Classical Inflammatory Markers Research Articles

A multicenter study of asymmetric and symmetric dimethylarginine as predictors of mortality risk in hospitalized COVID-19 patients

Mortality of patients hospitalized with COVID-19 has remained high during the consecutive SARS-CoV-2 pandemic waves. Early discrimination of patients at high mortality risk is crucial for optimal patient care. Symmetric (SDMA) and asymmetric dimethylarginine (ADMA) have been proposed as possible biomarkers to improve risk prediction of COVID-19 patients. We measured SDMA, ADMA, and other L-arginine-related metabolites in 180 patients admitted with COVID-19 in four German university hospitals as compared to 127 healthy controls. Patients were treated according to accepted clinical guidelines and followed-up until death or hospital discharge. Classical inflammatory markers (leukocytes, CRP, PCT), renal function (eGFR), and clinical scores (SOFA) were taken from hospital records. In a small subgroup of 23 COVID-19 patients, sequential blood samples were available and analyzed for biomarker trends over time until 14 days after admission. Patients had significantly elevated SDMA, ADMA, and L-ornithine and lower L-citrulline concentrations than controls. Within COVID-19 patients, SDMA and ADMA were significantly higher in non-survivors (n = 41, 22.8%) than in survivors. In ROC analysis, the optimal cut-off to discriminate non-survivors from survivors was 0.579 µmol/L for SDMA and 0.599 µmol/L for ADMA (both p < 0.001). High SDMA and ADMA were associated with odds ratios for death of 11.45 (3.37–38.87) and 5.95 (2.63–13.45), respectively. Analysis of SDMA and ADMA allowed discrimination of a high-risk (mortality, 43.7%), medium-risk (15.1%), and low-risk group (3.6%); risk prediction was significantly improved over classical laboratory markers. We conclude that analysis of ADMA and SDMA after hospital admission significantly improves risk prediction in COVID-19.

A multicenter study of asymmetric and symmetric dimethylarginine as predictors of mortality risk in hospitalized COVID-19 patients

Mortality of patients hospitalized with COVID-19 has remained high during the consecutive SARS-CoV-2 pandemic waves. Early discrimination of patients at high mortality risk is crucial for optimal patient care. Symmetric (SDMA) and asymmetric dimethylarginine (ADMA) have been proposed as possible biomarkers to improve risk prediction of COVID-19 patients. We measured SDMA, ADMA, and other L-arginine-related metabolites in 180 patients admitted with COVID-19 in four German university hospitals as compared to 127 healthy controls. Patients were treated according to accepted clinical guidelines and followed-up until death or hospital discharge. Classical inflammatory markers (leukocytes, CRP, PCT), renal function (eGFR), and clinical scores (SOFA) were taken from hospital records. In a small subgroup of 23 COVID-19 patients, sequential blood samples were available and analyzed for biomarker trends over time until 14 days after admission. Patients had significantly elevated SDMA, ADMA, and L-ornithine and lower L-citrulline concentrations than controls. Within COVID-19 patients, SDMA and ADMA were significantly higher in non-survivors (n = 41, 22.8%) than in survivors. In ROC analysis, the optimal cut-off to discriminate non-survivors from survivors was 0.579 µmol/L for SDMA and 0.599 µmol/L for ADMA (both p < 0.001). High SDMA and ADMA were associated with odds ratios for death of 11.45 (3.37–38.87) and 5.95 (2.63–13.45), respectively. Analysis of SDMA and ADMA allowed discrimination of a high-risk (mortality, 43.7%), medium-risk (15.1%), and low-risk group (3.6%); risk prediction was significantly improved over classical laboratory markers. We conclude that analysis of ADMA and SDMA after hospital admission significantly improves risk prediction in COVID-19.

Cholinesterase as a predictor of skeletal muscle loss after gastrectomy for gastric cancer.

Cholinesterase is a classical nutritional and inflammatory marker. The aim of the present study was to evaluate the value of cholinesterase as a predictive marker for postoperative skeletal muscle loss after gastrectomy for gastric cancer. The study comprised 68 patients who had undergone gastrectomy for gastric cancer. Skeletal muscle mass was evaluated using skeletal mass index, and major skeletal muscle loss was defined as less than or equal to the median change rate (1-year postoperative/preoperative) of skeletal mass index in all patients. We explored the relationship between postoperative major skeletal muscle loss and disease-free survival and overall survival. Then we investigated the relationship between change rate of skeletal muscle index and serum cholinesterase levels after gastrectomy. The median value of change rate of skeletal mass index was 0.93. Postoperative major skeletal muscle loss was significantly associated with disease-free survival after gastrectomy (P=0.003). Although major skeletal muscle loss had worse overall survival, it was not significant (P=0.058). The change rate of skeletal mass index and cholinesterase had a stronger positive correlation compared with other nutritional indices according to Spearman's rank correlation coefficient (r=0.438, P≤0.001). Evaluation of serum cholinesterase levels may be valuable for predicting postoperative skeletal muscle loss after gastrectomy, suggesting the importance of cholinesterase in postoperative nutritional management of patients with gastric cancer.

Performance of classical serum inflammatory markers in healed and unhealed treated patients with joint and prosthetic joint infections

BackgroundSerum markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer, are currently used by clinicians and orthopedic surgeons in diagnosing and managing joint infections (JI), although conflicting results exist on their performance. The aim of this study was to evaluate their performance in assessing healing or unhealing of patients with JI or with prosthetic joint infection (PJI). MethodsESR, CRP and D-dimer serum levels were evaluated before, during and after antibiotic treatment in 61 patients (65.1 ± 12.6 years): 49 affected by PJI and 12 by JI, between 2020 and 2022. These patients had undergone orthopedic surgery and were treated with antibiotics. ResultsESR, CRP and D-dimer were significantly lower after treatment than before (p value: 0.001, 0.001 and 0.003, respectively) in healed and unhealed patients. A moderate correlation was found between the three inflammatory markers. ConclusionsUsing a cut off value of 25 mm/h for ESR, 0.5 mg/L for CRP, and 700 ng/ml for D-dimer, it might be possible to discriminate healed from unhealed patients (PPV and NPV: ESR 65.5% and 68.8%, CRP 71.9% and 79.3%, D-dimer 76.9% and 81.8%). The combined use of these three inflammatory markers might be useful in the management of joint infections.

Comparative analysis of inflammatory profiles between COVID-19 patients and healthy controls and its correlation with disease severity

Several reports have highlighted the significant role of inflammation in the pathogenesis of coronavirus Disease-19 (COVID-19). The hyper-inflammatory response triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is believed to contribute to disease severity and adverse clinical outcomes. Consequently, classical inflammatory markers have been proposed as potential indicators of COVID-19 severity. However, there is still a critical need for extensive analysis of the predictive value of inflammatory biomarkers in large cohorts of patients. The main objective of this study was to evaluate Plasma inflammatory Levels in COVID-19 Patients and Healthy Controls and its association with COVID-19 severity levels. This study employed cross-sectional and case-control study designs. The study population comprised of SARS-CoV-2 positive patients at Ndola Teaching Hospital (NTH) and Levy Mwanawasa University Teaching Hospital (LMUTH). The laboratory tests involved the assessment of inflammatory profiles in COVID-19 patients compared to control subjects. Furthermore, the study investigated the use of inflammatory profiles in classifying COVID-19 severity in relation to WHO guidelines. Data analysis was conducted using SPSS version 21. Our study observed elevated plasma levels of inflammatory profiles such as CRP, Ferritin, procalcitonin, Neutrophils, Neutrophil Lymphocyte Ratio (NLR), Erythrocyte Sedimentation Ratio (ESR) and inflammatory cytokines such as IL-1, IL-6,IL-8 and Tumour Necrosis Factor (TNF) in COVID-19 patients compared to the control group. In contrast the mean Lymphocyte count in Covid-19 patients was significantly lower than the control subjects. Additionally, COVID-19 patients exhibited a higher prevalence of hyperinflammation compared to control participants. The study also found that the frequency of hyperinflammation increased with COVID-19 severity. Furthermore, statistically significant differences in mean haemostatic plasma concentration were observed in relation to different levels COVID-19 disease severity. Inflammatory profile results indicate that COVID-19 patients were more prone to hyper inflammatory state than the Sars-CoV-2 negative individuals and these parameters were observed to correlate with COVID-19 severity levels. The study provides valuable insights into the inflammatory mechanisms of COVID-19 and identifies potential biomarkers for hyperinflammation. Clinicians can utilize this information to identify patients with a poor prognosis and assess disease severity, enabling early intervention.

Spinal Tuberculosis: Features and Early Predictive Factors of Poor Outcomes.

Tuberculosis is still endemic in Tunisia. Among musculoskeletal involvement, spinal tuberculosis (STB) or «Pott's Disease» is the most common and can lead to serious neurological complications. The purpose of our study was to focus on STB features (clinical, biological, and radiological) and to identify factors associated with early unfavorable outcomes. This was a monocentric retrospective study, over a period of 20 years (2000-2020). Only patients treated appropriately were included. Patients' informations were noted. We defined the favorable outcome criterion as weight gain, apyrexia, improvement of the general state, relief of pain, improvement in the classic inflammatory markers (CRP), and absence of vertebral deformities, neurological impairment, or sepsis. The outcome was considered unfavorable otherwise. Our study involved 52 patients. Their average age was 55.21 years±17.79. The average symptom duration was 8.9 months±6.54. Spinal pain was the most common functional sign (90.4%) often inflammatory. Physical signs were dominated by segmental spinal stiffness (71.2%). Spinal magnetic resonance imaging was performed in 38 patients. The disco-vertebral biopsy puncture confirmed the diagnosis in 15 cases. All patients received anti-tuberculosis treatments with an average duration of 10.02±1.97months. The outcome at one month of follow-up was favorable in 32 cases. Poor prognosis factors were normochromic normocytic anaemia (p=0.018), initial lymphocytosis (p=0.048), and fever (p=0.01). However, vertebral fracture at standard X-ray was predictive of favorable outcome (p=0.001). STB is a frequent condition that needs to be treated rapidly. Poor prognosis factors were identified in this study such as normocytic normochromic anemia, initial lymphocytosis, and fever at baseline.

Copolymer functional groups modulate extracellular trap accumulation and inflammatory markers in HL60 and murine neutrophils

Undesirable host responses to implants commonly lead to impaired device function. As the first immune cell to respond to inflammation, activated neutrophils release antimicrobials and neutrophil extracellular traps (NETs) that prime microenvironments for macrophages and other infiltrating cells. This research aims to understand how functional groups in copolymers of isodecyl acrylate (IDA) that are known to modulate healing in vivo, modulate neutrophil cells. Phorbol myristate acetate-activated HL60 cells and bone marrow-derived murine neutrophils (BMDN) were incubated with coatings of IDA copolymerized with, methacrylic acid (MAA films), methyl methacrylate (MM films), or MM functionalized with hexamethylenediamine (HMD films). Cells incubated on HMD films resulted in increased accumulation of NETs at the film’s surface in comparison to other copolymers because of increased adhesion of HL60 onto HMD films or increased rates of NETosis from BMDN. Overall, lower inflammation was observed with cells on MAA films. HL60 cells had no increase in classical inflammatory markers such as tumor necrosis factor alpha and intracellular adhesion molecule-1, whereas HL60 on HMD films had increases in these same markers. Taken together, these studies give important insights into how neutrophils interact differently with functionalized copolymers and the proteins that adsorb to them, with MAA (carboxyl groups) leading to behavior associated with lower inflammation and HMD (amine groups) with higher inflammation and accumulation of NETs.

C-reactive protein/albumin and C-reactive protein/fibrinogen ratios for the diagnosis of periprosthetic joint infection in revision total joint arthroplasty.

Testing for systemic inflammation markers is considered a simpler method for diagnosing periprosthetic joint infection (PJI). Changes in the C-reactive protein/albumin ratio (CRP/Alb ratio) and C-reactive protein/fibrinogen ratio (CRP/Fib ratio) are associated with PJI. This study aimed to evaluate the application of CRP/Alb and CRP/Fib ratios as novel inflammation-based markers for the diagnosis of PJI. We retrospectively evaluated 445 patients who underwent total hip and knee revision arthroplasties between January 2010 and February 2021. Of these, 129 patients were also independently evaluated for PJI with coagulation-related comorbidities. The patients were divided into two groups: the aseptic revision (268 patients) and PJI revision groups (187 patients). Subsequently, we evaluated the diagnostic value of the CRP/Alb and CRP/Fib ratios compared to other inflammation-based diagnoses using the area under the curve (AUC) values. The AUC values of the CRP/Alb and CRP/Fib ratios were 0.880 and 0.872, respectively, suggesting similar diagnostic potentials for PJI. The CRP/Alb and CRP/Fib ratios were better than the erythrocyte sedimentation rate (ESR), Alb, and Fib, whose AUC values were 0.765, 0.352, and 0.730, respectively, for the diagnosis of PJI. The optimal cut-off for the CRP/Alb ratio was 0.13, with good sensitivity (85.0%) and specificity (78.4%). The optimal cut-off CRP/Fib ratio was 2.04, with good sensitivity (81.3%) and specificity (80.6%). Notably, the CRP/Alb and CRP/Fib ratios had the highest sensitivity, followed by four conventional inflammatory markers, namely, CRP, ESR, Alb, and Fib, which had sensitivities of 80.2%, 67.4%, 50.8%, and 54.0%, respectively. Similar findings were observed in patients with coagulation-related comorbidities. Both the CRP/Alb and CRP/Fib ratios were significantly higher in patients with PJI than in those with aseptic failure and showed better sensitivity and specificity for diagnosing PJI than classical inflammatory markers.

Cellular immunity in subacute thyroiditis: a new perspective through neopterin.

Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid gland. Although its etiology is not fully understood, it is believed to occur shortly after viral infections and is mostly associated with human leukocyte antigen (HLA)-B*35. Cellular immunity is prominent in SAT. Neopterin is produced by activated monocytes/macrophages and is a marker of cellular immunity. Its production is stimulated by interferon gamma (IFN-γ), provided mainly by activated helper T lymphocytes type 1 (Th1) in the adaptive immune system. Therefore, with these cells' activation, an increase in serum neopterin levels is expected. We aimed to evaluate neopterin levels in demonstrating cellular immunity in SAT and compared 15 SAT patients with 16 healthy controls. Since all SAT patients were in the active thyrotoxic phase, we found a significant difference in thyroid functions. Classical inflammatory markers, erythrocyte sedimentation rate, and C-reactive protein were markedly elevated in the patient group. Although we expected to find an increase considering that cellular immunity is at the forefront in the pathogenesis of SAT, we found serum neopterin levels significantly lower in the patient group than in the control group. There is an increase in CD8+ T cells in the thyroid tissue in SAT. The possible relationship with HLA-B*35- major histocompatibility complex class I in SAT, and the antigen presentation to CD8+ T cells may be the reason why we observed low serum neopterin levels in patients due to the cytokine imbalance. Neopterin provides unique and independent data from classical acute phase response indicators.

P290 Baseline monocyte count may help make a diagnosis of giant cell arteritis: results of routinely collected audit data from two centres

Abstract Background/Aims Giant cell arteritis is a large vessel vasculitis classically affecting the head and neck. If untreated it leads to permanent vision loss. Diagnosis of GCA is based on clinical judgement of the likelihood of GCA combined with blood tests, imaging and/or temporal artery biopsy. Biopsy is considered the gold standard, but access has been restricted at many centres during the pandemic. It is recognised that some patients will have a negative ultrasound but still deemed to have GCA based on the clinical history and physical findings. In a previous audit at Yeovil District Hospital, we evaluated factors associated with biopsy-proven GCA to explore how routine tests help guide diagnosis, particularly in cases where initial imaging is negative and biopsy is unavailable. This audit found that the baseline monocyte count had good diagnostic accuracy compared to classical inflammatory markers and clinical parameters (area under the curve [AUC] 0.81, 95% confidence interval [CI] 0.67-0.95, p = 0.0034). Although novel, this finding involved a small number of patients and requires further investigation. We aimed to repeat the audit in a larger cohort and investigate blood biomarkers, including monocytes, in GCA patients as defined by physician diagnosis. Methods At the Royal National Hospital for Rheumatic Diseases, data were collected retrospectively on patients that were referred between 01/2020 and 09/2021 from hospital records, the GP referral, and pathology systems. A positive diagnosis of GCA was determined by presentation, inflammatory response, vascular imaging and clinical course, and was confirmed by a rheumatologist. Sensitivity, specificity and ROC analysis were calculated for each biomarker, including monocyte count, platelets, CRP, and plasma viscosity (PV). Results 301 referrals were made to the GCA clinic over the period audited. 109/301 (36%) were diagnosed with GCA, of which 98/109 (90%) had imaging studies and 62/98 (67%) had had a positive test. 55/301 referrals had already started glucocorticoids before baseline blood monitoring. ROC analysis found monocyte count was predictive of GCA (AUC 0.83, 95%CI 0.77-0.90, p &amp;lt; 0.0001). A cut-off value of ≥ 0.9 x 106/L gave a specificity of &amp;gt; 95% and a positive likelihood ratio (LR) of 10 for a diagnosis of GCA in this cohort. However, monocytes were heavily influenced by glucocorticoids and after ≥1 dose there was a drop in sensitivity of 20%. Conclusion In a second, larger cohort of GCA cases, we have again identified monocytes as a potential biomarker of GCA. However, they appear to be highly sensitive to glucocorticoids and their use as a biomarker may be limited to glucocorticoid-naïve patients. A prospective research study is now being planned to take these findings further. Disclosure B. Mulhearn: None. J. Ellis: None. T. Somoskeoy: None. A. Bourn: None. S. Knights: None. S. Skeoch: None. S. Tansley: None.

Oxidized linoleic acid metabolites maintain mechanical and thermal hypersensitivity during sub-chronic inflammatory pain

Inflammatory pain serves as a protective defense mechanism which becomes pathological when it turns into chronic inflammatory pain. This transition is mediated by a variety of peripheral mediators that sensitize nociceptors and increase pain perception in sensory neurons. Besides cytokines, chemokines and growth factors, accumulating evidence shows that oxidized lipids, such as eicosanoids and oxidized linoleic acid metabolites, contribute to this sensitization process. Most notably, the oxidized linoleic acid metabolite and partial TRPV1 agonist 9-HODE (hydroxyoctadecadienoic acid) was shown to be involved in this sensitization process. However, it is still unknown how some of the oxidized linoleic acid metabolites are synthesized in the inflammatory environment and in which phase of inflammation they become relevant.Here we show that the concentrations of oxidized linoleic acid metabolites, especially 9-HODE and 13-HODE, are significantly increased in inflamed paw tissue and the corresponding dorsal root ganglia in the sub-chronic phase of inflammation. Surprisingly, classical inflammatory lipid markers, such as prostaglandins were at basal levels in this phase of inflammation. Moreover, we revealed the cell type specific synthesis pathways of oxidized linoleic acid metabolites in primary macrophages, primary neutrophils and dorsal root ganglia. Finally, we show that blocking the most elevated metabolites 9-HODE and 13-HODE at the site of inflammation in the sub-chronic phase of inflammation, leads to a significant relief of mechanical and thermal hypersensitivity in vivo. In summary, these data offer an approach to specifically target oxidized linoleic acid metabolites in the transition of acute inflammatory pain to chronic inflammatory pain.

The role of yoga in inflammatory markers

Yoga is an ancient system for integrating the mind, body, and spirit. In the hatha yoga ashtanga tradition (the eight limb Patanjali Yoga), three of the limbs are meditation, breathwork (pranayama) and physical postures (asana), which are widely practised in yoga classes. The benefits of yoga for mental and physical health are rooted in the practice's origins: in yoga, stress is said to be the root of all diseases.The established fields of psychoneuroimmunology and immunopsychiatry study the interplay between the immune system and mood or mental states. This mini-review has shifted the emphasis from research that focuses on yoga's benefits for stress, the most commonly studied outcome of yoga research, to a summary of the research on the effects of yoga practices on the immune system. The current literature bears strong evidence for the benefits of yoga on the levels of circulating cortisol and classical inflammatory markers, such as C-reactive protein (CRP) and cytokines such as interleukin-1 beta (IL-1β), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ). The evidence for other less studied markers, telomerase activity, β-endorphins, Immunoglobulin A (IgA) and brain-derived neurotrophic factor (BDNF) is also growing. This mini-review centres around the interplay between yoga and these markers in stress management and depression, vascular and immune function in the older population, cardiovascular and metabolic diseases, auto-immune diseases, breast cancer and pregnancy.Overall, the literature examined reveals the novelty of this field of research and sheds light on methodological challenges; however, it uncovers the potential for yoga to be used as adjuvant therapy in conditions with an inflammatory component.

Chronic intracerebroventricular administration is a reliable method in brain studies on monkeys

Intracerebroventricular (ICV) administration through cannulas is a direct way to deliver large molecules and substances that are blocked by the blood-brain barrier into the central nervous system (CNS). It is widely used in brain studies on monkeys. However, this method is invasive, as it requires guide cannulas to be implanted into the brain. Whether the long-term implantation of the cannula and the administration of molecule-delivering vehicles, usually saline, can affect the brain by inducing chronic CNS inflammation or even worse brain atrophy, remains an issue to be solved. To answer this question, we investigated inflammatory markers and brain structures on three vehicle-control monkeys who received cannula implantation and one-year ICV saline administration in another study. During the experiment, the monkeys’ cerebrospinal fluid (CSF) samples were collected periodically, and the level of three classic inflammatory markers (IL-1β, IL-6, and TNF-α) were measured by electrochemiluminescence immunoassay. The monkeys’ brain structures were imaged in vivo periodically by 9.4 Tesla magnetic resonance imaging, which can provide the best-resolution magnetic resonance images of living monkeys, and the volume of the hippocampus was measured to evaluate the brain atrophy. The data reveal that, during the administrating period, the long-term levels of the inflammatory markers in the CSF and the volumes of the hippocampus did not change significantly compared with the baseline. These results suggest that the long-term ICV administration of saline through cannulas did not induce chronic neuroinflammation or brain atrophy in these rhesus monkeys, suggesting chronic ICV administration via implanted cannulas is a reliable method in monkey brain research.

The Roles of Carotenoid Consumption and Bioavailability in Cardiovascular Health.

Carotenoids are natural pigments generally with a polyene chain consisting of 9–11 double bonds. In recent years, there has been increasing research interest in carotenoids because of their protective roles in cardiovascular diseases (CVDs). While the consumption of carotenoids may have a beneficial effect on CVDs, the literature shows inconsistencies between carotenoid consumption and reductions in the risk of CVDs. Therefore, this review aims to provide a summary of the association between dietary carotenoid intake and the risk of CVDs from published epidemiological studies. Meanwhile, to further elucidate the roles of carotenoid intake in CVD protection, this review outlines the evidence reporting the effects of carotenoids on cardiovascular health from randomized controlled trials by assessing classical CVD risk factors, oxidative stress, inflammatory markers and vascular health-related parameters, respectively. Given the considerable discrepancies among the published results, this review underlines the importance of bioavailability and summarizes the current dietary strategies for improving the bioavailability of carotenoids. In conclusion, this review supports the protective roles of carotenoids against CVDs, possibly by attenuating oxidative stress and mitigating inflammatory response. In addition, this review suggests that the bioavailability of carotenoids should be considered when evaluating the roles of carotenoids in CVD protection.

The inflammatory biomarkers profile of hospitalized patients with COVID-19 and its association with patient's outcome: A single centered study.

Several reports highlighted the central role of inflammation in the pathogenesis of corona virus disease-19 (COVID-19) disease. Also, the hyper-inflammatory response that is triggered by severe acute respiratory syndrom-Covid-2 (SARS-CoV-2) infection was believed to play an essential role in disease severity and adverse clinical course. For that reason, the classical inflammatory markers were proposed as a possible indicator for COVID-19 severity. However, an extensive analysis of the predictive value of inflammatory biomarkers in large patients’ cohorts is still limited and critically needed. In this study we investigated the predictive value of the classical inflammatory biomarkers in a patient cohort consists of 541 COVID-19 patients admitted to Al Kuwait Hospital, Dubai, UAE. A detailed analysis of the association between the essential inflammatory markers and clinical characteristics as well as clinical outcome of the patients were made. In addition, the correlation between those markers and a wide range of laboratory biomarkers and incidence of acute organs injury were investigated. Our results showed a significant elevation of many inflammatory markers including white cell count (WBC) count, neutrophils count, C-reactive protein (CRP), D-Dimer, ferritin, procalcitonin (PCT), and lactate dehydrogenase (LDH) levels in patients with more severe illness. Also, our results highlighted that higher levels of those markers can predict worse patient outcome including the need of ventilation, intensive care unit (ICU) admission, multiple organs dysfunction as well as death. In addition, Our results showed that the presence of lymphopenia and lower absolute lymphocyte count (ALC) at the time of admission were associated with severe to critical COVID-19 illness (P<0.0001), presence of acute respiratory distress syndrome (ARDS) (P<0.0001) and the need for ventilation and ICU admission., Moreover, our results showed a strong association between lower ALC count and multiple organs dysfunction and patient’s death (P<0.0001). In conclusion, our results highlighted the possible use of classical inflammatory biomarkers at time of admission as a potential predictive marker for more severe clinical course in COVID-19 patients that might need more aggressive therapeutic approach including the need of ventilators and ICU admission. The presence of such predictive markers might improve patient’s stratification and help in the direction of the available resources to patients in need, which in turn help in improving our response to the disease pandemic.

Quantification of glycoproteins by nuclear magnetic resonance associated with preclinical carotid atherosclerosis in patients with type 1 diabetes

Background and aimsGlycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (1H-NMR), and preclinical atherosclerosis in these patients. Methods and resultsWe selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and 1H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7–55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p < 0.05), with no association in patients receiving this drug (p for interaction <0.05; in ≥2 plaques). Finally, in models adjusted for other classical and T1D-specific risk factors, GlycA and GlycB H/W ratios remained associated with carotid plaque (OR 1.39 [1.12–1.90] and OR 6.89 [1.85–25.62], respectively). ConclusionIn T1D individuals without lipid-lowering treatment, 1H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.

Reversal of β-Amyloid-Induced Microglial Toxicity In Vitro by Activation of Fpr2/3.

Microglial inflammatory activity is thought to be a major contributor to the pathology of neurodegenerative conditions such as Alzheimer's disease (AD), and strategies to restrain their behaviour are under active investigation. Classically, anti-inflammatory approaches are aimed at suppressing proinflammatory mediator production, but exploitation of inflammatory resolution, the endogenous process whereby an inflammatory reaction is terminated, has not been fully investigated as a therapeutic approach in AD. In this study, we sought to provide proof-of-principle that the major proresolving actor, formyl peptide receptor 2, Fpr2, could be targeted to reverse microglial activation induced by the AD-associated proinflammatory stimulus, oligomeric β-amyloid (oAβ). The immortalised murine microglial cell line BV2 was employed as a model system to investigate the proresolving effects of the Fpr2 ligand QC1 upon oAβ-induced inflammatory, oxidative, and metabolic behaviour. Cytotoxic behaviour of BV2 cells was assessed through the use of cocultures with retinoic acid-differentiated human SH-SY5Y cells. Stimulation of BV2 cells with oAβ at 100 nM did not induce classical inflammatory marker production but did stimulate production of reactive oxygen species (ROS), an effect that could be reversed by subsequent treatment with the Fpr2 ligand QC1. Further investigation revealed that oAβ-induced ROS production was associated with NADPH oxidase activation and a shift in BV2 cell metabolic phenotype, activating the pentose phosphate pathway and NADPH production, changes that were again reversed by QC1 treatment. Microglial oAβ-stimulated ROS production was sufficient to induce apoptosis of bystander SH-SY5Y cells, an effect that could be prevented by QC1 treatment. In this study, we provide proof-of-concept data that indicate exploitation of the proresolving receptor Fpr2 can reverse damaging oAβ-induced microglial activation. Future strategies that are aimed at restraining neuroinflammation in conditions such as AD should examine proresolving actors as a mechanism to harness the brain's endogenous healing pathways and limit neuroinflammatory damage.

CXCL-8 in Preoperative Colorectal Cancer Patients: Significance for Diagnosis and Cancer Progression.

Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal–Wallis test and confirmed by the post hoc Dwass–Steele–Critchlow–Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve—ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression.

Title: Human Serum/Plasma Glycoprotein Analysis by 1H-NMR, an Emerging Method of Inflammatory Assessment.

Several studies suggest that variations in the concentration of plasma glycoproteins can influence cellular changes in a large number of diseases. In recent years, proton nuclear magnetic resonance (1H-NMR) has played a major role as an analytical tool for serum and plasma samples. In recent years, there is an increasing interest in the characterization of glycoproteins through 1H-NMR in order to search for reliable and robust biomarkers of disease. The objective of this review was to examine the existing studies in the literature related to the study of glycoproteins from an analytical and clinical point of view. There are currently several techniques to characterize circulating glycoproteins in serum or plasma, but in this review, we focus on 1H-NMR due to its great robustness and recent interest in its translation to the clinical setting. In fact, there is already a marker in H-NMR representing the acetyl groups of the glycoproteins, GlycA, which has been increasingly studied in clinical studies. A broad search of the literature was performed showing a general consensus that GlycA is a robust marker of systemic inflammation. The results also suggested that GlycA better captures systemic inflammation even more than C-reactive protein (CRP), a widely used classical inflammatory marker. The applications reviewed here demonstrated that GlycA was potentially a key biomarker in a wide range of diseases such as cancer, metabolic diseases, cardiovascular risk, and chronic inflammatory diseases among others. The profiling of glycoproteins through 1H-NMR launches an encouraging new paradigm for its future incorporation in clinical diagnosis.

The adipose-derived Nerve Growth Factor is associated with abdominal obesity in prepubertal and pubertal children

AbstractIntroductionObesity is known to be associated with a low-grade inflammatory state. Most studies reporting inflammation in obesity have been done in pubertal children or adults or have focused only on the relation between body mass index (BMI) and the classical inflammatory markers. Nerve growth factor (NGF), monocyte chemoattractant protein–1 (MCP-1) and hepatocyte growth factor (HGF) are adipokines previously shown to be involved in the inflammatory context of obesity and metabolic syndrome but few studies have been conducted in children.ObjectiveTo evaluate the association between NGF, MCP-1, HGF with total and abdominal adiposity and in prepubertal and pubertal children.Methods889 children participated in a prospective obesity case-control study (50.2% males, 72% prepubertals, 27% overweight and 43% obesity), paired by age and sex. The relationship between total fat (assessed using the BMI, the sum of skinfolds thickness (SF) and fat mass index (FMI) from bioelectrical impedance analysis and waist circumference as a surrogate marker of abdominal obesity) and plasma concentrations of MCP-1, HGF, and NGF was studied in prepubertal and pubertal children.Linear regression analysis for prepubertal and pubertal children, adjusting for age, sex and center was used.ResultsNGF was associated with WC, with a stronger association in prepubertal than in pubertal children. MCP-1 was positively associated with WC, SF, FMI and BMI in pubertal children whereas HGF was positively associated with WC and BMI only in prepubertal children. The strongest associations were between WC and NGF (β 0.123 95%CI 0.133, 0.709; p &lt; 0.001) in prepubertal children and WC and MCP-1 (β 0.123 95%CI 0.438, 2.035; p &lt; 0.001) in pubertal children.DiscussionTotal and abdominal adiposity are related to plasma concentrations of adipokines in prepubertal and pubertal children with obesity. Adipokines such as NGF, HGF and MCP-1 have not been so well studied so far in obese children. Particularly, NGF was associated with WC and BMI in prepubertal children and with WC in pubertal children. The association between this neurotrophin, secreted by adipose tissue and involved in the development and survival of sympathetic neurons, with adiposity, especially in prepubertal children, could suggest an anti-inflammatory mechanism and thus be a potential therapeutic target.Conflict of interestNone