The association between inflammatory biomarkers and low back disorder: a systematic review and meta-analysis.

INTRODUCTION: Low back disorder (LBD) is a major cause of disability worldwide. Inflammation results in proliferation of cytokines or consequent degradation products (collectively known as inflammatory biomarkers) that activate pain pathways which can result in non-specific LBD. This systematic review and meta-analysis aim to evaluate the relationship between inflammatory biomarkers and clinical outcomes in patients with LBD. METHODS: The PRISMA guideline was followed for the systematic reivew. Three online databases were searched. Four RCTs and sixteen observational studies with 1142 LBD patients were analysed. The primary outcomes were back and leg pain scores, back-specific disability scores and expression of inflammatory biomarkers. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were evaluated. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to summarize the strength of evidence. RESULTS: Four RCTs and sixteen observational studies were included in the analysis of 1142 patients with LBD. There was a statistically significant reduction in back pain score and IL-1 beta and increase in the expression of CTX-1 and IL-10 levels post treatment. There was a significant relationship between increase in the expression of MCP- and reduction in the expression of hsCRP with increase in back pain. Significant relationship was also observed between increase in the expression of MCP-1 and reduction in the expression of IL-6 with increase in leg pain. Increase in the expression of IL-8 and reduction in the expression of hsCRP was also associated with increased disability score. CONCLUSION: Inflammatory biomarkers play a significant role in the pathogenesis of LBD. CTX-1, IL-10 and IL-1 beta may be responsible for the decrease in back pain scores post treatment. There is a relationship between MCP-1, IL-6, IL-8 and hsCRP with clinical and functional assessments for LBD. Further studies will improve understanding of the pathogenesis of LBD and aid in targeted management strategies.

Dysregulation of Plasma Growth Factors and Chemokines in Cocaine Use Disorder: Implications for Dual Diagnosis with Schizophrenia and Antisocial Personality Disorder in an Exploratory Study.

INTRODUCTION: Dual diagnosis in individuals with cocaine use disorders (CUDs) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD). METHODS: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N = 25) or as a dual diagnosis (DD group. N = 30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis. RESULTS: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis. CONCLUSIONS: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics.

Effects of Active Chronic Cigarette-Smoke Exposure on Circulating Fibrocytes.

PURPOSE: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis. METHODS: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers. RESULTS: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p = < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03). CONCLUSION: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable.

Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support.

There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.

Circulating Monocyte Chemoattractant Protein-1 (MCP-1) in Patients with Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that leads to the destruction of the intrahepatic bile ducts. While the inflammatory process can be mediated by monocyte chemotactic protein-1 (MCP-1), the importance of circulating MCP-1 as a biomarker is unclear. Our aim was to assess the diagnostic significance of the serum concentrations of MCP-1 in PBC patients. We compared circulating MCP-1 with biochemical, immunological and histological parameters. Serum samples were collected from 120 PBC patients, 60 pathologic controls and 30 healthy donors. MCP-1 levels were determined by using commercial enzyme-linked immunosorbent assay (ELISA). Elevated serum MCP-1 levels were detected in 66% of PBC patients with a specificity of 97%. Significantly higher levels of MCP-1 protein were found in the sera of patients with PBC than in the group of healthy individuals-410.2 pg/mL vs. 176.0 pg/mL, p < 0.01). Patients with higher concentrations of alkaline phosphatase also had higher levels of MCP-1 (r = 0.4, p < 0.01). In accordance with Ludwig's classification, a positive correlation of serum MCP-1 concentration with the degree of fibrosis was observed, OR = 6.1, p = 0.0003. We compared the MCP-1 with procollagen type III, hyaluronic acid (HA), FIB-4 index, APRI and collagen type IV when predicting the advance of liver fibrosis. Circulating MCP-1 is better correlated with liver fibrosis and is also associated with the occurrence of specific antimitochondrial autoantibodies and specific anti-nuclear autoantibodies-anti-gp210. MPC-1 can be considered to be a tool for diagnosing the degree of fibrosis in PBC, and combinations of MCP-1 and other specific biomarkers could support the diagnosis of PBC.

Killer Function of Circulating Neutrophils in Relation to Cytokines in Uterine Myoma and Endometrial Cancer.

The study presents the killer functions of circulating neutrophils: myeloperoxidase activity, the ability to generate ROS, phagocytic activity, receptor status, NETosis, as well as the level of cytokines IL-2, IL-4, IL-6, IL-17A, and IL-18, granulocyte CSF, monocyte chemotactic protein 1, and neutrophil elastase in the serum of patients with uterine myoma and endometrial cancer (FIGO stages I-III). The phagocytic ability of neutrophils in uterine myoma was influenced by serum levels of granulocyte CSF and IL-2 in 54% of the total variance. The degranulation ability of neutrophils in endometrial cancer was determined by circulating IL-18 in 50% of the total variance. In uterine myoma, 66% of the total variance in neutrophil myeloperoxidase activity was explained by a model dependent on blood levels of IL-17A, IL-6, and IL-4. The risk of endometrial cancer increases when elevated levels of monocyte chemotactic protein 1 in circulating neutrophils are associated with reduced ability to capture particles via extracellular traps (96% probability).

[The influence of diet therapy and regular physical trainings on monocyte chemoattractant protein-1 (MCP-1) secretion by monocytes among obese patients with coronary heart disease].

Chronic systemic inflammation is one of the leading pathogenetic pathways for the development of atherosclerosis in obese patients. In this regard, it seems promising to evaluate the effect of the diet and physical exertion on the proinflammatory activity of monocytes. The purpose of this research was to evaluate the effect of the diet and regular physical trainings on the secretion of monocyte chemotactic factor 1 (MCP-1) by monocytes in obese patients with coronary artery disease. Material and methods. 27 obese participants (body mass index >30 kg/m2) with a confirmed diagnosis of coronary heart disease were recruited. All participants were prescribed with 12 weeks of a specialized diet with a restriction of simple carbohydrates and salt, a 500-kcal daily energy deficit, and with inclusion of cruciferous (200 g per day), seasonal dark berries (70 g per day) and green tea (200 ml per day). The regular assisted physical trainings were also administered. The body composition, blood biochemical parameters and MCP-1 secretion rates in the primary culture of monocytes isolated from blood samples via the immunomagnetic separation method were assessed before and after the intervention. Results. As a result, after the 12-weeks intervention the reliable body weight loss (-4.0%), waist circumference (-4.2%), visceral fat (-5.4%), total cholesterol (-9.8%), LDL-cholesterol (-16.6%) and triglycerides (-26.0%), an improvement in the results of the 6-minute walk test (+10.33%) was achieved, as well as an LPS-stimulated monocytes secretion of MCP-1 decreased by 2.8 times (p=0.005). Conclusion. Overall, the results suggest that diet and regular physical activity in patients with obesity and coronary heart disease may decrease the functional "proinflammatory" activity of monocytes.

Blood levels of MCP-1 modulate the genetic risks of Alzheimer's disease mediated by HLA-DRB1 and APOE for Alzheimer's disease.

INTRODUCTION: C-Reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) are both implicated in the peripheral proinflammatory cascade and blood-brain barrier (BBB) disruption. Since the blood CRP level increases Alzheimer's disease (AD) risk depending on the apolipoprotein E (APOE) genotype, we hypothesized that the blood MCP-1 level exerts different effects on the AD risk depending on the genotypes. METHODS: Using multiple regression analyses, data from the Framingham Heart Study (n = 2884) and Alzheimer's Disease Neuroimaging Initiative study (n = 231) were analyzed. RESULTS: An elevated blood MCP-1 level was associated with AD risk in major histocompatibility complex, Class II, DR beta 1 (HLA-DRB1) rs9271192-AC/CC (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 1.50-6.28, p = 0.002) and in APOE ε4 carriers (HR = 3.22, 95% CI = 1.59-6.53, p = 0.001). In contrast, among HLA-DRB1 rs9271192-AA and APOE ε4 noncarriers, blood MCP-1 levels were not associated with these phenotypes. DISCUSSION: Since HLA-DRB1 and APOE are expressed in the BBB, blood MCP-1 released in the peripheral inflammatory cascade may function as a mediator of the effects of HLA-DRB1 rs9271192-AC/CC and APOE ε4 genotypes on AD pathogenesis in the brain via the BBB pathways.

A close-up view of dynamic biomarkers in the setting of COVID-19: Striking focus on cardiovascular system.

Based on the recent reports, cardiovascular events encompass a large portion of the mortality caused by the COVID-19 pandemic, which drawn cardiologists into the management of the admitted ill patients. Given that common laboratory values may provide key insights into the illness caused by the life-threatening SARS-CoV-2 virus, it would be more helpful for screening, clinical management and on-time therapeutic strategies. Commensurate with these issues, this review article aimed to discuss the dynamic changes of the common laboratory parameters during COVID-19 and their association with cardiovascular diseases. Besides, the values that changed in the early stage of the disease were considered and monitored during the recovery process. The time required for returning biomarkers to basal levels was also discussed. Finally, of particular interest, we tended to abridge the latest updates regarding the cardiovascular biomarkers as prognostic and diagnostic criteria to determine the severity of COVID-19.

Systemic Inflammation in Preclinical Ulcerative Colitis.

BACKGROUND & AIMS: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins. METHODS: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored. RESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1ß, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis. CONCLUSIONS: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.

Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability.

[Figure: see text].

Usefulness of serum CCL2 as prognostic biomarker in prostate cancer: a long-term follow-up study.

OBJECTIVE: Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100 ng/mL and chemokine (CC motif) ligand 2 ≥ 320 pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system. METHODS: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker. RESULTS: Patients with chemokine (CC motif) ligand 2 ≥ 320 pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2 < 320 pg/mL. Multivariate analysis was performed to determine whether chemokine (CC motif) ligand 2 was a useful prognostic factor. Independent significant predictors of worse overall survival were prostate-specific antigen ≥ 100 ng/mL, Gleason score ≥ 8 and chemokine (CC motif) ligand 2 ≥ 320 pg/dL. Prognostic predictors of prostate cancer-specific survival or cancer-free survival in multivariate analysis were prostate-specific antigen ≥ 100 ng/mL and Gleason score ≥ 8. A novel risk classification system was created to predict overall survival in patients based on the number of risk factors present (chemokine (CC motif) ligand 2 ≥ 320 pg/mL, prostate-specific antigen ≥ 100 ng/mL, Gleason score ≥ 8). Scores 2 or 3, 1 and 0 indicated Poor, Intermediate and Good risk groups, respectively. CONCLUSIONS: This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.

Interleukin-6 Is an Early Plasma Marker of Severe Postoperative Complications in Thoracic Surgery: Exploratory Results From a Substudy of a Randomized Controlled Multicenter Trial.

BACKGROUND: Postoperative complications in surgery are a significant burden, not only for the patients but also economically. While several predicting factors have already been identified, it is still not well known if increased levels of inflammatory markers in the immediate perioperative phase correlate with a higher incidence of postoperative complications. This study aimed to evaluate which patient characteristics and intraoperative parameters correlate with increased plasma values of monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) of thoracic surgery patients. A second goal was to explore whether MCP-1 and IL-6 are associated with the incidence of postoperative complications. We hypothesized that there is a positive association between inflammatory markers and the occurrence of complications within 6 months after surgery. METHODS: This is a substudy of a recent randomized controlled trial, which defined the effect of desflurane versus propofol anesthesia on morbidity and mortality in patients undergoing thoracic surgery. MCP-1 and IL-6 were determined in plasma obtained before and 30 minutes after 1-lung ventilation, 6 hours after surgery, and on postoperative days 1 and 2. Complications were recorded for 6 months. Mixed linear models were used to examine factors associated with MCP-1 and IL-6 levels. Logistic regression models and receiver operating characteristic curves were used to determine the association between MCP-1 and IL-6 and postoperative complications. RESULTS: In the original study, 460 patients were included, MCP-1 and IL-6 levels were determined in 428 patients. MCP-1 was positively associated with the duration of surgery (P = .016), whereas IL-6 levels increased with both the length (P < .001) and invasiveness of lung surgery (thoracoscopic wedge resection or lobectomy versus open lobectomy, P = .005; thoracoscopic wedge resection or lobectomy versus pneumonectomy, P = .021). In an exploratory approach, elevated IL-6 plasma peaks were associated with the occurrence of severe complications defined as Clavien-Dindo score grade ≥IVa during the postoperative phase up to 6 months after thoracic surgery (P = .006). CONCLUSIONS: In summary, this substudy reveals factors, which correlate with high MCP-1 and IL-6 values. Moreover, higher IL-6 seems to be associated with postoperative severe complications. Perioperative IL-6 monitoring might be helpful for risk estimation in the perioperative setting of patients after lung surgery.

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals. METHODS: In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m2 at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change. RESULTS: Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline. CONCLUSIONS: Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.

Monocyte chemoattractant protein-1 is not predictive of cardiac events in patients with non-low-risk chest pain.

BACKGROUND: Prior studies suggest monocyte chemoattractant protein-1 (MCP-1) may be useful for risk stratifying ED patients with chest pain. We hypothesise that MCP-1 will be predictive of 90-day major adverse cardiovascular events (MACEs) in non-low-risk patients. METHODS: A case-control study was nested within a prospective multicentre cohort (STOP-CP), which enrolled adult patients being evaluated for acute coronary syndrome at eight US EDs from 25 January 2017 to 06 September 2018. Patients with a History, ECG, Age, and Risk factor score (HEAR score) ≥4 or coronary artery disease (CAD), a non-ischaemic ECG, and non-elevated contemporary troponins at 0 and 3 hours were included. Cases were patients with 90-day MACE (all-cause death, myocardial infarction or revascularisation). Controls were patients without MACE selected with frequency matching using age, sex, race, and HEAR score or the presence of CAD. Serum MCP-1 was measured. Sensitivity and specificity were determined for cut-off points of 194 pg/mL, 200 pg/mL, 238 pg/mL and 281 pg/mL. Logistic regression adjusting for age, sex, race, and HEAR score/presence of CAD was used to determine the association between MCP-1 and 90-day MACE. A separate logistic model also included high-sensitivity troponin (hs-cTnT). RESULTS: Among 40 cases and 179 controls, there was no difference in age (p=0.90), sex (p=1.00), race (p=0.85), or HEAR score/presence of CAD (p=0.89). MCP-1 was similar in cases (median 191.9 pg/mL, IQR: 161.8-260.1) and controls (median 196.6 pg/mL, IQR: 163.0-261.1) (p=0.48). At a cut-off point of 194 pg/mL, MCP-1 was 50.0% (95% CI 33.8% to 66.2%) sensitive and 46.9% (95% CI 39.4% to 54.5%) specific for 90-day MACE. After adjusting for covariates, MCP-1 was not associated with 90-day MACE at any cut-off point (at 194 pg/mL, OR 0.88 (95% CI 0.43 to 1.79)). When including hs-cTnT in the model, MCP-1 was not associated with 90-day MACE at any cut-off point (at 194 pg/mL, OR 0.85 (95% CI 0.42 to 1.73)). CONCLUSION: MCP-1 is not predictive of 90-day MACE in patients with non-low-risk chest pain.

Measurement of 45 cytokine, chemokine and growth factors in established cell culture supernatants and autologous serum from advanced melanoma patients.

Melanoma is one of the most aggressive forms of human cancer and its incidence has significantly increased worldwide over the last decades. This neoplasia has been characterized by the release of a wide variety of soluble factors, which could stimulate tumor cell proliferation and survival in an autocrine and paracrine manner. Consequently, we sought to evaluate the pattern of soluble factors produced by pre-metastatic and metastatic melanoma established cultures, and to determine whether these factors can be detected in the autologous serum of malignant melanoma patients. Our results showed that both melanoma cultures had a common profile of 27 soluble factors mainly characterized by the high expression of VEGF-A, IL-6, MCP-1, IL-8, and SDF-1. In addition, when we compared supernatants, we observed significant differences in VEGF-A, BDNF, FGF-2, and NGF-ß concentrations. As we found in melanoma cultures, serum samples also had their specific production pattern composed by 21 soluble factors. Surprisingly, PDGF-BB and EGF were only found in serum, whereas IL-2, IL-4, IL-8, IL31, FGF2, and GRO-α were only expressed in the supernatant. Significant differences in PDGF-BB, MIP-1ß, HGF, PIGF-1, BDNF, EGF, Eotaxin, and IP-10 were also found after comparing autologous serum with healthy controls. According to this, no correlation was found between culture supernatants and autologous serum samples, which suggests that some factors may act locally, and others systemically. Nonetheless, after validation of our results in an independent cohort of patients, we concluded that PDGF-BB, VEGF-A, and IP-10 serum levels could be used to monitor different melanoma stages.

Association between post-treatment circulating biomarkers of inflammation and survival among stage II-III colorectal cancer patients.

BACKGROUND: Biomarker studies on colorectal cancer (CRC) prognosis are limited to pre-diagnostic or pre-operative measures. Post-treatment biomarkers are not well understood for their associations with CRC survival. METHODS: We included 306 eligible incident stage II-III CRC cases from the population-based Seattle Colon Cancer Family Registry. Concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), adiponectin, and leptin were measured using post-treatment plasma samples. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CRC-specific mortality were calculated using Cox proportional hazard models. RESULTS: Elevated levels of CRP, IL-6, MCP-1, and adiponectin were significantly associated with a higher risk of all-cause mortality within 10 years post blood draw with HRs (95% CI) of 1.32 (1.10-2.59), 2.72 (2.07-3.56), 1.97 (1.18-3.28) and 1.71 (1.14-2.58), respectively. IL-6 and adiponectin had a dose-response effect (Ptrend < 0.0001). For CRC-specific mortality, we observed positive associations for CRP (HR = 1.75, 95% CI: 1.2-2.56), IL-6 (HR = 5.02, 95% CI: 2.92-8.59), MCP-1 (HR = 3.78, 95% CI: 1.41-10.08), and adiponectin (HR = 3.16, 95% CI: 1.27-7.86), and inverse association for leptin (HR = 0.44, 95% CI: 0.29-0.68) within the first year of blood draw, whereas the association for IL-6 remained statistically significant over 10 years. CONCLUSION: Our results support the role of chronic inflammation in CRC progression and suggested several post-treatment inflammatory biomarkers, particularly IL-6, are promising prognostic markers for stage II-III CRC patients.

Immune response in children with COVID-19 is characterized by lower levels of T-cell activation than infected adults.

Study of immunological features of immune response in 14 children (aged from 12 days up to 15 years) and of 10 adults who developed COVID-19 show increased number of activated CD4 and CD8 cells expressing DR and higher plasmatic levels of IL-12 and IL-1ß in adults with COVID-19, but not in children. In addition, plasmatic levels of CCL5/RANTES are higher in children and adults with COVID-19, while CXCL9/MIG was only increased in adults. Higher number of activated T cells and expression of IL-12 and CXCL9 suggest prominent Th1 polarization of immune response against SARS-CoV2 in infected adults as compared with children.

Cytokine Profile Elevations on Admission Can Determine Risks of Severe Acute Pancreatitis in Children.

OBJECTIVES: To utilize a Luminex platform to examine multiple cytokines simultaneously as well as clinical laboratory testing to identify markers that predict acute pancreatitis severity in the pediatric population on admission. STUDY DESIGN: Patients (<19 years of age) prospectively enrolled over a 4-year period in a single institution acute pancreatitis database were included in separate derivation and validation cohorts. Plasma samples were obtained within 48 hours of admission and stored for analysis. Samples from mild acute pancreatitis and severe acute pancreatitis (moderately severe and severe combined) were analyzed using Luminex panels and C-reactive protein (CRP) testing. RESULTS: The derivation cohort examined 62 cytokines in 66 subject samples (20 control, 36 mild acute pancreatitis, 10 severe acute pancreatitis) and identified interleukin 6 (IL-6) (P = .02) and monocyte chemotactic protein-1 (MCP-1) (P = .02) as cytokines that were differentially expressed between mild and severe acute pancreatitis. Our validation cohort analyzed 76 cytokines between 10 controls, 19 mild acute pancreatitis, and 6 severe acute pancreatitis subjects. IL-6 (P = .02) and MCP-1 (P = .007) were again found to differentiate mild acute pancreatitis from severe acute pancreatitis. CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P < .0001). CONCLUSIONS: This study identified and validated IL-6 and MCP-1 as predictors of severe acute pancreatitis using 2 distinct cohorts and showed that CRP elevation is a marker of progression to severe acute pancreatitis. These biomarkers have not been extensively studied in the pediatric acute pancreatitis population. Our data allows for risk-stratification of patients with acute pancreatitis, and represent novel insight into the immunologic response in severe acute pancreatitis.

Tibiofemoral articular cartilage composition differs based on serum biochemical profiles following anterior cruciate ligament reconstruction.

OBJECTIVE: Biochemical joint changes contribute to posttraumatic osteoarthritis (PTOA) development following anterior cruciate ligament reconstruction (ACLR). The purpose of this longitudinal cohort study was to compare tibiofemoral cartilage composition between ACLR patients with different serum biochemical profiles. We hypothesized that profiles of increased inflammation (monocyte chemoattractant protein-1 [MCP-1]), type-II collagen turnover (type-II collagen breakdown [C2C]:synthesis [CPII]), matrix degradation (matrix metalloproteinase-3 [MMP-3] and cartilage oligomeric matrix protein [COMP]) preoperatively to 6-months post-ACLR would be associated with greater tibiofemoral cartilage T1ρ relaxation times 12-months post-ACLR. DESIGN: Serum was collected from 24 patients (46% female, 22.1 ± 4.2 years old, 24.0 ± 2.6 kg/m2 body mass index [BMI]) preoperatively (6.4 ± 3.6 days post injury) and 6-months post-ACLR. T1ρ Magnetic Resonance Imaging (MRI) was collected for medial and lateral tibiofemoral articular cartilage at 12-months post-ACLR. A k-means cluster analysis was used to identify profiles based on biomarker changes over time and T1ρ relaxation times were compared between cluster groups controlling for sex, age, BMI, concomitant injury (either meniscal or chondral pathology), and Marx Score. RESULTS: One cluster exhibited increases in MCP-1 and COMP while the other demonstrated decreases in MCP-1 and COMP preoperatively to 6-months post-ACLR. The cluster group with increases in MCP-1 and COMP demonstrated greater lateral tibial (adjusted mean difference = 3.88, 95% confidence intervals [1.97-5.78]) and femoral (adjusted mean difference = 12.71, 95% confidence intervals [0.41-23.81]) T1ρ relaxation times. CONCLUSION: Profiles of increased serum levels of inflammation and matrix degradation markers preoperatively to 6-months post-ACLR are associated with MRI changes consistent with lesser lateral tibiofemoral cartilage proteoglycan density 12-months post-ACLR.