Background: Current guidelines for diagnosis and management of heart failure (HF) rely on clinical findings and natriuretic peptide values, but evidence suggests that recently identified cardiac biomarkers may aid in early detection of HF and improve risk stratification. The aim of this study was to assess the diagnostic and prognostic utility of multiple biomarkers in patients with HF and left ventricular systolic dysfunction (LVSD).
Methods: High-sensitivity cardiac troponin I (cTnI), N-terminal pro b-type natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), endothelin-1 (ET-1), pro-matrix metalloproteinase-9 (pMMP-9), and tumor necrosis factor-alpha (TNF-α) were measured using single-molecule counting technology in 200 patients with varying stages of HF. Plasma detection with cross-sectional associations of biomarkers across all HF stages, and advanced-therapy and transplant-free survival were assessed using multivariate analysis and Cox regression analyses, respectively.
Results: NTproBNP, pMMP-9, IL-6 were elevated in early, asymptomatic stages of HF, and increased with HF severity. Higher circulating levels of combined IL-6, NTproBNP, and cTnI predicted significantly worse survival at 1500-day follow-up. Cox regression analysis adjusted for ACC/AHA HF stages demonstrated that a higher concentration of IL-6 and cTnI conferred greater risks in terms of time to death, implantation of left ventricular assist device (LVAD), or heart transplantation.
Conclusion: Biomarkers of inflammation, LV remodeling, and myocardial injury were elevated in HF and increased with HF severity. Patients had a significantly higher risk of serious cardiac events if multiple biomarkers were elevated. These findings support measuring NTproBNP, cTnI and IL-6 among patients with HF and LVSD for diagnostic and prognostic purposes.
Background: Inflammation is associated with enhanced cardiovascular risk profile and increased cardiovascular mortality in end-stage kidney disease patients undergoing hemodialysis. Mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified. As successful treatment of the inflammatory condition in these patients may improve long-term survival, we studied potential changes in different inflammatory biomarkers of cardiovascular risk in end-stage kidney disease patients after a mid-week hemodialysis session.
Methods: Inflammatory biomarkers of cardiovascular risk (cystatin-C, homocysteine, C-reactive protein, procalcitonin, pentraxin-3, serum amyloid-A) and atherogenic plasma lipoproteins (Lipoprotein(a), cholesterol low and high density lipoproteins) were studied in 21 end-stage kidney disease patients previously and after a mid-week hemodialysis session.
Results: We found a significant reduction in serum levels of low molecular weight molecules: cystatin-C (5.56 to 1.85 mg/L, 66.73%, p < 0.001), homocysteine (22.85 to 13.25 µmol/L, 42.01%, p < 0.001) and procalcitonin (0.788 to 0.457 ng/mL, 42.01%, p < 0.001). Large molecules as C-reactive protein (9.70 to 9.90 mg/L, 2.06%, p = 0.022) and pentraxin-3 (1.67 to 4.28 ng/mL, 156%, p < 0.001) increased, but serum amyloid-A decreased (15.90 to 12.70 mg/L, 20.13%, p < 0.05). There was no change in Lipoprotein (a) levels.
Conclusion: Pentraxin-3 was a more specific inflammatory vascular marker than C-reactive protein, and the best inflammatory marker associated with hemodialysis. Homocysteine, procalcitonin and the other small proteins could be released and removed during hemodialysis session. Further studies are needed to understand the behavior and significance of these markers after successive hemodialysis.
Biomarkers have been used in the diagnosis of disease and other conditions for many decades. There are diverse ranges of analytical targets, including metabolites, nucleic acids and proteins were used as a biomarker. Clinical diagnoses already rely heavily on these for patient disease classification, management, and informing treatment and care pathways. For that there is always a need of rapid and point of care test. However, until fairly recently, studies of biomarker efficacy in a clinical setting were mainly limited to single or dual use, and the landscape was complex, confused, and often inconsistent. Few candidates emerged from this somewhat clouded picture: C-reactive protein, procalcitonin (PCT) for sepsis, ADA for mycobacterium tuberculosis and a Circulating miRNAs serve as molecular markers for diverse physiological and pathological conditions.
Background: Mesenchymal stem cell (MSC) effects can shift immune responses toward anti-inflammatory and tolerogenic phenotypes, potentially helping patients with bronchiolitis obliterans syndrome (BOS).
Methods: We evaluated the effect of infusing allogeneic MSC intravenously in 9 patients with moderate BOS refractory to standard therapy who were not candidates for retransplant, dividing them into 3 dosing groups: Group 1, 1×106 MSC/kg (n=3); Group 2, 2×106 MSC/kg (n=3); and Group 3, 4×106 MSC/kg (n=3). We recorded pulmonary function tests, laboratory variables, and serum biomarkers pre- and post-MSC infusion.
Results: These patients had significant decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) over 1 year pre-MSC infusion (mean ± SD) FVC, 3.11±0.98 L, and FEV1 1.99+0.64 L versus FVC 2.58±1.03 and FEV1 1.61±0.52 just before infusion (P<0.05); representing a mean loss of 530 mL in FVC and 374 mL in FEV1 over 12 months. One year post-MSC infusion, mean FVC and FEV1 increased to 2.66±1.01 L and 1.63±0.55 L, respectively (changes no longer significant compared to before MSC infusion). Patients in Group 1 showed elevation of tolerance-inducing T regulatory cells and increased levels of epidermal growth factor. Tolerance-inducing Th-2 cytokines increased in Groups 1 and 2. These changes were not significantly different in these small sub-groups.
Conclusion: MSC infusion appears to slow down or reverse the progressive decline in lung function in some patients with moderate BOS, possibly by inducing anti-inflammatory effects and promoting cell proliferation and angiogenesis.
We present below a mechanistic molecular approach for development of Anti-Inflammatory biomarkers of Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses arrroaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory bathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary componenents on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.
Inflammatory Bowel Disease (IBD)-associated arthritis is called Enteropathic Arthritis (EA) which is classified among the group of Spondyloarthritis (SpA), because its presentation is variable. The current trend is to classify them as autoinflammatory rather than autoimmune diseases, since no antibodies have yet been identified. The study of biomarkers (BM) will help us with early identification and hence, to provide treatment in the early stages, prior to radiographic progression, which will enable prompt identification of the disease phenotype. 42 patients diagnosed with IBD were included, of which 48% were females; the mean age of the study group was 48.12 ± 5.02 (95% CI). The average time of evolution of disease was 37.57 ± 14.28 months; most patients referred to the rheumatologist had a diagnosis of ulcerative colitis (83%). According to our analysis, we were able to determine that the three most significant variables influencing the development of sacroiliitis were: Lactoferrin, ANCA and HLA B27 (p < 0.5). The variable that can be ruled out because of its almost neglectable contribution was fecal calprotectin.
Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR.
Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness.
Background and objectives: New AKI biomarkers (on the top of it NGAL biomarker) have demonstrated better performance for prediction of AKI in critically ill patients with heterogeneous illness. Renal angina index was recently reported to enhance prediction of severe AKI at the time of intensive care unit admission. This study tested the hypothesis that incorporation of uNGAL in patients with renal angina improves the prediction of severe AKI.
Design, setting, participants & measurements: In our study 53critically ill children admitted to the pediatric intensive care unit in Zagazig university hospital, Measurement of urine neutrophil gelatinase– associated lipocalin (uNGAL) was determined individually by ELISA kit and in combination with the RAI which is calculated in each critically ill child for severe AKI. Statistical analysis was done for these data.
Results: Individual uNGAL demonstrated marginal discrimination for severe AKI (area under curve [AUC]: NGAL, 0.877), little higher than prediction by RAI (AUC=0.847). Incorporation of uNGAL significantly added to the renal angina index AKI prediction (AUC=0.847, increased to 0.893).
Conclusion: This study shows that incorporation of uNGAL into the RAI improves detection ability of severe AKI in critically ill children.
Chronic fatigue syndrome (CFS) is a poorly-understood respiratory condition that affects millions of individuals. Hyperbaric oxygen therapy (HBOT) is a treatment option being considered to address CFS as it is suggested to combat fatigue and increase oxygenation. HBOT provides two opportunities in advancing research of CFS: it may provide data on symptom amelioration and be utilized in the search for a biomarker. By either identifying biomarkers before using HBOT to compare epigenomes of patients before and after treatment or using HBOT to find epigenetic discrepancies between patients with and without treatment, matching epigenetic regulation with symptom amelioration may significantly advance the understanding of the etiology and treatment mechanism for CFS. EPAS1/HIF-2α is a leading candidate for an epigenetic biomarker as it responds differentially to hypoxic and normoxic conditions, which degrades more slowly in hypoxic conditions. Epigenetic regulation of EPAS1/HIF-2α in such differential conditions may be explored in HBOT experiments. In addition to HBOT as a promising treatment option for CFS symptoms, it may aid the identification of biomarkers in CFS. Further research into both outcomes is strongly encouraged.
Allogeneic hematopoietic stem cell transplant (alloHSCT) is a curative treatment for many hematologic malignancies. Unfortunately, about 30-50% of all recipients undergoing alloHSCT develop acute graft-versus-host-disease (aGVHD), which is associated with high morbidity and mortality [1,2]. Treatment of aGVHD involves the use of immune suppressive drugs such as high dose of steroids that leads to further immunosuppression and risk for opportunistic infections. Often patients are refractory to steroids therapy making the prognosis dismal. Thus, it is critical to identify robust biomarkers to detect aGVHD before onset of clinical symptoms so that therapeutic strategies can be implemented that may result in better treatment responses and less toxicity.
Nehomar Pajaro Galvis*, Jorge Rico-Fontalvo, Rodrigo Daza-Arnedo, Maria Ximena Cardona-Blanco, Emilio Abuabara-Franco, Victor Leal-Martínez, Jose Cabrales-Juan, José Correa-Guerrero, José Bohórquez-Rivero, José Sáenz-López, José Restom-Arrieta, Milton Rivera-Moreno, Estefany Rivera-Moreno, Maria Monterrosa-Robles, Alonso Pomares-Lara, Dayana Ayola-Rosales and Ana Alonso-Henriquez
Acute kidney injury is a common condition associated with high morbidity and short-term mortality. Its pathophysiology varies according to the numerous conditions associated with its genesis. Biomarkers allow detecting changes at the level of kidney function; therefore, they play an important role in the prevention, early diagnosis, therapeutic response and prognosis of acute kidney injury. The search for biomarkers for acute kidney injury began over 15 years ago; initially, only serum creatinine was available for diagnosis. However, throughout history, great advances have been made in research, which have allowed the finding of new biomarkers in order to improve the health and quality of life of patients. A narrative review of the literature is carried out on the basis of available scientific evidence to clarify the role and importance of biomarkers in the context of acute renal injury.
Severe Acute Kidney Injury (AKI) is a common, serious problem affecting critically ill children that lacks effective treatment options. Currently, there are no treatment options for AKI other than supportive care. Continuous renal replacement therapy (CRRT) is employed to reduce Fluid Overload (FO) burden and treat metabolic disturbances in AKI. Identifying patients upon admission who may require CRRT has potential clinical care implications. The aim of this study was to determine if the RAI had diagnostic capabilities to identify patients who would require CRRT.
The analytic cohort consisted of patients who required CRRT and illness severity score matched controls who did not require CRRT at a single center. Patients who required CRRT had higher mortality rates, length of stay, and use of ventilatory and inotropic support. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) assessed and compared the discriminatory accuracy of three scores: 1) the renal angina index (RAI), 2) serum-creatinine (sCr) based AKI on day 0 and 3) modified RAI created with an additional RAI injury tranche that corresponded to severe stage 3 AKI sCr elevation.
Compared to Day0AKI (AUC 0.78, 0.70-0.87; sensitivity 0.63, 0.45-0.79; specificity 0.93, 0.870.97) and RAI (AUC 0.76, 0.69-0.82; sensitivity 0.94, 0.81-0.99; specificity 0.57, 0.47-0.66), the modified RAI had the highest AUC (0.79; 0.72-0.85) with a high sensitivity (0.91; 0.77-0.98) and moderate specificity (0.65; 0.56-0.75) for prediction of CRRT requirements. As a more accurate tool for discriminating patients in need of CRRT, a modified RAI has numerous potential implications. Identifying patients who ultimately require CRRT at an earlier timepoint may influence timing of CRRT initiation in an attempt to avoid further FO, or may influence nephrotoxin administration. The diagnostic capabilities of the modified RAI may be refined by the addition of urinary biomarkers. These findings should be validated in a larger cohort.
Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.
In this study we describe a method for the detection of biomolecules (in the polypeptide m/z range) directly from the surface of plant leaves by using Mass Spectrometry Imaging. The plant-pathogen interaction between Arabidopsis thaliana and the bacterium Xanthomonas campestris pv. campestris was analyzed by comparing infected and non-infected leaf discs submitted to mass spectrometry. The total surface area of ion distribution was calculated for both samples, revealing 23 ions, out of which 3 showed statistical significance. Although these ions were not identified, the results showed that this approach can be successfully applied for the detection of potential polypeptide biomarkers directly on leaf tissue, which is a major challenge in MALDI-Imaging studies.
Background: Perinatal asphyxia (PA) which may result in hypoxic ischaemic encephalopathy (HIE) affects four million neonates worldwide and accounts for the death of one million of affected babies. The science of metabolomics has become an area of growing interest in neonatal research, with a potential role in identifying useful biomarkers that can accurately predict injury severity in perinatal asphyxia and HIE.The aim of this review is to look at the evidence of the usefulness of urine metabolomics in predicting outcome in PA/HIE. Methods: The key words used in the advanced search ‘urine metabolomics’ AND ‘perinatal asphyxia’ OR ‘hypoxic ischaemic encephalopathy’, yielded 13 articles. Results: Of the selected thirteen studies, 38% (n = 5) were human studies, 31% (n = 4) were animal studies and 31% (n = 4) were review articles. The studies confirmed the involvement of known pathways in the development of PA/HIE, primarily the Krebs cycle evidenced by accumulation of TCA cycle intermediates (citrate, α-ketoglutarate, succinate) and anaerobic pathways indicated by increased lactate. Other pathways involved include amino acid and carbohydrate pathways. Conclusion: Metabolomic studies so far are promising in highlighting potential biomarker profiles in PA/HIE. Further research is necessary to further clarify the role of identified metabolites in predicting outcome and prognosis in neonates affected by PA/HIE.
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