Systemic Inflammatory Biomarkers Research Articles

#748 Association between systemic inflammation biomarkers and mortality in patients with SA-AKI receiving CKRT

Abstract Background and Aims Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. Method This multi-centre, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, KRT dependence at discharge, and lengths of ICU and hospital stays. Results When added to the widely accepted Acute Physiology and Chronic Health Evaluation-II score, platelet-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% CI, 0.00-0.02) and 0.02 (95% CI, 0.01-0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. Conclusion Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

Acute Kidney Injury, Systemic Inflammation and Long-term Cognitive Function: ASSESS-AKI.

Cognitive dysfunction is a well-known complication of chronic kidney disease, but it is less known whether cognitive decline occurs in survivors after acute kidney injury (AKI). We hypothesized that an episode of AKI is associated with poorer cognitive function, mediated, at least in part, by persistent systemic inflammation. ASSESS-AKI enrolled patients surviving three months after hospitalization with and without AKI matched based on demographics, comorbidities, and baseline kidney function. A subset underwent cognitive testing using the modified mini-mental status examination (3MS) at 3, 12, and 36 months. We examined the association of AKI with 3MS scores using mixed linear models and assessed the proportion of risk mediated by systemic inflammatory biomarkers. Among 1538 participants in ASSESS-AKI, 1420 (92%) completed the 3MS assessment at 3 months and had a corresponding matched participant. Participants with AKI had lower 3MS scores at three years (difference -1.1 (95% CI: -2.0, -0.3) P=0.009) compared to participants without AKI. A higher proportion of AKI participants had a clinically meaningful (≥ 5 point) reduction in 3MS scores at three years compared to participants without AKI (14% vs. 10%, P=0.04). In mediation analyses, plasma soluble tumor necrosis factor receptor-1 (sTNFR-1) at three months after AKI mediated 35% (P=0.02) of the AKI related risk for 3MS scores at three years. AKI was associated with lower 3MS scores and sTNFR-1 concentrations appeared to mediate a significant proportion of the risk of long-term cognitive impairment. Further work is needed to determine if AKI is causal or a marker for cognitive impairment.

Genetic association of inflammatory marker GlycA with lung function and respiratory diseases

Association of circulating glycoprotein acetyls (GlycA), a systemic inflammation biomarker, with lung function and respiratory diseases remain to be investigated. We examined the genetic correlation, shared genetics, and potential causality of GlycA (N = 115,078) with lung function and respiratory diseases (N = 497,000). GlycA showed significant genetic correlation with FEV1 (rg = −0.14), FVC (rg = −0.18), asthma (rg = 0.21) and COPD (rg = 0.31). We consistently identified ten shared loci (including chr3p21.31 and chr8p23.1) at both SNP and gene level revealing potential shared biological mechanisms involving ubiquitination, immune response, Wnt/β-catenin signaling, cell growth and differentiation in tissues or cells including blood, epithelium, fibroblast, fetal thymus, and fetal intestine. Genetically elevated GlycA was significantly correlated with lung function and asthma susceptibility (354.13 ml decrement of FEV1, 442.28 ml decrement of FVC, and 144% increased risk of asthma per SD increment of GlycA) from MR analyses. Our findings provide insights into biological mechanisms of GlycA in relating to lung function, asthma, and COPD.

Abstract PO3-09-06: Role of Obesity-Related Biomarkers on Mortality Among Black Breast Cancer Survivors in the Women’s Circle of Health Followup Study

Abstract Background: Central obesity and higher adiposity have been recently associated with higher all-cause and breast cancer-specific mortality in Black breast cancer survivors participating in the Women’s Circle of Health Followup Study. Adipose tissue is a dynamic organ producing adipocytokines, including leptin, adiponectin, adipsin, resistin, lipocalin-2/NGAL, plasminogen-activator inhibitor type 1 (PAI-1) and CXCL11, TNFα, and IL-6, which modulate inflammatory markers in obesity, including the release of proinflammatory C-reactive protein (CRP). These circulating biomarkers play important roles linking obesity with insulin resistance, hyperinsulinemia, chronic inflammation, and altered immunity, which may impact overall and breast cancer mortality. The goal of this analysis was to determine if circulating adipocytokines and obesity-related biomarkers of systemic inflammation are associated with breast cancer and overall survival in Black breast cancer survivors. Methods: Circulating biomarkers were assayed for 460 Black breast cancer survivors who provided a blood sample 2 years post-diagnosis in the Women’s Circle of Health Followup Study, a population-based cohort of Black breast cancer survivors in New Jersey enrolled within 12 months of diagnosis. Associations between biomarkers (by tertiles) and overall survival were assessed using multivariable Cox regression models. Breast cancer specific survival was assessed based on competing risk analyses using the Fine and Gray subdistribution hazard model. Multivariable models were adjusted for age, body mass index as a measure of overall adiposity, education, menopausal status, stage, grade, subtype, and chemotherapy, hormonal therapy, and radiation treatments received. All tests were two-sided at Analyses were conducted at P=0.05. Results: In multivariable analyses, lipocalin-2, CXCL11, and CRP, biomarkers of adipose tissue inflammation closely related to insulin resistance, were associated with worse overall but not breast cancer specific survival. Compared to women in the lowest tertile of lipocalin-2, women in the highest tertile had a 3-fold increased risk of dying from any cause (T3 vs T1, HR=3.08, 95% CI: 1.29-7.39, p= 0.004) and a ~2-fold increased risk of dying from breast cancer, which was not statistically significant (HR= 1.84, 95% CI: 0.59-5.79, p=0.30). Similarly, women in the highest tertile of CXCL11 were at 2-fold increased risk of dying of any cause (HR: 2.10, 95% CI: 0.96-4.57, p=0.06) but no associations were observed with risk of dying from breast cancer (HR:1.31, 0.42-4.13, p=0.64). Circulating CRP, as a marker of systemic inflammation, was also associated with worse overall survival (T3 vs T1 HR: 2.51, 95% CI: 1.07-5.89, p=0.03), showing a borderline significant association with increased breast cancer specific survival (T3 vs T1 HR: 4.32, 95% CI: 0.87-21.38, p=0.07). No associations with overall or breast cancer specific mortality were observed for any of the other adipocytokines examined. Conclusion: In this population-based cohort study of Black breast cancer survivors, biomarkers associated with adipose tissue related inflammation and insulin resistance were associated with reduced overall survival. Relationships with breast cancer survival were not significant, possibly due to limited sample size. Citation Format: Shipra Gandhi, Chi-Chen Hong, Anthony George, Kristopher Attwood, Bo Quin, Nur Zeinomar, Yong Lin, Christine Ambrosone, Kitaw Demissie, Elisa Bandera. Role of Obesity-Related Biomarkers on Mortality Among Black Breast Cancer Survivors in the Women’s Circle of Health Followup Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-06.

The connection of vitamin D with biomarkers of systemic inflammation in patients with COVID-19

The connection of vitamin D with biomarkers of systemic inflammation in patients with COVID-19

Associations between trans fatty acids and systemic immune-inflammation index: a cross-sectional study

BackgroundPrevious studies have demonstrated that trans fatty acids (TFAs) intake was linked to an increased risk of chronic diseases. As a novel systemic inflammatory biomarker, the clinical value and efficacy of the systemic immune-inflammation index (SII) have been widely explored. However, the association between TFAs and SII is still unclear. Therefore, the study aims to investigate the connection between TFAs and SII in US adults.MethodsThe study retrieved data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999–2000 and 2009–2010. Following the exclusion of ineligible participants, the study encompassed a total of 3047 individuals. The research employed a multivariate linear regression model to investigate the connection between circulating TFAs and SII. Furthermore, the restricted cubic spline (RCS) model was utilized to evaluate the potential nonlinear association. Subgroup analysis was also conducted to investigate the latent interactive factors.ResultsIn this investigation, participants exhibited a mean age of 47.40 years, with 53.91% of them being female. Utilizing a multivariate linear regression model, the independent positive associations between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, and the log2-transformed-total sum of TFAs with the SII (all P < 0.05) were noted. In the RCS analysis, no nonlinear relationship was observed between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, the log2-transformed-total sum of TFAs and the SII (all P for nonlinear > 0.05). For the stratified analysis, the relationship between the circulating TFAs and the SII differed by the obesity status and the smoking status.ConclusionsA positive association was investigated between three types of TFA, the sum of TFAs, and the SII in the US population. Additional rigorously designed studies are needed to verify the results and explore the potential mechanism.

Prognostic Biomarkers of Systemic Inflammation in Non-Small Cell Lung Cancer: A Narrative Review of Challenges and Opportunities.

Non-small cell lung cancer (NSCLC) is a common malignancy and is associated with poor survival outcomes. Biomarkers of systemic inflammation derived from blood tests collected as part of routine clinical care offer prognostic information for patients with NSCLC that may assist clinical decision making. They are an attractive tool, as they are inexpensive, easily measured, and reproducible in a variety of healthcare settings. Despite the wealth of evidence available to support them, these inflammatory biomarkers are not yet routinely used in clinical practice. In this narrative review, the key inflammatory indices reported in the literature and their prognostic significance in NSCLC are described. Key challenges limiting their clinical application are highlighted, including the need to define the optimal biomarker of systemic inflammation, a lack of understanding of the systemic inflammatory landscape of NSCLC as a heterogenous disease, and the lack of clinical relevance in reported outcomes. These challenges may be overcome with standardised recording and reporting of inflammatory biomarkers, clinicopathological factors, and survival outcomes. This will require a collaborative approach, to which this field of research lends itself. This work may be aided by the rise of data-driven research, including the potential to utilise modern electronic patient records and advanced data-analysis techniques.

Association of two novel systemic inflammatory biomarkers and frailty based on NHANES 2007-2018.

Frailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States. This study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot. This study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24-1.54) and 1.69 (1.53-1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55-2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10-1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95-2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty. The results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma

The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain. To determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma. EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during three years of observation in 480 participants in the Severe Asthma Research Program (SARP)-3. Over three years, EPX levels in asthma patients were higher than normal in 27-31% of serum samples and 36-53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (rs values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts < 150 cells/uL and 42% of participants with blood eosinophil counts 150-299 cells/uL. Patients with persistently high sputum EPX values for three years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 asthma patients who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized. Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation.

Evaluation of Ocular Surface Parameters and Systemic Inflammatory Biomarkers in Hazelnut Harvesters

ABSTRACT Aim To assess the relationship between systemic inflammation markers and ocular surface parameters in hazelnut harvesters. Material and Method This prospective study included 30 patients presenting with moderate ocular surface diseases during the hazelnut harvesting season. A detailed ophthalmological examination was performed during the harvesting season and the first month after the end of treatment (control). Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) scores were determined. In complete blood count analysis, in addition to the evaluation of inflammatory cells, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were calculated. Results Eosinophil percentage had a high level of negative correlation with the TBUT and Schirmer values and a high level of positive correlation with the OSDI score during the hazelnut picking season (r = –0.727, r = –0.735, r = 0.750, respectively). During the hazelnut harvesting season, the NLR and SII parameters had a moderate level of negative correlation with the TBUT (r = –0.29 and r = −0.276) and Schirmer (r = –0.33 and r = −0.298) values and a moderate level of positive correlation with the OSDI score (r = 0.389 and r = 0.264). Conclusion In hazelnut harvesters, ocular allergy and inflammation may be associated with systemic biomarkers.

Genetic factors associated with age-related macular degeneration modulating plasma inflammatory biomarker levels in patients with AIDS

ABSTRACT Introduction Patients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS. Materials and Methods Cryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C × 3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C × 3motif chemokine receptor 1 (CX3CR1). Results In Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels. Conclusions Genetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS.

Racial Differences in Vaginal Fluid Metabolites and Association with Systemic Inflammation Markers among Ovarian Cancer Patients: A Pilot Study.

The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50-70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1β, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.

Abstract 7649: Inflammatory biomarkers by sarcopenia status in diverse individuals with lung cancer

Abstract Background: Sarcopenia and inflammation are independent prognostic indicators of poor survival in lung cancer. Systemic inflammation contributes to sarcopenia or low muscle mass through increased catabolism and decreased synthesis of muscle protein. In turn, sarcopenia leads to inflammation in the muscle and exacerbation of systemic inflammation. Specific Aim: The aim of this study was to determine the association between sarcopenia and systemic biomarkers of inflammation including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and albumin in diverse individuals with lung cancer and determine their use as prognostic indicators of sarcopenia. Methods: This retrospective cross-sectional study included 218 non-Hispanic Black (n=111) and White (n=107) individuals with lung cancer. Computed tomography scans were analyzed to calculate skeletal mass index (SMI) at the third lumbar vertebra. Sarcopenia was defined using published sex-specific criteria for SMI in healthy individuals then categorized into the binary variable of sarcopenia/no sarcopenia. NLR, PLR, and albumin were analyzed as both continuous and categorical variables, with NLR&amp;gt; 3, PLR &amp;gt;150, and albumin &amp;lt;3.5 defining moderate to high inflammation. T-tests, Mann Whitney U, Chi square, and adjusted Logistic Regression were used as appropriate. Results: Subjects presented with a mean age of 68.5 + 9.8 years, BMI of 26.3 + 5.9 kg/m2, 50.9% non-Hispanic Black, and 49.5% female with significantly higher prevalence of late-stage lung cancer (61.9% versus 38.1% early-stage, p&amp;lt;0.001) and no differences in age and BMI by race/ethnicity. Mean NLR (6.2 + 7.2), PLR (226.9 + 157.9), and albumin (3.2 + 0.6) indicated an inflammatory state in diverse individuals with lung cancer, with significantly higher NLR (8.5 + 9.7 versus 4.7 + 4.2, p&amp;lt;0.001) and PLR (268.9 + 204.5 versus 198.7 + 108.9, p&amp;lt;0.01) and significantly lower albumin (3.1 + 0.7 versus 3.4 + 0.5, p&amp;lt;0.01) in those with sarcopenia compared to those without sarcopenia. The odds of sarcopenia were 2.2 higher with NLR &amp;gt; 3 compared to NLR &amp;lt;3 (95% CI: 1.1, 4.4) and 2.5 higher with albumin &amp;lt;3.5 compared to albumin &amp;gt;3.5 (95% CI: 1.2, 5.3) after controlling for race/ethnicity, stage of cancer, age, and BMI. PLR &amp;gt; 150 was not a significant predictor of sarcopenia. Conclusion: Diverse individuals with sarcopenia of lung cancer present with higher inflammation compared to individuals with lung cancer but without sarcopenia as indicated by NLR, PLR, and albumin levels. Moderate to high levels of inflammation as indicated by high NLR and low albumin may help predict sarcopenia status in diverse individuals with lung cancer. Citation Format: Cecily A. Byrne, Giamila Fantuzzi, Vanessa M. Oddo, Sage Kim, Timothy J. Koh, Sandra L. Gomez. Inflammatory biomarkers by sarcopenia status in diverse individuals with lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7649.

Indoor and ambient black carbon and fine particulate matter associations with blood biomarkers in COPD patients

BackgroundSystemic inflammation contributes to cardiovascular risk and chronic obstructive pulmonary disease (COPD) pathophysiology. Associations between systemic inflammation and exposure to ambient fine particulate matter (PM ≤ 2.5 μm diameter; PM2.5), and black carbon (BC), a PM2.5 component attributable to traffic and other sources of combustion, infiltrating indoors are not well described. MethodsBetween 2012 and 2017, COPD patients completed in-home air sampling over one-week intervals, up to four times (seasonally), followed by measurement of plasma biomarkers of systemic inflammation, C-reactive protein (CRP) and interleukin-6 (IL-6), and endothelial activation, soluble vascular adhesion molecule-1 (sVCAM-1). Ambient PM2.5, BC and sulfur were measured at a central site. The ratio of indoor/ambient sulfur in PM2.5, a surrogate for fine particle infiltration, was used to estimate indoor BC and PM2.5 of ambient origin. Linear mixed effects regression with a random intercept for each participant was used to assess associations between indoor and indoor of ambient origin PM2.5 and BC with each biomarker. Results144 participants resulting in 482 observations were included in the analysis. There were significant positive associations between indoor BC and indoor BC of ambient origin with CRP [%-increase per interquartile range (IQR);95 % CI (13.2 %;5.2–21.8 and 11.4 %;1.7–22.1, respectively)]. Associations with indoor PM2.5 and indoor PM2.5 of ambient origin were weaker. There were no associations with IL-6 or sVCAM-1. ConclusionsIn homes of patients with COPD without major sources of combustion, indoor BC is mainly attributable to the infiltration of ambient sources of combustion indoors. Indoor BC of ambient origin is associated with increases in systemic inflammation in patients with COPD, even when staying indoors.

Abstract 7621: Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer

Abstract Background: Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy. Methods: Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers, could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy. Results: Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20-2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P&amp;lt;.0001, HR 0.33, 95% CI: 0.20-0.55) and the metastatic cohort (P&amp;lt;.0001, HR 0.28, 95% CI: 0.15-0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P&amp;lt;.0001). Conclusion: Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy. Citation Format: Zhanpeng Kuang, Jessica Miao, Xiaoli Zhang. Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7621.

Biomarkers of systemic inflammation are associated with disease severity and metabolic syndrome in patients with hidradenitis suppurativa

BackgroundBiomarkers associated with disease severity and comorbid metabolic syndrome (MetS) in patients with hidradenitis suppurativa (HS) are lacking. ObjectiveTo identify biomarkers associated with disease severity and comorbid MetS in patients with HS. MethodsData on hospital outpatients with HS were obtained through clinical examination and interviews. Indicators of systemic inflammation; C-reactive protein (CRP), erythrocyte sedimentation-rate (ESR), neutrophil/lymphocyte-ratio (NLR), platelet/lymphocyte-ratio (PLR), monocyte/lymphocyte-ratio (MLR), platelet/neutrophil-ratio (PNR), pan-immune-inflammation-value (PIV) and systemic-immune-inflammatory-index (SII), were calculated from blood samples. Results700 patients were included; of those 444 (63.4%) and 256 (36.6%) were female and male, respectively, with a median age of 38.3 years (IQR=27.9-51.0). Increasing CRP, ESR, NLR, PIV, and SII (p<0.001) were significantly associated with increasing Hurley-stage and IHS4-scores in adjusted analysis. A doubling in CRP (OR 1.59 (1.36-1.85), p<0.001), ESR (OR 1.39 (1.17-1.66), p<0.001) and PIV (OR 1.41 (1.12-1.77) p=0.002) was associated with MetS in adjusted analysis. ESR was the best estimator for severe IHS4 (AUC=0.72 (0.66-0.77), p<0.001) and Hurley III (AUC=0.79 (0.73-0.85), p<0.001) whereas CRP was best for MetS (AUC=0.67 (0.62-0.72), p<0.001). LimitationsPatients in a hospital setting tend to have more severe disease. ConclusionBiomarkers like CRP, ESR, and PIV measuring systemic inflammation were associated with disease severity and comorbid MetS in patients with HS.

Association of intrinsic capacity with functional ability, sarcopenia and systemic inflammation in pre-frail older adults.

Decline in intrinsic capacity (IC) has been shown to accelerate progression to disability. The study aims to explore association of IC composite score with functional ability, sarcopenia and systemic inflammation in pre-frail older adults. Cross-sectional study of pre-frail older adults ≥60 years old recruited from the community and primary care centers. Composite scores of four domains of IC were measured: locomotion, vitality, cognition and psychological. FRAIL scale was used to define pre-frailty. Muscle mass was measured using the bioelectrical impedance analysis. Systemic inflammation biomarkers [Interleukin-6 (IL-6), Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), and Growth differentiated factor 15 (GDF-15)] were measured. Participants in the lowest tertile (T1) exhibited greater decline in IC. A total of 398 pre-frail older adults were recruited, mean age was 72.7 ± 5.8 years, 60.1% female, education level 7.8 years, and 85.2% were of Chinese ethnicity. A total of 75.1% had decline in locomotion, 40.5% in vitality, 53.2% in cognition and 41.7% in psychological domain. A total of 95% had decline in at least one domain. T1 was significantly associated with ADL impairment (aOR 3.36, 95% CI 1.78-6.32), IADL impairment (aOR 2.37, 95% CI 1.36-4.13), poor perceived health (aOR 0.96, 95% CI 0.95-0.98), fall (aOR 1.63, 95% CI 1.05-2.84), cognitive impairment (aOR 8.21, 95% CI 4.69-14.39), depression (aOR 101.82, 95% CI 33.62-308.37), and sarcopenia (aOR 2.40, 95% CI 1.60-5.45). T1 had significant associations with GDF-15, IL-10, and IL-10 to TNF-α ratio. Decline in IC composite score among pre-frail older adults was associated with functional limitation, sarcopenia, and systemic inflammation.

Rapid and Convenient Single-Chain Variable Fragment-Employed Electrochemical C-Reactive Protein Detection System.

Although IgG-free immunosensors are in high demand owing to ethical concerns, the development of convenient immunosensors that alternatively integrate recombinantly produced antibody fragments, such as single-chain variable fragments (scFvs), remains challenging. The low affinity of antibody fragments, unlike IgG, caused by monovalent binding to targets often leads to decreased sensitivity. We improved the affinity owing to the bivalent effect by fabricating a bivalent antibody-enzyme complex (AEC) composed of two scFvs and a single glucose dehydrogenase, and developed a rapid and convenient scFv-employed electrochemical detection system for the C-reactive protein (CRP), which is a homopentameric protein biomarker of systemic inflammation. The development of a point-of-care testing (POCT) system is highly desirable; however, no scFv-based CRP-POCT immunosensors have been developed. As expected, the bivalent AEC showed higher affinity than the single scFv and contributed to the high sensitivity of CRP detection. The electrochemical CRP detection using scFv-immobilized magnetic beads and the bivalent AEC as capture and detection antibodies, respectively, was achieved in 20 min without washing steps in human serum and the linear range was 1-10 nM with the limit of detection of 2.9 nM, which has potential to meet the criteria required for POCT application in rapidity, convenience, and hand-held detection devices without employing IgGs.

Depth of invasion of oral squamous cell carcinoma in Nos2-knockout mice correlated to alterations in systemic inflammatory markers following 4NQO treatment.

Peripheral blood analysis is a non-invasive and low-cost technique of prognostic value for several diseases, including oral cancer. Considering the role of inducible nitric oxide synthase in tumor-associated inflammation, this study purposed to evaluate the influence of this enzyme on peripheral blood parameters and systemic inflammatory biomarkers during murine oral carcinogenesis. A 50 μg/mL solution of 4-nitroquinoleine-N-oxide was provided to 15 C57BL/6J (Nos2+/+ ) and 16 B6.129P2-Nos2tm1Lau /J (Nos2-/- ) for 16 weeks. Animals were followed for 8 weeks after treatment. Blood samples and tongues were collected for hematological and histopathological analyses. Red blood cells, white blood cells, and platelet cell parameters were analyzed. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index were also calculated. The depth of invasion of all carcinomas was measured. Differences were found in several blood parameters. The depth of invasion in Nos2-/- was lower than in Nos2+/+ (p = 0.009), and strong correlations were found between depth of invasion and neutrophil count (ρ = -0.68, p = 0.017), lymphocyte count (ρ = 0.72, p = 0.011), neutrophil-to-lymphocyte ratio (ρ = -0.65, p = 0.025), platelet-to-lymphocyte ratio (ρ = -0.73, p = 0.013), and systemic immune-inflammation index (ρ = -0.67, p = 0.037) in Nos2-/- mice. Inducible nitric oxide synthase seems to have an important role in OSCC invasion and progression, which might be associated to alterations in immune-inflammatory cell dynamics evidenced by peripheral blood and systemic inflammatory biomarkers.

Impact of subgingival instrumentation on systemic inflammation and serum bone resorption marker in premenopausal women with periodontitis: a prospective interventional study.

Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health.