Serum Inflammatory Biomarkers Research Articles

Abstract PO5-15-01: Prospective Biomarker Assessment of Cardiotoxicity Among Ethnically Diverse Women with Early Breast Cancer

Abstract Background: Approximately 4.1 million women in the United States are living with breast cancer1. Cardiac dysfunction is a significant adverse effect of commonly used breast cancer therapies like doxorubicin (D) and trastuzumab (T). The cardiotoxicity (CTox) associated with these agents manifests as a reduction in left ventricular ejection fraction (LVEF) with or without signs and symptoms of heart failure. Purpose: The objective of this study is to evaluate serum cardiac and inflammatory biomarkers over time and their association with CTox development. Methods: A total of 133 newly diagnosed stage I-III invasive breast cancer patients were enrolled in a prospective clinical trial (2013-2017) and received standard of care T and/or D based systemic therapy. They underwent serial echocardiograms every 6 months for two years and then based on clinical need for a total of six years. CTox was defined as a >10% drop in LVEF, and/or LVEF < 50%. Biomarker data was collected at baseline, 12 and 24 months and included both cardiac biomarkers (Troponin-I, TN-I and amino terminal B-type natriuretic peptide, NT-proBNP) and measures of inflammation (C-reactive protein, CRP). Of the 32 with CTox patients, 15 had adequate serum samples and were matched with 15 patients without CTox (N=30), controlling for age, race, and treatment regimen prior to serum sample analysis. Results: The mean LVEF at baseline was similar between CTox and non-CTox patients (64% vs 62%, p=0.342). However, over the course of 12 and 24 months, CTox patients experienced a statistically significant decrease in LVEF compared to their baseline values (55% and 56%, respectively, p < 0.001). At baseline, CTox patients had higher CRP levels compared to non-CTox (13.4 mg/L vs 3.35 mg/L), however this difference did not reach statistical significance (P >0.05). Although this difference seemed to narrow at 12 months (3.88 mg/L vs 1.52 mg/L, p< 0.05) and 24 months (6.85 mg/L vs 2.36 mg/L, p< 0.05), CTox patients consistently had higher mean CRP levels. Mean TN-I levels increased at both 12 and 24 months compared to baseline (CTox 1.13 ng/L, 7.13 ng/L, 4.13 ng/L vs non-CTox 0.800 ng/L, 8.13 ng/L, 4.60 ng/L, p< 0.05) but there were no significant differences between the two groups (p >0.05). While baseline NT-proBNP levels did not differ significantly between the CTox and non-CTox patients, there were statistically significant increases in CTox patients at 12 and 24 months (205 pg/mL vs 74 pg/mL, and 200 pg/mL vs 96 pg/mL, p < 0.01, respectively). Conclusion: In a well characterized, diverse, matched subset of patients with early breast cancer who were prospectively followed with serial echocardiograms, distinct biomarker patterns were observed. Measures of inflammation (CRP) at baseline were different and these changes appeared to diminish over time. While the cardiac biomarker TN-I appeared to increase in both +CTox and -CTox group over time, only those with differential NT-proBNP elevations were associated with cardiotoxicity. 1Lisa Gallicchio, PhD and others, Estimation of the Number of Individuals Living With Metastatic Cancer in the United States, JNCI: Journal of the National Cancer Institute, Volume 114, Issue 11, November 2022, Pages 1476–1483 Citation Format: Shahzaad Jahangier, Rubina Qamar, Maharaj Singh, Vinay Thohan, James Weese, Bijoy Khandheria, Anna Kamke-Jordan. Prospective Biomarker Assessment of Cardiotoxicity Among Ethnically Diverse Women with Early Breast Cancer [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 PO5-15-01.

A Prediction Model for Prolonged Hospital Length of Stay (ProLOS) in Coronavirus Disease 2019 (COVID-19) Patients.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the normalization of COVID-19 globally, it is crucial to construct a prediction model that enables clinicians to identify patients at risk for ProLOS based on demographics and serum inflammatory biomarkers. The study included hospitalized patients with a confirmed diagnosis of COVID-19. These patients were randomly grouped into a training (80%) and a test (20%) cohort. The LASSO regression and ten-fold cross-validation method were applied to filter variables. The training cohort utilized multifactorial logistic regression analyses to identify the independent factors of ProLOS in COVID-19 patients. A 4-variable nomogram was created for clinical use. ROC curves were plotted, and the area under the curve (AUC) was calculated to evaluate the model's discrimination; calibration analysis was planned to assess the validity of the nomogram, and decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model. The results showed that among 310 patients with COVID-19, 80 had extended hospitalization (80/310). Four independent risk factors for COVID-19 patients were identified: age, coexisting chronic respiratory diseases, white blood cell count (WBC), and serum albumin (ALB). A nomogram based on these variables was created. The AUC in the training cohort was 0.808 (95% CI: 0.75 - 0.8671), and the AUC in the test cohort was 0.815 (95% CI: 0.7031 - 0.9282). The model demonstrates good calibration and can be used with threshold probabilities ranging from 0% to 100% to obtain clinical net benefits. A predictive model has been created to accurately predict whether the hospitalization duration of COVID-19 patients will be prolonged. This model incorporates serum WBC, ALB levels, age, and the presence of chronic respiratory system diseases.

Development and Validation of an Inflammatory Prognostic Index to Predict Outcomes in Advanced/Metastatic Urothelial Cancer Patients Receiving Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) improve overall survival (OS) in advanced/metastatic urothelial cancer (a/mUC) patients. Preliminary evidence suggests a prognostic role of inflammatory biomarkers in this setting. We aimed to develop a disease-specific prognostic inflammatory index for a/mUC patients on ICIs. Fifteen variables were retrospectively correlated with OS and progression-free survival (PFS) in a development (D, n = 264) and a validation (V, n = 132) cohort of platinum-pretreated a/mUC pts receiving ICIs at L2 or further line. A nomogram and inflammatory prognostic index (U-IPI) were developed. The index was also tested in a control cohort of patients treated with chemotherapy only (C, n = 114). The strongest predictors of OS were baseline platelet/lymphocyte (PLR) and neutrophil/lymphocyte (NLR) ratios, and lactate dehydrogenase (LDH), NLR, and albumin changes at 4 weeks. These were used to build the U-IPI, which can distinctly classify patients into good or poor response groups. The nomogram scoring is significant for PFS and OS (p < 0.001 in the D, V, and combined cohorts) for the immunotherapy (IO) cohort, but not for the control cohort. The lack of a baseline systemic inflammatory profile and the absence of early serum inflammatory biomarker changes are associated with significantly better outcomes on ICIs in a/mUC pts. The U-IPI is an easily applicable dynamic prognostic tool for PFS and OS, allowing for the early identification of a sub-group with dismal outcomes that would not benefit from ICIs, while distinguishing another that draws an important benefit.

Valsartan Mitigates the Progression of Methotrexate-Induced Acute Kidney Injury in Rats via the Attenuation of Renal Inflammation and Oxidative Stress.

Methotrexate (MTX) is a folic acid antagonist, commonly administered for the treatment of a variety of cancers. However, methotrexate toxicity including bone marrow suppression and hepatic and renal toxicity limits its use. Angiotensin AT1 receptor blockers including Valsartan (Val) possess the ability to ameliorate MTX-induced toxicity through various mechanisms. In this study, we explored the potential reno-protective effects of Val against MTX-induced acute kidney injury in rats. Twenty-four Wistar rats were randomly segregated into 3 groups. Group 1 served as the control group and received an oral dose of 1mL/kg of normal saline. Group 2 received a single dose of 20 mg/kg of MTX intraperitoneally (IP) for 5 days. Group 3 received a single IP dose of 20 mg/kg of MTX followed by an oral dose of 10 mg/kg of Valsartan for 5 days. At the end of the experiment, the levels of serum kidney biomarkers, inflammatory and oxidative stress markers were accessed. Furthermore, the effect of MTX on kidney tissue histology was examined. Our results showed that MTX treatment increased the level of serum kidney and inflammatory biomarkers and decreased the level of antioxidants SOD and GSH while increasing the lipid peroxidation contents. Furthermore, MTX treatment caused structural changes to kidney histology. However, the administration of Val significantly prevented these changes. Valsartan possesses nephroprotective potential and might serve as a potential therapeutic strategy against MTX-induced kidney injury.

Persistence of a Skewed Repertoire of NK Cells in People with HIV-1 on Long-Term Antiretroviral Therapy.

HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear. To address this, we performed a longitudinal analysis detailing conventional and memory-like NK cell characteristics in n = 60 PWH during the first 4 y of ART. Throughout this regimen, a skewed repertoire of cytokine unresponsive FcRγ- memory-like NK cells persisted and accompanied an overall increase in NK surface expression of CD57 and KLRG1, suggestive of progression toward immune senescence. These traits were linked to elevated serum inflammatory biomarkers and increasing Ab titers to human CMV, with human CMV viremia detected in approximately one-third of PWH at years 1-4 of ART. Interestingly, 40% of PWH displayed atypical NK cell subsets, representing intermediate stages of NK-poiesis based on single-cell multiomic trajectory analysis. Our findings indicate that NK cell irregularities persist in PWH despite long-term ART, underscoring the need to better understand the causative mechanisms that prevent full restoration of immune health in PWH.

Serum Inflammatory Markers Used in Cardiovascular Disease Risk Prediction Models: A Systematic Review.

The aim of this review was to perform a critical appraisal of serum inflammatory biomarkers used for the prediction of cardiovascular disease (CVD) risk. We conducted a systematic review of studies listed on MEDLINE and Scopus from January 2000 to December 2023, focused on the prognostic value of serum inflammatory biomarkers [i.e., C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)] in individuals without known CVD. Eligible studies used a multivariate prediction model and included discrimination or risk reclassification analysis. The Quality in Prognostic Studies (QUIPS) tool was used to evaluate study quality and potential bias. Thirty-five studies (i.e., total 208,897 participants) that evaluated the added prognostic value of CRP, IL-6, TNF-α on CVD risk prediction were retrieved. Significant improvements in CVD risk model's predictive ability were observed in 7 out of 32 studies relating CRP and 1 out of 8 studies relating IL-6 with CVD risk. The single study found no added prognostic value of TNF-α use in CVD risk model. The integration of serum inflammatory biomarkers into CVD risk prediction models does not appear to improve risk discrimination models, suggesting that these biomarkers may act as surrogate markers, but not as predictors of atherosclerotic CVD.

Serum and salivary inflammatory biomarkers in juvenile idiopathic arthritis—an explorative cross-sectional study

BackgroundBiomarkers may be useful in monitoring disease activity in juvenile idiopathic arthritis (JIA). With new treatment options and treatment goals in JIA, there is an urgent need for more sensitive and responsive biomarkers.ObjectiveWe aimed to investigate the patterns of 92 inflammation-related biomarkers in serum and saliva in a group of Norwegian children and adolescents with JIA and controls and in active and inactive JIA. In addition, we explored whether treatment with tumor necrosis factor inhibitors (TNFi) affected the biomarker levels.MethodsThis explorative, cross-sectional study comprised a subset of children and adolescents with non-systemic JIA and matched controls from the Norwegian juvenile idiopathic arthritis study (NorJIA Study). The JIA group included individuals with clinically active or inactive JIA. Serum and unstimulated saliva were analyzed using a multiplex assay of 92 inflammation-related biomarkers. Welch’s t-test and Mann–Whitney U-test were used to analyze the differences in biomarker levels between JIA and controls and between active and inactive disease.ResultsWe included 42 participants with JIA and 30 controls, predominantly females, with a median age of 14 years. Of the 92 biomarkers, 87 were detected in serum, 73 in saliva, and 71 in both biofluids. A pronounced difference between serum and salivary biomarker patterns was found. Most biomarkers had higher levels in serum and lower levels in saliva in JIA versus controls, and in active versus inactive disease. In serum, TNF and S100A12 levels were notably higher in JIA and active disease. The TNF increase was less pronounced when excluding TNFi-treated individuals. In saliva, several biomarkers from the chemokine family were distinctly lower in the JIA group, and levels were even lower in active disease.ConclusionIn this explorative study, the serum and salivary biomarker patterns differed markedly, suggesting that saliva may not be a suitable substitute for serum when assessing systemic inflammation in JIA. Increased TNF levels in serum may not be a reliable biomarker for inflammatory activity in TNFi-treated children and adolescents with JIA. The lower levels of chemokines in saliva in JIA compared to controls and in active compared to inactive disease, warrant further investigation.

Fabrication and sensing properties of a molecularly imprinted polymer on a photonic PDMS substrate for the optical detection of C-reactive protein

This work presents the development of a novel photonic-based sensor on a nanoscale patterned polydimethylsiloxane (PDMS) substrate acting as transducer, combined with a molecularly imprinted polymer for the rapid and sensitive detection of C-reactive protein (CRP). A silicon wafer was patterned using electron-beam lithography with a one-dimensional (1D) reflective grating (periodicity of about 400 nm) and then replicated using nanoimprint lithography. The latter silicon mould was used for replica moulding to generate a patterned PDMS. The unique 1D design gave PDMS photonic properties that were suitable as a substrate to assemble the biorecognition layer. The surface of the photonic PDMS was modified to become hydrophilic and additionally functionalized with vinyl silane groups to bind the imprinted polymer, resulting in a photonic molecularly imprinted polymer substrate (PMIPS). The developed method was successfully used to detect CRP in serum samples. The reflectance intensity decreased with increasing CRP concentrations, and the sensing PMIPS showed a linear response between 0.005 and 1.215 µg mL−1, a limit of detection of 0.003 µg mL−1, and a selective response to CRP when tested against serum calprotectin. Overall, this novel optical sensor can be used to detect CRP, a serum biomarker of inflammation, particularly in inflammatory bowel diseases.

Evidence of MRI image features and inflammatory biomarkers association with low back pain in patients with lumbar disc herniation

BACKGROUND CONTEXTWhile MRI image features and inflammatory biomarkers are frequently used for guiding treatment decisions in patients with lumbar disc herniation (LDH) and low back pain (LBP), our understanding of the connections between these features and LBP remains incomplete. There is a growing interest in the potential significance of MRI image features and inflammatory biomarkers, both for quantification and as emerging therapeutic tools for LBP. PURPOSETo investigate the evidence supporting MRI image features and inflammatory biomarkers as predictors of LBP and to determine their relationship with pain intensity. STUDY DESIGNProspective cohort study. PATIENT SAMPLEAll consecutive patients with LDH who underwent discectomy surgery at our institution from February 2020 to June 2023 at the author's institution were included. OUTCOME MEASURESMRI image features in discogenic, osseous, facetogenic, and paraspinal muscles, as well as inflammatory biomarkers in serum (including CRP (C-reactive protein), ESR (erythrocyte sedimentation rate), PCT (procalcitonin), TNF (tumor necrosis factor), interleukin-1 beta (IL-1β), and IL-6), and paraspinal muscles (including TNF, IL-1β, IL-6, IL-10, and transforming growth factor beta 1 (TGF-β1)). METHODSA series of continuous patients diagnosed with LDH were categorized into acute LBP (<12 weeks), chronic LBP (≥12 weeks), and non-LBP groups. MRI image features and inflammatory biomarkers relation to pain intensity was assessed using the independent t-test, Chi-squared tests, Spearman rank correlation coefficient, and logistic regression test. RESULTSCompared to the non-LBP group, the chronic LBP group exhibited a higher incidence of intervertebral disc (IVD) degeneration (≥ grade 3) and high-fat infiltration in paraspinal muscles, alongside a significant reduction in the cross-sectional area (CSA) and fatty degeneration of the multifidus muscle. Furthermore, there was a greater expression of IL-6 in serum and TNF in paraspinal muscles in the chronic LBP group and a greater expression of CRP and IL-6 in serum and TNF in paraspinal muscles in the acute LBP group. CSA and fatty degeneration of multifidus muscle were moderately negatively correlated with chronic LBP scores. The expression of TNF and IL-6 in serum and the expression of TNF in the multifidus muscle were moderately correlated with preoperative LBP. IVD degeneration and high-fat infiltration were identified as risk factors for chronic LBP. CONCLUSIONThe results provide evidence that IVD degeneration, high-fat infiltration, and the reduction of CSA in paraspinal muscles were associated with the development of chronic LBP in patients with LDH, and these associations are linked to inflammatory regulation. This deepens our understanding of the etiology and pathophysiology of LBP, potentially leading to improved patient stratification and more targeted interventions.

Plausible prediction of renoprotective effects of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney diseases.

This narrative review was conducted due to uncertainty in predicting the beneficial impact of sodium-glucose cotransporter-2 (SGLT2) inhibitors on a dip of estimated glomerular filtration rate (eGFR), regardless of albuminuria presence, with the aim of elucidating plausible predictors of kidney function outcome among patients treated with SGLT2 inhibitors. The PubMed and Web of Science databases were searched in May 2023 for relevant articles published in English between 2013 and 2023. A total of 25 full-length scientific publications (comprising 11 large randomized trials and two cohort studies) were included for analysis. The majority of studies demonstrated a limited value of conventional biomarkers, such as initial decline in eGFR, a trajectory of eGFR during SGLT2 inhibitor administration, and urine albumin-to-creatinine ratio (UACR), in prediction of renoprotection. Included studies showed that the tendency to decreased eGFR, UACR, hemoglobin, glycosylated hemoglobin, lipid profile, serum uric acid, inflammatory biomarkers and natriuretic peptides did not predict clinical outcomes in groups without heart failure (HF) treated with SGLT2 inhibitors. In HF groups, biomarkers of inflammation, kidney injury, oxidative stress, mitochondrial dysfunction, ketogenesis, energy metabolism, and adipose tissue dysfunction (adropin and irisin), were detected with the aim of finding potential biomarkers. Biomarkers of adipose tissue dysfunction and inflammation may be promising for predicting SGLT2 inhibitor benefit compared with N-terminal pro-B-type natriuretic peptide and energy metabolism indicators.

Phthalate exposure increases interferon-γ during pregnancy: The Atlanta African American Maternal-Child Cohort

BackgroundThe immune system undergoes unique adaptations during pregnancy and is particularly sensitive to environmental chemicals, such as phthalates, which are associated with acute and chronic inflammatory medical conditions. However, current knowledge of how phthalate exposures are associated with systemic inflammation in pregnant people is limited by cross-sectional study designs and single chemical models. Our objective was to estimate the association between repeated measures of prenatal phthalate exposures, examined individually and collectively, and a panel of clinical inflammatory biomarkers. MethodsIn the Atlanta African American Maternal-Child Cohort, biospecimens were collected at mean 11 and 26 weeks gestation (N = 126). Concentrations of eight urinary phthalate metabolites and five serum inflammatory biomarkers, including CRP, IFN-γ, IL-6, IL-10, and TNF-α, were measured. Linear mixed effect regression and quantile g-computation models were used to estimate the associations for single phthalates and their exposure mixture, respectively. ResultsParticipants who self-reported any use of alcohol, tobacco, or marijuana in the month prior to pregnancy had increased MEP, MBP, MiBP, and CRP, relative to those with no substance use. IFN-γ was elevated in response to MECPP (% change = 17.35, 95 % confidence interval [CI] = 0.32, 32.27), MEHHP (% change = 12.75, 95 % CI = 2.22, 24.36), MEOHP (% change = 11.63, 95 % CI = 1.21, 23.12), and their parent phthalate, ΣDEHP (% change = 15.03, 95 % CI = 0.28, 31.94). The phthalate mixture was also associated with an increase in IFN-γ (% change = 15.03, 95 % CI = 6.18, 24.61). ConclusionsOur findings suggest DEHP metabolites induce systemic inflammation during pregnancy. The pro-inflammatory cytokine IFN-γ may play an important role in the relationship between prenatal phthalate exposures and adverse pregnancy outcomes.

Serum biomarkers of inflammation and vascular damage upon SARS-Cov-2 mRNA vaccine in patients with thymic epithelial tumors.

Thymic epithelial tumors (TET) patients are at high risk of autoimmune and hypoimmune complications. Limited evidence is available on the potential risk of immune-related and inflammatory reactions induced by SARS-Cov-2 vaccine in this patient population. In order to identify subjects at higher risk for vaccine complications, we prospectively evaluated a panel of serum biomarkers related to inflammation (TNF-α, IL-1β,-6,-10,-12, and-17A, IFN-α, β and γ, MPO, MMP-9), and vascular damage (E-and P-selectin, VEGF-A, P-ANCA and MCP-1) in 44 TET patients and in 30 healthy controls along the whole SARS-Cov-2 vaccine cycle. About 50 % of subjects (either TET and controls) showed an increase of serum biochemical markers of inflammation and endothelial damage with a large heterogeneity of values. Such increase appeared early, after the first dose in control subjects and later, after the second dose in TET patients (in which we observed mainly an increase of inflammatory biomarkers). The values normalized after about 3months and did not increase after the third, booster dose. No autoimmune or vascular complications were observed in the study subjects and no difference was observed in terms of vaccine response among subjects showing serum biomarkers increase and those who experienced no changes. Our data highlight the relevance of Sars-Cov-2 vaccine in TET patients, as it resulted safe and prevented severe COVID-19. However, further studies are awaited to explore the mechanisms and the potential consequences of the observed increase of serum inflammatory and vascular damage biomarkers.

Correlations between Resting Electrocardiogram Findings and Disease Profiles: Insights from the Qatar Biobank Cohort.

Resting electrocardiogram (ECG) is a valuable non-invasive diagnostic tool used in clinical medicine to assess the electrical activity of the heart while the patient is resting. Abnormalities in ECG may be associated with clinical biomarkers and can predict early stages of diseases. In this study, we evaluated the association between ECG traits, clinical biomarkers, and diseases and developed risk scores to predict the risk of developing coronary artery disease (CAD) in the Qatar Biobank. This study used 12-lead ECG data from 13,827 participants. The ECG traits used for association analysis were RR, PR, QRS, QTc, PW, and JT. Association analysis using regression models was conducted between ECG variables and serum electrolytes, sugars, lipids, blood pressure (BP), blood and inflammatory biomarkers, and diseases (e.g., type 2 diabetes, CAD, and stroke). ECG-based and clinical risk scores were developed, and their performance was assessed to predict CAD. Classical regression and machine-learning models were used for risk score development. Significant associations were observed with ECG traits. RR showed the largest number of associations: e.g., positive associations with bicarbonate, chloride, HDL-C, and monocytes, and negative associations with glucose, insulin, neutrophil, calcium, and risk of T2D. QRS was positively associated with phosphorus, bicarbonate, and risk of CAD. Elevated QTc was observed in CAD patients, whereas decreased QTc was correlated with decreased levels of calcium and potassium. Risk scores developed using regression models were outperformed by machine-learning models. The area under the receiver operating curve reached 0.84 using a machine-learning model that contains ECG traits, sugars, lipids, serum electrolytes, and cardiovascular disease risk factors. The odds ratio for the top decile of CAD risk score compared to the remaining deciles was 13.99. ECG abnormalities were associated with serum electrolytes, sugars, lipids, and blood and inflammatory biomarkers. These abnormalities were also observed in T2D and CAD patients. Risk scores showed great predictive performance in predicting CAD.

Effects of Vitamin D Supplementation in Elite Athletes: A Systematic Review.

Deficiency in vitamin D has been shown to increase the risk of injury. To synthesize current placebo-controlled randomized trials investigating the effect of vitamin D supplementation in elite athletes on (1) aerobic capacity; (2) anaerobic measures, such as strength, speed, and anaerobic power; (3) serum biomarkers of inflammation; and (4) bone health. Systematic review; Level of evidence, 1. A literature search was conducted on November 30, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included were randomized, placebo-controlled studies of longer than 2 weeks on subjects with active participation in organized sport. Excluded were nonrandomized controlled trial study designs, vitamin D administration routes other than oral, studies that did not use vitamin D supplementation as the sole intervention, and studies with nonathletic or military populations. Out of 2331 initial studies, 14 studies (482 athletes) were included. Of the 3 studies that assessed aerobic capacity, 2 demonstrated significantly greater improvements in maximal oxygen uptake and physical working capacity-170 (P < .05) in supplemented versus nonsupplemented athletes. Measurements of anaerobic power and strength were consistently increased in supplemented groups compared with nonsupplemented groups in 5 out of the 7 studies that assessed this. Of the 6 studies that assessed sprint speed, 4 found no significant difference between supplemented and nonsupplemented groups. Aside from 1 study that found significantly lower interleukin-6 levels in supplemented athletes, measures of other inflammatory cytokines were not affected consistently by supplementation. The 4 studies that assessed markers of bone health were conflicting regarding benefits of supplementation. One study found demonstrated improvements in bone mineral density in response to supplementation (P = .02) compared with control whereas another found no significant difference between supplemented and nonsupplemented groups. However, in 3 other studies, serum biomarkers of bone turnover such as bone-specific alkaline phosphatase, parathyroid hormone, and N-terminal telopeptide appeared to be higher in subjects with lower serum vitamin D levels (P < .05). Results of this systematic review indicated that the greatest benefit of vitamin D supplementation in elite athletes may be improving aerobic endurance, anaerobic power, and strength. More research is needed to determine the effect of vitamin D supplementation on bone health and injury risk in this population.

Clinicopathological studies on ulcerative lymphangitis in cattle: Alterations in serum inflammatory cytokines, anti-microbial, organs functions, and oxidative stress-related biomarkers.

Affection with Corynebacterium pseudotuberculosis (C. pseudotuberculosis) and development of cellulitis and/or abscess formation with cutaneous lymphangitis in cattle is rare to some extent, so literature about the biochemical changes that would accompany this infection is rare. In this context, the present study was designed to screen the effect of the infection with C. pseudotuberculosis cutaneous lymphangitis on the release of some immune molecules, organ functions, and redox state in Baladi cows. Fourteen Baladi cows from a small dairy farm in El-Behira, Egypt, were selected to complete this study. After bacteriological culture confirmation, seven of them were found suffering from cutaneous lesions due to infection with C. pseudotuberculosis (Diseased group), while the others were healthy (Healthy group). Serum samples were obtained to evaluate the presumptive changes in some clinicopathological parameters. Serum analysis revealed a significant decrease in the levels of interferon-gamma and interleukin-17 as well as a significant decrement in the concentration of beta-defensin (β-defensin) and lipocalin-2. While serum level of interleukin-10 recorded a significant increase in these animals when compared to healthy control animals. Concurrently, the affected animals recorded a significant elevation in serum levels of hepato-cardiac enzymes, urea, and creatinine in addition to disturbance in the serum redox state. In conclusion, infection with C. pseudotuberculosis cattle may disturb the defensive immune state, body organ function, and redox state of the animals.

Correlation of lymphocyte subsets and inflammatory biomarkers with disease severity in COVID-19 patients.

To determine the correlation of lymphocyte subsets and soluble serum inflammatory biomarkers with disease severity in coronavirus disease-2019 infection. The retrospective study was conducted at the Department of Immunology, Sindh Institute of Urology and Transplantation (SIUI), Karachi, Pakistan from September 1 to November 30, 2021, and comprised data of patients admitted from June to July 2021 who tested positive for coronavirus disease-2019 on the basis of reverse transcription-polymerase chain reaction of nasopharyngeal swab specimens. The patients were categorised into severe group A and non-severe group B. Initial investigations included complete blood count, neutrophil-to-lymphocytes ratio, C-reactive protein, D-Dimers and serum ferritin levels. Lymphocyte subsets included cluster of differentiation-3+, cluster of differentiation-4+/ cluster of differentiation-3+, cluster of differentiation-8+ T lymphocytes, cluster of differentiation-19+B lymphocytes, cluster of differentiation-16+ cluster of differentiation-56+ Natural Killer cells and serum cytokine levels of interleukin-2, interleukin- 4, interleukin-6, interleukin-10, tumour necrosis factor-alpha and interferon gamma. They were correlated with disease severity. Data was analysed using SPSS 20. Of the 54 patients, 33(61.1%) were males and 21(38.9%) were females. There were 29(53.70%) patients in group A with median age 52 years (interquartile range: 43.5-65 years), and 25(46.29%) in group B with median age 50 years (interquartile range: 36.5-59 years) (p=0.241). Disease was significantly more severe in male patients compared to female (p=0.002). In group A, cluster of differentiation-3+ T cells were reduced in 21(72.4%) patients, cluster of differentiation-8+ T cells in 16(55.2%), cluster of differentiation-4+ T cells in 23(79.3%) and cluster of differentiation-19+ B cells in 8(27.6%). In group B, cluster of differentiation-3+ T cells were reduced in 10(40%) subjects, cluster of differentiation-8+ T cells in 7(28%), cluster of differentiation-4+ T cells in 12(48%) and cluster of differentiation-19+ B cells in 4(16%) patients. Serum cytokine levels were not significantly different between the groups (p>0.05). In group A, 7(24.13%) patients died, and in such cases, the neutrophil-to-lymphocytes ratio was significantly higher (p=0.037). Pro-inflammatory markers and cytokine levels increased, while lymphocyte subsets decreased with increasing severity of the disease.

Increased production of inflammatory cytokines by circulating monocytes in mesial temporal lobe epilepsy: A possible role in drug resistance

We analyzed peripheral blood mononuclear cells (PBMCs) and serum inflammatory biomarkers in patients with mesial temporal lobe epilepsy (drug-resistant – DR, vs. drug-sensitive – DS). Patients with epilepsy showed higher levels of serum CCL2, CCL3, IL-8 and AOPP, and lower levels of FRAP and thiols compared to healthy controls (HC). Although none of the serum biomarkers distinguished DR from DS patients, when analysing intracellular cytokines after in vitro stimulation, DR patients presented higher percentages of IL-1β and IL-6 positive monocytes compared to DS patients and HC. Circulating innate immune cells might be implicated in DR epilepsy and constitute potential new targets for treatments.

Pro-inflammatory and pro-oxidant diets are associated with increased odds of cataracts and serum biomarkers of inflammation and oxidative stress: Hospital-based case-control study

BackgroundOxidative stress and inflammation play an important role in cataracts' causal network. In this study, we used the Dietary Inflammatory Index (DII) and Dietary Antioxidant Index (DAI) to comprehensively examine the nutritional status related to inflammation and oxidative stress and investigate their association with the odds of cataracts. We hypothesize that higher DII scores (a pro-inflammatory diet) and lower DAI (a pro-oxidant diet) are associated with related serum biomarkers and increase the odds of cataracts. MethodsThe study included 263 patients with cataracts and 326 healthy controls. A valid 168-item food frequency questionnaire (FFQ) evaluated the participants' dietary intake over the past year. DII and DAI were calculated based on FFQ, and blood/serum indicators, e.g., hs-CRP, TNF-a, etc., were extracted from patients' records. ResultsBased on the multivariable linear regression models, there was a significant association between DII and hs-CRP (Beta = 0.095, CI95 %: 0.001–0.189) and between DAI and TNF-a (Beta = 0.494, CI95 %: 0.121–0.866) and LDL-C (Beta = 1.037, CI95 %: 0.159–1.915). In addition, in logistic regression models, after adjusting for multiple confounders, there was a significant association between DII (continuous variable) (OR = 1.27, CI95 %: 1.08–1.50) and DAI (continuous variable) (OR = 0.93, CI95 %: 0.87–0.99) and odds of cataracts. ConclusionThis study confirms the association between pro-inflammatory and pro-oxidant diets, as indicated by higher DII scores and lower DAI, with serum biomarkers of inflammation and oxidative stress. Our study supports the notion that dietary interventions targeting inflammation and oxidative stress may have a potential role in preventing or delaying the onset of cataracts.

#211 : The Causal Effects of Circulating Biomarkers of Immunity and Inflammation on Endometriosis: A Bidirectional Mendelian Randomization Analysis

Background and Aims: Endometriosis is a chronic gynecological disease with a high prevalence among reproductive-aged women. Several studies have investigated the causal effect of different serum biomarkers of immunity and inflammation on the occurrence and progression of endometriosis. However, the results of these studies remained inconclusive and even controversial. Herein, this study aims to analyze the causal associations of genetically predicted levels of different circulating biomarkers of immunity and inflammation with the risk of endometriosis using a bidirectional two-sample Mendelian randomization (MR) approach. Methods: The single-nucleotide polymorphisms (SNPs) of exposures which indicate the genetic variants were used as instrumental variables (IVs) and were all obtained from the genome-wide association study (GWAS) of European ancestry from the IEU GWAS database. Besides, we performed bidirectional MR analysis to test the associations. The causal effects were estimated through the inverse-variance weighted method (IVW). The sensitivity examinations of each result after the MR analysis were performed to detect if any heterogeneity and pleiotropy existed. Results: Our results demonstrated that higher interleukin-9 (IL-9) level was associated with the occurrence of endometriosis, while macrophage colony stimulating factor (MCSF) level, TNF-related apoptosis inducing ligand (TRAIL), sE-Selectin and basophil count showed the opposite. Genetically predicted endometriosis was related to higher immunoglobulin E (IgE) level and platelet count. No evidence of bidirectional association was detected on the other serum inflammatory biomarkers with endometriosis. Neither pleiotropy nor heterogeneity was found in our study. Conclusion: Our results suggested that some dysregulated circulating biomarkers of immunity and inflammation is causally associated with the occurrence of endometriosis, and at the same time endometriosis may lead to the abnormality of some of these factors. Our findings provided genetic insights on potential novel strategies in the primary prevention, diagnosis and treatment of endometriosis.

Study of Cervical Mucus Cytology and Serum Inflammatory Biomarkers in Preterm Labour Compared to Term Pregnancy Cases in a Tertiary Care Center of Western Uttar Pradesh (UP), India.

The onset of labor prior to 37 weeks of gestation is preterm labor. Incidence ranges from 5% to 7% of live births in developed countries, but higher in developing countries (10-13%). Preterm birth is a major threat in perinatal health care, as well as a risk factor for neurological impairment and disability. Considering that infection is the major risk factor for preterm labor in rural areas, this study was performed to assess the cytological changes in the cervical mucus of normal-term and preterm labor cases. A hospital-based cross-sectional observational study was conducted in the Department of Obstetrics and Gynecology at a tertiary care center in western Uttar Pradesh (UP), India. The sample size calculated was 90. The neutrophil-to-lymphocyte ratio (NLR) in cervical mucus, along with serum inflammatory biomarkers such as CRP and serum alkaline phosphatase, were compared in both groups. The incidence of preterm labor increased with an increase in parity, and progression to preterm delivery is faster in the higher parity group. C-reactive protein (CRP) (pvalue= < 0.001) and serum alkaline phosphatases (taking 220IU/L as the cutoff value), as well as the NLR (pvalue < 0.001) in cervical mucus in preterm labor, are significantly higher than those in term labor cases, which can be used to predict preterm labor. Higher levels of serum alkaline phosphatase (> 220 IU/L) and CRP positivity can be used as prognostic markers. Using a cutoff value of 5 for the NLR in the cervical mucusof preterm labor patients proved to be a highly accurate predictor (82.2%) for preterm labor diagnosis.