A Magnetic Bead-Based Sensor for the Quantification of Multiple Prostate Cancer Biomarkers.

Novel biomarker assays and upgraded analytical tools are urgently needed to accurately discriminate benign prostatic hypertrophy (BPH) from prostate cancer (CaP). To address this unmet clinical need, we report a piezeoelectric/magnetic bead-based assay to quantitate prostate specific antigen (PSA; free and total), prostatic acid phosphatase, carbonic anhydrase 1 (CA1), osteonectin, IL-6 soluble receptor (IL-6sr), and spondin-2. We used the sensor to measure these seven proteins in serum samples from 120 benign prostate hypertrophy patients and 100 Gleason score 6 and 7 CaP using serum samples previously collected and banked. The results were analyzed with receiver operator characteristic curve analysis. There were significant differences between BPH and CaP patients in the PSA, CA1, and spondin-2 assays. The highest AUC discrimination was achieved with a spondin-2 OR free/total PSA operation--the area under the curve was 0.84 with a p value below 10(-6). Some of these data seem to contradict previous reports and highlight the importance of sample selection and proper assay building in the development of biomarker measurement schemes. This bead-based system offers important advantages in assay building including low cost, high throughput, and rapid identification of an optimal matched antibody pair

Diagnostic value of combined serum biomarkers for the evaluation of liver fibrosis in chronic hepatitis C infection: A multicenter, noninterventional, observational study

Background/Aims: The hepatitis C virus (HCV) infection is important cause of chronic hepatitis. Liver biopsy is considered the gold standard for assessment of fibrosis but this procedure is an invasive procedure. We aimed to evaluate the diagnostic efficiency of non-invasive serum biomarkers, separately and in combinations, on liver fibrosis in treatment-naive chronic hepatitis C (CHC) patients. Materials and Methods: Two hundred and sixteen treatment-naive CHC patients were enrolled from 32 locations across Turkey in this open-labelled, non-interventional prospective observational study. FibroTest®, aspartate aminotransferase-to-platelet ratio index(APRI), aspartate aminotransferase and alanine aminotransferase ratio (AAR), fibrosis index based on four factors (FIB-4), Age-platelet(AP) index and Forns index were measured and compared with Metavir scores got from liver biopsies. Results: Data from 182 patients with baseline liver biopsy were suitable for analysis. One hundred and twenty patients (65.9%) had F0-F1 fibrosis and 62 patients (34.1%) had F2-F4 fibrosis. APRI 0.732 area under the curve(AUC) indicated advanced fibrosis with 69% sensitivity and 77% specificity. FIB-4 0.732 AUC and FibroTest 0.715 AUC indicated advanced fibrosis with 69% and 78.4% sensitivity, and 75% and 71.4% specificity, respectively. The combined use of tests also led to an increase in AUC and specificity. Combinations of FibroTest with APRI and/or FIB-4, and FIB-4 with APRI were optimal for the evaluation of liver fibrosis. Conclusion: Fibrotest, FIB-4, APRI, AP index and Forns index exhibit good diagnostic performance for determining liver fibrosis in CHC patients, and the use of at least two tests together will increase their diagnostic value still further. © Copyright 2018 by The Turkish Society of Gastroenterology

New serum biomarker for rheumatoid arthritis

Development of hypercellular invasive pannus tissue within synovial joints is a hallmark of Rheumatoid Arthritis (RA). Pannus produces proteases that damage bone and cartilage. Non-invasive monitoring of pannus activity is important for clinical assessment of patients as well as for control of the efficacy of therapeutic interventions. Available biomarkers are not satisfactory in terms of pannus specificity and sensitivity for monitoring local inflammation and bone erosion. Our goal is collecting clinical samples of synovial fluid and plasma from patients with RA and/or osteoarthritis (OA) to study the role of WNT signaling in pannus formation and developing set of serum biomarkers to monitor pannus activity

Thiopurines are negatively associated with anthropometric parameters in pediatric Crohn's disease.

AimTo determine the distribution of anthropometric parameter (AP)-z-scores and characterize associations between medications/serum biomarkers and AP-z-scores in pediatric Crohn's disease (CD).MethodsCD patients [< chronological age (CA) 21 years] were enrolled in a cross-sectional study. Descriptive statistics were generated for participants' demographic characteristics and key variables of interest. Paired t-tests were used to compare AP-z-scores calculated based on CA (CA z-scores) and bone age (BA) (BA z-scores) for interpretation of AP's. Linear regression was utilized to examine associations between medications and serum biomarkers with AP-z-scores calculated based on CA (n = 82) and BA (n = 49). We reported regression coefficients as well as their corresponding p-values and 95% confidence intervals.ResultsMean CA at the time of the study visit was 15.3 ± 3.5 (SD; range = 4.8-20.7) years. Mean triceps skinfold (P = 0.039), subscapular skinfold (P = 0.002) and mid-arm circumference (MAC) (P = 0.001) BA z-scores were higher than corresponding CA z-scores. Medications were positively associated with subscapular skinfold [adalimumab (P = 0.018) and methotrexate (P = 0.027)] and BMI CA z-scores [adalimumab (P = 0.029)]. Azathioprine/6-mercaptopurine were negatively associated with MAC (P = 0.045), subscapular skinfold (P = 0.014), weight (P = 0.002) and BMI (P = 0.013) CA z-scores. ESR, CRP, and WBC count were negatively associated, while albumin and IGF-1 BA z-scores were positively associated, with specific AP z-scores (P < 0.05). Mean height CA z-scores were higher in females, not males, treated with infliximab (P = 0.038). Hemoglobin (P = 0.018) was positively associated, while platelets (P = 0.005), ESR (P = 0.003) and CRP (P = 0.039) were negatively associated with height CA z-scores in males, not females.ConclusionOur results suggest poor efficacy of thiopurines and a possible sex difference in statural growth response to infliximab in pediatric CD. Prospective longitudinal studies are required

Interleukin-8 predicts fatigue at 12 months post-injury in children with traumatic brain injury

Despite many children experiencing fatigue after childhood brain injury, little is known about the predictors of this complaint. To date, traditional indices of traumatic brain injury (TBI) severity have not reliably predicted persisting fatigue (up to 3 years post‐injury). This study aimed to establish if persisting fatigue is predicted by serum biomarker concentrations in child TBI. We examined if acute serum biomarker expression would improve prediction models of 12‐month fatigue based on injury severity. Blood samples were collected from 87 children (1 – 17 years at injury) sustaining mild to severe TBI (GCS range 3‐15; mean 12.43; classified as mild TBI (n=50, 57%) vs moderate/severe TBI n=37, 43%), and presenting to the Emergency Departments (ED) and Pediatric Intensive Care Units (PICU) at one of three tertiary pediatric hospitals (Royal Children’s Hospital (RCH); Hospital for Sick Children (HSC), Toronto St Justine Children’s Hospital (SJH), Montreal). Six serum biomarker concentrations were measured within 24 hours of injury [interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), soluble vascular cell adhesion molecule (SVCAM), S100 calcium binding protein B (S100B), neuron specific enolase (NSE), and soluble neural cell adhesion molecule (sNCAM)]. Fatigue at 12 months post‐injury was measured using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (parent report), classified as present/absent using previously derived cut‐points. At 12 months post‐injury, 22% of participants experienced fatigue. A model including interleukin‐8 (IL‐8) was the best serum biomarker for estimating the probability of children experiencing fatigue at 12 months post‐injury. IL‐8 also significantly improved predictive models of fatigue based on severity

Non-skeletal activities of vitamin d: From physiology to brain pathology

Vitamin D is a secosteroid hormone regulating the expression of almost 900 genes, and it is involved in the regulation of calcium and phosphate metabolism, immune response, and brain development. Low blood vitamin D levels have been reported in patients affected by various diseases. Despite a large amount of literature data, there is uncertainty surrounding the role of vitamin D as a serum biomarker in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Indeed, the lack of internationally recognized 25(OH)D3 reference measurement procedures and standard materials in the past led to unstandardized serum total 25(OH)D3 results among research and clinical care laboratories. Thus, most of the literature studies reported unstandardized data, which are of little use and make it difficult to draw conclusions of the role of vitamin D in AD and PD. This review summarizes the extra-skeletal actions of vitamin D, focusing its role in immunomodulation and brain function, and reports the issue of lacking standardized literature data concerning the usefulness of vitamin D as a biomarker in AD and PD

Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome.

Body fluid biomarkers of central nervous system damage may help improve the prognostic and diagnostic accuracy in ischemic stroke. We studied 53 patients. Stroke severity and outcome was rated using the National Institutes of Health Stroke Scale and modified Rankin scale. Ferritin, S100B, and NfH were measured in cerebrospinal fluid (CSF) and serum. Infarct volume was calculated from T2W images. CSF S100B (median 1.00 ng/mL) and CSF ferritin (10.0 ng/mL) levels were elevated in patients with stroke compared with control subjects (0.62 ng/mL, P < .0001; 2.34 ng/mL, P < .0001). Serum S100B (0.09 ng/mL) was higher in patients with stroke compared with control subjects (0.01 ng/mL). CSF S100B levels were higher in patients with a cardioembolic stroke (2.88 ng/mL) than in those with small-vessel disease (0.89 ng/mL, P < .05). CSF S100B levels correlated with the National Institutes of Health Stroke Scale score on admission (R = 0.56, P < .01) and the stroke volume (R = 0.44, P = .01). CSF S100B and NfH-SMI35 levels correlated with outcome on the modified Rankin scale. CSF S100B levels were related to stroke severity and infarct volume and highest in cardioembolic stroke

Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.

IntroductionPrevious studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury.MethodsNon-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40&nbsp;μg/kg/dose), high-dose ALN (1,000&nbsp;μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56&nbsp;days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption.ResultsμCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14&nbsp;days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56&nbsp;days post-injury, and was able to partially preserve articular cartilage 14&nbsp;days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56&nbsp;days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14&nbsp;days post-injury, with no change in bone formation at any time points.ConclusionsHigh-dose ALN treatment was able to prevent early trabecular bone loss and cartilage degeneration following non-invasive knee injury, but was not able to mitigate long-term joint degeneration. These data contribute to understanding the effect of bisphosphonates on the development of osteoarthritis, and may support the use of anti-resorptive drugs to prevent joint degeneration following injury, although further investigation is warranted

Identification of a serum biomarker panel for the differential diagnosis of cholangiocarcinoma and primary sclerosing cholagnitis

The non-invasive differentiation of malignant and benign biliary disease is a clinical challenge. Carbohydrate antigen 19-9 (CA19-9), leucine-rich α2-glycoprotein (LRG1), interleukin 6 (IL6), pyruvate kinase M2 (PKM2), cytokeratin 19 fragment (CYFRA21.1) and mucin 5AC (MUC5AC) have reported utility for differentiating cholangiocarcinoma (CCA) from benign biliary disease. Herein, serum levels of these markers were tested in 66 cases of CCA and 62 cases of primary sclerosing cholangitis (PSC) and compared with markers of liver function and inflammation. Markers panels were assessed for their ability to discriminate malignant and benign disease. Several of the markers were also assessed in pre-diagnosis biliary tract cancer (BTC) samples with performances evaluated at different times prior to diagnosis. We show that LRG1 and IL6 were unable to accurately distinguish CCA from PSC, whereas CA19-9, PKM2, CYFRA21.1 and MUC5AC were significantly elevated in malignancy. Area under the receiver operating characteristic curves for these individual markers ranged from 0.73–0.84, with the best single marker (PKM2) providing 61% sensitivity at 90% specificity. A panel combining PKM2, CYFRA21.1 and MUC5AC gave 76% sensitivity at 90% specificity, which increased to 82% sensitivity by adding gamma-glutamyltransferase (GGT). In the pre-diagnosis setting, LRG1, IL6 and PKM2 were poor predictors of BTC, whilst CA19-9 and C-reactive protein were elevated up to 2 years before diagnosis. In conclusion, LRG1, IL6 and PKM2 were not useful for early detection of BTC, whilst a model combining PKM2, CYFRA21.1, MUC5AC and GGT was beneficial in differentiating malignant from benign biliary disease, warranting validation in a prospective trial