gallbladder cancer

Chile has high incidence rates of gallbladder cancer globally, particularly among Amerindian women, who also have a high prevalence of gallstones. We examined differences in inflammatory biomarkers between Mapuche and non-Mapuche women from the Chile Biliary Longitudinal Study, a cohort of women with ultrasound-detected gallstones. We randomly selected 200 Mapuche women frequency matched to non-Mapuche women on age and statin use Inflammatory biomarkers were analyzed using a multiplex assay and linear regression to assess associations of a priori markers (CCL20, CXCL10, IL-6, and IL-8) with ethnicity. Novel biomarkers were analyzed using exploratory factor analysis (EFA) and sufficient dimension reduction (SDR) to identify correlated marker groups, followed by linear regression to examine their association with ethnicity. The mean values of IL-8 were higher in Mapuche than non-Mapuche women (P = 0.04), while CCL20, CXCL10, and IL-6 did not differ significantly by ethnicity. EFA revealed two marker groups associated with ethnicity (P = 0.03 and P < 0.001). SDR analysis confirmed correlation between the biomarkers and ethnicity. We found higher IL-8 levels among Mapuche than non-Mapuche women. Novel inflammatory biomarkers were correlated with ethnicity and should be studied further for their role in gallbladder disease. These findings may elucidate underlying ethnic disparities in gallstones and carcinogenesis among Amerindians.

Acute Differences in Inflammatory Biomarkers Following Controlled Exposures to Cookstove Air Pollution in the STOVES Study

Background/Aim: Household air pollution from cooking with solid fuels is an important risk factor for global morbidity and mortality. Improved cookstoves have been designed and distributed to reduce household air pollution exposures, but whether such stoves meaningfully improve health remains unclear. We used a crossover design in a laboratory setting to assess the effect of pollution emitted from multiple cookstoves on acute differences in inflammatory biomarkers in healthy, young adults.Methods: Participants (n=48) were assigned to treatment sequences of 2-hour controlled exposures to air pollution emitted from five cookstoves and a filtered-air control. The treatments, administered at least 2 weeks apart, each had a fine particulate matter target concentration (µg/m3): control (0); liquefied petroleum gas (10); gasifier (35); fan rocket (100); rocket elbow (250); and three stone fire (500). Inflammatory biomarkers were measured before and 0, 3, and 24 hours after treatments: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), C-reactive protein (CRP), serum amyloid-A, tumor necrosis factor-alpha, interleukin-6, and interleukin-8. We used linear mixed models to assess differences in inflammatory biomarkers for treatments versus control.Results: ICAM-1 and VCAM-1 were higher 3 hours after all cookstove treatments (relative to control). For example, 3 hours after the three stone fire treatment, ICAM-1 was 13.1 ng/mL (95% confidence interval: 2.0, 24.3) higher than control and VCAM-1 was 6.9 ng/mL (-2.1, 16.0) higher than control. There was also evidence that CRP was higher 24 hours after cookstove treatments versus control, although confidence intervals were wide. Differences for outcomes at other time points were not consistent.Conclusions: Short-term controlled exposures to air pollution from improved and traditional cookstoves acutely impact vascular adhesion molecules and CRP. These findings may provide insight into the initial, underlying health impacts following cookstove air pollution exposures. This abstract does not represent EPA policy.

Combination therapy in inflammatory bowel disease patients: do we need to maximize the dose of azathioprine?

Background The use of combination therapy of anti-TNFα and thiopurines in inflammatory bowel disease (IBD) is associated with greater efficacy and lower immunogenicity. However, the dose of thiopurine in this setting remains to be elucidated. Aim To compare the trough levels, anti-TNFα antibodies and the inflammatory biomarkers between three groups in combotherapy: group 1 (dose of azathioprine <1 mg/kg); group 2 (dose of azathioprine ≥1 and <2 mg/kg), and group 3 (dose of azathioprine ≥2 mg/kg). Methods A retrospective study was performed, selecting all patients with established diagnosis of IBD who were on combined maintenance treatment. Results We included 99 patients, 52.5% female with median age 33 (17–61) years. Eighty patients (80.8%) were diagnosed with Crohn’s disease and 19 (19.2%) with ulcerative colitis. Seventy-one (71.8%) patients were on infliximab (IFX) and 28 (28.3%) were on adalimumab (ADA). In patients treated with IFX, there were no differences in trough levels (p=.976) or formation of antibodies anti-IFX (p=.478) between groups. Moreover, there were no differences in inflammatory biomarkers: CRP (p=.385) and fecal calprotectin (p=.576) among the three groups. Regarding patients treated with ADA, there were no differences in trough levels of ADA (p=.249), formation of antibodies anti-ADA (p=.706) or in inflammatory biomarkers: CRP (p=.738) and fecal calprotectin (p=.269) among the three groups. Conclusion In our cohort, there were no differences between anti-TNFα trough levels, formation of anti-TNFα antibodies or inflammatory biomarkers among patients in combotherapy with azathioprine, irrespective of its dosage. In conclusion, our study suggests that maintaining therapeutic levels of anti-TNFα drugs without antibodies formation is feasible with lower doses of azathioprine, minimizing its side effects.

Metabolically Healthy, but Obese Individuals and Associations with Echocardiographic Parameters and Inflammatory Biomarkers: Results from the CARLA Study.

IntroductionThe research on heterogeneity among obese individuals has identified the metabolically healthy, but obese (MHO) phenotype as a distinct group that does not experience the typical cardiovascular-related diseases (CVD). It is unclear if this group differs with regard to preconditions for CVDs. Our aim was to assess differences in echocardiographic parameters and inflammatory biomarkers between MHO and metabolically healthy, normal weight individuals (MHNW).MethodsThe analyses used data from 1412 elderly participants from a German population-based cohort study (CARLA), which collected detailed information on demographic, biochemical, and echocardiographic variables. Participants were subdivided into four groups (MHNW, MHO, MUNW (metabolically unhealthy, normal weight) and MUO (metabolically unhealthy, obese)) based on BMI≥30 kg/m2 (obese or normal weight) and presence of components of the metabolic syndrome. The clinical characteristics of the 4 groups were compared with ANOVA or Chi-Square test, in addition to two linear regression models for 16 echocardiographic parameters. The difference in inflammatory biomarkers (hsCRP, IL-6 and sTNF-RI) between the groups was examined with a multinomial logistic regression model.ResultsThe MHO individuals were on average 64.2±8.4 years old, with a higher proportion of women (71.6%), low percentage of smokers, larger waist circumference (109.3±10.5 cm vs 89.1±10.8 cm, p<0.0001) and higher odds ratios for hsCRP, IL-6 and sTNF-RI compared to MHNW individuals. Linear regression models revealed greater left atrial (LA) diameter (2.73 (95% CI: 1.35–4.11) mm), LA volume (7.86 (95% CI: 2.88–12.83) mL), and left ventricular mass index (LVMI) (11.82 (95% CI: 4.43–19.22) g/m1.7) in the MHO group compared to the MHNW group.ConclusionThe MHO phenotype is associated with echocardiographic markers of cardiac remodeling (LA diameter, volume and LVMI) and higher odds ratios for inflammatory biomarkers.

Human adenovirus 36 improves insulin sensitivity and lipid profiles and increases inflammatory markers in Wistar rats

Human adenovirus 36 (Ad-36) causes obesity with increased adiposity, in contrast, Ad-36 infection reduces glucose and lipid metabolism; the results, however, are not consistent. In the current study, the effects...

P562 5-ASA in ulcerative colitis: Are they really needed in the biological therapy era?

Abstract Background Biologic therapy has demonstrated efficacy for induction and maintenance of remission in ulcerative colitis (UC). However, it remains unclear whether oral aminosalicylates (5-ASA) should be continued or stopped after treatment escalation to biologics. The aim of the study was to evaluate differences in inflammatory biomarkers or the occurrence of complications in UC patients being treated with a combination of 5-ASA and biologics vs. biologics alone. Methods Retrospective study, including patients with UC and on biologic therapy with a minimum follow-up of 6 months. Collected inflammatory biomarkers were faecal calprotectin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The occurrence of complications was defined as the need of hospitalisation, need of corticosteroids or other top-up therapy, surgery and the occurrence of dysplasia or colorectal cancer. Results We included 65 patients with UC, 56.9% female with a mean age of 32.8 (±12.8) years. The median follow-up was 30 (6–132) months. Regarding extension, 61.5% were E3, 35.4% E2 and 3.1% E1. While 44 patients (67.7%) were on 5-ASA and biologics (infliximab = 32, adalimumab = 6, vedolizumab = 6), 21 (32.3%) were on biologics alone (infliximab = 13, adalimumab = 3, vedolizumab = 5). The median duration of biologic therapy was 30 (6–126) months. Regarding baseline characteristics, including age, gender, duration of the disease or biologic therapy and age at UC diagnosis, there were no differences between groups. No differences regarding inflammatory biomarkers were observed – fecal calprotectin (p = 0.39), CRP (p = 0.9) and ESR (p = 0.61). No differences were found regarding complications, namely the need of hospitalisation (p = 0.06) or need of corticosteroids (p = 0.89). Only one patient developed dysplasia (under infliximab and 5-ASA). Any of the included patients needed surgery or developed colorectal cancer. Conclusion About two-thirds of the UC patients under biologics are co-treated with 5-ASA. No differences between UC patients under combination biologics+5-ASA vs. biologics alone were found regarding inflammatory biomarkers or the occurrence of complications. These results raise the question if continuing 5-ASA in UC patients under biologics is really necessary.

Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): A meta-analysis of observational studies.

BackgroundThe aim of this study was to summarize and discuss the similarities and differences in inflammatory biomarkers in postoperative delirium (POD) and cognitive dysfunction (POCD).MethodsA systematic retrieval of literature up to June 2017 in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, and the Wanfang database was conducted. Extracted data were analyzed with STATA (version 14). The standardized mean difference (SMD) and the 95% confidence interval (95% CI) of each indicator were calculated using a random effect model. We also performed tests of heterogeneity, sensitivity analysis, assessments of bias, and meta-regression in this meta-analysis.ResultsA total of 54 observational studies were included. By meta-analysis we found significantly increased C-reactive protein (CRP) (9 studies, SMD 0.883, 95% CI 0.130 to 1.637, P = 0.022 in POD; 10 studies, SMD -0.133, 95% CI -0.512 to 0.246, P = 0.429 in POCD) and interleukin (IL)-6 (7 studies, SMD 0.386, 95% CI 0.054 to 0.717, P = 0.022 in POD; 16 studies, SMD 0.089, 95% CI -0.133 to 0.311, P = 0.433 in POCD) concentrations in both POD and POCD patients. We also found that the SMDs of CRP and IL-6 from POCD patients were positively correlated with surgery type in the meta-regression (CRP: Coefficient = 1.555365, P = 0.001, 10 studies; IL-6: Coefficient = -0.6455521, P = 0.086, 16 studies).ConclusionAvailable evidence from medium-to-high quality observational studies suggests that POD and POCD are indeed correlated with the concentration of peripheral and cerebrospinal fluid (CSF) inflammatory markers. Some of these markers, such as CRP and IL-6, play roles in both POD and POCD, while others are specific to either one of them.

Role of inflammatory and hemostatic biomarkers in Alzheimer's and vascular dementia - A pilot study from a tertiary center in Northern India.

A reliable plasma biomarker in differentiating between Alzheimer's disease (AD) and Vascular dementia (VaD) is the need of the hour, in most memory clinics. Even though there is no disease modifying treatment, it is important to know the type of dementia for both symptomatic treatment and prognostication. Neuropsychological assessment, MRI brain, FDG-PET brain and CSF biomarkers of AD (Aβ42 and total tau) were used for establishing the diagnosis of Mild Cognitive Impairment (MCI), AD or VaD. 68 diagnosed patients of AD/MCI/VaD were included. FDG PET brain, plasma fibrinogen, d dimer, IL6 and CRP were done in all 68 patients while 48 patients underwent CSF biomarker analysis. Sixteen patients had MCI, of which 11 were MCI-AD and 5 were MCI-VaSC. There were 41 patients with AD (Mild AD-9, Mod AD-23, Severe AD-9) and 11 patients with VaD. Alzheimer group (MCI-AD and AD) and Vascular group (MCI VaSC & VaD) consisted of 52 and 16 patients respectively. Alzheimer and Vascular groups did not exhibit significant difference in IL6 and CRP levels. Plasma fibrinogen levels were significantly higher in VaD and vascular group as compared to Alzheimer group. But MCI-VaSC was not significantly different from MCI-AD. Plasma d dimer levels were significantly higher in all vascular subgroups compared to Alzheimer subgroups except between MCI-VaSC and MCI-AD. Hemostatic biomarkers were higher in Vascular group compared to Alzheimer group whereas there was no difference in inflammatory biomarkers. But the sensitivity and specificity of fibrinogen and d-dimer were not high enough for routine clinical use. Further studies in a larger sample are required to confirm these results.

Impact of pelvic fractures on the early clinical outcomes of severely injured trauma patients.

Pelvic fractures contribute to morbidity and mortality following injury. We sought to study the impact of pelvic fractures on the clinical course and outcomes of trauma patients with a pelvic fracture in comparison to patients with similar injury severity without pelvic fracture to identify potential parameters to track patients' clinical course post-injury. A cohort of 206 consecutive blunt trauma survivors, studied over a 5-year period in a level I trauma center of which 75 patients (36.4%) had a pelvic fracture, was included in the study. To perform a retrospective cohort study with matched controls, 60 patients of the pelvic fracture group [(PF), 41 males and 19 females; age: 40 ± 17; injury severity score (ISS): 26.6 ± 9.3] were compared to 60 patients without pelvic fracture (non-PF) trauma as controls (41 males and 19 females; age: 40 ± 13; ISS: 26.9 ± 7.7), both with matching age (±5 years), sex, and ISS (±5 points). Statistically significant differences were observed in Intensive Care Unit (ICU) length of stay (LOS), total LOS, and Marshall MOD score between PF and non-PF groups, respectively. Acid-base markers such as pH, lactate, LDH, and base deficit were all significantly altered in PF compared to non-PF cohort upon admission. Moreover, our analysis showed significant differences in inflammatory biomarkers (Prolactin, CRP, and IL-6), and clinical parameters (CPK, Hgb, Platelets count, and WBC) over the 7-day clinical course in patients with PF when compared to non-PF cohort. In this matched cohort, patients with pelvic fractures exhibited biochemical and physiological alterations upon admission. Furthermore, our results suggest that pelvic fracture affects the clinical outcomes in severely injured patients, independently of injury severity, mechanism of injury, age or gender.

Pharmacological treatment and impairment of pulmonary function in patients with type 2 diabetes: a cross-sectional study.

There is no clear relationship between type 2 diabetes mellitus and lung function decline; it is also unclear whether the type of treatment can modify spirometric variables and levels of inflammatory biomarkers. To compare pulmonary function in patients with type 2 diabetes treated with an insulin-sensitizing agent (metformin) and in those treated with secretagogues, as well as combined with insulin, and to evaluate differences in inflammatory biomarkers between treatment groups. We conducted a cross-sectional analytic study in 196 diabetic patients with type 2 diabetic mellitus. Spirometric variables and levels of inflammatory biomarkers (ferritin, fibrinogen, C-reactive protein, interleukin 6, tumor necrosis factor-alpha), were obtained. Residual values (observed minus expected) for forced vital capacity and for forced expiratory volume were calculated and compared between treatment types. Differences in median levels of biomarkers were also compared. After adjustment by known determinants of lung function, and by the control and duration of type 2 diabetes, patients treated with the insulin-sensitizing agent had statistically significant lower differences against expected values for forced vital capacity compared with secretagogues (-212.1 ml vs 270.2 ml, p=0.039), as well as for forced expiratory volume, but without statistical significance (-133.2 mL vs -174.8 mL, p>0.05). In the group of patients treated with the insulin-sensitizing agent, ferritin and tumor necrosis factor-alpha levels were lower (p<0.01). This study supports the hypothesis that insulin-sensitizing agents appear to be associated with less deterioration of lung function and less systemic inflammation in type 2 diabetes. The present study serves to formulate new hypothesis and research projects.

Cardiometabolic and Inflammatory Biomarkers as Mediators Between Educational Attainment and Functioning at the Age of 90 Years.

Low socioeconomic status is associated both with poorer functioning and elevated levels of inflammatory and cardiometabolic biomarkers; however, knowledge of such relations for the oldest old is limited. Our aim was to study whether education is associated with cardiometabolic (cholesterol levels, body mass index, and leptin) and inflammatory (C-reactive protein, interleukin-6, interleukin-1Ra) biomarkers for the 90-year-olds who participated in the Vitality 90+ study. In addition, we investigated whether these biomarkers explain educational inequalities in functioning. All persons in Tampere, Finland, who were born in 1909 or 1910, were invited to participate, irrespective of their health status or dwelling place. The sample consisted of 262 participants who went through the home interview and blood tests. The socioeconomic status indicator used was the highest education, and physical functioning was assessed using the Barthel index. The association of education with individual and combined biomarker scores, and with functioning, was analyzed cross-sectionally applying generalized linear models. The low- and mid-level-educated participants had greater odds of belonging to the high risk group in cardiometabolic biomarkers than did the high-educated. Differences were statistically significant in three individual biomarkers (high-density lipoprotein-cholesterol, leptin, and body mass index) and in a cardiometabolic score. There were no educational differences in inflammatory biomarkers. When all biomarkers were combined, they mediated educational differences in functioning on an average of 23%. After controlling for smoking, alcohol use and diseases, biomarkers mediated part of the differences between the mid-level- and high-educated. High education was associated with better cardiometabolic biomarkers and functioning among the 90-year-olds. In part, educational inequalities in functioning were explained by cardiometabolic biomarkers.