Inflammatory Biomarkers Research Articles

Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker

IntroductionUntreated gout is characterised by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated by asymptomatic phases. Both phases are inflammatory conditions of variable intensity. Gout...

Effects of Probiotics on Inflammatory Biomarkers and Its Associations With Cardiac Autonomic Function in Women With Arterial Hypertension: A Secondary Analysis of a Randomized Clinical Trial.

Preclinical evidence suggests that probiotic administration may exert an anti-inflammatory effect and reduce autonomic dysfunction and blood pressure. This study evaluated the effects of probiotic therapy on inflammatory biomarkers and characterized the correlations between inflammation and cardiac autonomic function in women with arterial hypertension. Women were randomized into probiotics (n = 20) or placebo (n = 20). The probiotic group received 109CFU/day of Lactobacillus (L.) paracasei LPC-37, L. rhamnosus HN001, L. acidophilus NCFM, and Bifidobacterium lactis HN019, and the placebo group received polydextrose. Clinical, electrocardiogram, heart rate variability (HRV) analysis, and cytokine levels were assessed at baseline and after 8weeks. Women who received probiotics for 8weeks had increased serum levels of IL-17A (p = 0.02) and decreased INF-γ (p = 0.02) compared to baseline. Probiotic supplementation increased serum levels of IL-10 compared to the placebo group (p = 0.03). Probiotic or placebo administration did not change serum levels of TNFα and IL-6. Serum levels of IL-2 (p = 0.001, and p = 0.001) and IL-4 (p = 0.001, and p = 0.001) were reduced in women receiving placebo or probiotics, respectively. Correlations between HRV indices and inflammatory variables showed that INF-γ was positively correlated with heart rate (HR) and sympathetic HRV indices and negatively correlated with vagal HRV indices. IL-10 was negatively correlated with HR and sympathetic HRV indices. IL-6 was negatively correlated with parasympathetic HRV indices and positively correlated with SD2/SD1 ratio. Probiotic therapy has a discreet anti-inflammatory effect in hypertensive women, and pro-inflammatory cytokines were negatively correlated with vagal modulation and positively correlated with sympathetic modulation of HRV.The clinical trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-9mj2dt.

Biomarkers of inflammation and coagulation after minimally invasive mitral valve surgery: a prospective comparison to conventional surgery

STRUCTURED ABSTRACT Objectives Minimally invasive cardiac surgery techniques are increasingly used but have longer cardiopulmonary bypass time, which may increase inflammatory response and negatively affect coagulation. Our aim was to compare biomarkers of inflammation and coagulation as well as transfusion rates after minimally invasive mitral valve repair and mitral valve surgery using conventional sternotomy. Design A prospective non-randomized study was performed enrolling 71 patients undergoing mitral valve surgery (35 right mini-thoracotomy and 36 conventional sternotomy procedures). Blood samples were collected pre- and postoperatively to assess inflammatory response. Thromboelastometry (ROTEM) was performed to assess coagulation, and transfusion rates were monitored. Results The minimally invasive group had longer cardiopulmonary bypass times compared to the sternotomy group: 127 min ([115–146] vs 79 min [65–112], p < 0.001) and were cooled to a lower temperature during cardiopulmonary bypass, 34 °C vs 36 °C (p = 0.04). IL-6 was lower in the minimally invasive group compared to the conventional sternotomy group when measured at the end of the surgical procedure, (38 [23–69] vs 61[41–139], p = 0.008), but no differences were found at postoperative day 1 or postoperative day 3. The transfusion rate was lower in the minimally invasive group (14%) compared to full sternotomy (35%, p = 0.04) and the chest tube output was reduced, (395 ml [190-705] vs 570 ml [400–1040], p = 0.04). Conclusions Our data showed that despite the longer use of extra corporal circulation during surgery, minimally invasive mitral valve repair is associated with reduced inflammatory response, lower rates of transfusion, and reduced chest tube output.

Fibrinogen-albumin ratio predicts treatment response in phospholipase A2 receptor-associated membranous nephropathy with nephrotic syndrome

Background The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. Methods 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman’s correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. Results In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. Conclusions FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

Blood flow restriction Exercise in the perioperative setting to Prevent loss of muscle mass in patients with pancreatic, biliary tract, and liver cancer: study protocol for the PREV-Ex randomized controlled trial

BackgroundPatients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer.MethodsThe PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6–10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients’ medical records; (v) explorative outcomes of patients’ experience of the exercise program which will be evaluated using focus group/individual interviews.DiscussionIt is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs.Trial registrationClinicalTrials.gov NCT05044065. Registered on September 14, 2021.

Pleiotropic Effects of Direct Oral Anticoagulants in Chronic Heart Failure and Atrial Fibrillation: Machine Learning Analysis.

Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of anticoagulation therapy before 2010, and direct-acting oral anticoagulants (DOACs, namely dabigatran etexilate, rivaroxaban, apixaban, edoxaban), approved for the prevention of AF stroke over the last thirteen years. Due to the lower risk of major bleeding associated with DOACs, anticoagulant switching is a common practice in AF patients. Nevertheless, there are issues related to OAT switching that still need to be fully understood, especially for patients in whom AF and heart failure (HF) coexist. Herein, the effective impact of the therapeutic switching from warfarin to DOACs in HF patients with AF, in terms of cardiac remodeling, clinical status, endothelial function and inflammatory biomarkers, was assessed by a machine learning (ML) analysis of a clinical database, which ultimately shed light on the real positive and pleiotropic effects mediated by DOACs in addition to their anticoagulant activity.

Colchicine in acute heart failure: Rationale and design of a randomized double-blind placebo-controlled trial (COLICA).

Heart failure (HF) elicits a pro-inflammatory state, which is associated with impaired clinical outcomes, but no anti-inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin-1 axis are overactivated during episodes of acute HF. Colchicine, an anti-inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients. COLICA is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new-onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m2). The primary efficacy endpoint is the time-averaged proportional change in NT-proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events. COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF.

Clinical evaluation of droplet digital PCR in the early identification of suspected sepsis patients in the emergency department: a prospective observational study.

Rapid and accurate diagnosis of the causative agents is essential for clinical management of bloodstream infections (BSIs) that might induce sepsis/septic shock. A considerable number of suspected sepsis patients initially enter the health-care system through an emergency department (ED), hence it is vital to establish an early strategy to recognize sepsis and initiate prompt care in ED. This study aimed to evaluate the diagnostic performance and clinical value of droplet digital PCR (ddPCR) assay in suspected sepsis patients in the ED. This was a prospective single-centered observational study including patients admitted to the ED from 25 October 2022 to 3 June 2023 with suspected BSIs screened by Modified Shapiro Score (MSS) score. The comparison between ddPCR and blood culture (BC) was performed to evaluate the diagnostic performance of ddPCR for BSIs. Meanwhile, correlative analysis between ddPCR and the inflammatory and prognostic-related biomarkers were conducted to explore the relevance. Further, the health economic evaluation of the ddPCR was analyzed. 258 samples from 228 patients, with BC and ddPCR performed simultaneously, were included in this study. We found that ddPCR results were positive in 48.13% (103 of 214) of episodes, with identification of 132 pathogens. In contrast, BC only detected 18 positives, 88.89% of which were identified by ddPCR. When considering culture-proven BSIs, ddPCR shows an overall sensitivity of 88.89% and specificity of 55.61%, the optimal diagnostic power for quantifying BSI through ddPCR is achieved with a copy cutoff of 155.5. We further found that ddPCR exhibited a high accuracy especially in liver abscess patients. Among all the identified virus by ddPCR, EBV has a substantially higher positive rate with a link to immunosuppression. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity as well as prognosis. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs. The multiplexed ddPCR delivers precise and quantitative load data on the causal pathogen, offers the ability to monitor the patient's condition and may serve as early warning of sepsis in time-urgent clinical situations as ED. Early detection and effective administration of antibiotics are essential to improve clinical outcomes for those with life-threatening infection in the emergency department. ddPCR, an emerging tool for rapid and sensitive pathogen identification used as a precise bedside test, has developed to address the current challenges of BSI diagnosis and precise treatment. It characterizes sensitivity, specificity, reproducibility, and absolute quantifications without a standard curve. ddPCR can detect causative pathogens and related resistance genes in patients with suspected BSIs within a span of three hours. In addition, it can identify polymicrobial BSIs and dynamically monitor changes in pathogenic microorganisms in the blood and can be used to evaluate antibiotic efficacy and survival prognosis. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs.

Kinetics of cardiovascular and inflammatory biomarkers in paediatric dengue shock syndrome

Abstract Objectives Glycocalyx disruption and hyperinflammatory responses are implicated in the pathogenesis of dengue-associated vascular leak, however little is known about their association with clinical outcomes of patients with dengue shock syndrome (DSS). We investigated the association of vascular and inflammatory biomarkers with clinical outcomes and their correlations with clinical markers of vascular leakage. Methods We performed a prospective cohort study in Viet Nam. Children ≥ 5 years of age with a clinical diagnosis of DSS were enrolled into this study. Blood samples were taken daily during ICU stay and 7–10 days after hospital discharge for measurements of plasma levels of Syndecan-1, Hyaluronan, Suppression of tumorigenicity 2 (ST-2), Ferritin, N-terminal pro Brain Natriuretic Peptide (NT-proBNP), and Atrial Natriuretic Peptide (ANP). The primary outcome was recurrent shock. Results 90 DSS patients were enrolled. Recurrent shock occurred in 16 patients. All biomarkers, except NT-proBNP, were elevated at presentation with shock. There were no differences between compensated and decompensated DSS patients. Glycocalyx markers were positively correlated with inflammatory biomarkers, haematocrit, percentage hemoconcentration, and negatively correlated with stroke volume index. While Syndecan-1, Hyaluronan, Ferritin, and ST-2 improved with time, ANP continued to be raised at follow-up. Enrolment Syndecan-1 levels were observed to be associated with developing recurrent shock although the association did not reach the statistical significance at the P &amp;lt; 0.01 (OR = 1.82, 95% CI 1.07–3.35, P = 0.038). Conclusions Cardiovascular and inflammatory biomarkers are elevated in DSS, correlate with clinical vascular leakage parameters and follow different kinetics over time. Syndecan-1 may have potential utility in risk stratifying DSS patients in ICU.

Milk protein concentrate supplementation improved appetite, metabolic parameters, adipocytokines, and body composition in dieting women with obesity: a randomized controlled trial

BackgroundDairy consumption is associated with many health benefits. However, to our knowledge, no clinical trials examined the effects of milk protein concentrate (MPC) on metabolic health in overweight and obese adults. This study investigated the effect of supplementation with MPC on glycaemic status, lipid profile, biomarkers of inflammation, and anthropometric measurements in women with obesity under a weight loss diet.MethodsThis is a single-blind, open-labelled, parallel-group, randomized trial. Forty-four healthy women with obesity were randomized into a control (n = 22) or MPC (n = 22) group. Participants in the MPC group were supplemented with 30 g of MPC per day for 8 weeks. Both groups were on a calorie-restricted diet plan with 800 Kcal lower intakes than their needs. Blood samples, dietary intake, and body composition were assessed before and after the intervention.ResultsMPC group had a significantly lower body mass index (P = 0.009), waist circumference (P = 0.013), fat mass (P = 0.021), appetite score (P = 0.002), fasting blood sugar (P < 0.001), insulin (P = 0.027), low-density lipoprotein cholesterol (P = 0.025), and leptin (P = 0.014) levels and higher high-density lipoprotein cholesterol (P = 0.001) and adiponectin (P = 0.032) compared to the control group after supplementation. Lean body mass, total cholesterol, and triglyceride did not differ significantly (P > 0.05).ConclusionDaily intake of 30 g of MPC for 8 weeks may improve several anthropometric and metabolic markers in women with obesity under a hypocaloric diet.

C-reactive protein (CRP) in high altitude Bolivian peri-urban adolescents varies by adiposity, current illness, height, socioeconomic status, sex, and menarcheal status: The potential benefits and costs of adipose reserves in arduous environments.

In non-industrialized and low-income populations, adipose stores can serve as a valuable buffer against harsh conditions such as seasonal food scarcity. However, these reserves may incur costs due to adipocytes' production of pro-inflammatory cytokines; inflammation is associated with increased risk for cardiometabolic diseases later in life. Life history theory posits that, especially in populations with high juvenile mortality, higher adiposity may nonetheless be advantageous if its benefits in early life outweigh its later costs. Relatively little is known about adolescents' C-reactive protein concentration (CRP; an inflammation biomarker) in such environments. We investigated CRP and its associations with several hypothesized predictors in adolescents in an economically diverse peri-urban Andean community. We measured CRP in dried blood spots and collected data on anthropometrics, illnesses, socioeconomic status (SES), and menarcheal status in 59 female and 40 male adolescents ("Alteños", 11.0-14.9 years old) with normal vital signs in El Alto, Bolivia (~4150 m amsl). We used Cole's LMS method to standardize all anthropometrics for sex and age, and principal components analysis to construct a "fat-factor" variable loading on these standardized z-scores. We used multiple linear regression to assess the influence of fat-factor and other likely predictors on CRP rank. Compared to a national Bolivian growth reference, Alteños were, on average, shorter and leaner; only 6% were classified as overweight and none were obese. Pre-menarche females were on average leaner than post-menarche females. The best-fitting model explained 24% of the variance in CRP rank. Significant predictors were fat-factor, SES, current illness for males and pre-menarche females, and z-height for females. Our results are consistent with a tradeoff between investments in growth versus immune functioning, as might be expected in an environment with limited resources and high pathogen exposure (e.g., soil-transmitted helminths, poor sanitation). Thinner Alteños appear to maintain a minimum CRP concentration independent of fat-factor, while fatter (or less-thin) Alteños' CRP rises with fat-factor. Female Alteños appear to be trading off investment in immune response for investment in growth and maturation. Alteños' high rate of stunting and absence of obesity suggests chronic, presumably multifactorial, stress. Adipose stores likely buffer against some of these stressors and, in an environment such as this-in which many lack sufficient nutritious foods, potable water, adequate sewage, and health care-may confer a net lifetime benefit.

Does physical activity and inflammation mediate the job stress-headache relationship? A sequential mediation analysis in the ELSA-Brasil study

BackgroundEvidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. ObjectiveTo test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. MethodsWe cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. ResultsIn total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = −0.039 (95 %CI: −0.074, −0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. ConclusionIn the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.

Multiple Infections, Nutrient Deficiencies, and Inflammation as Determinants of Anemia and Iron Status during Pregnancy: The MINDI Cohort.

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.

Performance of an automated immunoturbidimetric assay for bovine serum amyloid A.

Acute phase proteins are a group of vital constituents of the innate immune system, which may also serve as circulatory biomarkers of inflammation. The major acute phase protein serum amyloid A (SAA) is a reliable and sensitive biomarker in cows, allowing for rapid detection of inflammatory disease. A multispecies automated immunoturbidimetric assay (VET-SAA, Eiken) has been validated for horses, dogs, and cats, and it has been used to measure SAA concentrations in bovine samples. The aim of the present study was to perform an analytical validation of the VET-SAA immunoturbidometric assay based on monoclonal antihuman SAA antibodies for the measurement of SAA in clinical samples from cows. The validation included an assessment of imprecision, inaccuracy, and detection limit, as well as an evaluation of the overlap performance, using banked serum from healthy and sick cows with or without inflammatory disease. Intra- and interassay variation ranged from 0.91% to 2.9% and 2.5% to 5.8%, respectively. The assay was performed with acceptable accuracy within a clinically relevant range of SAA, although minor signs of inaccuracy were detected. Overlap performance was acceptable, with the VET-SAA assay able to differentiate between healthy cows and cows with inflammatory and noninflammatory conditions. The automated VET-SAA assay is considered acceptable for the measurement of SAA in cows.

Antioxidative and Anti-inflammatory Effects of Plant-derived Hypoglycemic Medicines: An In vivo/In vitro Systematic Review.

The activation of oxidative stress and inflammatory conditions has been associated with acceleration in diabetes (DM) onset and complications. Despite various anti-DM medications, there is a growing trend to discover inexpensive and effective treatments with low adverse effects from plants as one of the promising sources for drug development. This study aimed to systematically investigate the simultaneous anti-inflammatory and antioxidant effects of plant-derived hypoglycemic medicines in diabetic experimental models. The search terms consisted of "diabetes", "herbal medicine", "antioxidant", "Inflammatory biomarker", and their equivalents among PubMed, Scopus, Web of Science, and Cochrane Library databases up to 17 August 2021. Throughout the search of databases, 201 eligible experimental studies were recorded. The results showed that the most commonly assessed inflammatory and oxidative stress biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL) 6, IL-1β, IL-10, malondialdehyde (MDA), and nitric oxide (NO). The activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were assessed in the present review. Among herbal treatments, Trigonella foenum-graecum L., Centella asiatica (L.) Urb., Vitis vinifera L., and Moringa oleifera Lam. were most commonly used for diabetic complications. Due to the dispersion of the treatments, meta-analysis was not applicable. Our findings showed that the application of different plant-derived hypoglycemic treatments in animal models improved diabetes and its complications, as well as modulated concomitant inflammatory and oxidative stress biomarkers. These findings suggest that plant-based antidiabetic medicines and food supplements have the potential to manage diabetes and its complications.

Hemoglobin and Its Relationship with Fatigue in Long-COVID Patients Three to Six Months after SARS-CoV-2 Infection.

Background: While some long-term effects of COVID-19 are respiratory in nature, a non-respiratory effect gaining attention has been a decline in hemoglobin, potentially mediated by inflammatory processes. In this study, we examined the correlations between hemoglobin levels and inflammatory biomarkers and evaluated the association between hemoglobin and fatigue in a cohort of Long-COVID patients. Methods: This prospective cohort study in the Netherlands evaluated 95 (mostly hospitalized) patients, aged 40-65 years, 3-6 months post SARS-CoV-2 infection, examining their venous hemoglobin concentration, anemia (hemoglobin < 7.5 mmol/L in women and <8.5 mmol/L in men), inflammatory blood biomarkers, average FSS (Fatigue Severity Score), demographics, and clinical features. Follow-up hemoglobin was compared against hemoglobin during acute infection. Spearman correlation was used for assessing the relationship between hemoglobin concentrations and inflammatory biomarkers, and the association between hemoglobin and fatigue was examined using logistic regression. Results: In total, 11 (16.4%) participants were suffering from anemia 3-6 months after SARS-CoV-2 infection. The mean hemoglobin value increased by 0.3 mmol/L 3-6 months after infection compared to the hemoglobin during the acute phase (p-value = 0.003). Whilst logistic regression showed that a 1 mmol/L greater increase in hemoglobin is related to a decrease in experiencing fatigue in Long-COVID patients (adjusted OR 0.38 [95%CI 0.13-1.09]), we observed no correlations between hemoglobin and any of the inflammatory biomarkers examined. Conclusion: Our results indicate that hemoglobin impairment might play a role in developing Long-COVID fatigue. Further investigation is necessary to identify the precise mechanism causing hemoglobin alteration in these patients.

Inflammatory biomarkers and frailty transitions in older adults with cancer: Findings from a national cohort study.

e13772 Background: Approximately 67% of cancer survivors were aged 65 or older in the U.S.; they face a heightened risk of frailty, as both cancer and anti-cancer treatment impose additional stressors on the older adults’ physiological reserves. Inflammatory biomarkers such as serum C-reactive protein (CRP) and Interleukin-6 (IL-6) levels were associated with frailty. However, the role of inflammatory biomarkers on the transitions of frailty states remains unclear. This study aimed to describe transitions between frailty states and death and quantify the predictive effect of inflammatory biomarkers on transitions. Methods: We used data from the National Health and Aging Trends Study (NHATS) from 2017 to 2022. A total of 1,219 older cancer survivors (&gt;67 years) were included. Frailty was assessed annually using the Fried Frailty Phenotype (exhaustion, low physical activity, shrinking, low walking speed, and weakness) to categorize participants as “non-frail,” “pre-frail,” and “frail.” Inflammatory biomarkers were obtained via dried blood spots at baseline (2017). Plasma-equivalent values of CRP and IL-6 were used. Covariates included sex, age category, race, education level, marital status, obesity, and number of comorbidities. We defined four states that included three frailty states (non-frail, pre-frail, and frail) and an absorbing state of death. The multi-state Markov models were performed to capture possible transitions between frailty states and examine the effect of CRP and IL-6 on the five main transitions between states (non-frail to pre-frail, pre-frail to non-frail, pre-frail to frail, frail to pre-frail, frail to death). Results: At baseline, 25.27% were non-frail, 52.34% were pre-frail, and 22.40% were frail. During the follow-up time of 5 years, 1,396 transitions were observed, with 950 (68.05%) progressions (or to death) and 446 (31.95%) reversals. For participants who were non-frail, they were highly likely to develop pre-frailty (transition intensity=0.63). For participants with pre-frailty, progression to frailty was a little more likely than recovery to non-frailty (0.25 vs 0.21). Once entering the frail state, the likelihood of death outweighed that of recovery (0.30 vs 0.28). A higher level of CRP or IL-6 was associated with frailty progression (non-frail to pre-frail and frail to death), while a lower level of CRP or IL-6 was associated with recovery of frailty (pre-frail to non-frail and frail to pre-frail). Conclusions: This study is the first to investigate the longitudinal relationship between inflammatory biomarkers and frailty transitions in older cancer survivors using a nationally representative survey dataset. Our findings outlined potential transitions between frailty states and death, highlighting the role of elevated serum CRP and IL-6 levels on the increased risk of frailty progression and reduced risk of frailty recovery over 5 years.

Psychoneurological symptoms, inflammatory biomarkers and gut microbiome richness and diversity in individuals receiving hematopoietic cell transplantation (HCT).

e24053 Background: Hematopoietic Stem Cell Transplantation (HCT) is a potentially curative treatment for certain hematologic cancers. Although survival rates are markedly higher than in the past, there are a growing number of long-term HCT survivors who are at risk for short and long-term sequela, which can negatively affect quality of life. Psychoneurological (PN) symptoms are common occurrences associated with heightened inflammation in other cancers and chronic conditions. Emerging research links the gut microbiota to inflammatory biomarkers and suggests that gut-microbiota-brain crosstalk impacts the severity of psychoneurological symptoms among HCT recipients. Methods: This longitudinal descriptive study investigated the relationship among a cluster of PN symptoms (pain, fatigue, and depression), inflammatory biomarkers (IL-6, IL-10, C-reactive protein (CRP), and microbiota diversity measures (Shannon and Chao Beta diversity indexes) in 55 individuals receiving HCT for a hematologic malignancy. The time periods examined covered pre-transplant, 30-days, and 100-days following transplant. The PN symptoms were collected through self-reported questionnaires via computer with assistance from study staff, along with blood samples and stool specimens obtained at each study visit. Inflammatory marker values were log-transformed when used as dependent variables. Gut microbiota samples were analyzed using 16S ribosomal gene (V4 region) amplicons using Illumina MiSeq. Data analysis was performed using SAS 9.4, with PROC MIXED used for the mixed model analyses. Results: The analysis characterized mean changes in microbiota diversity over time for both Shannon and Chao indexes. IL6 levels were consistent over time, with an inverse association with Chao but not Shannon index. IL10 and CRP levels changed over time, but without associations with either Shannon or Chao. Pain severity and interference changed over time, but with no associations with inflammatory markers or gut microbiome beta diversity. Fatigue severity and interference changed over time and were positively associated with IL10. Depression did not change over time and was not associated with inflammatory markers or diversity. Conclusions: This study provides preliminary information related to associations between PN symptoms, inflammatory markers, and selected measures of gut microbiome diversity in HCT recipients. Further research is needed to explore and validate these findings to examine the implications for microbiota diversity on inflammatory factors and PN symptoms. Clinical trial information: NCT02398708 .

Molecular imaging research on 18F-FDG PET/CT and biomarker analysis to predict the efficacy of neoadjuvant camrelizumab combined with chemotherapy for resectable stage IIIA-IIIB NSCLC.

e15065 Background: The purpose of this study was to explore the predictive value of tumor and secondary lymphoid metabolic parameters on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and circulating biomarkers for pathological response of neoadjuvant camrelizumab combined with chemotherapy in patients with non-small cell lung cancer (NSCLC). Methods: We included 22 patients who was diagnosed with NSCLC (stage IIIA-IIIB (T3-4N2)) and underwent curative surgery after receiving 3 cycles of camrelizumab plus chemotherapy between January 2023 and January 2024 in Shandong Cancer Hospital. Radical surgery was performed within 4-6 weeks after neoadjuvant therapy. Patients undergo 18F-FDG PET/CT scans in 1 week before treatment and 1 week before surgery. Pathological outcomes were assessed and divided into pathologic complete response (pCR) and non-pCR (defined as residual tumor &gt; 0%). The PET/CT parameters were measured, including tumor metabolic parameters such as maximum normalized uptake value (SUVmax), average normalized uptake value (SUVmean), total pathological glycolysis (TLG), and metabolic tumor volume (MTV). Additionally, secondary lymphoid organ metabolic parameters like the spleno-liver SUVmax ratio (SLR) and bone marrow-liver SUVmax ratio (BLR) were assessed. Furthermore, lymphocyte subsets and inflammatory biomarkers in peripheral blood were analyzed. The correlation between PET/CT metabolic parameters, lymphocyte subsets, inflammatory biomarkers and pathological response was analyzed. Results: pCR was achieved in 8 of the 22 patients. SUVmax in both pCR (p&lt;0.001) and non-pCR patients (p&lt;0.001) decreased before surgery. Among patients with pCR, the absolute value of decreased SUVmax (p = 0.024) and the rate of decreased SUVmax (ΔSUVmax%) (p = 0.042) before surgery was higher than those in non-pCR patients. In pCR group, SLR has a decreasing trend before surgery (p = 0.083). In circulating biomarker analysis, the percentage of NK cells changes (ΔNK%) of patients with pCR before surgery was higher than that of patients with non-pCR (p = 0.029). Neutrophil-to-lymphocyte ratio (NLR) in pCR group decreased significantly (p = 0.021) before surgery and there also had declining trend in the non-pCR group (p = 0.062). Before surgery, systemic immune-inflammation index (SII) was significantly decreased in both pCR (p = 0.028) and non-pCR (p&lt;0.001) groups. There also had significant decrease in derived neutrophil-to-lymphocyte ratio (dNLR) before surgery in both pCR (p = 0.01) and non-pCR (p = 0.031) groups. Conclusions: The SUVmax of the primary site at baseline, ΔSUVmax% and ΔNK% have good value in pCR for patients with stage IIIA-IIIB NSCLC receiving neoadjuvant camrelizumab combined with chemotherapy. More analysis of biomarkers is ongoing.

Prevalence of chronic rhinosinusitis without/with nasal polyps according to severity in Spain.

The worldwide prevalence range of chronic rhinosinusitis (CRS) is 5-12%; from this, 20 % have nasal polyps. Due to the little epidemiological data about CRS in the Spanish population, this study analyses the prevalence and severity of CRS with (CRSwNP) or without (CRSsNP) nasal polyps, and their connection with other coexisting type 2 inflammatory diseases in Spain. This is a retrospective, large-scale, nationwide, epidemiological study based on the electronic medical records from the BIG-PAC® database. Patients diagnosed of CRSsNP and CRSwNP were identified using specific disease codes. The severe form of the disease was defined as patients who received at least a long course of antibiotics in CRSsNP or ≥2 short courses of systemic corticosteroids in CRSwNP in ≤12 months during the last 2 years, and/or had previous sinus surgery. Physician-diagnosed prevalence, sociodemographic and clinical characteristics, and disease severity were assessed. Out of a cohort of 1,012,257 patients (≥18 years old), 42,863 and 7,550 patients with diagnosed CRSsNP and CRSwNP, respectively, were analysed. The overall prevalence of diagnosed CRS was 5.1%, being 4.3% and 0.8% for CRSsNP and CRSwNP, respectively. Patients with CRSwNP and severe forms of the disease were older and had higher levels of type 2 inflammatory biomarkers than CRSsNP patients and non-severe disease. Although CRSsNP was more prevalent than CRSwNP, the severe forms of CRS were more frequent in patients with CRSwNP. In addition, CRSwNP patients had a higher incidence of coexisting type 2 inflammatory diseases.