Inflammatory Biomarkers In Patients Research Articles

The Impact of Sodium-Glucose Co-Transporter-2 Inhibition on Insulin Resistance and Inflammation in Patients with Type 2 Diabetes: A Retrospective Study

Background and Objectives: Insulin resistance (IR) is a key factor involved in the development of type 2 diabetes (T2D). Besides its role in the pathogenesis of T2D, insulin resistance is associated with impairment of glycemic control, reduced achievement of glycemic targets, and increases in cardiovascular risk and diabetes complications, being thus a negative prognosis factor. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are therapies for T2D which demonstrated, besides glycemic control, improvements of biomarkers traditionally associated with IR and inflammation. This study aimed to evaluate the impact of SGLT2i treatment on IR and inflammation biomarkers in patients with T2D. Materials and Methods: In a retrospective study, 246 patients with T2D treated with SGLT2i for a median of 5 years were evaluated regarding IR (estimated glucose disposal rate—eGDR, triglyceride/glucose index, triglyceride/HDLc index) and inflammation biomarkers (neutrophils to lymphocyte ratio, platelets to lymphocytes ratio and C-reactive protein) before and after intervention with SGLT2i. Results: After a median 5 years of SGLT2i treatment, patients with T2D had a higher eGDR (6.07 vs. 5.24 mg/kg/min; p < 0.001), lower triglyceride/HDLc ratio (3.34 vs. 3.52, p < 0.001) and lower triglyceride/glucose index (9.23 vs. 9.58; p < 0.001). The inflammation biomarkers decreased after SGLT2i therapy: C-reactive protein (3.07 mg/L vs. 4.37 mg/L), NLR (0.68 vs. 0.72; p < 0.001), and PLR (115 vs. 122; p < 0.001). Intervention with SGLT2i also improved the biomarkers associated with diabetes complications and cardiovascular risk: HbA1c (7.1% vs. 8.4%; p < 0.001), body mass index (30.0 vs. 31.5 kg/m2; p < 0.001) and urinary albumin to creatinine ratio (4.75 vs. 11.00 mg/g; p < 0.001). Conclusions: Treatment with SGLT2i in patients with T2D leads to decreases in IR and inflammation. These mechanisms may partially explain the additional cardiovascular and renal risk reductions associated with SGLT2i therapy, alongside the improvements in glycemic control, in patients with T2D.

Features of infl ammatory biomarkers in patients with occupational COPD and cardiovascular comorbidity

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, with over 30% of these patients dying from cardiovascular diseases. Objective: to study the pathophysiological links between echocardiography, spirometry indicators, and inflammatory biomarkers in patients with various clinical phenotypes of occupational COPD with cardiovascular comorbidity. Material and methods. The study included 111 patients with occupational COPD and cardiovascular comorbidity. Based on spirometry results, patients were divided into 4 groups (clinical phenotypes). Clinical examinations, echocardiography, and serum concentrations of troponin I, endothelin-1 (E-1), endothelial synthase (ES), hyaluronic acid (HA), and myoglobin were performed. Results. The concentrations of troponin I, myoglobin, and E-1 were normal in all groups. HA concentration was highest among phenotype “E” patients (p = 0.0008). ES concentration in phenotype “E” was more than 2.5 times higher compared to other groups (p = 0.0022). Myoglobin concentration positively correlated with left ventricular myocardium thickness, ES, eosinophil levels, and coronary heart disease (p < 0.05), while ES concentration correlated positively with hypertension. HA concentration negatively correlated with spirometry and echocardiography indicators and positively correlated with eosinophil levels and exacerbations (p < 0.05). Conclusion. Further research is needed to identify biomarkers reflecting the risk of exacerbations in cardiovascular comorbidities in patients with occupational COPD

Aspirin modulates inflammatory biomarkers in patients with subcortical silent brain infarcts.

This study aimed to identify differences in the levels of inflammation-related biomarkers between patients with subcortical silent brain infarcts (SBIs) and healthy controls. We also evaluated the effect of aspirin on the subcortical SBI inflammatory processes. Consecutive patients diagnosed with subcortical SBIs without a history of acute stroke were included. The demographic and clinical data of the 26 subjects with subcortical SBIs, such as the number and location of subcortical SBIs, were reviewed. Plasma levels of macrophage migration inhibitory factor (MIF), matrix metalloproteinase-9 (MMP-9), and visfatin were measured in patients with subcortical SBIs and ten healthy participants. These biomarkers were rechecked in patients with subcortical SBI 3 months after taking aspirin (100 mg/day). MIF and MMP-9 levels were significantly higher in patients with subcortical SBIs than in healthy control group (p = 0.031 and p = 0.026, respectively). Although MIF and MMP-9 did not show significant changes after taking aspirin for 3 months, the median plasma level of visfatin was significantly decreased from 1.00 ng/mL (range, 0.86-1.16 ng/mL) to 0.84 ng/mL (range, 0.77-0.91 ng/mL) (p = 0.002) after taking aspirin. Inflammation could be an essential factor in the pathogenesis of subcortical SBIs, and aspirin affects several inflammation-related biomarkers.

Prognostic Value of Blood-Based Inflammatory Markers in Cancer Patients Receiving Immune Checkpoint Inhibitors.

Background: Although immune checkpoint inhibitors (ICIs) have significantly improved cancer treatment, a substantial proportion of patients do not benefit from these therapies, revealing the crucial need to identify reliable biomarkers. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), pan-immune inflammation value (PIV), systemic inflammation response index (SIRI), lactate dehydrogenase (LDH), and C-reactive protein (CRP), may provide insights into treatment outcomes. Objectives: This study aimed to evaluate the prognostic value of multiple inflammatory markers in patients with cancer receiving ICI-based therapies. Methods: A retrospective analysis was performed on 226 patients treated with ICI-based therapies at a single center between 2012 and 2023. The inflammatory markers NLR, PIV, SII, SIRI, LDH, CRP, and albumin were assessed. Cut-off values were determined using maximally selected rank statistics, and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox regression analysis. Results: High NLR, PIV, SII, SIRI, LDH, and CRP, as well as low albumin levels, were associated with worse OS and PFS (p < 0.001). In the multivariate analysis, high CRP, LDH, NLR, PIV, and SII independently predicted worse OS. Conclusions: Our findings confirm the prognostic utility of several inflammatory biomarkers in patients with cancer receiving ICIs, highlighting their potential for treatment stratification. Further studies are necessary to standardize cut-off values and validate these findings across broader, more diverse populations.

Uric Acid Correlates with Serum Levels of Mineral Bone Metabolism and Inflammation Biomarkers in Patients with Stage 3a-5 Chronic Kidney Disease.

Background and Objectives: Uric acid (UA) and the markers of mineral bone metabolism and inflammation are commonly altered in patients with chronic kidney disease (CKD) and are associated with the risk of cardiovascular complications and death. Studies point to a link between high serum UA and mineral bone homeostasis and inflammation, but controversy remains. The aim of this study was to evaluate the relationship between UA levels and mineral bone metabolism and inflammation biomarkers in a sample of Mexican patients with CKD 3a-5. Materials and Methods: This cross-sectional study included 146 Mexican patients with CKD 3a-5. In addition, 25 healthy subjects were included in the study with the aim of generating reference data for comparisons. Metabolic parameters including UA serum concentrations, mineral bone metabolism (parathormone (PTH), fibroblast growth factor 23 (FGF23), calcium, and phosphate), and inflammation (interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α)) biomarkers were measured in all of the samples and compared as a function of the estimated glomerular function rate (eGFR) or UA levels. Results: Intact PTH, FGF23, and cytokines were higher in advanced CKD stages. Patients with hyperuricemia had significantly higher values of FGF23 and TNF-α compared with those without hyperuricemia. The eGFR was found to be significantly and negatively correlated with all markers. Uric acid was significantly correlated with phosphate, iPTH, FGF23, and TNF-α, whereas iPTH was significantly correlated with FGF23, TNF-α, and FGF23. Finally, a multivariate analysis confirmed the relationship of eGFR with all the tested biomarkers, as well as other relationships of iPTH with UA and TNF-α and of FGF23 with UA and TNF-α. Conclusions: This study supports the relationship between uric acid and levels of mineral bone metabolism and inflammation biomarkers in patients with CKD at middle to advanced stages. In the follow-up of patients with CKD, monitoring and controlling UA levels through nutritional or pharmacological interventions could help in the prevention of alterations related to mineral bone metabolism.

Relationship Between White Blood Cell, Neutrophil-to-Lymphocyte Ratio, Procalcitonin, and Severe Community-Acquired Pneumonia in a Private Tertiary Hospital

Background: Studies have tried to determine the diagnostic value of serum inflammatory biomarkers in patients with community-acquired pneumonia (CAP) to help guide clinical decision making. This study aimed to determine the relationship between white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), and severe CAP. Methodology: This study reviewed records of patients aged 18 years and above diagnosed with CAP from January 2022 to January 2024 at Perpetual Help Medical Center—Las Piñas. Data collected were demographics, WBC and neutrophil and lymphocyte counts, procalcitonin, and CURB-65 scores. ROC curve analysis was done to determine the best cut-off for WBC, NLR, and procalcitonin in diagnosing severe CAP (CURB-65 score 3-5). Pearson correlation test was used to determine pairwise correlations between WBC, NLR, and procalcitonin. Results: A total of 120 patients were included. The mean WBC count and mean NLR were higher among patients with elevated PCT than those with normal PCT (15.2 ± 5.8 vs 10.7 ± 3.7; p &lt;0.001 and 18.6 ± 17.9 vs 8.6 ± 7.9; p = 0.005, respectively). The prevalence of severe pneumonia was higher in patients with elevated PCT than those with normal PCT (65.8% vs 12.8%; p &lt;0.001). Procalcitonin level at a threshold of 0.5 ng/mL showed the highest sensitivity (90%, 95% confidence interval [CI] 0.77 to 0.97) and best test performance (area under the ROC 0.79, 95% CI 0.72 to 0.86) in diagnosing severe pneumonia. The mean NLR was weakly correlated with WBC (r = 0.300; p = 0.002). The mean PCT was moderately correlated with WBC (r = 0.637, p = 0.04) and NLR (r = 0.750, p = 0.03). Conclusion: Procalcitonin shows acceptable performance in diagnosing severe pneumonia. This study also suggests a significant correlation between WBC, NLR, and PCT. Multicenter studies are recommended to better generalize the results to the larger population.

Estimation of lipid profile and some inflammatory biomarkers in patients with diabetes mellitus type 2 linked to hypertension

Diabetes Mellitus (DM) and hypertension are two common diseases that impact a significant section of the population . Pro-inflammatory mediators such as Interferon Gamma (IFN-γ) and C-Reactive Protein (CRP) levels are proposed to be linked to these diseases. The present study was aimed to explore the link between IFN- γ, CRP and lipid profile levels In type 2 diabetes mellitus (T2DM) connected to hypertension. The current study included 78 patients who had T2DM and 40 samples were collected from healthy people, both aged from 35 to 60 years. The total number of T2DM patients group were divided into two groups: 41 patients with Hypertension (HP) and 37 patients without HP, and according to their Body Mass Index (BMI). In addition, the relationship between gender and these diseases was also investigated. The results showed that the levels of Total Cholesterol (TC), Triglycerides (TG), Low-Density Lipoproteins (LDL), and Very Low-Density Lipoproteins (VLDL) were significantly increased in T2DM patients in both women and men. The results also showed a significant increase in the levels of TC, TG, LDL and VLDL in overweighted T2DM patients with HP. However, the levels of High-Density Lipoprotein (HDL) were significantly decreased in all T2DM patients. Moreover, the levels of CRP were significantly increased in T2DM female and male patients. However, the levels of IFN-γ significantly decreased in T2DM female and male patients. Furthermore, body fat percentage and waist/hip ratio significantly increased and were associated with Fasting Blood Sugar (FBS), TC, and CRP in T2DM patients. The findings confirm that lipid profile and pro-inflammatory parameters, such as CRP and IFN-γ, could have a significant impact on T2DM burden that is connected to the presence of HP. Therefore, regulating of lipid profile and pro-inflammatory parameters (CRP and IFN-γ) could protect against development and progression of T2DM accompanied by HP.

Retrospective Analysis of Blood Inflammatory Biomarkers in Patients with Oral Lichen Planus: Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio.

Objectives: Oral lichen planus (OLP) is a potentially malignant disorder and a chronic inflammatory condition of an immune nature. The aim of this study was to investigate the association between immune-inflammatory biomarkers in patients with OLP and a control group. Materials and Methods: This was a retrospective study with 129 patients (62 with OLP and 67 controls) in which clinical and laboratory data were analyzed. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the mean platelet volume (MPV) index, and the parameter of systemic immune-inflammation index (SII) were assessed. Results: In patients with OLP, the average time of progression was significantly longer when the condition manifested in the atrophic-erosive form (4.3 ± 3.2 years) as opposed to the reticular form (1.8 ± 0.9 years) (p = 0.018). With regard to NLR, no differences were found in terms of age (p = 0.346 (r = 0.08)), tobacco use (p = 0.807), sex (p = 0.088), alcohol consumption (p = 0.281), clinical form of OLP (p = 0.55), time of progression of OLP (p = 0.309 (r = -0.13)), and number of sites (p = 0.217). The same was observed for the systemic immune-inflammation index. Conclusion: The lack of significant statistical associations between the biomarkers and parameters (NLR, PLR, MPV, and SII index) in patients with oral lichen planus makes such parameters of very limited use in clinical OLP practice.

Noninvasive, Multimodal Inflammatory Biomarker Discovery for Systemic Inflammation (NOVA Study): Protocol for a Cross-Sectional Study.

Prolonged systemic inflammation is recognized as a major contributor to the development of various chronic inflammatory diseases. Daily measurements of inflammatory biomarkers can significantly improve disease monitoring of systemic inflammation, thus contributing to reducing the burden on patients and the health care system. There exists, however, no scalable, cost-efficient, and noninvasive biomarker for remote assessment of systemic inflammation. To this end, we propose a novel, multimodal, and noninvasive approach for measuring inflammatory biomarkers. This study aimed to evaluate the relationship between the levels of inflammatory biomarkers in serum (gold standard) and those measured noninvasively in urine, sweat, saliva, exhaled breath, stool, and core body temperature in patients with systemic inflammation. This study is a single-center, cross-sectional study and includes a total of 20 participants (10 patients with systemic inflammation and 10 control patients). Eligible participants provide serum, urine, sweat, saliva, exhaled breath, and stool samples for biomarker analyses. Core body temperature is measured using a sensor. The primary end point is the level of C-reactive protein (CRP). The secondary end points are interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels. The tertiary end points are fractional exhaled nitric oxide, calprotectin, and core body temperature. Samples will be collected in 2 batches, enabling preliminary analysis of the first batch (patients 1-5 from each group). The full analysis will include both batches. CRP and cytokine levels will be measured using enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. For statistical analysis, the Shapiro-Wilk test will be used to evaluate the normality of the distribution in each variable. We will perform the 2-tailed t test or Wilcoxon rank sum test to compare the levels of inflammatory biomarkers between patients with systemic inflammations and control patients. Pearson and Spearman correlation coefficients will assess the relationship between inflammatory biomarkers from noninvasive methods and serum biomarkers. Using all-subset regression analysis, we will determine the combination of noninvasive methods yielding the highest predictive accuracy for serum CRP levels. Participants' preferences for sampling methods will be assessed through a questionnaire. The study received ethics approval from the independent research ethics committee of Canton Zurich on October 28, 2022. A total of 20 participants participated in the study measurements. Data collection started on February 22, 2023, and was completed on September 22, 2023. Participants were on average 52.8 (SD 14.4; range 24-82) years of age, and 70% (14/20) of them were women. The analysis results reporting findings are expected to be published in 2025. This study aims to evaluate the feasibility of noninvasive, multimodal assessment of inflammatory biomarkers in patients with systemic inflammation. Promising results could lead to the creation of noninvasive and potentially digital biomarkers for systemic inflammation, enabling continuous monitoring and early diagnosis of inflammatory activity in a remote setting. DERR1-10.2196/62877.

Characterization of Genetic Landscape and Novel Inflammatory Biomarkers in Patients With Adult-Onset Still's Disease.

Adult-onset Still disease (AOSD) is a systemic autoinflammatory disorder (AID) of unknown etiology. Genetic studies have been limited. Here, we conducted detailed genetic and inflammatory biomarker analysis of a large cohort with AOSD to investigate the underlying pathology and identify novel targets for potential treatment. We investigated AOSD cases (n = 60) for rare germline and somatic variants using whole exome sequencing with virtual gene panels. Transcriptome profiles were investigated by bulk RNA sequencing whole blood. Cytokine profiling was performed on an extended patient cohort (n = 106) alongside measurements of NLRP3 inflammasome activation using a custom assay and type I interferon (IFN) score using a novel method. We observed higher than expected frequencies of rare germline variants associated with monogenic AIDs in AOSD cases (AOSD 38.4% vs healthy controls [HCs] 20.4%) and earlier onset of putative somatic variants associated with clonal hematopoiesis of indeterminate potential. Transcriptome profiling revealed a positive correlation between Still Activity Score and gene expression associated with the innate immune system. ASC/NLRP3 specks levels and type I IFN scores were significantly elevated in AOSD cases compared with HCs (P = 0.0001 and 0.0015, respectively), in addition to several cytokines: interleukin (IL)-6 (P < 0.0001), IL-10 (P < 0.0075), IL-12p70 (P = 0.0005), IL-18 (P < 0.0001), IL-23 (P < 0.0001), IFN-α2 (P = 0.0009), and IFNγ (P = 0.0002). Our study shows considerable genetic complexity within AOSD and demonstrates the potential utility of the ASC/NLRP3 specks assay for disease stratification and targeted treatment. The enriched genetic variants identified may not by themselves be sufficient to cause disease, but may contribute to a polygenic model for AOSD.

Relationship between Diet-Related Inflammation and Hospitalization Risk and Disease Severity in Patients with COVID-19

Background: Increased serum concentrations of inflammatory biomarkers in patients indicate a strong association between COVID-19 and inflammation. However, the association between diet-related inflammation and COVID-19 has been less investigated. The aim of this study is to investigate whether the inflammatory scores of the diet are associated with the severity of COVID-19 disease and the probability of hospitalization of patients. Methods: The authors conducted a cross-sectional study involving 141 patients with COVID-19. The empirical dietary inflammatory pattern (EDIP) and dietary inflammation scores (DIS) were calculated based on a 147-item semi-quantitative food frequency questionnaire. The association between serum levels of inflammatory biomarkers and diet-related inflammation was also investigated. Results: 74 inpatients and 87 outpatients participated in this study. Higher DIS scores were significantly associated with an increased risk of COVID-related hospitalization (Tertile3 vs. tertile1: OR = 3·62; 95 % CI 1·43 to 9·14, P=0·008 after fully adjustment). This association with EDIP was also observed, but it was not significant. Conclusion: The data from this provide evidence that a pro-inflammatory diet was associated with higher risk of hospitalization due to high severity of COVID-19.

Eblasakimab, an Anti-IL‑13Rα1 Antibody, Reduces Atopy-Associated Serum Biomarkers in Moderate‑to‑Severe Atopic Dermatitis.

Eblasakimab, a first-in-class monoclonal antibody with a unique mechanism to target the interleukin (IL)-13 receptor alpha 1 (IL-13Rα1), inhibits IL-4/IL-13 signaling in the pathophysiology of atopic dermatitis (AD). This study investigates the impact of eblasakimab on type 2 inflammatory biomarkers in patients with moderate-to-severe AD. A double‑blind, multiple ascending dose, phase Ib study evaluated the effect of eblasakimab (200, 400, 600mg) or placebo administered subcutaneously once weekly for 8 weeks in patients with moderate‑to‑severe AD. Serum levels of thymus and activation-regulated chemokine (TARC), total immunoglobulin E (IgE), and lactate dehydrogenase (LDH) were assessed. Eblasakimab suppressed TARC, IgE, and LDH in the 400-mg and 600-mg groups over 8 weeks of treatment. Patients in the 400-mg and 600-mg groups experienced a reduction of 72.8% (p=0.004) and 62.9% (p=0.003), respectively, for TARC, 35.1% (p=0.006) and 20.9% (not significant; NS), respectively, for IgE, and 24.6% (NS) and 23.1% (NS), respectively, for LDH between baseline and Week 8. Reduction in serum TARC in the 400-mg group was significantly greater than placebo as early as Week 1, whereas reductions in total IgE were more gradual. Serum TARC and total IgE remained suppressed in the 400-mg and 600-mg eblasakimab groups for 4-6 weeks following the last administered dose. The effect of eblasakimab on circulating AD‑associated biomarker levels was accompanied by improvements in signs and symptoms of AD, consistent with the inhibition of IL-13 and IL-4 signaling via the type 2 receptor. NCT04090229.

Complete Blood Collection-based Systemic Inflammation Biomarkers as a Severity Biomarker in Alopecia Areata: A Cross-sectional Study.

Previous studies have suggested that alopecia areata (AA) is an organ-specific disease characterized by loss of immune privilege of hair follicles. However, an increasing body of research indicates that it not only affects the skin but may also be accompanied by systemic inflammatory reactions. Therefore, searching for simple and easily available biomarkers to describe the underlying systemic inflammation in AA patients is of great clinical significance. Complete blood collection-based systemic inflammation biomarkers have been shown to be associated with the severity and prognosis of various skin and autoimmune diseases. They involve multiple cell lineages and can reveal different pathways of immune-inflammatory responses. The aim of this study was to investigate the level of complete blood collection-based systemic inflammation biomarkers in patients with AA, and to analyse their relationship with the disease severity. A total of 302 AA patients and 296 healthy controls were included in this study and the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune inflammation index (SII), and white blood cell/lymphocyte ratio (WLR) were calculated. The differences in these indicators between the 2 groups were compared, and the relationship between NLR, PLR, SII, WLR, and the risk of severe AA were analysed. AA patients had higher NLR, SII, and WLR compared with healthy controls (p = 0.004, 0.002, and 0.002 respectively). PLR and SII were higher in the severe AA group compared with the mild-to-moderate AA patients (p = 0.005 and 0.011 respectively). The risk of severe AA increased with the increasing of PLR, SII, NLR, and WLR (p for trend was 0.001, 0.006, 0.022, and 0.021, respectively). The levels of systemic inflammation biomark-ers in AA patients are higher than in healthy people. NLR, PLR, SII, and WLR are risk factors for severe AA, suggesting a close association between systemic inflammation and disease occurrence in AA patients.

Investigating the Effect of High-Dose Vitamin D3 Administration on Inflammatory Biomarkers in Patients with Moderate to Severe Traumatic Brain Injury: A Randomized Clinical Trial.

Traumatic brain injury (TBI) is one of the most common neurological disorders worldwide. We aimed to investigate the efficacy of high-dose vitamin D3 on inflammatory biomarkers in patients with moderate to severe TBI. Thirty-five moderate to severe TBI patients were randomly assigned to intervention and control groups. Patients in the intervention group received a single intramuscular (IM) dose of 300,000 IU vitamin D. The primary endpoints were interleukin levels (IL-1β and IL-6), and the secondary endpoints were changes in neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), Glasgow Coma scale (GCS), and Glasgow Outcome Scale-Extended (GOS-E) scores compared between intervention and control arms of the study. The linear Generalized Estimating Equations were used for trend analysis and evaluating the association of independent factors to each outcome. The results revealed a significant decrease in IL-1β levels (-2.71±3.02, in the intervention group: P=0.001 vs. -0.14±3.70, in the control group: P=0.876) and IL-6 (-88.05±148.45, in the intervention group: P=0.0001 vs. -35.54±175.79, in the control groupL P=0.325) 3 days after the intervention. The improvement in the GCS score (P=0.001), reduction in NLR (P=0.001) and PLR (P=0.002), and improvement in the GOS-E score (P=0.039) was found to be greater in the vitamin D3 arm of the study than the control group. Administration of high-dose vitamin D3 in the acute phase of TBI could be effective in lowering the inflammatory markers and improving the level of consciousness and long-term performance outcomes.Trial Registration Number: IRCT20180522039777N2.

S178 Obeticholic Acid Normalizes Inflammatory Biomarkers in Patients With Primary Biliary Cholangitis

S178 Obeticholic Acid Normalizes Inflammatory Biomarkers in Patients With Primary Biliary Cholangitis

Neutrophil-to-HDL-C Ratio as an inflammatory biomarker in patients with anxiety and obstructive coronary artery disease: A retrospective study

BackgroundAnxiety is a common comorbidity with coronary artery disease (CAD). The neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-high-density lipoprotein cholesterol (HDL-C) ratio (NHR), lymphocyte-to-HDL-C ratio (LHR), and monocytes-to-lymphocyte ratio (MLR) can predict the severity of CAD. This retrospective study aimed to explore the relationship between NLR, NHR, LHR, and MLR and the presence of obstructive or severe CAD (OCAD, SCAD) in patients with comorbid anxiety and chest pain. MethodsA total of 1063 patients with anxiety and chest pain were divided into an NOCAD group and OCAD group according to computed topography angiography (CCTA). The 455 patients in the OCAD group were further divided into the NSCAD group (n = 216) and SCAD group (n = 239) according to coronary angiography (CAG) results, and the Gensini score (GS) was calculated. Demographic and laboratory data were collected. ResultsMultiple regression analysis showed that higher NLR, NHR, and LHR served as independent risk factors for OCAD in patients with anxiety and chest pain (OR 1.37, 95%CI: 1.13–1.65, p = 0.001; OR 2.24, 95%CI: 1.89–2.65, p < 0.001; OR 2.47, 95%CI: 1.87–3.62, p < 0.001), and both were significantly associated with SCAD (OR 1.93, 95%CI: 1.44–2.59, p < 0.001; OR 4.45, 95%CI: 3.28–6.31, p < 0.001; OR 2.86, 95%CI: 1.93–4.25, p < 0.001). Area under the receiver operating characteristic curve analysis showed that NHR had the highest predictive value for OCAD and SCAD compared with NLR and LHR (AUC 0.71, sensitivity 57.14 %, specificity 68.20 %; AUC 0.86, sensitivity 83.68 %, specificity 74.54 %, respectively). When NHR and GS were combined, the predictive value for SCAD further increased compared to other parameters (AUC 0.94, sensitivity 92.05 %, specificity 87.05 %). ConclusionNLR, NHR, and LHR were associated with severity of coronary stenosis in patients with comorbid anxiety and chest pain. Among these systemic inflammatory markers, NHR served as a more effective independent predictor of OCAD and SCAD in these patients.

The Inflammatory Cytokines in Rheumatoid Arthritis and Their effect in the Progression and Pathogenesis of the Disease

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disorder affected the entire body. Aims of the study: Estimation of levels of inflammatory biomarkers in patients with RA and investigation of their impact on the development and severity of the disease. Methodology: This trial is a case-control one involving 44 patients with RA and 44 healthy age matched controls. Blood samples (5 ml) were collected from each participant, anti-CCP, RF, CRP, and ANA levels were measured using a Cobas device, while TNF-α, IL-10, IL-6 and IL-1β, were determined by an ELISA assay. Result: The results showed no significant variations in age, place of residence, and smoking between the RA and control groups, while there were significant variations in BMI, gender, and professional status. The levels of ESR, anti-CCP, RF, ANA, and CRP were significantly elevated in the RA group (P&lt;0.001 for each) than in the control group. The study of cytokine levels also showed significant variations between the two groups, with an increase in TNF-α, IL-6 and IL-1β, and a decrease in IL-10 in the patients. IL-1β was positively correlated with age, IL-6, IL-10, and TNF-α. Conclusions: The results indicate that cytokines levels such as TNF-α, IL-6, IL-1β, and CRP are elevated in RA patients, reflecting elevated inflammatory activity, while levels of IL-10 are decreased, which may contribute to the exacerbation of the disease.

Adipocytes Size of the Epicardial Adipose Tissue in Patients With Coronary Artery Disease and Coronary Atherosclerosis: Relationship With Parameters of Blood Lipid Transport Function, Carbohydrate Metabolism and Inflammatory Markers

Aim. To assess the potential relationship between morphometric characteristics of adipocytes in epicardial and subcutaneous adipose tissue (EAT, SAT) and the lipid transport function of the blood, glucose e metabolism, and inflammatory biomarkers in patients with ischemic heart disease (IHD) after coronary artery bypass grafting.Material and methods. The study included 47 patients (33 men and 14 women) aged 53-72 years with chronic IHD. The study material was EAT and SAT adipocytes obtained from intraoperative explants. The size of EAT and SAT adipocytes and the proportion of EAT and SAT adipocytes with ≥100 μm and ≤50 μm sizes were determined. Carbohydrate metabolism parameters, blood lipid transport function, and inflammatory biomarkers were assessed. Surrogate indices of insulin resistance (IR) were calculated.Results. The mean size of EAT adipocytes, in contrast to SAT adipocytes, correlated (p&lt;0.05) with serum concentrations of tumor necrosis factor alpha (TNF-α) (rs=0.43), triglycerides (TG) (rs=0.36), interleukin (IL)-1β (rs=0.29), basal C-peptide (rs=0.40) and TyG index (rs=0.32). Male gender and blood concentrations of basal C-peptide and TG in combination were identified as statistically significant determinants of an increase in the mean size of EAT adipocytes. The threshold values of TG and non-high-density lipoprotein cholesterol (nHDL-C) associated with an increase in the mean size of EAT adipocytes ≥87.61 μm were 1.4 and 2.63 mM, respectively. Patients with TG concentrations ≥1.4 mM had a greater size and proportion of hypertrophied EAT adipocytes, IR indices, and higher blood concentrations of basal glucose, high-sensitivity C-reactive protein, TNF-α, and IL-1β. TG concentrations of 1.2-1.4 mM, compared with concentrations &lt;1.2 mM, were associated with a greater mean size of EAT adipocytes and higher serum IL-10 concentrations. Patients with non-HDL-C ≥2.63 mM, compared with its lower concentrations, had more pronounced hypertrophy of EAT adipocytes.Conclusion. Disorders in the morphometric characteristics of EAT adipocytes, in contrast to SAT adipocytes, are associated with increased blood concentrations of TG, non-HDL-C, inflammatory markers, and increased IR indices. It was shown for the first time that a combination of three factors, male gender, blood concentrations of basal C-peptide, and TG, independently of other indicators describe the variability of the mean size of EAT adipocytes. Increases in TG from 1.2 to 1.4 mM are associated with a larger size of EAT adipocytes and cytokine imbalance. Our data confirm the validity of identifying optimal blood concentrations of TG and non-HDL-C in patients with IHD and coronary atherosclerosis.

Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy.

The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged. To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma (dCCA) who underwent pancreatoduodenectomy (PD). This single-center study included 216 patients with dCCA after PD between January 1, 2011, and December 31, 2022. The individuals were categorized into two sets based on their systemic inflammatory response index (SIRI) levels: A low SIRI group (SIRI < 1.5, n = 123) and a high SIRI group (SIRI ≥ 1.5, n = 93). Inflammatory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves. Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival (OS) and recurrence-free survival (RFS). The study included a total of 216 patients, with 58.3% being male and a mean age of 65.6 ± 9.6 years. 123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA. SIRI had an area under the curve value of 0.674 for diagnosing dCCA, showing better performance than other inflammatory biomarkers. Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD, leading to lower OS [hazard ratios (HR) = 1.868, P = 0.006] and RFS (HR = 0.949, P < 0.001). Additionally, survival analysis indicated a significantly better prognosis for patients in the low SIRI group (P < 0.001). It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.

Real-World Outcomes in Patients with Advanced Penile Squamous Cell Carcinoma Receiving Immune Checkpoint Inhibitors: A Single Institution Experience.

Advanced penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy with a poor prognosis and an unmet need for biomarkers. We performed a retrospective evaluation of real-world efficacy, safety outcomes, and baseline inflammatory biomarkers in patients with advanced pSCC treated with immune checkpoint inhibitors (ICIs). We performed a retrospective review of patients with advanced pSCC who received ICIs from 2012 to 2023 at the Winship Cancer Institute of Emory University in Atlanta, GA. Demographics, disease characteristics, and optimal cutoffs of baseline biomarkers obtained before ICI initiation were described. Human papillomavirus (HPV)/p16+ status was determined by immunohistochemistry. Programmed death-ligand 1 (PD-L1) positivity was defined as >1%. Immune-related adverse events (irAEs) were graded per Common Terminology Criteria for Adverse Events criteria and captured through clinical documentation. Clinical benefit was defined as complete response, partial response, or stable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and univariate Cox regression (UVA) using a significance level set at p < 0.05. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were collected from complete blood count data. Twenty-one patients were included of whom 71.4% were White and 28.6% were Black. Median age at ICI initiation was 56 years (38-76 years). Most patients had Eastern Cooperative Oncology Group performance status ≥2 (61.9%). At diagnosis, 4.8%, 33.3%, and 61.9% were stage 2, 3, and 4, respectively, of whom eight patients had initial distal metastases. Of patients with available data, 7 of 11 patients (63.6%) were PD-L1+ and 8 of 9 (89%) patients were HPV+. Median follow-up was 8.4 months and median time to ICI treatment from diagnosis was 15.6 months. ICI was first line (1L) in 1 patient (4.8%), 2L in 13 (61.9%), 3L in 6 (28.6%), and 4L in 1 (4.8%). Five patients achieved clinical benefit of whom three had partial response and two had stable disease. Median OS was 8.2 months (95% CI, 2.3-15.7) and PFS was 1.9 months (95% CI, 1.3-3.2). Notably, three patients with PD-L1 positivity, microsatellite instability (MSI)-high, or high tumor mutational burden (TMB) demonstrated response to ICI. Higher baseline NLR (hazard ratio, 10.0; 95% CI, 2.73-54.2) at optimal cutoff was associated with shorter OS and PFS on UVA. Three patients (14.3%) developed grade 3/4 ICI-related adverse events. Our real-world analysis summarizes our institutional experience and provides granular clinical and molecular attributes of patients with therapeutic response, which may aid in patient stratification within ICI-based clinical trials. Overall, we confirm poor response rates of pSCC to ICI in an unselected approach, consistent with multicenter studies. ICIs may be effective and tolerable therapy in a subset of patients. NLR may be a potential biomarker to assess ICI response in pSCC.