Changes In Inflammatory Biomarkers Research Articles

Mirikizumab Sustained Impact on Fatigue in Patients with Moderately to Severely Active Crohn's Disease in the Phase 2 AMAG Study.

Fatigue is a burdensome,under-recognized, multidimensional symptom experienced by patients with Crohn's disease (CD). We evaluated the impact of mirikizumab on fatigue and the association between changes in select patient-reported outcomes and clinical measures with changes in fatigue from baseline to week 104 (W104). Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200mg, 600mg, or 1000mg of mirikizumab, administered intravenously (IV) every 4 weeks at W0, W4, and W8. Patients who achieved ≥1 point improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) and received mirikizumab at W12 (rerandomized maintenance cohort) were rerandomized to continue induction IV treatment assignment (IV-C) or received 300mg of mirikizumab subcutaneously (SC) until W52. Nonrandomized maintenance cohort had endoscopic nonimprovers (1000mg) and PBO patients (PBO/1000mg) who received 1000mg of mirikizumab until W52. Subjects from the maintenance period with clinical benefit received 300mg SC Q4W from W52 to W104. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was used to assess fatigue, and the FACIT-F associations were assessed using Pearson correlation coefficient. At W12, mirikizumab groups reported improved FACIT-F scores compared with PBO, and improvement was maintained through W52 and W104. Changes in FACIT-F at W52 and W104 had strong correlations with changes at the same time point in quality of life (QoL) scores but lacked correlations with changes in inflammatory biomarkers. Mirikizumab treatment significantly improved fatigue in patients with moderately to severely active CD, which was sustained to W104. The improvement in fatigue was correlated with improvement in clinical measures and was strongly correlated with improvement in QoL.

Inflammatory biomarker changes in healthy adults secondary to electronic cigarette use: A scoping review (PubMed).

Inflammatory biomarker changes in healthy adults secondary to electronic cigarette use: A scoping review (PubMed).

#624 The impact of hemoadsorption in patients with borderline chronic kidney disease undergoing coronary artery bypass grafting

Abstract Background and Aims With an annual incidence of up to 30%, cardiac surgery–associated acute kidney injury (CSA-AKI) may be one of the most underappreciated yet frequent complications and renal protective adjustments are crucial. We evaluated the impact of hemoadsorption as adjunctive therapy on clinical outcome in Kidney Disease Improving Global Outcomes (KDIGO) G2/A2) patients undergoing coronary artery bypass grafting (CABG). Method During a three-year period, 40 patients undergoing CABG with borderline chronic kidney disease (KDIGO-G2/A2) were treated with adjunctive hemoadsorption therapy and were compared by propensity score-matched 40 patients (KDIGO G2/A2) (Control). Primary endpoints were the need for renal replacement therapy (RRT)/dialysis and/or worsening of KDIGO stage in the perioperative period. Secondary endpoints were the change in inflammatory biomarkers, vasopressor requirement and ICU/hospital stay. In the study group, a 300 mL hemoadsorber (Cytosorbents Inc, NJ) was used for the entire duration of cardiopulmonary bypass (CPB). All patients were prepared via enhanced recovery after surgery (ERAS) protocol and surgical procedures were performed under moderate hypothermia with pulsatile flow and ultrafiltration. Patients with septic shock, limited life expectancy and refused to give consent were excluded. Results After institutional ethics committee approval was obtained, written informed consent was received from each patient. No significant difference was noted between groups in demographic, operative data and preoperative baseline laboratory. At the end of CPB; s-Creatinine (mg/dL) (1.85 ± 0.6 vs 2.751 ± 0.6; p = 0.035), NT-proBNP (pg/L) (130 ± 30 vs 180 ± 40; p = 0.04), IL-6 (pg/mL) (8.2 ± 4 vs 22.2 ± 4; p = 0.012) and myoglobulin (pg/L) (210 ± 75 vs 310 ± 80; p = 0.04) levels were significantly lower in the study group versus control. Clinical outcome is summarized in Figure. Conclusion This pioneering study demonstrated the additional protective effects of hemoadsorption in patients with borderline chronic kidney disease (KDIGO-G2/A2) undergoing CABG. Elimination of inflammatory parameters might be a complementary mechanism resulting in lesser worsening of kidney function/need of RRT and ICU stay. These findings require validation in large, multicenter trials.

Exercise attenuates high-fat diet-induced PVAT dysfunction through improved inflammatory response and BMP4-regulated adipose tissue browning.

Perivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways. Sprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed. Chronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p < 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p < 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT. Regular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.

Abstract PO3-19-02: White Button Mushroom and Biomarkers of Immune Cell and Inflammatory Responses in Obese Postmenopausal Women at High Risk of Breast Cancer

Abstract Background: White Button Mushroom (WBM), Agaricus bisporus, has anti-tumor and anti-inflammatory effects. Oral WBM mitigated the effects of a high fat diet on hepatic steatosis and insulin resistance in ovariectomized mice. A Phase I trial of WBM in men with prostate cancer demonstrated decreased myeloid derived suppressor cells (MDSC) in those with decreased PSA; MDSC have been linked to different cancers, including breast, and conditions of chronic inflammation. Design: This is a preliminary evidence trail in postmenopausal, obese women at high risk of breast cancer with a single intervention arm of 14g of WBM taken as 28 tablets daily for 3 months to assess effects on inflammation. Participants undergo a physical exam, measuring height, weight, and waist circumference, an optional fine needle aspiration (FNA) of breast tissue, a blood draw, a food frequency questionnaire and a 24-hour food recall at baseline and final visits. Participants are contacted monthly for tolerance and adherence. Blood samples and FNA adipose are used for metabolic measurements and processed for biomarkers of inflammation and immune response. Peripheral blood mononuclear cells (PBMC) will be used for RNA single-cell analysis to assess for immune cell profiles and expression with an interest in evaluating MDSC. Red blood cells will be assessed for fatty acid profiles. Eligibility: Postmenopausal, obese (BMI ≥30, Asian ≥25) women with high risk for breast cancer who can swallow pills are eligible. Patients are high risk if their relative risk of breast cancer is ≥2 times that of the general population; this includes women with a strong family history, a genetic mutation associated with hereditary breast cancer, a high-risk breast histology, Gail model 5-year risk &amp;gt;1.67, or a previous history of stage I-II breast cancer. Participants are excluded for an active malignancy within 5 years, ongoing active or preventative cancer treatment, or lab abnormalities of serum creatinine and total bilirubin &amp;gt;1.5 the upper limit of normal, hemoglobin of &amp;lt; 9.0 g/dL, platelets of &amp;lt; 100,000/mm3, or a total white blood cell count of &amp;lt; 3,500/mm3. Participants cannot be taking mushroom supplements, immunosuppressants, or non-steroidal anti-inflammatories. Specific Aims: This study aims to evaluate the effects of WBM on regulating immune response and inflammation in obese women at high risk for breast cancer. Our primary objective is the assessment of PBMC, specifically MDSC immune profiles before and after treatment. Our secondary objective is to evaluate changes in biomarkers of inflammation, immune cell profiles in breast adipose tissue, BMI, waist circumference, and metabolic biomarkers. Additionally, the study aims to assess tolerability of the WBM dose and effects on diet quality. Statistical Methods: 26 patients will provide 80% power to detect a change in %MDSC of -0.67, assuming a standard deviation of 1.15, and a 2-sided type I error of 5%. We will have similar power to evaluate changes in other immune subsets, inflammatory markers, metabolic markers, anthropometric measurements, and diet quality. FNA adipose tissue analysis will be used as a safety signal to evaluate the potential for unwanted inflammation with taking WBM. 13 patients with FNA will provide 80% power to detect a change of 85% of the standard deviation of the difference in the measure of biomarkers such as Interleukin-6 with a 2-sided type I error of 5%. As a safety signal, the signal will be reported without adjustment for multiple comparisons. Any conclusions based on such secondary endpoints will make note of the multiple comparison issue. Accrual: The accrual target is 26 evaluable patients with an estimated need to enroll 31. The study has enrolled 27 patients, 14 completed the study and 5 are currently on treatment. 8 participants were removed; 3 never started treatment, 1 was diagnosed with breast cancer, and 4 had other medical issues preventing continuation. Contact: Jessica Dzubnar, MD: jdzubnar@coh.org Citation Format: Jessica Dzubnar, Lisa Yee, Shiuan Chen. White Button Mushroom and Biomarkers of Immune Cell and Inflammatory Responses in Obese Postmenopausal Women at High Risk of 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 PO3-19-02.

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.

Blood Biomarker and Physical Activity Correlations in Persons with Parkinson’s Disease

Parkinson’s disease (PD) is a debilitating disease that reduces an individual’s quality of life (QOL). PD has a complex pathophysiology, but inflammation is a major contributor. Inflammation is a biological process that removes harmful stimuli and initiates the healing cascade. Researchers commonly use inflammatory markers, such as tumor necrosis factor-alpha (TNFα),interferon-gamma (IFNγ), and interleukin 1-beta (IL1β), to study PD pathologies. While PD is irreversible, physical activity is a non-pharmacological treatment exhibiting beneficial outcomes related to PD and inflammation. To determine if exercise frequency affects the quality of life (QOL) and the magnitude of change in inflammatorybiomarkers associated with PD. Researchers recruited 10 individuals diagnosed with PD to participate in a cross-sectional study. Participants completed four questionnaires to determine their current physical activity (PA) level and QOL. Blood samples were analyzed to determine differences in serum TNFα, IFNγ, and IL1β concentrations between different PA levels of persons with PD. With an alpha level of 0.05, this project only yielded two significant results: an unexpected positive relationship between IL1β and PA level and an expected negative relationship between IL1β and QOL. Although they were not significant, several results trended in the expected directions. Discussion: Observed trends indicated that increasing physical activity decreases inflammatory blood biomarker levels and increases QOL while increasing sedentary behavior increases inflammatory blood biomarker levels and decreases QOL.

The effect of a combined lifestyle intervention with and without protein drink on inflammation in older adults with obesity and type 2 diabetes

BackgroundChronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D. MethodsIn this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test). ResultsThere were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers. Conclusion13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status.

The changes of blood-based inflammatory biomarkers after non-pharmacologic interventions for chronic low back pain: a systematic review

BackgroundChronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP.MethodsA thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities.ResultsThirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1β, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT.ConclusionResults suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.

Exploring the interplay between posttraumatic stress disorder, gut microbiota, and inflammatory biomarkers: a comprehensive meta-analysis.

Posttraumatic stress disorder (PTSD) is the most common mental health disorder to develop following exposure to trauma. Studies have reported conflicting results regarding changes in immune biomarkers and alterations in the abundance of bacterial taxa and microbial diversity in patients with PTSD. The purpose of this meta-analysis is to summarize existing studies examining gut microbiota characteristics and changes in immune biomarkers in patients with PTSD. Relevant studies were systematically searched in PubMed, Scopus, and Embase, published in English between January 1, 1960, and December 1, 2023. The outcomes included changes in abundance and diversity in gut microbiota (gut microbiota part) and changes in immune biomarkers (immune part). The meta-analysis included a total of 15 studies, with 9 focusing on changes in inflammatory biomarkers and 6 focusing on changes in gut microbiota composition in patients with PTSD. No differences were observed between groups for all inflammatory biomarkers (P≥0.05). Two of the six studies found that people with PTSD had less alpha diversity. However, the overall Standardized Mean Difference (SMD) for the Shannon Diversity Index was not significant (SMD 0.27, 95% CI -0.62-0.609, p = 0.110). Regarding changes in abundance, in two of the studies, a significant decrease in Lachnospiraceae bacteria was observed. This meta-analysis provides a comprehensive overview of gut microbiota characteristics in PTSD, suggesting potential associations with immune dysregulation. Future research should address study limitations, explore causal relationships, and consider additional factors influencing immune function in individuals with PTSD. https://www.crd.york.ac.uk, identifier CRD42023476590.

Adherence to the MIND diet and the odds of mild cognitive impairment in generally healthy older adults: The 3-year DO-HEALTH study

BackgroundThe Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet. ObjectiveTo examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years. MethodsAdherence to the MIND diet was assessed by food frequency questionnaire (FFQ) at baseline and after three years. Presence of MCI based on the Montreal Cognitive Assessment (MoCA) was defined as <26 (MCI26), or <24 (MCI24). We performed a minimally adjusted model controlling for sex, prior fall, linear spline at age 85, time, treatment and study site. The fully adjusted model also adjusted for education, BMI, physical activity, depression score, daily energy intake, and comorbidity score. To assess the change in inflammatory markers from baseline, we used linear-mixed-effect models adjusted for the same variables plus the respective baseline concentrations. Sensitivity analyses accounting for practice effects of repeated cognitive tests using the reliable change index for both MoCA cut-offs were done. ResultsWe included 2028 of 2157 DO-HEALTH participants (60.5% women; mean age 74.88 years) with complete data. Adherence to the MIND diet at baseline was not associated with cognitive decline over three years, neither at MoCA < 26 (OR (95%CI) = 0.99 (0.94–1.04)) nor at MoCA < 24 (OR (95%CI) = 1.03 (0.96–1.1)). Applying the reliable change index to the two cut-offs confirmed the findings. Further, the MIND diet adherence was not associated with the change in MoCA score from baseline in DO-HEALTH. For inflammatory biomarkers MIND-diet baseline adherence was not associated with changes in hsCRP or IL-6. ConclusionAdherence to the MIND-diet was neither associated with the odds of MCI, nor with hsCRP or IL-6 at baseline. Moreover, change in MIND-diet over three years was not associated with changes in hsCRP or IL-6.

Inflammatory biomarker changes in healthy adults secondary to electronic cigarette use: A scoping review.

There has been a global increase in the use of electronic cigarettes (EC). However, to our knowledge, no review has summarized or categorized changes in inflammatory biomarkers after EC use in the extant literature. To evaluate changes in general, cardiopulmonary, and oxidative stress-related inflammatory biomarkers in healthy adults who use ECs. A scoping review was conducted according to the Arksey and O'Malley framework. PubMed and MEDLINE (Ovid) databases were used for our search. After initial pilot searches and discussions, we performed a final search with medical subject headingsand plain language terms related to inflammation, biomarkers, ECs, and adult humans. All full-text articles, gray literature, and primary studies dating from the inception of the searched databases to the present were included. Studies of human participants with known confounding medical histories were excluded. Thirty-seven studies met the inclusion criteria. After short-term (<1 month) use, ECs containing nicotine moderately increased cardiovascular (CV) and oxidative stress markers of inflammation. Of all reported results, 50% of CV biomarkers were increased, and 64% of oxidative stress markers were increased. After long-term (>1 month) use, ECs containing nicotine produced mixed results. Two commonly measured biomarkers in this group, matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6), were elevated in 75% and 60% of measured instances, respectively. The results of studies evaluated in our scoping review suggested that short-term use of nicotine-containing ECs may result in increased CV and oxidative stress inflammation, contributing to potential CV or neurologic disease development. The results of studies evaluated in our scoping review also suggested that long-term use of nicotine-containing ECs resulted in no significant changes in general inflammatory biomarker levels. A rigorous systematic review and meta-analysis is necessary to corroborate our findings and to determine the effect of long-term EC use on MMP-9 and IL-6 levels.

Brief communications: changes in inflammatory biomarkers and lipid profiles after switching to long-acting cabotegravir plus rilpivirine

We assessed whether the impact of cabotegravir plus rilpivirine on inflammation reduction differs from that of oral antiretrovirals, using real-world data. Inflammatory biomarkers and lipid profiles were followed from baseline to 8 months after switching. Seventy-eight participants were analyzed. The CD4/CD8 ratio and C-reactive protein did not change. There were transient decreases in CD8 and CD4 counts in the group that switched from the dolutegravir-based regimen, but not in the tenofovir alafenamide-based regimen group. High-density lipoprotein (HDL) cholesterol increased, resulting in a decrease in the total-cholesterol to HDL cholesterol ratio, whereas there was no significant change in low-density lipoprotein cholesterol.

A Scoping Review to Explore the Potential Benefits of Nutrition Interventions for Latino/a Adult Cancer Survivors in the US.

Despite evidence for the role of healthy diets in preventing cancer, little is known about how nutrition can support positive health outcomes after a cancer diagnosis for Latino/a cancer survivors in the United States (U.S.). The purpose of this scoping review is to understand the potential benefits of nutrition interventions in supporting healthy survivorship among Latino/a cancer survivors in the U.S. A team compiled, evaluated, and summarized the available evidence. Potentially relevant studies were identified from a comprehensive search of peer-reviewed databases and the gray literature. Eligible studies included Latino/a adult cancer survivors with a nutrition education, dietary change, or behavioral intervention; and a nutrition-related health outcome. Data were extracted and summarized using tables. The review included 10 randomized controlled trials, with samples or subsamples of Latino/a cancer survivors. Interventions mostly focused on breast cancer survivors. The results showed some evidence that dietary behaviors, like fruit and vegetable intake, were related to positive outcomes, like a decreased risk of cancer (through changes in DNA methylation), decreased risk breast cancer recurrence (through changes in inflammatory biomarkers), or improved perception of health status. The findings highlight a need for community-engaged and culturally relevant nutrition interventions for Latino/a adults, especially for rural communities; and innovative intervention approaches, including m/ehealth approaches with long-term follow-up.

Abstract 12958: Temporal Association of Systemic Inflammatory Biomarkers With Incidence of Postoperative Atrial Fibrillation After Botulinum Toxin Type A Administration in Epicardial Fat Pads

Background: A one-time injection of botulinum toxin type A (BoNT/A) in epicardial fat pads was evaluated for post-operative atrial fibrillation (POAF) in patients undergoing open-chest cardiac surgery in the Ph2 NOVA trial. Treatment with 125U BoNT/A numerically reduced the incidence of POAF in the mITT (36.5% vs 46.1%) and CABG populations (28.4% vs 40.0%), with statistical significance observed in the CABG + ≥65 years subgroup (27.5% vs 56.4%; P &lt;0.01). No significant reduction was observed in the 250U group vs placebo. Purpose: Explore systemic inflammatory biomarker changes after treatment with BoNT/A and the temporal relation to incidence of POAF. Methods: This analysis included 308 patients who received 125U BoNT/A (n=103), 250U BoNT/A (n=103), or placebo (n=102). Subgroup analysis was done for CABG (n=198), age ≥65 years (n=185), and CABG + ≥65 years (n=118). Serum samples were collected preoperatively prior to dosing on Day 1, then post-treatment on Days 2-4 to test for IL-6, IL-10, and hsCRP. A 2-sample t test was used for mean concentrations and a linear mixed model was used for fold change (FC) from baseline. Results: Baseline levels of IL-6, IL-10, and hsCRP were similar between treatment groups. Reduction of IL-6 (45.7 ± 4.4 vs 62.4 ± 5.8 pg/mL, P &lt;0.05; 10.8 vs 15.9 FC, P &lt;0.01) and IL-10 (1.49 ± 0.13 vs 2.04 ± 0.24 pg/mL, P &lt;0.05; 1.96 vs 2.66 FC, P &lt;0.01) was most significant on Day 2 in CABG patients treated with 125U vs placebo, which aligns with the highest rate and risk of POAF (Figure 1). Mean hsCRP was most significantly reduced on Day 4 in the 250U group among CABG patients (193 ± 8 vs 227 ± 10 mg/dL, P &lt;0.01) followed by 125U vs placebo (196 ± 10 vs 227 ± 10 mg/dL, P &lt;0.05); a similar dose-dependent reduction was observed by FC analysis. Conclusions: Treatment with 125U BoNT/A in cardiac surgery patients lowered the incidence of POAF vs placebo and reduced postoperative systemic IL-6 and IL-10 on Day 2, most significantly in the CABG population.

Dityrosine Aggravates Hepatic Insulin Resistance in Obese Mice by Altering Gut Microbiota and the LPS/TLR4/NF-κB Inflammatory Pathway.

Dityrosine is the main product of protein oxidation, which has been proved to be a threat to human health. This study aims to investigate whether dityrosine exacerbates insulin resistance by inducing gut flora disturbance and associated inflammatory responses. Mice fed with normal diet or high-fat diet (HFD) received daily gavage of dityrosine (320µgkg-1 BW) or saline for consecutive 13 weeks. The effects of dityrosine on gut microbiota are verified by in vitro fermentation using fecal microbiota from db/m mice and db/db mice. As a result, dityrosine causes the insulin resistance in mice fed normal diet, and aggravates the effects of HFD on insulin sensitivity. Dityrosine increases the levels of lipopolysaccharide (LPS), lipopolysaccharide-binding protein (LBP), toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) but decreases levels of interleukin-10 (IL-10) in the plasma of CON and HFD-fed mice. The changes of gut flora composition caused by dityrosine are significantly correlated with the changes of inflammatory biomarkers. The effects of dityrosine on insulin resistance may be attributed to the reshaping of the gut microbiota composition and promoting the activity of the LPS/TLR4/NF-κB inflammatory pathway in HFD-induced obese individuals.

Changes in Inflammatory Biomarkers in Patients with Schizophrenia: A 3-Year Retrospective Study.

Accumulating evidence suggested that immune system activation might be involved in the pathophysiology of schizophrenia. The neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) can measure inflammation. This study aimed to investigate the inflammatory state in patients with schizophrenia by using these indicators. In this study, the complete blood count data for 187 continuing hospitalized patients with schizophrenia and 187 age- and sex-matched healthy participants was collected annually from 2017 to 2019. Platelet (PLT), lymphocyte (LYM), monocyte (MON) and neutrophil (NEU) counts were aggregated and NLR, MLR, PLR, and SII were calculated. Using a generalized linear mixed model, we assessed the impact of age, sex, diagnosis, and sampling year on the above indicators and evaluated the interaction between the factors. According to the estimation results of the generalized linear mixed model, the NLR increased by 0.319 (p = 0.004), the MLR increased by 0.037 (p < 0.001), and the SII increased by 57.858 (p = 0.018) in patients with schizophrenia. Data after two years of continuous antipsychotic treatment showed that the NLR and MLR were higher in patients with schizophrenia than those in healthy controls, while the PLT and LYM counts were decreased in patients with schizophrenia. The schizophrenia diagnosis was correlated to the MON and LYM count, NLR, MLR, and SII (p < 0.05). The differences in these markers were stable and cannot be eliminated by a full course of treatment. This study provides impetus for the inflammatory hypothesis of schizophrenia.

The relationship between inflammatory biomarker trajectory and cognitive change following elective non‐cardiac surgery in older adults

AbstractBackgroundSurgery in the older patient is associated with short‐ and long‐term cognitive changes, including delirium, post‐operative cognitive dysfunction (POCD) and neurocognitive decline (NCD). The inflammatory response to surgery may be a contributing factor. We investigated the association between inflammatory biomarkers and cognitive change up to 3 months following surgery.MethodWe recruited 70 older adults undergoing elective non‐cardiac surgery. Baseline and 3 month neurocognitive and functional assessments were performed, and delirium was assessed for 5 days following surgery. A control group of age‐similar subjects underwent assessment at similar time points. Blood was collected in 55 patients at baseline and post‐surgery at 30 min, 6h, 24h and 48h for inflammatory biomarker analysis (Tumor Necrosis Factor (TNF)‐α, Interleukin (IL)‐6, IL‐10, IL‐18). POCD was attributed if there was ≥ 1.96 SD decline in two or more neuropsychological tests compared with time‐matched controls. NCD major and mild was attributed according to DSM‐V criteria.ResultPatients underwent a range of non‐cardiac surgical procedures and were aged 69.5 (SD 6.7)y and 48.6% were female. Mean baseline MMSE was 27.1 (7.5). Delirium was identified post‐operatively in 4% of subjects. At 3 months, 18 (32.7%) subjects had some form of cognitive decline: POCD 7%, Mild NCD 16% or Major NCD 15%. IL‐6 was significantly elevated following surgery and remained so to 48h. IL‐10 was elevated at 6h but declined to baseline by 48h. Both IL‐18 and TNF‐α were transiently lower than baseline at 30 minutes, but then returned to close to baseline levels. There was no association between inflammatory biomarker levels and delirium or cognitive change at 3 months.ConclusionWe have confirmed the presence of new cognitive decline in a significant number of older patients up to 3 months following non‐cardiac surgery. We identified changes in inflammatory biomarkers, especially IL‐6 which was elevated for at least 48h, but no association with cognitive change. Ongoing research will address more specific biomarkers of neuronal injury.

Tumour Necrosis Factor-α, Chemokines, and Leukocyte Infiltrate Are Biomarkers for Pathology in the Brains of Venezuelan Equine Encephalitis (VEEV)-Infected Mice.

Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the encephalitic aspects of the disease were analysed to identify biomarkers associated with inflammation. Sequential sampling of lethally challenged mice (infected subcutaneously) confirmed a rapid onset systemic infection with subsequent spread to the brain within 24 h of the challenge. Changes in inflammatory biomarkers (TNF-α, CCL-2, and CCL-5) and CD45+ cell counts were found to correlate strongly to pathology (R>0.9) and present previously unproven biomarkers for disease severity in the model, more so than viral titre. The greatest level of pathology was observed within the olfactory bulb and midbrain/thalamus. The virus was distributed throughout the brain/encephalon, often in areas not associated with pathology. The principal component analysis identified five principal factors across two independent experiments, with the first two describing almost half of the data: (1) confirmation of a systemic Th1-biased inflammatory response to VEEV infection, and (2) a clear correlation between specific inflammation of the brain and clinical signs of disease. Targeting strongly associated biomarkers of deleterious inflammation may ameliorate or even eliminate the encephalitic syndrome of this disease.

Inflammation-associated long non-coding RNA signature in radicular cyst tissues.

Radicular cysts are characterized by significant levels of changes in inflammatory biomarkers. Among them, interleukins and growth factors have been reported to be deregulated in radicular cyst tissues. Moreover, long non-coding RNAs are recently discovered non-coding RNA molecules that regulate various intracellular stimuli to keep homeostasis in balance. A growing body of evidence suggests that lncRNAs are significantly involved in the regulation of inflammation by targeting various inflammatory biomarkers. Accordingly, the present study was aimed to investigate the gene expression levels of inflammation-related lncRNAs in radicular cysts and show their possible roles in the development of radicular cysts. For the study, a total of 25 patients with a radiologically and pathologically confirmed radicular cyst were enrolled. For the determination of non-coding RNA expression levels, real-time qPCR was used. As a result of the current study, expression levels of PACER and THRIL were found to be significantly elevated in radicular cyst tissues compared to control tissue samples. However, MALAT1, ANRIL, and NEAT1 expression levels were not significantly altered in radicular cyst tissues compared to control tissue samples. In conclusion, long non-coding RNAs, PACER and THRIL, seem to have significant pathophysiological roles by acquiring molecular changes during inflammation and might be involved in the development and formation of radicular cysts.