Effect of whole-body vibration stimulation on plasma soluble TNF receptors in elderly with sarcopenia: a randomized controlled trial.

Sarcopenia is a pathology resulting from a progressive and severe loss of muscle mass, strength, and function in the course of aging, which has deleterious consequences on quality of life. Among the most widespread studies on the issue are those focused on the effect of different types of physical exercise on patients with sarcopenia. This randomized controlled study aimed to compare the effects of a whole-body vibration exercise (WBV) session on the inflammatory parameters of non-sarcopenic (NSG, n=22) and sarcopenic elderly (SG, n=22). NSG and SG participants were randomly divided into two protocols: intervention (squat with WBV) and control (squat without WBV). After a one-week washout period, participants switched protocols, so that everyone performed both protocols. Body composition was assessed by dual-energy radiological absorptiometry (DXA) and function through the six-minute walk test (6MWD) and Short Physical Performance Battery (SPPB). Plasma soluble tumor necrosis factor receptors (sTNFR) were determined by enzyme-linked immunosorbent assay (ELISA) and measured before and immediately after each protocol. After exercise with WBV, there was an increase in sTNFR2 levels in the NSG (P<0.01; d=-0.69 (-1.30; -0.08) and SG (P<0.01, d=-0.95 (-1.57; -0.32) groups. In conclusion, an acute session of WBV influenced sTNFr2 levels, with sarcopenic individuals showing a greater effect. This suggested that WBV had a more pronounced impact on sTNFr2 in those with loss of muscle strength and/or physical performance. Additionally, WBV is gaining recognition as an efficient strategy for those with persistent health issues.

Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia.

This study investigated whether blood-based biomarkers were related to functional test performance and respiratory muscle strength in older adults with COPD and sarcopenia. The participants included in this cross-sectional study were from both sexes and sixty years or older. Based on clinical assessment, participants were categorized in COPD (n = 43) and non-COPD (NCOPD) (n = 43) groups. They were also assessed for body composition and muscular mass by dual-energy X-ray absorptiometry, using the relative skeletal muscle index for the diagnosis of sarcopenia. A series of functional tests, including short physical performance battery (SPPB), 6-minute walking test (6MWT), maximal inspiratory and expiratory pressures (MIP and MEP), were carried out. Plasma levels of myokines (Irisin and BDNF), and soluble TNF receptors (sTNFR1 and sTNFR2) were determined by ELISA. In the multivariate analysis, 6MWD was associated with age, COPD-related sarcopenia and BDNF (R2 = 0.29; f2 = 0.41). SPPB score was associated with COPD-related sarcopenia and sTNFR1 (R2 = 0.25; f2 = 0.33). MIP value was associated with sex, COPD-related sarcopenia, sTNFR2 and Irisin (R2 = 0.24; f2 = 0.31). Finally, MEP value was associated with sex COPD-related sarcopenia (R2 = 0.18; f2 = 0.22). Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia.

Soluble TNF receptors predict acute kidney injury and mortality in critically ill COVID-19 patients: A prospective observational study.

BACKGROUND: Although pneumonia is the hallmark of coronavirus disease 2019 (COVID-19), multiple organ failure may develop in severe disease. TNFα receptors in their soluble form (sTNFR) are involved in the immune cascade in other systemic inflammatory processes such as septic shock, and could mediate the inflammatory activation of distant organs. The aim of this study is to analyse plasma levels of sTNFR 1 and 2 in association with organ failure and outcome in critically ill patients with COVID-19. METHODS: After informed consent, we included 122 adult patients with PCR-confirmed COVID-19 at ICU admission. Demographic data, illness severity scores, organ failure and survival at 30 days were collected. Plasma sTNFR 1 and 2 levels were quantified during the first days after ICU admission. Twenty-five healthy blood donors were used as control group. RESULTS: Levels of sTNFR were higher in severe COVID-19 patients compared to controls (p < 0.001). Plasma levels of sTNFR were associated to illness severity scores (SAPS 3 and SOFA), inflammation biomarkers such as IL-6, ferritin and PCT as well as development of AKI during ICU stay. sTNFR 1 higher than 2.29 ng/mL and? sTNFR 2 higher than 11.7 ng/mL were identified as optimal cut-offs to discriminate survivors and non-survivors 30 days after ICU admission and had an area under the curve in receiver operating characteristic curve of 0.75 and 0.67 respectively. CONCLUSION: Plasma levels of sTNFR 1 and 2 were higher in COVID-19 patients compared to controls and were strongly associated with other inflammatory biomarkers, severity of illness and acute kidney injury development during ICU stay. In addition, sTNFR 1 was an independent predictor of 30-day mortality after adjustment for age and respiratory failure.

Confounders in Identification and Analysis of Inflammatory Biomarkers in Cardiovascular Diseases.

Proinflammatory biomarkers have been increasingly used in epidemiologic and intervention studies over the past decades to evaluate and identify an association of systemic inflammation with cardiovascular diseases. Although there is a strong correlation between the elevated level of inflammatory biomarkers and the pathology of various cardiovascular diseases, the mechanisms of the underlying cause are unclear. Identification of pro-inflammatory biomarkers such as cytokines, chemokines, acute phase proteins, and other soluble immune factors can help in the early diagnosis of disease. The presence of certain confounding factors such as variations in age, sex, socio-economic status, body mass index, medication and other substance use, and medical illness, as well as inconsistencies in methodological practices such as sample collection, assaying, and data cleaning and transformation, may contribute to variations in results. The purpose of the review is to identify and summarize the effect of demographic factors, epidemiological factors, medication use, and analytical and pre-analytical factors with a panel of inflammatory biomarkers CRP, IL-1b, IL-6, TNFa, and the soluble TNF receptors on the concentration of these inflammatory biomarkers in serum.

Cytokine Signaling and Matrix Remodeling Pathways Associated with Cardiac Sarcoidosis Disease Activity Defined Using FDG PET Imaging.

While cardiac imaging has improved the diagnosis and risk assessment for cardiac sarcoidosis (CS), treatment regimens have consisted of generalized heart failure therapies and non-specific anti-inflammatory regimens. The overall goal of this study was to perform high-sensitivity plasma profiling of specific inflammatory pathways in patients with sarcoidosis and with CS.Specific inflammatory/proteolytic cascades were upregulated in sarcoidosis patients, and certain profiles emerged for CS patients.Plasma samples were collected from patients with biopsy-confirmed sarcoidosis undergoing F-18 fluorodeoxyglucose positron emission tomography (n = 47) and compared to those of referent control subjects (n = 6). Using a high-sensitivity, automated multiplex array, cytokines, soluble cytokine receptor profiles (an index of cytokine activation), as well as matrix metalloproteinase (MMP), and endogenous MMP inhibitors (TIMPs) were examined.The plasma tumor necrosis factor (TNF) and soluble TNF receptors sCD30 and sTNFRI were increased using sarcoidosis, and sTNFRII increased in CS patients (n = 18). The soluble interleukin sIL-2R and vascular endothelial growth factor receptors (sVEGFR2 and sVEGFR3) increased to the greatest degree in CS patients. When computed as a function of referent control values, the majority of soluble cytokine receptors increased in both sarcoidosis and CS groups. Plasma MMP-9 levels increased in sarcoidosis but not in the CS subset. Plasma TIMP levels declined in both groups.The findings from this study were the identification of increased activation of a cluster of soluble cytokine receptors, which augment not only inflammatory cell maturation but also transmigration in patients with sarcoidosis and patients with cardiac involvement.

Chronic capsiate supplementation increases fat-free mass and upper body strength but not the inflammatory response to resistance exercise in young untrained men: a randomized, placebo-controlled and double-blind study.

BACKGROUND: Acute capsaicinoid and capsinoid supplementation has endurance and resistance exercise benefits; however, if these short-term performance benefits translate into chronic benefits when combined with resistance training is currently unknown. This study investigated changes of chronic Capsiate supplementation on muscular adaptations, inflammatory response and performance in untrained men. METHODS: Twenty untrained men were randomized to ingest 12 mg Capsiate (CAP) or placebo in a parallel, double-blind design. Body composition and performance were measured at pre-training and after 6 weeks of resistance training. An acute resistance exercise session test was performed pre and post-intervention. Blood samples were collected at rest and post-resistance exercise to analyze Tumor necrosis factor- (TNF-), Soluble TNF- receptor (sTNF-r), Interleukin-6 (IL-6) and Interleukin-10 (IL-10). RESULTS: Exercise and CAP supplementation increased fat-free mass in comparison to baseline by 1.5 kg (P < 0.001), however, the majority of the increase (1.0 kg) resulted from an increase in total body water. The CAP change scores for fat-free mass were significantly greater in comparison to the placebo (CAP ∆%= 2.1 ± 1.8 %, PLA ∆%= 0.7 ± 1.3 %, P = 0.043) and there was a significant difference between groups in the bench press exercise (P = 0.034) with greater upper body strength change score for CAP (∆%= 13.4 ± 9.1 %) compared to placebo (∆%= 5.8 ± 5.2 %), P = 0.041. CAP had no effect on lower body strength and no supplementation interactions were observed for all cytokines in response to acute resistance exercise (P > 0.05). CONCLUSION: Chronic Capsiate supplementation combined with resistance training during short period (6 weeks) increased fat-free mass and upper body strength but not inflammatory response and performance in young untrained men.

Can Cytokines be used as an Activation Marker in Rheumatoid Arthritis?

AIMS: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However, the role of the cytokines play an important part in this mechanism. We aimed to bring a new approach to the concept of 'remission' in patients with RA. BACKGROUND: RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling, tenderness and morning stiffness are typical of the joints involved. Although it is approached as primary joint disease, a wide variety of extra-articular involvements may also occur. It is an interesting pathophysiological process, the exact cause of which is still unknown, with many environmental, genetic and potentially undiscovered possible factors in a chaotic manner. OBJECTIVE: In this cross-sectional study, sedimentation rate (ESR), C- Reactive protein (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10 were measured in three groups which were healthy volunteers, patients with RA in the active period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated in active RA and RA in remission. METHODS: This study included 20 healthy volunteers, 20 remission patients with RA and 20 active RA patients. Venous blood samples were collected from patients in both healthy and RA groups. RESULTS: RA group consisted 43 (71.6%) female and 17 (28.4%) male. Control group consisted 11 (55%) female and 9 (45%) male. TNF-R was significantly high only in the active group according to the healthy group (p=0.002). IL-10 was significantly high in active RA, according to RA in remission (p=0.03). DAS-28 was significantly high in active RA, according to RA in remission (p=0.001). In the active RA group, ESR and TNF-R had a positive correlation (r:0.442; p=0.048). In the active RA group, there was also a positive correlation between TNF-R and CRP (r:0.621; p=0,003). Both healthy and active RA group had significant positive correlation between ESR and CRP (r: 0.481; p=0.032 and r: 0,697; p=0,001 respectively). CONCLUSION: TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be very important in revealing the effect of TNF on the disease and the value of this effect in the treatment and ensuring the follow-up of the disease with CRP instead of ESR in activation.

Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction.

BACKGROUND: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. METHODS: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. RESULTS: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min-1 /1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. CONCLUSION: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.

Clinical significance of progranulin correlated with serum soluble Oxford 40 ligand in primary Sjögren's syndrome.

The present study aimed to investigate the association between the expressions of serum progranulin (PGRN) and serum soluble Oxford 40 ligand (sOX40L) and determine their clinical significances in primary Sjögren's syndrome (pSS).The present study included a total of 68 patients with pSS and 50 healthy controls. Demographic data and clinical basic information were collected. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum levels of PGRN, sOX40L and interleukins. Spearman's correlation coefficient and Mann-Whitney U test were used to determine the correlation between PGRN, and sOX40L and the association between PGRN and sOX40L and disease activity and disease severity.Serum interleukin (IL)-4, IL-6, IL-10, PGRN, and sOX40L levels were significantly higher in pSS patients as compared to the healthy controls. A positive correlation was observed between PGRN and sOX40L. Patients with elevated levels of PGRN or sOX40L exhibited higher disease activity compared to those with lower levels. Patients with III to IV stages of pSS or multiple system damage showed higher serum levels of PGRN and sOX40L.Elevated serum PGRN, and sOX40L levels were relevant with disease activity and severity in patients with pSS.

The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial.

Chronic hyperglycemia increases oxidative stress, activates inflammatory pathways and reduces nerve growth factor (NGF) among diabetic patients, which contribute to development of diabetic peripheral neuropathy (DPN). Tocotrienol-Rich Vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties which are postulated to target these pathogeneses in order to ameliorate DPN. This study aims to evaluate the effects of Tocovid on nerve conduction parameters and serum biomarkers among diabetic patients. This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on 80 eligible participants. The intervention group (n = 39) was randomly allocated to receive 200 mg of Tocovid twice a day, and the control group (n = 41) received placebo twice a day. At the end of eight weeks, the nerve conduction parameters, as assessed by nerve conduction study, as well as serum biomarkers (NGF, malondialdehyde, vascular cell adhesion molecule 1, tumor necrosis factor receptor 1 and thromboxane B2) were compared between the two groups. Compared to placebo, Tocovid significantly improves the nerve conduction velocities of all nerves (+1.25 m/s, interquartile range [IQR] 3.35, p < 0.001, median nerve; +1.60 m/s, IQR 1.80, p < 0.001, sural nerve; +0.75 m/s, IQR 2.25, p < 0.001, tibial nerve). Meanwhile, the levels of serum NGF were significantly higher in the Tocovid group as compared to placebo at eight weeks post-intervention. Participants receiving Tocovid illustrated highly significant improvement in terms of nerve conduction velocities for all nerves tested after eight weeks of supplementation. In addition, Tocovid supplementation elevated the levels of serum NGF, in which its increase is postulated to reflect enhanced neuronal functions. This novel finding suggests that Tocovid could be a disease-modifying agent targeting serum NGF to improve nerve conduction velocities.

Circulating Tumor Necrosis Factor Receptors: A Potential Biomarker for the Progression of Diabetic Kidney Disease.

Despite considerable advancements in medicine, the optimal treatment for chronic kidney disease (CKD), especially diabetic kidney disease (DKD), remains a major challenge. More patients with DKD succumb to death due to cardiovascular events than due to progression to end-stage renal disease (ESRD). Moreover, patients with DKD and ESRD have remarkably poor prognosis. Current studies have appreciated the contribution of inflammation and inflammatory mediators, such as tumor necrosis factor (TNF)-related biomarkers, on the development/progression of DKD. The present review focuses on molecular roles, serum concentrations of TNF receptors (TNFRs), and their association with increased albuminuria, eGFR decline, and all-cause mortality in diabetes. Experimental studies have suggested that DKD progression occurs through the TNFα-TNFR2 inflammatory pathway. Moreover, serum TNFR levels were positively associated with albuminuria and negatively associated with estimated glomerular filtration rate (eGFR), while circulating levels of TNFRs exhibited an independent effect on all-cause mortality and eGFR decline, including ESRD, even after adjusting for existing risk factors. However, their precise function has yet to be elucidated and requires further studies.

Antioxidant and Anti-inflammatory Diagnostic Biomarkers in Multiple Sclerosis: A Machine Learning Study.

An imbalance of inflammatory/anti-inflammatory and oxidant/antioxidant molecules has been implicated in the demyelination and axonal damage in multiple sclerosis (MS). The current study aimed to evaluate the plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, sTNFR2, adiponectin, hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites, total plasma antioxidant capacity using the total radical-trapping antioxidant parameter (TRAP), sulfhydryl (SH) groups, as well as serum levels of zinc in 174 MS patients and 182 controls. The results show that MS is characterized by lowered levels of zinc, adiponectin, TRAP, and SH groups and increased levels of AOPP. MS was best predicted by a combination of lowered levels of zinc, adiponectin, TRAP, and SH groups yielding an area under the receiver operating characteristic (AUC/ROC) curve of 0.986 (±0.005). The combination of these four antioxidants with sTNFR2 showed an AUC/ROC of 0.997 and TRAP, adiponectin, and zinc are the most important biomarkers for MS diagnosis followed at a distance by sTNFR2. Support vector machine with tenfold validation performed on the four antioxidants showed a training accuracy of 92.9% and a validation accuracy of 90.6%. The results indicate that lowered levels of those four antioxidants are associated with MS and that these antioxidants are more important biomarkers of MS than TNF-α signaling and nitro-oxidative biomarkers. Adiponectin, TRAP, SH groups, zinc, and sTNFR2 play a role in the pathophysiology of MS, and a combination of these biomarkers is useful for predicting MS with high sensitivity, specificity, and accuracy. Drugs that increase the antioxidant capacity may offer novel therapeutic opportunities for MS.

Soluble interleukin-6 receptor in young adults and its relationship with body composition and autonomic nervous system.

BACKGROUND: The immune system generates inflammatory responses through cytokines like Interleukin 6 (IL-6) and the Tumor Necrosis Factor alpha (TNF α); these cytokines mediate cellular responses aided by the presence of soluble receptors such as: Soluble Interleukin 6 Receptor (sIL6R) and Soluble Tumor Necrosis Factor Receptors Type 1 and 2 (sTNFR1, sTNFR2); the literature is limited about the relationship between this cytokines and the role of its soluble receptors. OBJECTIVES: This study is to determine a possible relationship between specific inflammatory markers and their soluble receptors with the autonomic nervous system's activity and body composition. METHODS: 27 subjects (13 men of 19.3 ± 1.6 years old and 14 women of 19.1 ± 1.7 years old) were evaluated. Body composition, autonomic nervous system activity and plasma concentration of inflammatory markers IL-6, TNF α, sIL6R, sTNFR1 and sTNFR2 were measured using bio-impedance, heart rate variability and ELISA respectively. RESULTS: A positive association between body-fat percentage and the sIL6R (0.47, p = .013) as well as inverse relationship between muscular mass and the sIL6R (-0.45, p = .019) were found. The sIL6R was also positively correlated with sympathetic activity markers: Relation LF/HF (0.52, p = .006), cardiac sympathetic index (0.45, p = .008), and cardiac vagal index (-0.44, p = .022). CONCLUSION: This study suggested that the IL-6 trans-signaling involving both the soluble receptor, sIL6R, and gp130 membrane co-receptor could produce inflammatory responses that generate an impact on the autonomic nervous system, possibly due to its direct action on the hypothalamus, the solitary tract nucleus, or the heart.

Ligands and receptors of the TNF superfamily are decreased in major depression and during early antidepressant therapy.

BACKGROUND: The up-regulation of pro-inflammatory agents, amongst them tumor necrosis factor (TNF), may represent low-grade inflammation in major depression. To further elucidate inflammatory mechanisms related to TNF in depression, the aim of the current study was to investigate the involvement of ligands and receptors of the TNF/TNF-receptor-superfamily yet un- or little explored in major depression. METHODS: Serum levels of ligands (TNF, TNF-related weak inducer of apoptosis [TWEAK], B-cell activating factor [BAFF], tumor necrosis factor superfamily member 14 [TNFSF14; LIGHT], A proliferation-inducing ligand [APRIL]) and receptor molecules (TNF receptor superfamily member 8 [TNFRSF8; sCD30], soluble TNF receptor type 1 [sTNFR1] and type 2 [sTNFR2]) of the TNF/TNF-receptor-superfamily were measured in 50 unmedicated patients suffering from major depression and 48 healthy controls and were reassessed in 37 of the depressed patients two weeks after the initiation of antidepressive treatment. RESULTS: In comparison to the healthy controls, the interrelated serum levels of TWEAK, BAFF, TNFSF8, sTNFR1 and sTNFR2 were reduced both in the unmedicated and medicated depressed patients. Serum levels of BAFF and TNF significantly increased during the initiation of antidepressive treatment. In the combined sample of unmedicated depressed and healthy controls, but not the separate groups, scores of the BDI-II inversely correlated with levels of TWEAK, BAFF, sTNFR1, sTNFR2 and TNFSF8. CONCLUSION: The current findings give evidence for a role of the TNF/TNF-receptor-superfamily in the pathophysiology of major depression that may involve reduced tissue regeneration and neurogenesis rather than an acceleration of pro-inflammatory pathways.

Immunologic findings precede rapid lupus flare after transient steroid therapy.

Systemic lupus erythematosus (SLE) flares elicit progressive organ damage, leading to disability and early mortality. This study evaluated clinical and immunologic factors associated with impending flare in the Biomarkers of Lupus Disease study. Autoantibodies and 32 soluble mediators were measured by multiplex assays, immune pathway activation by gene expression module scores, and immune cell subset frequencies and activation states by flow cytometry. After providing baseline samples, participants received transient steroids to suppress disease and were followed until flare. Flare occurred early (within 60 days of baseline) in 21 participants and late (90-165 days) in 13. At baseline, compared to the late flare group, the early flare group had differential gene expression in monocyte, T cell, interferon, and inflammation modules, as well as significantly higher frequencies of activated (aCD11b+) neutrophils and monocytes, and activated (CD86hi) naïve B cells. Random forest models showed three subgroups of early flare patients, distinguished by greater baseline frequencies of aCD11b+ monocytes, or CD86hi naïve B cells, or both. Increases in these cell populations were the most accurate biomarkers for early flare in this study. These results suggest that SLE flares may arise from an overlapping spectrum of lymphoid and myeloid mechanisms in different patients.

HIV infection is associated with elevated biomarkers of immune activation in Ugandan adults with pneumonia.

INTRODUCTION: Pneumonia is an important cause of morbidity and mortality in persons living with human immunodeficiency virus (HIV) infection. How immune activation differs among HIV-infected and HIV-uninfected adults with pneumonia is unknown. METHODS: The Inflammation, Aging, Microbes, and Obstructive Lung Disease (I AM OLD) Cohort is a prospective cohort of adults with pneumonia in Uganda. In this cross-sectional analysis, plasma was collected at pneumonia presentation to measure the following 12 biomarkers: interleukin 6 (IL-6), soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2), high sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer, soluble CD27 (sCD27), interferon gamma-inducible protein 10 (IP-10), soluble CD14 (sCD14), soluble CD163 (sCD163), hyaluronan, and intestinal fatty acid binding protein. We asked whether biomarker levels differed between HIV-infected and HIV-uninfected participants, and whether higher levels of these biomarkers were associated with mortality. RESULTS: One hundred seventy-three participants were enrolled. Fifty-three percent were HIV-infected. Eight plasma biomarkers-sTNFR-1, sTNFR-2, hsCRP, D-dimer, sCD27, IP-10, sCD14, and hyaluronan-were higher among participants with HIV infection, after adjustment for pneumonia severity. Higher levels of 8 biomarkers-IL-6, sTNFR-1, sTNFR-2, hsCRP, IP-10, sCD14, sCD163, and hyaluronan-were associated with increased 2-month mortality. CONCLUSIONS: As in other clinical contexts, HIV infection is associated with a greater degree of immune activation among Ugandan adults with pneumonia. Some of these are also associated with short-term mortality. Further study is needed to explore whether these biomarkers might predict poor long-term outcomes-such as the development of obstructive lung disease-in patients with HIV who have recovered from pneumonia.

A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes.

Chronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.

Utility of novel serum biomarkers to predict subclinical atherosclerosis: A sub-analysis of the EISNER study.

BACKGROUND AND AIMS: Certain novel biomarkers may predict atherosclerotic cardiovascular disease (ASCVD) events; however, data on their relationship to coronary atherosclerosis and its progression as measured by coronary artery calcium (CAC) scanning is lacking. We evaluated the association between novel biomarkers and presence or progression of CAC. METHODS: The EISNER study was a prospective trial of patients without known ASCVD. Data on CAC and several biomarkers (hs-CRP, LTßR, osteopontin [OPN], RAGE, TNFR1α and TROY) were available at baseline and 4-year follow-up. Biomarkers were standardized and summed for a composite score. CAC progression was defined by the square-root (CACSQRT) method and rapid (top decile) progression. Adjusted regression models created a final prediction model for baseline CAC and CAC progression. RESULTS: 1207 subjects (mean age 58.4 ±â€¯8 years, 53% male) were evaluated; 621 had a baseline CAC >0, in whom 323 progressed by CACSQRT, and 121 rapidly progressed. Baseline CAC was associated only with OPN (p = 0.03), TROY (p = 0.0058) and TNFR1α (p = 0.0039) in unadjusted analyses. In adjusted analyses, only OPN was independently related to CAC progression using CACSQRT (p = 0.04). CONCLUSIONS: OPN identifies progression of atherosclerosis in persons free of ASCVD at baseline and may be a useful predictive tool to guide ASCVD prevention management.

Age-Related Adverse Inflammatory and Metabolic Changes Begin Early in Adulthood.

Aging is characterized by deleterious immune and metabolic changes, but the onset of these changes is unknown. We measured immune and metabolic biomarkers in adults beginning at age 30. To our knowledge, this is the first study to evaluate these biomarkers in adults aged 30 to over 80. Biomarkers were quantified in 961 adults. Tumor necrosis factor alpha (TNF-α), tumor necrosis factor receptor I (TNFR-I), tumor necrosis factor receptor II (TNFR-II), interleukin (IL)-2, IL-6, VCAM-I, D-Dimer, G-CSF, regulated on activation, normal T cell expressed and secreted (RANTES), matrix metalloproteinase-3 (MMP-3), adiponectin, and paraoxonase activity were measured by ELISA. Acylcarnitines and amino acids (AAs) were measured by mass spectrometry and reduced to a single factor using principal components analysis (PCA). Glycine was analyzed separately. The relationship between age and biomarkers was analyzed by linear regression with sex, race, and body mass index (BMI) as covariates. Age was positively correlated with TNF-α, TNFR-I, TNFR-II, IL-6, IL-2, VCAM-1, D-Dimer, MMP-3, adiponectin, acylcarnitines, and AAs. Age was negative correlated with G-CSF, RANTES, and paraoxonase activity. BMI was significant for all biomarkers except IL-2, VCAM-1, RANTES, paraoxonase activity, and the AA factor. Excluding MMP-3, greater BMI was associated with potentially adverse changes in biomarker concentrations. Age-related changes in immune and metabolic biomarkers, known to be associated with poor outcomes in older adults, begin as early as the thirties.

Predicting functional outcome of ischemic stroke patients in Romania based on plasma CRP, sTNFR-1, D-Dimers, NGAL and NSE measured using a biochip array.

In cerebral ischemia, evaluation of multiple biomarkers involved in various pathological pathways is a useful tool in assessing the outcome of the patients even from the early stages of the disease. In this study we investigated the utility of a panel of 5 peripheral biomarkers of inflammatory status, neuronal destruction and secondary fibrinolysis in the acute phase of ischemia, and evaluated the impact of these biomarkers on functional outcome after ischemic stroke. The 5 biomarkers (plasma CRP, D-Dimers, sTNFR-1, NGAL and NSE) were measured using a biochip array technology. Eighty nine patients in Romania were divided into 2 subgroups using the modified Rankin Scale evaluated at 3 months after ischemic stroke; the possible impact of analyzed biomarkers on unfavorable functional outcome was tested by binomial logistic regression. The subgroup with unfavorable outcome had higher concentrations of CRP, NGAL, sTNFR-1 and D-dimers, but CRP and NGAL values were not statistically different between the two subgroups. The univariate logistic regression analysis of plasma biomarkers revealed that CRP, D-Dimers, NGAL, sTNFR-1 were significant predictors of unfavorable clinical outcome. In the case of D-Dimers and sTNFR-1 we noticed an increased discrimination ability (versus baseline clinical model) to classify poor functional outcome with a tendency toward statistical signification. During the acute phase of the ischemic stroke, plasma concentrations of CRP, D-Dimers and sTNFR-1 were elevated in unfavorable outcome patients. D-Dimers and sTNFR-1 were independent predictors of poor outcome at 3 months after ischemic stroke. The biochip array technology offers the possibility to simultaneously measure several parameters involved in multiple pathophysiological pathways, in a small sample volume.