High pre-transplant serum nitrate levels predict risk of acute steroid-refractory graft-versus-host disease in the absence of statin therapy

PubMed Central

Dietrich, Sascha; Okun, Jürgen G.; Schmidt, Kathrin; Falk, Christine S.; Wagner, Andreas H.; Karamustafa, Suzan; Radujkovic, Aleksandar; Hegenbart, Ute; Ho, Anthony D.; Dreger, Peter; Luft, Thomas

2014-01-01

Steroid-refractory graft-versus-host disease is a life-threatening complication after allogeneic stem cell transplantation. Evidence is accumulating that steroid-refractory graft-versus-host disease is associated with endothelial distress. Endothelial cell homeostasis is regulated by nitric oxide, and serum nitrates are derived from nitric oxide synthase activity or dietary sources. In this retrospective study based on 417 patients allografted at our institution we investigated whether quantification of serum nitrates could predict steroid-refractory graft-versus-host disease. Elevated pre-transplant levels of serum nitrates (>26.5 μM) predicted steroid-refractory graft-versus-host disease (P=0.026) and non-relapse mortality (P=0.028), particularly in combination with high pre-transplant angiopoietin-2 levels (P=0.0007 and P=0.021, respectively). Multivariate analyses confirmed serum nitrates as independent predictors of steroid-refractory graft-versus-host disease and non-relapse mortality. Differences in serum nitrate levels did not correlate with serum levels of tumor necrosis factor or C-reactive protein or expression of inducible nitric oxide synthase in blood cells. Patients with high pre-transplant nitrate levels had significantly reduced rates of refractory graft-versus-host disease (P=0.031) when pravastatin was taken. In summary, patients at high risk of developing steroid-refractory graft-versus-host disease could be identified prior to transplantation by serum markers linked to endothelial cell function. Retrospectively, statin medication was associated with a reduced incidence of refractory graft-versus-host disease in this endothelial high-risk cohort. PMID:24142995

Can Serum Albumin Level and Total Lymphocyte Count be Surrogates for Malnutrition to Predict Wound Complications After Total Knee Arthroplasty?

PubMed

Morey, Vivek M; Song, Young Dong; Whang, Ji Sup; Kang, Yeon Gwi; Kim, Tae Kyun

2016-06-01

Although the serum albumin level and total lymphocyte count (TLC) have been reported as valid and reliable markers for defining malnutrition, their cutoff levels and predictive values for wound complications in patients undergoing total knee arthroplasty (TKA) remain questionable. A total of 3169 TKAs performed between April 2003 and December 2013 were retrospectively reviewed. We determined the prevalence of malnutrition on applying different definitions, with various cutoff values of serum albumin and TLC and analyzed the variations in outcome. The differences between groups with and without malnutrition in terms of functional outcome and complications were determined using Student's t test and analysis of variance. Multivariate logistic regression analysis was conducted to identify the independent risk factors. Among all the patients (N = 3169), the serum albumin level and TLC varied widely, with means of 4.1 g/dL and 2189 cells/mm(3), respectively. The prevalence of malnutrition (21%) as per the conventional definition (serum albumin level <3.5 g/dL or a serum TLC <1500 cells/mm(3)) dropped to only 1.6% when malnutrition was defined as serum albumin <3.5 g/dL "and" TLC <1500/mm(3), indicating a very small overlap between the 2 markers. No differences were observed between 2 groups in functional outcomes and incidence of wound complications. Our findings call into question the values of serum albumin level and TLC as a surrogate of malnutrition for predicting wound complications after TKA. Copyright © 2015 Elsevier Inc. All rights reserved.

Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective

PubMed Central

Fisher, W.; Wang, Jian; George, Nysia I.; Gearhart, Jeffery M.; McLanahan, Eva D.

2016-01-01

The Institute of Medicine recommends that lactating women ingest 290 μg iodide/d and a nursing infant, less than two years of age, 110 μg/d. The World Health Organization, United Nations Children’s Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 μg/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150–180 μg/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 μg iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 μg/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 μg/L and the predicted average breast milk iodide concentration, 157 μg/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately predicted for most data. For moderate iodide deficient conditions, where dietary iodide intake may range from 50 to 150 μg/d for the lactating mother, the model satisfactorily described the iodide measurements, although with some variation, in urine and breast milk. Predictions of serum thyroid hormones in moderately iodide deficient lactating women (50 μg/d) and nursing infants did not closely agree with mean reported serum thyroid hormone levels, however, predictions were usually within a factor of two. Excellent agreement between prediction and observation was obtained for a recent moderate iodide deficiency study in lactating women. Measurements included iodide levels in urine of infant and mother, iodide in breast milk, and serum thyroid hormone levels in infant and mother. A maternal iodide intake of 50 μg/d resulted in a predicted 29–32% reduction in serum T4 and fT4 in nursing infants, however the reduced serum levels of T4 and fT4 were within most of the published reference intervals for infant. This biologically based model is an important first step at integrating the rapid changes that occur in the thyroid system of the nursing newborn in order to predict adverse outcomes from exposure to thyroid acting chemicals, drugs, radioactive materials or iodine deficiency. PMID:26930410

Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective.

PubMed

Fisher, W; Wang, Jian; George, Nysia I; Gearhart, Jeffery M; McLanahan, Eva D

2016-01-01

The Institute of Medicine recommends that lactating women ingest 290 μg iodide/d and a nursing infant, less than two years of age, 110 μg/d. The World Health Organization, United Nations Children's Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 μg/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150-180 μg/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 μg iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 μg/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 μg/L and the predicted average breast milk iodide concentration, 157 μg/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately predicted for most data. For moderate iodide deficient conditions, where dietary iodide intake may range from 50 to 150 μg/d for the lactating mother, the model satisfactorily described the iodide measurements, although with some variation, in urine and breast milk. Predictions of serum thyroid hormones in moderately iodide deficient lactating women (50 μg/d) and nursing infants did not closely agree with mean reported serum thyroid hormone levels, however, predictions were usually within a factor of two. Excellent agreement between prediction and observation was obtained for a recent moderate iodide deficiency study in lactating women. Measurements included iodide levels in urine of infant and mother, iodide in breast milk, and serum thyroid hormone levels in infant and mother. A maternal iodide intake of 50 μg/d resulted in a predicted 29-32% reduction in serum T4 and fT4 in nursing infants, however the reduced serum levels of T4 and fT4 were within most of the published reference intervals for infant. This biologically based model is an important first step at integrating the rapid changes that occur in the thyroid system of the nursing newborn in order to predict adverse outcomes from exposure to thyroid acting chemicals, drugs, radioactive materials or iodine deficiency.

Serum HBV RNA as a Predictor of Peginterferon Alfa-2a (40KD) Response in Patients With HBeAg-Positive Chronic Hepatitis B.

PubMed

van Bömmel, Florian; van Bömmel, Alena; Krauel, Alexander; Wat, Cynthia; Pavlovic, Vedran; Yang, Lei; Deichsel, Danilo; Berg, Thomas; Böhm, Stephan

2018-05-08

Hepatitis B virus (HBV) RNA is a novel serum biomarker that has the potential to predict treatment response in patients with chronic hepatitis B. We explored whether HBV RNA serum levels can predict hepatitis B e antigen (HBeAg) seroconversion in patients treated with peginterferon alfa-2a. Serum samples from HBeAg-positive patients previously treated with peginterferon alfa-2a in two large randomized controlled trials were retrospectively analyzed. HBV RNA levels were measured using a real-time polymerase chain reaction assay. Ability of individual biomarkers to predict HBeAg seroconversion at 24 weeks post-treatment was evaluated using receiver operating characteristics (ROC) analyses. The study included 131 subjects (70% male, 96% Asians, 35% HBV genotypes B and 61% C), 76 treated with peginterferon alfa-2a alone and 55 in combination with LAM. Median HBV RNA levels were significantly lower, at all time points, in patients achieving HBeAg seroconversion. Levels of HBV RNA at treatment weeks 12 and 24 showed good ability to predict HBeAg seroconversion (AUROC scores >0.75, p<0.001). A HBV RNA cutoff of >5.5 log10 copies/mL identified 30% of non-responders at week 12 (negative predictive value >90%). Serum HBV RNA is an early predictor of HBeAg seroconversion in patients treated with peginterferon alfa-2a.

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves’ disease

PubMed Central

Kimura, Shihori; Takano, Noriyoshi; Yamashita, Kaoru; Seki, Yasufumi; Bokuda, Kanako; Yatabe, Midori; Yatabe, Junichi; Watanabe, Daisuke; Ando, Takashi

2018-01-01

Antithyroid drugs are generally selected as the first-line treatment for Graves’ Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves’ disease than in control subjects (P<0.005) and were significantly reduced after medical treatment for Graves’ disease. High serum s(P)RR levels were associated with resistance to antithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves’ disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves’ disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss. PMID:29621332

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves' disease.

PubMed

Mizuguchi, Yuki; Morimoto, Satoshi; Kimura, Shihori; Takano, Noriyoshi; Yamashita, Kaoru; Seki, Yasufumi; Bokuda, Kanako; Yatabe, Midori; Yatabe, Junichi; Watanabe, Daisuke; Ando, Takashi; Ichihara, Atsuhiro

2018-01-01

Antithyroid drugs are generally selected as the first-line treatment for Graves' Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves' disease than in control subjects (P<0.005) and were significantly reduced after medical treatment for Graves' disease. High serum s(P)RR levels were associated with resistance to antithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves' disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves' disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss.

Serum soluble CD30 in early arthritis: a sign of inflammation but not a predictor of outcome.

PubMed

Savolainen, E; Matinlauri, I; Kautiainen, H; Luosujärvi, R; Kaipiainen-Seppänen, O

2008-01-01

To evaluate serum soluble CD30 levels (sCD30) in an early arthritis series and assess their ability to predict the outcome in patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA) at one year follow-up. Serum sCD30 levels were measured by ELISA from 92 adult patients with RA and UA at baseline and from 60 adult controls. The patients were followed up for one year in the Kuopio 2000 Arthritis Survey. Receiver operating characteristic (ROC) curves were constructed to determine cut off points of sCD30 in RA and UA that select the inflammatory disease from controls. Sensitivity, specificity and positive likelihood ratio, and their 95 % CIs were calculated for sCD30 levels in RA and UA. Median serum sCD30 levels were higher in RA 25.1 (IQ range 16.3-38.6) IU/ml (p<0.001) and in UA 23.4 (15.4-35.6) IU/ml (p<0.001) than in controls 15.1 (10.7-20.8) IU/ml. No differences were recorded between RA and UA (p=0.840). Serum sCD30 levels at baseline did not predict remission at one year follow-up. Serum sCD30 levels were higher in RA and UA than in controls at baseline but they did not predict remission at one year follow-up in this series.

Prostate cancer prediction using the random forest algorithm that takes into account transrectal ultrasound findings, age, and serum levels of prostate-specific antigen.

PubMed

Xiao, Li-Hong; Chen, Pei-Ran; Gou, Zhong-Ping; Li, Yong-Zhong; Li, Mei; Xiang, Liang-Cheng; Feng, Ping

2017-01-01

The aim of this study is to evaluate the ability of the random forest algorithm that combines data on transrectal ultrasound findings, age, and serum levels of prostate-specific antigen to predict prostate carcinoma. Clinico-demographic data were analyzed for 941 patients with prostate diseases treated at our hospital, including age, serum prostate-specific antigen levels, transrectal ultrasound findings, and pathology diagnosis based on ultrasound-guided needle biopsy of the prostate. These data were compared between patients with and without prostate cancer using the Chi-square test, and then entered into the random forest model to predict diagnosis. Patients with and without prostate cancer differed significantly in age and serum prostate-specific antigen levels (P < 0.001), as well as in all transrectal ultrasound characteristics (P < 0.05) except uneven echo (P = 0.609). The random forest model based on age, prostate-specific antigen and ultrasound predicted prostate cancer with an accuracy of 83.10%, sensitivity of 65.64%, and specificity of 93.83%. Positive predictive value was 86.72%, and negative predictive value was 81.64%. By integrating age, prostate-specific antigen levels and transrectal ultrasound findings, the random forest algorithm shows better diagnostic performance for prostate cancer than either diagnostic indicator on its own. This algorithm may help improve diagnosis of the disease by identifying patients at high risk for biopsy.

[Role of parathyroid hormone measurement in prediction for symptomatic hypocalcaemia after total thyroidectomy].

PubMed

An, Chang-ming; Tang, Ping-zhang; Xu, Zhen-gang; Zhang, Bin; Zhang, Zong-min; Yan, Dan-gui; Li, Zheng-jiang

2010-03-01

To evaluate the role of parathyroid hormone (PTH) and serum calcium in prediction for hypocalcaemia after total thyroidectomy. One hundred and sixty-five patients undergoing total or complete total thyroidectomy were reviewed retrospectively. The indications included bilateral carcinoma, undifferential carcinoma, surroundings invasion, distant metastasis and huge benign lesions. Preoperative and postoperative PTH, calcium concentrations and their decline levels were compared between Jan. 2005 and May 2009. The role of PTH value and decline level predicting for symptomatic hypocalcaemia were analyzed by receiver operator characteristics (ROC) curve. After total thyroidectomy, 85 patients (51.5%) developed hypocalcemia. Symptoms were reported by 36 patients (21.8%). The mean concentration of PTH for normocalcaemia (80 cases), asymptomatic hypocalcaemia (49 cases) and symptomatic patients (36 cases) were 31.0 ng/L, 19.6 ng/L and 11.9 ng/L, respectively. The mean decline level for the three groups were 28.6%, 52.6% and 78.0%, respectively. PTH value and its decline level had a poor predicting value for symptomatic hypocalcaemia and high negative predicting value for asymptomatic patients. The serum calcium concentration more than 2.0 mmol/L, PTH level higher than 15 ng/L and PTH decline less than 50% had the good negative predicting value of 97.6%, 90.3% and 96.5%, respectively. Postoperative PTH and its decline level were significantly correlated with postoperative serum calcium concentration but had a low accuracy for predicting symptomatic hypocalcaemia. The serum calcium concentration more than 2.0 mmol/L, PTH level higher than 15 ng/L and PTH decline less than 50% had the good predicting value for asymptomatic patients. Calcium should be routinely supplemented in the first 24 h after total thyroidectomy to reduce the rate of hypocalcemia and the severity of hypocalcemia symptoms.

Cervical mucus and serum estradiol as predictors of response to progestin challenge.

PubMed

Rarick, L D; Shangold, M M; Ahmed, S W

1990-08-01

The present study was undertaken to assess the correlation between and relative predictive value of each of the following variables and progestin-induced withdrawal bleeding: cervical mucus appearance, serum E2 level, patient age, duration of amenorrhea, smoking and exercise habits, and body composition. Of 120 oligomenorrheic and amenorrheic women evaluated, only cervical mucus appearance and serum E2 level were significantly associated with response to progestin challenge. A multivariate logistical regression analysis showed cervical mucus to be the most predictive variable followed by serum E2 level. No absolute E2 level was found to discriminate between those who did and those who did not have withdrawal bleeding after progestin challenge. These data suggest that office examination of cervical mucus may be a useful indicator and guideline in planning therapy.

Serum Concentrations of New Predictive Cardiovascular Disease Biomarkers in Mexican Women Exposed to Lead.

PubMed

Ochoa-Martínez, Ángeles C; Cardona-Lozano, Elvia D; Carrizales-Yáñez, Leticia; Pérez-Maldonado, Iván N

2018-02-01

The purpose of this study was to evaluate lead exposure and its relationship with serum levels of predictive CVD biomarkers [asymmetric dimethylarginine (ADMA), adipocyte fatty acid-binding protein (FABP4), adiponectin, and chemerin] in women living in San Luis Potosi, Mexico. A mean blood lead level (BLL) of 11.5 ± 9.00 μg/dL (mean ± standard deviation) was found after all blood samples were analyzed. Regarding serum predictive CVD biomarkers, mean serum level of 0.68 ± 0.38 μmol/L, 20.5 ± 16.5 ng/mL, 12.5 ± 3.30 μg/mL, and 255 ± 130 ng/mL were found for ADMA, FABP4, adiponectin, and chemerin, respectively. Simple significant associations (Pearson´s correlations) between BLL and ADMA (r = 0.17; p = 0.04) and FABP4 (r = 0.23; p = 0.03) were found. Furthermore, a multivariate linear regression model showed that BLL was a significant predictor of serum ADMA (β = 0.06; p = 0.001) and FABP4 (β = 1.75; p = 0.0004) concentrations after adjusting by confounders. For serum chemerin and adiponectin levels, no associations were found with BLL. In conclusion, high serum ADMA and FABP4 (predictive CVD biomarkers) levels were found in women exposed to lead. Consequently, this research can be used as a point of departure for the prevention of CVD events in populations living in sites environmentally impacted with lead.

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

The genetics of hyperuricaemia and gout

PubMed Central

Reginato, Anthony M.; Mount, David B.; Yang, Irene; Choi, Hyon K.

2013-01-01

Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This Review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9, ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular–metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B*5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B*5801 alleles could be used to predict these potentially fatal adverse effects. PMID:22945592

Prognostic value of serum thioredoxin levels in ischemic stroke.

PubMed

Yu, Tieer; Zhang, Wanli; Lin, Yuanshao; Li, Qian; Xue, Jie; Cai, Zhengyi; Cheng, Yifan; Shao, Bei

2017-11-01

Thioredoxin (Trx) is one of significant antioxidative molecules to diminish oxidative stress. Current evidence suggests that Trx is a potent antioxidant with cytoprotective functions. The aim of our study was to investigate specifically the association between serum Trx levels and acute ischemic stroke (AIS) patients. 198 AIS patients and 75 controls were enrolled to the study. Serum Trx levels were measured using an enzyme-linked immunosorbent assay (ELISA). Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS) score on admission. Clinical endpoint was functional outcome measured by Barthel Index (BI) 3 months after admission. Multivariate binary logistic regression analyses were performed to identify predictors. We found that serum Trx levels were significantly increased in patients as compared to controls. Serum Trx was an independent biomarker to predict ischemic stroke (OR, 1.264; 95% CI, 1.04-1.537; P = 0.019). In addition, there was a negative correlation between NIHSS score at admission and serum Trx levels in cardioembolic stroke patients (r = -0.422; P = 0.013). Furthermore, higher serum Trx levels in AIS patients were associated with favorable functional outcome. Serum Trx was an independent predictor for the functional outcome (OR, 0.862; 95% CI, 0.75-0.991; P = 0.037). Serum Trx might be as a biomarker of cardioembolic stroke severity. Increased serum Trx levels could be a useful tool to predict good prognosis in patients with AIS.

Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

McPherson, Stuart; Henderson, Elsbeth; Burt, Alastair D; Day, Christopher P; Anstee, Quentin M

2014-05-01

A third of the population are estimated to have NAFLD of varying severity. Serum immunoglobulins are frequently elevated in patients with chronic liver disease, but little is known about serum immunoglobulin levels in patients with NAFLD. Aim of this study was to evaluate serum immunoglobulin levels (IgA, IgG, and IgM) in a large cohort of patients with biopsy-proven NAFLD and determine if immunoglobulin levels are associated with clinical or histological features. Patients seen in a tertiary fatty liver clinic between 1999 and 2009 were included. Liver biopsies were assessed using the Kleiner score. Immunoglobulin levels and other blood tests were taken at time of biopsy. 285 patients (110 simple steatosis and 175 NASH) had serum immunoglobulins measured within 6months of liver biopsy. 130 (46%) patients had elevated (>1× upper limit of normal) serum IgA levels, 28 (10%) patients had elevated IgG and 22 (8%) raised IgM. Serum IgA levels were elevated more frequently in patients with NASH compared with subjects with simple steatosis (55% vs. 31%, p<0.001). Overall, 55 (19%) patients had advanced liver fibrosis (Kleiner stage 3-4). There was a significant positive association between serum IgA levels and the stage of fibrosis (p<0.001). Serum IgA, age, platelets, AST/ALT ratio and BMI were all independently with advanced fibrosis following multivariate analysis. A model constructed from these independent predictors accurately predicted advanced fibrosis (AUROC 0.87). The serum IgA level was frequently elevated in patients with NAFLD and was an independent predictor of advanced fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Use of admission serum lactate and sodium levels to predict mortality in necrotizing soft-tissue infections.

PubMed

Yaghoubian, Arezou; de Virgilio, Christian; Dauphine, Christine; Lewis, Roger J; Lin, Matthew

2007-09-01

Simple admission laboratory values can be used to classify patients with necrotizing soft-tissue infection (NSTI) into high and low mortality risk groups. Chart review. Public teaching hospital. All patients with NSTI from 1997 through 2006. Variables analyzed included medical history, admission vital signs, laboratory values, and microbiologic findings. Data analyses included univariate and classification and regression tree analyses. Mortality. One hundred twenty-four patients were identified with NSTI. The overall mortality rate was 21 of 124 (17%). On univariate analysis, factors associated with mortality included a history of cancer (P = .03), intravenous drug abuse (P < .001), low systolic blood pressure on admission (P = .03), base deficit (P = .009), and elevated white blood cell count (P = .06). On exploratory classification and regression tree analysis, admission serum lactate and sodium levels were predictors of mortality, with a sensitivity of 100%, specificity of 28%, positive predictive value of 23%, and negative predictive value of 100%. A serum lactate level greater than or equal to 54.1 mg/dL (6 mmol/L) alone was associated with a 32% mortality, whereas a serum sodium level greater than or equal to 135 mEq/L combined with a lactate level less than 54.1 mg/dL was associated with a mortality of 0%. Mortality for NSTIs remains high. A simple model, using admission serum lactate and serum sodium levels, may help identify patients at greatest risk for death.

Higher serum sTNFR1 level predicts conversion from mild cognitive impairment to Alzheimer's disease.

PubMed

Diniz, Breno Satler; Teixeira, Antonio Lucio; Ojopi, Elida Benquique; Talib, Leda Leme; Mendonça, Vanessa Amaral; Gattaz, Wagner Farid; Forlenza, Orestes Vicente

2010-01-01

The activation of inflammatory cascades has been consistently demonstrated in the pathophysiology of Alzheimer's disease (AD). Among several putative neuroinflammatory mechanisms, the tumor necrosis factor α (TNF-α) signaling system has a central role in this process. Recent evidence indicates that the abnormal production of inflammatory factors may accompany the progression from mild cognitive impairment (MCI) to dementia. We aimed to examine serum levels of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in patients with MCI and AD as compared to cognitively unimpaired elderly subjects. We further aimed to investigate whether abnormal levels of these cytokines predict the progression from MCI to AD upon follow-up. We utilized cross-sectional determination of serum levels of TNF-α, sTNFR1, and sTNFR2 (ELISA method) in a test group comprising 167 older adults (31 AD, 72 MCI, and 64 healthy controls), and longitudinal reassessment of clinical status after 18.9 ± 10.0 months. At baseline, there were no statistically significant differences in serum TNF-α, sTNFR1, and sTNFR2 between patients with MCI and AD as compared to controls. Nevertheless, patients with MCI who progressed to AD had significantly higher serum sTNFR1 levels as opposed to patients who retained the diagnosis of MCI upon follow-up (p = 0.03). Cox regression analysis showed that high serum sTNFR1 levels predicted the conversion from MCI to AD (p = 0.003), whereas no significant differences were found with respect to serum levels of TNF-α and sTNFR2. Abnormal activation of TNF-α signaling system, represented by increased expression of sTNFR1, is associated with a higher risk of progression from MCI to AD.

Serum phosphate predicts temporary hypocalcaemia following thyroidectomy.

PubMed

Sam, Amir H; Dhillo, W S; Donaldson, M; Moolla, A; Meeran, K; Tolley, N S; Palazzo, F F

2011-03-01

Temporary hypocalcaemia occurs in up to 40% of patients following a total thyroidectomy. Serum calcium and parathyroid hormone (PTH) measurements are currently used to predict post-thyroidectomy hypocalcaemia. However, immediate access to PTH measurement is expensive and not widely available. Serum phosphate responds rapidly to changes in circulating PTH levels, and its measurement is readily available in all hospitals. We evaluated the use of serum phosphate to predict temporary hypocalcaemia post-thyroidectomy. We retrospectively assessed 111 consecutive patients who had total or completion thyroidectomy. Patients had serum calcium and phosphate measured preoperatively, on the evening of surgery (day 0), on the morning of day 1 and over the following week as clinically indicated. Serum PTH was measured on the morning of day 1. Vitamin D levels were measured preoperatively. Seventy-six patients did not develop treatment-demanding hypocalcaemia. In these patients, the mean serum phosphate concentration was lower on the morning of day 1 compared to that on the evening of surgery. Seventeen patients with a vitamin D>25 nmol/l developed hypocalcaemia requiring treatment from day 1 onwards. All had an overnight rise in serum phosphate to >1.44 mmol/l (100% sensitivity and specificity for predicting hypocalcaemia). Twelve patients who had a vitamin D<25 nmol/l also developed hypocalcaemia but had an attenuated rise in serum phosphate. Serum phosphate is a reliable biochemical predictor of post-thyroidectomy hypocalcaemia in patients without vitamin D deficiency. The use of serum phosphate may facilitate safe day 1 discharge of patients undergoing thyroidectomy. © 2011 Blackwell Publishing Ltd.

Serum creatinine role in predicting outcome after cardiac surgery beyond acute kidney injury

PubMed Central

Najafi, Mahdi

2014-01-01

Serum creatinine is still the most important determinant in the assessment of perioperative renal function and in the prediction of adverse outcome in cardiac surgery. Many biomarkers have been studied to date; still, there is no surrogate for serum creatinine measurement in clinical practice because it is feasible and inexpensive. High levels of serum creatinine and its equivalents have been the most important preoperative risk factor for postoperative renal injury. Moreover, creatinine is the mainstay in predicting risk models and risk factor reduction has enhanced its importance in outcome prediction. The future perspective is the development of new definitions and novel tools for the early diagnosis of acute kidney injury largely based on serum creatinine and a panel of novel biomarkers. PMID:25276301

Level of soluble CD30 after kidney transplantation correlates with acute rejection episodes.

PubMed

Yang, J L; Hao, H J; Zhang, B; Liu, Y X; Chen, S; Na, Y Q

2008-12-01

Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30 levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31 healthy individuals were selected as a control group. The results showed a relationship between sCD30 level in serum before kidney transplantation and the incidence of ARE. However, the relationship was more significant between serum sCD30 levels at day 7 after kidney transplantation and the incidence of ARE. There was no obvious relationship between serum sCD30 levels at day 28 after kidney transplantation and the incidence of ARE. These results suggested that the level of sCD30 at day 7 posttransplantation provides valuable data to predict ARE.

MMP-7, sFas and FasL serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer.

PubMed

Szarvas, Tibor; Sevcenco, Sabina; Módos, Orsolya; Keresztes, Dávid; Nyirády, Péter; Csizmarik, Anita; Ristl, Robin; Puhr, Martin; Hoffmann, Michèle J; Niedworok, Christian; Hadaschik, Boris; Maj-Hes, Agnieszka; Shariat, Shahrokh F; Kramer, Gero

2018-05-26

To assess the predictive value of pre-chemotherapy MMP-7, sFas, FasL serum levels as well as their changes during therapy. Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 CRPC patients; 21 docetaxel-resistant who received one single series and 75 docetaxel-sensitive who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. Higher pretreatment serum MMP-7, sFas and PSA levels were significantly associated with both docetaxel-resistance (p=0.007, p=0.001, p<0.001, respectively) and shorter cancer-specific survival (p<0.001, p=0.041, p<0.001, respectively). High MMP-7 remained an independent predictor of both docetaxel resistance (HR: 2.298, 95% CI: 1.354-3.899, p=0.002) and poor cancer-specific survival (HR=2.11, 95%Cl 1.36-3.30, p=0.001) in multivariable analyses. Higher increase of MMP-7 levels in the 2 nd treatment holiday and higher increase of PSA levels in the 1 st and 2 nd holidays were predictive of survival. Pretreatment serum MMP-7 levels may help to select CRPC patients who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 alone or in combination with PSA could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Ursodeoxycholic Acid Improves Bilirubin but Not Albumin in Primary Biliary Cirrhosis: Further Evidence for Nonefficacy

PubMed Central

Tsochatzis, Emmanuel A.; Feudjo, Maurille; Rigamonti, Cristina; Vlachogiannakos, Jiannis; Carpenter, James R.; Burroughs, Andrew K.

2013-01-01

Background/Aim. In randomised controlled trials (RCTs) of ursodeoxycholic acid (UDCA), although serum bilirubin is frequently reduced, its effect on disease progression and mortality is unclear. As serum albumin is an established independent prognostic marker, one might expect less deterioration of serum albumin values in a UDCA-treated group. We therefore modelled the typical evolution of serum bilirubin and albumin levels over time in UDCA-untreated patients and compared it with the observed levels in UDCA RCTs. Methods. Multilevel modelling was used to relate the evolution of serum albumin to serum bilirubin and time since patient referral. For each considered RCT, the derived model was used to predict the relationship between final mean serum albumin and bilirubin concentration, adjusted for mean serum albumin at referral and followup duration. Results. Five RCTs were eligible in terms of available data, of which two had long followup. In all trials, serum albumin did not significantly differ between UDCA- and placebo-treated patients, despite the UDCA effect on serum bilirubin. Therefore, there is no evidence over time for changes or maintenance of albumin levels for UDCA-treated patients above the levels predicted for placebo-treated patients. Conclusions. Our findings suggest that UDCA does not alter serum albumin in a way that is consistent with its effect on serum bilirubin. Therefore, reductions in serum bilirubin of UDCA-treated PBC do not parallel another validated and independent prognostic marker, further questioning the validity of serum bilirubin reduction with UDCA as a surrogate therapeutic marker. PMID:23984317

Longitudinal Trend in Lipid Profile of Incident Peritoneal Dialysis Patients is Not Influenced by the Use of Biocompatible Solutions

PubMed Central

Cho, Yeoungjee; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Hawley, Carmel M.; Dimeski, Goce; Clarke, Margaret; Johnson, David W.

2016-01-01

♦ Background: The longitudinal trends of lipid parameters and the impact of biocompatible peritoneal dialysis (PD) solutions on these levels remain to be fully defined. The present study aimed to a) evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solutions on serum lipid parameters, and b) explore the capacity of lipid parameters (total cholesterol [TC], triglyceride [TG], high density lipoprotein [HDL], TC/HDL, low density lipoprotein [LDL], very low density lipoprotein [VLDL]) to predict cardiovascular events (CVE) and mortality in PD patients. ♦ Methods: The study included 175 incident participants from the balANZ trial with at least 1 stored serum sample. A composite CVE score was used as a primary clinical outcome measure. Multilevel linear regression and Poisson regression models were fitted to describe the trend of lipid parameters over time and its ability to predict composite CVE, respectively. ♦ Results: Small but statistically significant increases in serum TG (coefficient 0.006, p < 0.001), TC/HDL (coefficient 0.004, p = 0.001), and VLDL cholesterol (coefficient 0.005, p = 0.001) levels and a decrease in the serum HDL cholesterol levels (coefficient −0.004, p = 0.009) were observed with longer time on PD, whilst the type of PD solution (biocompatible vs standard) received had no significant effect on these levels. Peritoneal dialysis glucose exposure was significantly associated with trends in TG, TC/HDL, HDL and VLDL levels. Baseline lipid parameter levels were not predictive of composite CVEs or all-cause mortality. ♦ Conclusion: Serum TG, TC/HDL, and VLDL levels increased and the serum HDL levels decreased with increasing PD duration. None of the lipid parameters were significantly modified by biocompatible PD solution use over the time period studied or predictive of composite CVE or mortality. PMID:26429421

Pre-operative serum alkaline phosphatase as a predictive indicator of post-operative hypocalcaemia in patients undergoing total thyroidectomy.

PubMed

Miah, M S; Mahendran, S; Mak, C; Leese, G; Smith, D

2015-11-01

This study aimed to evaluate whether a pre-operative elevated serum alkaline phosphatase level is a potential predictor of post-operative hypocalcaemia after total thyroidectomy. Data was retrospectively collected from the case notes of patients who had undergone total thyroidectomy. Patients were divided into Graves' disease and non-Graves' groups. Pre-operative and post-operative biochemical markers, including serum calcium, alkaline phosphatase and parathyroid hormone levels, were reviewed. A total of 225 patients met the inclusion criteria. Graves' disease was the most common indication (n = 134; 59.5 per cent) for thyroidectomy. Post-operative hypocalcaemia developed in 48 patients (21.3 per cent) and raised pre-operative serum alkaline phosphatase was noted in 94 patients (41.8 per cent). Raised pre-operative serum alkaline phosphatase was significantly associated with post-operative hypocalcaemia, particularly in Graves' disease patients (p < 0.05). Pre-operative serum alkaline phosphatase measurements help to predict post-thyroidectomy hypocalcaemia, especially in patients who do not develop hypoparathyroidism. Ascertaining the pre-operative serum alkaline phosphatase level in patients undergoing total thyroidectomy may help surgeons to identify at-risk patients.

ASSOCIATIONS OF ADIPONECTIN, LEPTIN LEVELS, AND THE CHANGE OF BODY COMPOSITION IN PATIENTS ON PERITONEAL DIALYSIS: A PROSPECTIVE COHORT STUDY.

PubMed

Xu, Xiao; Tian, Xue; Chen, Yuan; Yang, Zhi-Kai; Qu, Zhen; Dong, Jie

2018-04-19

Although the association between adipokines such as adiponectin, leptin, and body composition has been noted, whether they could predict the change of fat mass and lean body mass is unknown. We aimed to examine these associations in patients on peritoneal dialysis (PD) through a prospective cohort study. Body composition (by dual-energy x-ray absorptiometry) including fat mass and lean body mass were examined at baseline and then at year 3. Serum leptin and adiponectin levels were measured. Demographic data, comorbidity, biochemical data, inflammation (high-sensitive C-reactive protein [hs-CRP]) and insulin resistance (homeostatic model assessment [HOMA-IR]) were also examined. At baseline, serum adiponectin levels were significantly inversely correlated with weight, lean body mass index (LBMI), fat mass index (FMI), lean body mass (LBM), and fat mass (FM) in 213 prevalent patients. At year 3, FMI, LBMI, FM, and the percentage of FM (FM%) increased while the percentage of LBM (LBM%) significantly decreased despite unchanged weight and LBM among the remaining 112 patients. After adjustment for demographic data, comorbidities, hs-CRP, HOMA-IR, and daily energy intake (DEI), serum adiponectin at baseline was not associated with increases in LBMI, FMI, and FM, but independently associated with an increase in FM% and a decrease in LBM%. The predictive effect of high-serum adiponectin level on mortality disappeared after adjusting for diabetes and cardiovascular disease. Serum leptin was not associated with any changes in body composition during the follow-up, nor with the mortality in this cohort. A high adiponectin level could predict an increase in FM% and a decrease in LBM% during a 3-year follow-up in PD patients. Serum adiponectin could not independently predict mortality in PD patients.

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study.

PubMed

Austdal, Marie; Tangerås, Line H; Skråstad, Ragnhild B; Salvesen, Kjell; Austgulen, Rigmor; Iversen, Ann-Charlotte; Bathen, Tone F

2015-09-08

Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension). Preeclampsia developed in 26 (4.3%) and gestational hypertension in 21 (3.5%) women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia.

Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

Gallium 67 citrate scans and serum angiotension converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestation. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r = .436; p < .005). The frequency ofmore » abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical identification of inactive sarcoidosis.« less

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients.

PubMed

Shen, Shutong; Gao, Rongrong; Bei, Yihua; Li, Jin; Zhang, Haifeng; Zhou, Yanli; Yao, Wenming; Xu, Dongjie; Zhou, Fang; Jin, Mengchao; Wei, Siqi; Wang, Kai; Xu, Xuejuan; Li, Yongqin; Xiao, Junjie; Li, Xinli

2017-01-01

Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed. © 2017 The Author(s). Published by S. Karger AG, Basel.

Evaluation of pre- and posttransplantation serum interferon-gamma and soluble CD30 for predicting liver allograft rejection.

PubMed

Kim, K H; Oh, E-J; Jung, E-S; Park, Y-J; Choi, J Y; Kim, D-G; Lee, K Y; Kang, C S

2006-06-01

The aim of the present study was to identify whether the serum interferon-gamma (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of Th2 cytokine-producing T cells, predict acute cellular rejection episodes among liver graft patients. Pretransplant and posttransplant sera from 32 living donor liver transplant recipients obtained on days 1, 3, and 7 after surgery were tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14) displayed significantly higher IFNgamma concentrations pretransplant than did the patients with no ARE (n=18) (P<.05). The pretransplant serum levels of sCD30 were not different between the non-ARE and ARE groups. However, in comparison with the non-ARE group, who showed steadily decreasing serum sCD30 levels after transplantation, 12 among the 14 patients in the ARE group showed increasing sCD30 levels from day 1 to day 3 after transplantation (P<.05). These results suggest that the sCD30 increment during the early period after liver transplantation affects the immune response of rejection. This observation emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma, as predictive markers for acute liver graft rejection.

Body mass index and cholesterol level predict surgical outcome in patients with hepatocellular carcinoma in Taiwan - a cohort study.

PubMed

Lee, Ya-Ling; Li, Wan-Chun; Tsai, Tung-Hu; Chiang, Hsin-Yu; Ting, Chin-Tsung

2016-04-19

Curative surgical resection (CSR) remains the most effective therapeutic intervention for patients with hepatocellular carcinoma (HCC); however, frequent post-surgical recurrence leads to high cancer related mortality. This study aimed to clarify the role of body mass index (BMI) and serum cholesterol level in predicting post-surgical outcomes in HCC patients after CSR. A total of 484 HCC patients including 213 BMIhigh and 271 BMIlow patients were included. Overall survival (OS) and recurrence-free survival (RFS) rates were examined in patients with differential BMI and serum cholesterol level. The analysis showed that significant different 1-, 3- and 5-year cumulative OS rates (P-value=0.015) and RFS rate (P-value=0.010) between BMIlow and BMIhigh patients. Further analysis in groups with differential serum cholesterol levels among BMIlow and BMIhigh patients indicated that the BMIlow/Chollow patients exhibited the significant lower cumulative OS and RFS rates in comparison with the remaining subjects (P-value=0.007 and 0.039 for OS and RFS rates, respectively). In conclusion, the coexistence of low BMI and low serum cholesterol level could serve as prognostic factors to predict post-operative outcomes in HCC patients undergoing surgical hepatectomy.

Plasma inflammatory and immune proteins as predictors of intra-amniotic infection and spontaneous preterm delivery in women with preterm labor: a retrospective study.

PubMed

Park, Hyunsoo; Park, Kyo Hoon; Kim, Yu Mi; Kook, Song Yi; Jeon, Se Jeong; Yoo, Ha-Na

2018-05-09

We investigated whether various inflammatory and immune proteins in plasma predict intra-amniotic infection and imminent preterm delivery in women with preterm labor and compared their predictive ability with that of amniotic fluid (AF) interleukin (IL)-6 and serum C-reactive protein (CRP). This retrospective cohort study included 173 consecutive women with preterm labor who underwent amniocentesis for diagnosis of infection and/or inflammation in the AF. The AF was cultured, and assayed for IL-6. CRP levels and cervical length by transvaginal ultrasound were measured at the time of amniocentesis. The stored maternal plasma was assayed for IL-6, matrix metalloproteinase (MMP)-9, and complements C3a and C5a using ELISA kits. The primary and secondary outcome criteria were positive AF cultures and spontaneous preterm delivery (SPTD) within 48 h, respectively. Univariate, multivariate, and receiver operating characteristic analysis were used for the statistical analysis. In bivariate analyses, elevated plasma IL-6 level was significantly associated with intra-amniotic infection and imminent preterm delivery, whereas elevated plasma levels of MMP-9, C3a, and C5a were not associated with these two outcomes. On multivariate analyses, an elevated plasma IL-6 level was significantly associated with intra-amniotic infection and imminent preterm delivery after adjusting for confounders, including high serum CRP levels and short cervical length. In predicting intra-amniotic infection, the area under the curve (AUC) was significantly lower for plasma IL-6 than for AF IL-6 but was similar to that for serum CRP. Differences in the AUCs between plasma IL-6, AF IL-6, and serum CRP were not statistically significant in predicting imminent preterm delivery. Maternal plasma IL-6 independently predicts intra-amniotic infection in women with preterm labor; however, it has worse diagnostic performance than that of AF IL-6 and similar performance to that of serum CRP. To predict imminent preterm delivery, plasma IL-6 had an overall diagnostic performance similar to that of AF IL-6 and serum CRP. Plasma MMP-9, C3a, and C5a levels could not predict intra-amniotic infection or imminent preterm delivery.

A Serum Protein Profile Predictive of the Resistance to Neoadjuvant Chemotherapy in Advanced Breast Cancers*

PubMed Central

Hyung, Seok-Won; Lee, Min Young; Yu, Jong-Han; Shin, Byunghee; Jung, Hee-Jung; Park, Jong-Moon; Han, Wonshik; Lee, Kyung-Min; Moon, Hyeong-Gon; Zhang, Hui; Aebersold, Ruedi; Hwang, Daehee; Lee, Sang-Won; Yu, Myeong-Hee; Noh, Dong-Young

2011-01-01

Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to NACT) to discover serum biomarkers of chemoresistance using a label-free liquid chromatography-tandem MS method. By performing a series of statistical analyses of the proteomic data, we selected thirteen biomarker candidates and tested their differential serum levels by Western blotting in 13 independent samples (eight patients sensitive to and five patients resistant to NACT). Among the candidates, we then selected the final set of six potential serum biomarkers (AHSG, APOB, C3, C9, CP, and ORM1) whose differential expression was confirmed in the independent samples. Finally, we demonstrated that a multivariate classification model using the six proteins could predict responses to NACT and further predict relapse-free survival of patients. In summary, global N-glycoproteome profile in serum revealed a protein pattern predictive of the responses to NACT, which can be further validated in large clinical studies. PMID:21799047

Intraoperative serum parathyroid hormone level is an indicator of hypocalcaemia in total thyroidectomy patients.

PubMed

Islam, M S; Sultana, T; Paul, D; Huq, A H M Z; Chowdhury, A A; Ferdous, C; Ahmed, A N N

2012-12-01

Postoperative hypocalcaemia is the most frequent and common complication after total thyroidectomy. It is necessary to diagnose or to predict hypocalcaemia immediately after total thyroidectomy for minimizing complications. A prospective observational study was carried out in the Department of Clinical Pathology in collaboration with Department of Microbiology & Immunology, Department of Surgery, Department of Otolaryngology, Bangabandhu Sheikh Mujib Medical University (BSMMU) and Department of Otolaryngology, Dhaka Medical College & Hospital (DMC&H), Dhaka, during the period of September 2010 to August 2011 to evaluate intraoperative (20 minutes after total thyroidectomy) parathyroid hormone (PTH) measurement as a predictor of post thyroidectomy hypocalcaemia. Total 65 patients were enrolled in this study those came for total thyroidectomy. Postoperative hypocalcaemia developed in 25 cases. Intraoperative PTH was assessed and significant correlation was found between intraoperative PTH level and development of hypocalcaemia. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value of intraoperative serum PTH for prediction of post total thyroidectomy hypocalcaemia were 84.0%, 85.0%, 84.6%, 77.8%, and 89.5% respectively. Because of the high sensitivity, specificity and accuracy of intraoperative serum PTH of this study, the early prediction of hypocalcaemia could be made by single assay of intraoperative serum PTH level at 20 minutes after total thyroidectomy.

Interleukin-6 predicts recurrence and survival among head and neck cancer patients.

PubMed

Duffy, Sonia A; Taylor, Jeremy M G; Terrell, Jeffrey E; Islam, Mozaffarul; Li, Yun; Fowler, Karen E; Wolf, Gregory T; Teknos, Theodoros N

2008-08-15

Increased pretreatment serum interleukin (IL)-6 levels among patients with head and neck squamous cell carcinoma (HNSCC) have been shown to correlate with poor prognosis, but sample sizes in prior studies have been small and thus unable to control for other known prognostic variables. A longitudinal, prospective cohort study determined the correlation between pretreatment serum IL-6 levels, and tumor recurrence and all-cause survival in a large population (N = 444) of previously untreated HNSCC patients. Control variables included age, sex, smoking, cancer site and stage, and comorbidities. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to study the association between IL-6 levels, control variables, and time to recurrence and survival. The median serum IL-6 level was 13 pg/mL (range, 0-453). The 2-year recurrence rate was 35.2% (standard error, 2.67%). The 2-year death rate was 26.5% (standard error, 2.26%). Multivariate analyses showed that serum IL-6 levels independently predicted recurrence at significant levels [hazard ratio (HR) = 1.32; 95% confidence interval (CI), 1.11 to 1.58; P = .002] as did cancer site (oral/sinus). Serum IL-6 level was also a significant independent predictor of poor survival (HR = 1.22; 95% CI, 1.02 to 1.46; P = .03), as were older age, smoking, cancer site (oral/sinus), higher cancer stage, and comorbidities. Pretreatment serum IL-6 could be a valuable biomarker for predicting recurrence and overall survival among HNSCC patients. Using IL-6 as a biomarker for recurrence and survival may allow for earlier identification and treatment of disease relapse. 2008 American Cancer Society

High VEGF-D and Low MMP-2 Serum Levels Predict Nodal-Positive Disease in Invasive Bladder Cancer

PubMed Central

Benoit, Tobias; Keller, Etienne X.; Wolfsgruber, Pirmin; Hermanns, Thomas; Günthart, Michele; Banzola, Irina; Sulser, Tullio; Provenzano, Maurizio; Poyet, Cédric

2015-01-01

Background To investigate stromal variables including angiogenesis, lymphangiogenesis, and matrix metalloproteinase (MMP) in the serum of patients with urothelial carcinoma of the bladder (UCB) and to evaluate their association with histopathological characteristics and clinical outcome. Material/Methods Protein levels of vascular endothelial growth factors-A, -C, -D (VEGF-A/-C/-D), their receptors- VEGF-R2 and -R3 (VEGF-R2/-R3), and matrix metalloproteinases 2, -3, and -7 (MMP-2, MMP-3, MMP-7) were quantified in the blood serum samples of 71 patients with UCB before radical cystectomy (RC). Samples of patients with non-invasive UCB or no history of UCB were investigated as controls (n=20). Protein levels in the serum were measured using a flow cytometric cytokine assay. Results A positive association for VEGF-D (p<0.001) and an inverse association for MMP-2 (p=0.017) were observed in patients with positive lymph node (LN) status at the time of RC. VEGF-A (p<0.001), VEGF-C (p<0.001), MMP-2 (p<0.001), and MMP-7 (p=0.005) serum levels were different in serum of patients with invasive UCB compared with non-invasive UCB or healthy individuals. None of the serum markers were associated with disease progression. Conclusions High VEGF-D and low MMP-2 serum levels predict LN metastasis in patients with UCB at the time of RC. VEGF-A, VEGF-C, MMP-2, and MMP-7 serum levels varied significantly between invasive and non-invasive disease as well as in comparison with healthy individuals. Clinical implementation of these marker serum measurements may be valuable to select high-risk patients with more invasive or nodal-positive disease. PMID:26241709

Correlation of the association of serum lactate, random blood sugar, and revised trauma score as predictors of outcome in hemodynamically unstable abdominal emergencies.

PubMed

Allwell-Brown, E; Afuwape, O O; Ayandipo, O; Alonge, T

2016-01-01

Elevated levels of serum lactate and glucose during resuscitation have been demonstrated to be predictors of morbidity and mortality in hemodynamically unstable patients with surgical abdominal conditions. However, the rate of return to normal levels of both lactate and blood glucose may be better predictors of mortality and morbidity. The aims of this study are: (I) To determine the pattern of serum lactate and glucose changes in patients with surgical abdominal conditions requiring resuscitation within 48 hours of presentation. (II) To correlate the predictive capability of these two independent parameters. (III) To correlate the predictive values of these parameters with the revised trauma score (RTS). This is a prospective observational study conducted over three months. The patients admitted by the general surgery division requiring resuscitation from shock was included in this study. Resuscitation was carried out with crystalloids. The estimation of serum lactate and glucose levels was done at presentation (0 hours), 12, 24 and 48 hours after admission. The revised trauma score (RTS) was calculated for each patient at presentation and at 12, 24 and 48 hours subsequently. The patients were followed up four weeks or when death occurred within four weeks of presentation. Forty four patients were recruited in the study. There were seven mortalities. The mean serum levels of Plasma glucose and lactate of all the patients were elevated at presentation in the emergency department. Survival was better with a return to normal serum lactate within 12 hours. On the other hand the random plasma glucose (RPG) levels may not be useful in prognosticating patients. However a combination of serum lactate, RTS (at 24 and 48 hours) and RPG at 48 hours may improve predictive parameters in trauma related cases.

Decreased levels of serum omentin-1 in patients with inflammatory bowel disease.

PubMed

Yin, Jian; Hou, Peng; Wu, Zhiqiang; Nie, Yanxiao

2015-01-10

Inflammation is involved in the mechanism of inflammatory bowel disease (IBD). Omentin, a newly discovered adipokine, is thought to play an anti-inflammatory role. This study aimed to determine whether serum levels of omentin-1 are associated with the presence and disease activity of IBD. This study consisted of 192 patients with IBD: 100 with Crohn's disease [CD], 92 with ulcerative colitis [UC], and 104 healthy subjects. Serum levels of omentin-1 were measured using enzyme-linked immunosorbent assay (ELISA). Serum omentin-1 levels were significantly decreased in CD and UC patients compared with healthy controls. Multivariable logistic regression analysis revealed that serum omentin-1 levels were inversely associated with the presence of CD and UC. Active CD and UC patients both had significantly decreased levels of serum omentin-1 compared with inactive CD and UC patients. In both CD and UC patients, serum omentin-1 levels were significantly associated with decreased levels of body mass index (BMI) and C-reactive protein (CRP). Decreased serum omentin-1 levels could be considered as an independent predicting marker of the presence and disease activity of IBD.

Predicting age at menopause from serum antimüllerian hormone concentration.

PubMed

Tehrani, Fahimeh Ramezani; Shakeri, Nezhat; Solaymani-Dodaran, Masoud; Azizi, Fereidoun

2011-07-01

We aimed to estimate age at menopause using serum antimüllerian hormone (AMH) concentration. We randomly selected 266 study participants from a pool of 1,265 eligible women in the Tehran Lipid and Glucose Study cohort. We measured AMH levels three times at about 3-year intervals. There were 63 occurrences of menopause in our participants over an average of 6-year follow-up. We built an accelerated failure time model using serum AMH level at the start of follow-up to estimate age at menopause. The goodness of fit for the model was tested using Cox-Snell residuals and the Bland-Altman plot. We estimated ages at menopause for different levels of serum AMH concentration among women aged 20 to 49 years. For those who reached menopause, serum AMH concentrations about 6 years before the event provided fairly accurate estimates of the age at menopause. The Bland-Altman plot showed an acceptable agreement between predicted and observed values. Serum AMH concentrations can reasonably forecast the age at menopause for individual women.

Serum fetuin-A levels are associated with serum triglycerides before and 6 months after bariatric surgery.

PubMed

Verras, Christos G; Christou, Georgios A; Simos, Yannis V; Ayiomamitis, George D; Melidonis, Andreas J; Kiortsis, Dimitrios N

2017-07-01

The elucidation of the changes of fetuin-A in the context of bariatric surgery. Twenty obese patients (8 males, 12 females; body mass index = 42.5±3.4 kg/m2) were studied at baseline and 6 months after bariatric surgery. Serum fetuin-A levels did not differ with regard to the presence of each individual component of the Metabolic Syndrome (MetS) at baseline, except for hypertriglyceridaemia [increased serum fetuin-A levels (p=0.011)]. Circulating fetuin-A was positively correlated with serum triglycerides (TG) (r=0.461, p=0.047) and negatively correlated with serum globulins (r=-0.477, p=0.033) and C-reactive protein (CRP) (r=-0.604, p=0.010), while it independently predicted TG at baseline. Circulating fetuin-A did not change during the 6 months either in the whole population or in the subgroups of patients who were positive for each individual component of MetS at baseline and negative for this component at 6 months of follow-up, except for hypertriglyceridaemia [reduction of serum fetuin-A levels (p=0.046)]. The subgroup of patients with a decrease in circulating fetuin-A during the 6 months was characterized by a smaller reduction of serum globulins (p=0.003) and CRP (p=0.049). The change in serum fetuin-A levels over the 6 months was positively correlated with the change in TG (r=0.592, p=0.006) and negatively correlated with the change in serum globulins (r=-0.523, p=0.018) and CRP (r=-.494, p=0.037). Circulating fetuin-A predicted serum triglycerides before as well as 6 months after bariatric surgery.

Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis.

PubMed

Michelena, Javier; Altamirano, José; Abraldes, Juan G; Affò, Silvia; Morales-Ibanez, Oriol; Sancho-Bru, Pau; Dominguez, Marlene; García-Pagán, Juan Carlos; Fernández, Javier; Arroyo, Vicente; Ginès, Pere; Louvet, Alexandre; Mathurin, Philippe; Mehal, Wajahat Z; Caballería, Juan; Bataller, Ramón

2015-09-01

Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P < 0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P = 0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone. In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids. © 2015 by the American Association for the Study of Liver Diseases.

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

PubMed

Nafar, Mohsen; Farrokhi, Farhat; Vaezi, Mohammad; Entezari, Amir-Ebrahim; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Eniollahi, Behzad

2009-01-01

Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

Procalcitonin as a potential predicting factor for prognosis in bacterial meningitis.

PubMed

Park, Bong Soo; Kim, Si Eun; Park, Si Hyung; Kim, Jinseung; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Kim, Sung Eun; Lee, Byung In; Park, Kang Min

2017-02-01

We investigated the potential role of serum procalcitonin in differentiating bacterial meningitis from viral meningitis, and in predicting the prognosis in patients with bacterial meningitis. This was a retrospective study of 80 patients with bacterial meningitis (13 patients died). In addition, 58 patients with viral meningitis were included as the disease control groups for comparison. The serum procalcitonin level was measured in all patients at admission. Differences in demographic and laboratory data, including the procalcitonin level, were analyzed between the groups. We used the mortality rate during hospitalization as a marker of prognosis in patients with bacterial meningitis. Multiple logistic regression analysis showed that high serum levels of procalcitonin (>0.12ng/mL) were an independently significant variable for differentiating bacterial meningitis from viral meningitis. The risk of having bacterial meningitis with high serum levels of procalcitonin was at least 6 times higher than the risk of having viral meningitis (OR=6.76, 95% CI: 1.84-24.90, p=0.004). In addition, we found that high levels of procalcitonin (>7.26ng/mL) in the blood were an independently significant predictor for death in patients with bacterial meningitis. The risk of death in patients with bacterial meningitis with high serum levels of procalcitonin may be at least 9 times higher than those without death (OR=9.09, 95% CI: 1.74-47.12, p=0.016). We found that serum procalcitonin is a useful marker for differentiating bacterial meningitis from viral meningitis, and it is also a potential predicting factor for prognosis in patients with bacterial meningitis. Copyright © 2016 Elsevier Ltd. All rights reserved.

First-trimester serum folate levels and subsequent risk of abortion and preterm birth among Japanese women with singleton pregnancies.

PubMed

Yamada, Takashi; Morikawa, Mamoru; Yamada, Takahiro; Kishi, Reiko; Sengoku, Kazuo; Endo, Toshiaki; Saito, Tsuyoshi; Cho, Kazutoshi; Minakami, Hisanori

2013-01-01

To determine whether a low serum folate level during the first trimester predicts subsequent late abortion, preterm birth, or fetal growth restriction (FGR). A prospective cohort study involving 5,075 women whose serum folate levels were measured during the first trimester. The participants were informed of their serum folate levels. The pregnancy duration, birthweight, rate of late abortion/preterm birth, and the rate of FGR did not differ significantly among the four groups classified according to folate status. The mean serum folate levels did not differ among quartiles classified according to the gestational week at the time of delivery. Nineteen of the 20 women with folate deficiency gave birth at term to infants with a birthweight of 3.132 ± 321 g; only one infant had FGR. Low serum folate levels during the first trimester were not associated with the risk of late abortion, preterm birth, or FGR.

/sup 67/Ga citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

/sup 67/Ga citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n . 30) and in 71% of patients with inactive disease (n . 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r..436; p less than .005). The frequency of abnormalmore » /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical indentification of inactive sacoidosis.« less

Chymase Level Is a Predictive Biomarker of Dengue Hemorrhagic Fever in Pediatric and Adult Patients.

PubMed

Tissera, Hasitha; Rathore, Abhay P S; Leong, Wei Yee; Pike, Brian L; Warkentien, Tyler E; Farouk, Farouk S; Syenina, Ayesa; Eong Ooi, Eng; Gubler, Duane J; Wilder-Smith, Annelies; St John, Ashley L

2017-11-27

Most patients with dengue experience mild disease, dengue fever (DF), while few develop the life-threatening diseases dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). No laboratory tests predict DHF or DSS. We evaluated whether the serum chymase level can predict DHF or DSS in adult and pediatric patients and the influence of preexisting conditions (PECs) on chymase levels. Serum chymase levels were measured in patients presenting with undifferentiated fever to hospitals in Colombo District, Sri Lanka. The value of serum the chymase concentration and clinical signs and symptoms as predictors of DHF and/or DSS was evaluated by multivariate analysis. We assessed the influence of age, PECs, and day after fever onset on the robustness of the chymase level as a biomarker for DHF and/or DSS. An elevated chymase level in acute phase blood samples was highly indicative of later diagnosis of DHF or DSS for pediatric and adult patients with dengue. No recorded PECs prevented an increase in the chymase level during DHF. However, certain PECs (obesity and cardiac or lung-associated diseases) resulted in a concomitant increase in chymase levels among adult patients with DHF. These results show that patients with acute dengue who present with high levels of serum chymase consistently are at greater risk of DHF. The chymase level is a robust prognostic biomarker of severe dengue for adult and pediatric patients. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Serum Neutrophil Gelatinase-Associated Lipocalin Predicts Survival After Resuscitation From Cardiac Arrest.

PubMed

Elmer, Jonathan; Jeong, Kwonho; Abebe, Kaleab Z; Guyette, Francis X; Murugan, Raghavan; Callaway, Clifton W; Rittenberger, Jon C

2016-01-01

In the first days after cardiac arrest, accurate prognostication is challenging. Serum biomarkers are a potentially attractive adjunct for prognostication and risk stratification. Our primary objective in this exploratory study was to identify novel early serum biomarkers that predict survival after cardiac arrest earlier than currently possible. Prospective, observational study. A single academic medical center. Adult subjects who sustained cardiac arrest with return of spontaneous circulation. None. We obtained blood samples from each subject at enrollment, 6, 12, 24, 48, and 72 hours after return of spontaneous circulation. We measured the serum levels of novel biomarkers, including neutrophil gelatinase-associated lipocalin, high-mobility group protein B1, intracellular cell adhesion molecule-1, and leptin, as well as previously characterized biomarkers, including neuron-specific enolase and S100B protein. Our primary outcome of interest was survival-to-hospital discharge. We compared biomarker concentrations at each time point between survivors and nonsurvivors and used logistic regression to test the unadjusted associations of baseline clinical characteristics and enrollment biomarker levels with survival. Finally, we constructed a series of adjusted models to explore the independent association of each enrollment biomarker level with survival. A total of 86 subjects were enrolled. Enrollment levels of high-mobility group protein B1, neutrophil gelatinase-associated lipocalin, and S100B were higher in nonsurvivors than survivors. Enrollment leptin, neuron-specific enolase, and intracellular cell adhesion molecule-1 levels did not differ between nonsurvivors and survivors. The discriminatory power of enrollment neutrophil gelatinase-associated lipocalin level was the greatest (c-statistic, 0.78 [95% CI, 0.66-0.90]) and remained stable across all time points. In our adjusted models, enrollment neutrophil gelatinase-associated lipocalin level was independently associated with survival even after controlling for the development of acute kidney injury, and its addition to clinical models improved overall predictive accuracy. Serum neutrophil gelatinase-associated lipocalin levels are strongly predictive of survival-to-hospital discharge after cardiac arrest.

Predictive Risk Factors in the Development of Intraoperative Hyperkalemia in Adult Living Donor Liver Transplantation.

PubMed

Juang, S-E; Huang, C-E; Chen, C-L; Wang, C-H; Huang, C-J; Cheng, K-W; Wu, S-C; Shih, T-H; Yang, S-C; Wong, Z-W; Jawan, B; Lee, Y-E

2016-05-01

Hyperkalemia, defined as a serum potassium level higher than 5 mEq/L, is common in the liver transplantation setting. Severe hyperkalemia may induce fatal cardiac arrhythmias; therefore, it should be monitored and treated accordingly. The aim of the current retrospective study is to evaluate and indentify the predictive risk factors of hyperkalemia during living-donor liver transplantation (LDLT). Four hundred eighty-seven adult LDLT patients were included in the study. Intraoperative serum potassium levels were monitored at least five times during LDLT; patients with a potassium level higher than 5 mEq/L were included in group 1, and the others with normokalemia in group 2. Patients' categorical characteristics and intraoperative numeric variables with a P value <.1 were selected into a multiple binary logistic regression model. In multivariate analysis, a P value of <.05 is regarded as a risk factor in the development of hyperkalemia. Fifty-one of 487 (10.4%) patients had hyperkalemia with a serum potassium level higher than 5.0 mEq/L during LDLT. Predictive factors with P < .1 in univariate analysis (Table 1), such as anesthesia time, preoperative albumin level, Model for End-stage Liver Disease score, preoperative bilirubin level, amount of blood loss, red blood cell (RBC) and fresh frozen plasma transfused, 5% albumin administered, hemoglobin at the end of surgery, and the amount of furosemide used, were further analyzed by multivariate binary regression. Results show that the anesthesia time, preoperative serum albumin level, and RBC count are determinant risk factors in the development of the hyperkalemia in our LDLT serials. Prolonged anesthesia time, preoperative serum albumin level, and intraoperative RBC transfusion are three determinant factors in the development of intraoperative hyperkalemia, and close monitoring of serum potassium levels in patients with abovementioned risk factors are recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum Alkaline Phosphatase Levels Predict Infection-Related Mortality and Hospitalization in Peritoneal Dialysis Patients.

PubMed

Hwang, Seun Deuk; Kim, Su-Hyun; Kim, Young Ok; Jin, Dong Chan; Song, Ho Chul; Choi, Euy Jin; Kim, Yong-Lim; Kim, Yon-Su; Kang, Shin-Wook; Kim, Nam-Ho; Yang, Chul Woo; Kim, Yong Kyun

2016-01-01

Serum alkaline phosphatase (ALP) levels have been reported to be associated with all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients. However, it is unclear whether serum ALP levels predict infection-related clinical outcomes in PD patients. The aim of this study was to determine the relationships between serum ALP levels, infection-related mortality and hospitalization in PD patients. PD patients from the Clinical Research Center registry for end-stage renal disease, a multicenter prospective observational cohort study in Korea, were included in the present study. Patients were categorized into three groups by serum ALP tertiles as follows: Tertile 1, ALP <78 U/L; Tertile 2, ALP = 78-155 U/L; Tertile 3, ALP >155 U/L. Tertile 1 was used as the reference category. The primary outcomes were infection-related mortality and hospitalization. A total of 1,455 PD patients were included. The median follow-up period was 32 months. The most common cause of infection-related mortality and hospitalization was PD-related peritonitis. Multivariate Cox regression analyses showed that patients in the highest tertiles of serum ALP levels were at higher risk of infection-related mortality (HR 2.29, 95% CI, 1.42-5.21, P = 0.008) after adjustment for clinical variables. Higher tertiles of serum ALP levels were associated with higher risk of infection-related hospitalization (Tertile 2: HR 1.56, 95% CI, 1.18-2.19, P = 0.009, tertile 3: HR 1.34, 95% CI, 1.03-2.62, P = 0.031). Our data showed that elevated serum ALP levels were independently associated with a higher risk of infection-related mortality and hospitalization in PD patients.

[Use of C response protein in predicting postoperative anastomotic leakage in patients with rectal cancer].

PubMed

Lyu, Zejian; Wu, Deqing; Cai, Guanfu; Luo, Yuwen; Yang, Zifeng; Zhai, Yanyun; Yao, Chuli; Hu, Weixian; Wang, Junjiang; Li, Yong

To investigate the value and feasibility of C reactive protein (CRP) in predicting postoperative anastomotic leakage in rectal cancer patients with enhanced recovery after surgery (ERAS) for safer implementation of this ERAS. A cohort study on serum CRP of 455 rectal cancer patients undergoing laparoscopic radical resection according to the ERAS procedure at Gastrointestinal Unit of General Surgery Department, Guangdong General Hospital from August 2014 to June 2017 was retrospectively carried out. The serum CRP level was measured before operation and at postoperative days 1-7, and the serum CRP level of the groups with and without anastomotic leakage was compared to analyze its prediction for anastomotic leakage. Diagnostic standard of anastomotic leakage was based on the definition of postoperative anastomotic leakage in rectal cancer from International Study Group of Rectal Cancer (ISREC): (1) Postoperative localized or diffuse peritonitis occurred, or fecal liquid was found from the abdominal drainage tube; (2) When anastomotic leakage was uncertain, peritoneal or pelvic computed tomography scan should be used to confirm. All the 455 patients underwent surgery successfully, and 41 patients (9.0%) had anastomotic leakage postoperatively. Patients with anastomotic leakage were diagnosed (4.0±2.0) days postoperatively, of whom 8 cases (19.5%) were diagnosed more than 5 days postoperatively. Serum CRP levels in patients with anastomotic leakage continued to increase within 1-4 days postoperatively [(50.04±27.98) mg/L to (122.75±52.98) mg/L] and decreased 5 days postoperatively [(92.02±58.26) mg/L], both were higher than those of non-anastomotic leakage group, and the difference was statistically significant (all P<0.05, except postoperative day 2). The serum CRP level of non-anastomotic leakage group reached the peak on the second postoperative day [(83.10±37.45) mg/L] and decreased 3 days postoperatively [(48.01±27.59) mg/L]. The ROC curve was drawn with the anastomotic leakage as the state variable, and the CRP level as the detection variable. The area under the curve (AUC) at postoperative 1, 2, 4, 5, 6 and 7 days was 0.74, 0.58, 0.83, 0.82, 0.65, and 0.70, respectively. The maximum was at postoperative day 3 [0.93(95%CI: 0.86-0.99)]. The Youden index was 0.72, and the threshold of CRP was 80.09 mg/L, as the cut-off point to predict anastomotic leakage, with sensitivity, specificity, and positive predictive value of 79.3%, 92.3%, and 74.2%, respectively. Monitoring the postoperative serum CRP level can help predict the occurrence of anastomotic leakage after laparoscopic surgery for rectal cancer. When the serum CRP level is >80.09 mg/L on the third postoperative day, the CRP level has the largest value in predicting postoperative anastomotic leakage, and the safety of ERAS has a certain clinical significance as well.

Elevated serum levels of TPS and CYFRA 21-1 predict poor prognosis in advanced non-small-cell lung cancer patients treated with gefitinib.

PubMed

Chen, Fengsheng; Luo, Xi; Zhang, Jinbiao; Lu, Yang; Luo, Rongcheng

2010-09-01

Serum concentrations of tissue polypeptide-specific antigen (TPS) and Cytokeratin-19-Fragments (CYFRA 21-1) before operation or chemotherapy have been proved to be a useful prognostic tool for patients with NSCLC, but the related data for advanced NSCLC patients treated with gefitinib are limited. We retrospectively reviewed 122 advanced NSCLC patients treated with gefitinib between April 2002 and August 2007. Multiple clinical factors including pretreatment serum levels of TPS and CYFRA 21-1, age, gender, performance status (PS), smoking history, stage, histology, the number of prior chemotherapy and the patients' clinical outcomes were analyzed. Patients without elevated serum TPS levels had a more RR (36.8%) than those with elevated serum TPS levels (18.5%) (P = 0.023), nevertheless, a similar result was not seen in patients with normal CYFRA 21-1 levels. For patients with normal vs. high TPS levels, the median survival times (MSTs) were 15.9 vs. 7.3 months (P = 0.001). For patients with normal vs. high CYFRA 21-1, the MSTs were 15.4 vs. 7.5 months (P = 0.003). Moreover, for patients with both elevated, vs. one elevated and both normal TPS and CYFRA 21-1 levels, the MSTs were 5.4 vs. 11.4 months (P = 0.001), and 16.5 months (P < 0.001), respectively. In multivariate analysis, TPS (P = 0.001) and CYFRA 21-1 (P = 0.005) alone or combination (P < 0.001) remained significant correlation to survival. In NSCLC patients with gefitinib therapy, pretreatment serum levels of TPS and CYFRA 21-1 alone or combined might be independent prognostic factors, and the pretreatment serum TPS level may predict the tumor response.

Can urine dipstick predict an elevated serum creatinine?

PubMed

Shah, Kaushal; Kilian, Barbara; Hsieh, Wei-Jen; Kyrillou, Emily; Hedge, Vishal; Newman, David H

2010-06-01

Chart review studies have suggested that point-of-care urine dipstick testing may accurately predict an elevation in serum creatinine (Cr). We aimed to prospectively evaluate the test characteristics of proteinuria/hematuria in predicting elevated serum Cr. A prospective, observational study was conducted between March 2007 and June 2008 at 2 affiliated, urban hospitals with an annual emergency department census of 150,000. Patients undergoing laboratory urinalysis, point-of-care urine dipstick, and a serum chemistry panel were enrolled. Trained research assistants collected data on consecutive patients 18 hours per day using preformatted data forms and entry into an anonymized Access (Microsoft, Seattle, Wash) database. Demographic baseline variables including age, sex, chief complaint, vital signs, and source of sample (catheter vs "clean catch") were also collected. An elevated Cr level was defined as greater than 1.3 based on the laboratory reference range. Standard statistical methods were used to calculate diagnostic test operating characteristics of proteinuria or hematuria as a predictor of elevated serum Cr. Five thousand four hundred sixteen subjects were enrolled with 28.3% male and a mean age of 50.2 years. Elevated serum Cr greater than 1.3 mg/dL was found in 13.9% (755/5416) of subjects. The sensitivity of either proteinuria or hematuria for elevated Cr was 82.5% (95% confidence interval [CI], 80%-85%) and specificity was 34.4% (95% CI, 33%-36%). Positive predictive value was 16.9% (95% CI, 16%-18%) and negative predictive value was 92.4% (95% CI, 91-94%). The likelihood ratio for a positive test was 1.3 (95% CI, 1.1-1.5), and the likelihood ratio for a negative test was 0.5 (95% CI, 0.3-0.8). Although negative predictive value was high, the presence of proteinuria/hematuria was only moderately predictive of elevated serum Cr level. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Lipocalin-2 expression and serum levels as early predictors of type 2 diabetes mellitus in obese women.

PubMed

Rashad, Nearmeen M; El-Shal, Amal S; Etewa, Rasha L; Wadea, Fady M

2017-02-01

Obesity and diabetes are increasing in epidemic proportions globally. Lipocalin-2 (LCN-2) is an inflammatory adipocytokine and obesity-related marker of low-grade inflammation. We aimed to investigate, for first time, the possible role of LCN-2 expression and serum levels in prediction of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) among obese Egyptian women. This study included 188 obese women and 180 controls. Obese women were subdivided into three subgroups according to their fasting blood glucose, normal glucose tolerance (NGT), IGT and T2DM. Circulating LCN-2 expression levels were determined by real time polymerase chain reaction. Serum LCN-2 concentrations were assessed by ELISA. Our findings revealed that LCN-2 expression and serum levels were higher in obese women compared to lean controls. They were higher in IGT and T2DM obese cases than in NGT obese women. Receiver operating characteristic analyses revealed that LCN-2 expression level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.735 and 0.740, respectively). It was an independent predictor of IGT and T2DM among obese women. Serum LCN-2 level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.705 and 0.728, respectively). It was independent predictor of T2DM without predicting IGT among obese women. The power of combined LCN-2 serum levels and expression in discriminating between IGT from NGT and T2DM from IGT obese women was high (AUC = 0.717 and 0.741, respectively). In conclusion, LCN-2 expression and serum levels could discriminate IGT from NGT and T2DM from IGT obese women and early predicting T2DM among obese women. While, LCN-2 expression level was the independent predictor of IGT in obese women. Combination of both LCN-2 expression and serum levels improved their diagnostic value in early detection of IGT and T2DM among obese women. © 2017 IUBMB Life, 69(2):88-97, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Serum bilirubin: a simple routine surrogate marker of the progression of chronic kidney disease.

PubMed

Moolchandani, K; Priyadarssini, M; Rajappa, M; Parameswaran, S; Revathy, G

2016-10-01

Studies suggest that Chronic Kidney Disease (CKD) is a global burden health associated with significant comorbid conditions. Few biochemical parameters have gained significance in predicting the disease progression. The present work aimed to study the association of the simple biochemical parameter of serum bilirubin level with the estimated glomerular filtration rate (eGFR), and to assess their association with the co-morbid conditions in CKD. We recruited 188 patients with CKD who attended a Nephrology out-patient department. eGFR values were calculated based on the serum creatinine levels using CKD-EPI formula. Various biochemical parameters including glucose, creatinine, uric acid, total and direct bilirubin were assayed in all study subjects. Study subjects were categorized into subgroups based on their eGFR values and their diabetic status and the parameters were compared among the different subgroups. We observed a significantly decreased serum bilirubin levels (p < 0.001) in patients with lower eGFR values, compared to those with higher eGFR levels. There was a significant positive correlation between the eGFR levels and the total bilirubin levels (r = 0.92). We also observed a significant positive correlation between the eGFR levels and the direct bilirubin levels (r = 0.76). On multivariate linear regression analysis, we found that total and direct bilirubin independently predict eGFR, after adjusting for potential confounders (p < 0.001). Our results suggest that there is significant hypobilirubinemia in CKD, especially with increasing severity and co-existing diabetes mellitus. This finding has importance in the clinical setting, as assay of simple routine biochemical parameters such as serum bilirubin may help in predicting the early progression of CKD and more so in diabetic CKD.

Serum tenascin-C predicts severity and outcome of acute intracerebral hemorrhage.

PubMed

Wang, Lin-Guo; Huangfu, Xue-Qin; Tao, Bo; Zhong, Guan-Jin; Le, Zhou-Di

2018-06-01

Tenascin-C is a matricellular protein related to brain injury. We studied serum tenascin-C in acute intracerebral hemorrhage (ICH) and examined the associations with severity and outcome following the acute event. Tenascin-C samples were obtained from 162 patients with acute hemorrhagic stroke and 162 healthy controls. Poor 90-day functional outcome was defined as modified Rankin Scale score > 2. Early neurological deterioration (END) and hematoma growth (HG) were recorded at 24 h. Patients had higher tenascin-C levels than controls. Tenascin-C levels were positively correlated with hematoma volume or National Institutes of Health Stroke Scale score at baseline. Elevated tenascin-C levels were independently associated with END, HG, 90-day mortality and poor functional outcome. Moreover, tenascin-C levels significantly predicted END, HG and 90-day outcomes under receiver operating characteristic curves. An increase in serum tenascin-C level is associated with an adverse outcome in ICH patients, supporting the potential role of serum tenascin-C as a prognostic biomarker for hemorrhagic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Serum Amino Acid Profiles in Childhood Predict Triglyceride Level in Adulthood: A 7-Year Longitudinal Study in Girls.

PubMed

Wiklund, Petri; Zhang, Xiaobo; Tan, Xiao; Keinänen-Kiukaanniemi, Sirkka; Alen, Markku; Cheng, Sulin

2016-05-01

Branched-chain and aromatic amino acids are associated with high risk of developing dyslipidemia and type II diabetes in adults. This study aimed to examine whether serum amino acid profiles associate with triglyceride concentrations during pubertal growth and predict hypertriglyceridemia in early adulthood. This was a 7.5-year longitudinal study. The study was conducted at the Health Science Laboratory, University of Jyväskylä. A total of 396 nondiabetic Finnish girls aged 11.2 ± 0.8 years at the baseline participated in the study. Body composition was assessed by dual-energy x-ray absorptiometry; serum concentrations of glucose, insulin, and triglyceride by enzymatic photometric methods; and amino acids by nuclear magnetic resonance spectroscopy. Serum leucine and isoleucine correlated significantly with future triglyceride, independent of baseline triglyceride level (P < .05 for all). In early adulthood (at the age of 18 years), these amino acids were significantly associated with hypertriglyceridemia, whereas fat mass and homeostasis model assessment of insulin resistance were not. Leucine was the strongest determinant discriminating subjects with hypertriglyceridemia from those with normal triglyceride level (area under the curve, 0.822; 95% confidence interval, 0.740-0.903; P = .000001). Serum leucine and isoleucine were associated with future serum triglyceride levels in girls during pubertal growth and predicted hypertriglyceridemia in early adulthood. Therefore, these amino acid indices may serve as biomarkers to identify individuals at high risk for developing hypertriglyceridemia and cardiovascular disease later in life. Further studies are needed to elucidate the role these amino acids play in the lipid metabolism.

Utility of serum pancreatic enzyme levels in diagnosing blunt trauma to the pancreas: a prospective study with systematic review.

PubMed

Mahajan, Abhishek; Kadavigere, Rajagopal; Sripathi, Smiti; Rodrigues, Gabriel Sunil; Rao, Vedula Rajanikanth; Koteshwar, Prakashini

2014-09-01

Reliability of serum pancreatic enzyme levels in predicting pancreatic injuries has been a parameter of interest and the present recommendations on its utility are based primarily on anecdotal observations. The aim of this study was to evaluate the utility of serum pancreatic enzyme assessment in predicting blunt pancreatic injury with imaging and surgical correlation and compare our results with a systematic review of literature till date. A prospective cohort study conducted over 4 years in a tertiary care referral centre with 164 consecutive patients who presented to the emergency department with a history of blunt abdominal trauma and had serum pancreatic enzyme assessment, USG and subsequent diagnostic CECT were analyzed. The CT findings and AAST grade of pancreatic injury, various intra-abdominal injuries and time elapsed since injury and other associated factors were correlated with serum pancreatic enzyme levels. For systematic review of literature MEDLINE database was searched between 1940 and 2012, also the related citations and bibliographies of relevant articles were analyzed and 40 articles were included for review. We compared our results with the systematic critique of literature till date to formulate recommendations. 33(21%) patients had pancreatic injury documented on CT and were graded according to AAST. Statistically significant elevated serum amylase levels were observed in patients with pancreatic and bowel injuries. However, elevated serum lipase was observed specifically in patients with pancreatic injury with or without bowel injury. Combined serum amylase and lipase showed 100% specificity, 85% sensitivity in predicting pancreatic injury. Elevated (n=28, 85%) vs. normal (n=5, 15%) serum amylase and lipase levels showed sole statistically significant association with time elapse since injury to admission, with a cutoff of 3h. Based on our results and the systematic review of the literature till date we conclude, persistently elevated or rising combined estimation of serum amylase and lipase levels are reliable indicators of pancreatic injury and is time dependent, nondiagnostic within 6h or less after trauma. In resource constrained countries where CT is not available everywhere it may support a clinical suspicion of pancreatic injury and can be reliable and cost-effective as a screening tool. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Establishment of the prediction model for ischemic cardiovascular disease of elderly male population under current health care program].

PubMed

Chen, Jin-hong; Wu, Hai-yun; He, Kun-lun; He, Yao; Qin, Yin-he

2010-10-01

To establish and verify the prediction model for ischemic cardiovascular disease (ICVD) among the elderly population who were under the current health care programs. Statistical analysis on data from physical examination, hospitalization of the past years, from questionnaire and telephone interview was carried out in May, 2003. Data was from a hospital which implementing a health care program. Baseline population with a proportion of 4:1 was randomly selected to generate both module group and verification group. Baseline data was induced to make the verification group into regression model of module group and to generate the predictive value. Distinguished ability with area under ROC curve and the predictive veracity were verified through comparing the predictive incidence rate and actual incidence rate of every deciles group by Hosmer-Lemeshow test. Predictive veracity of the prediction model at population level was verified through comparing the predictive 6-year incidence rates of ICVD with actual 6-year accumulative incidence rates of ICVD with error rate calculated. The samples included 2271 males over the age of 65 with 1817 people for modeling population and 454 for verified population. All of the samples were stratified into two layers to establish hierarchical Cox proportional hazard regression model, including one advanced age group (greater than or equal to 75 years old), and another elderly group (less than 75 years old). Data from the statically analysis showed that the risk factors in aged group were age, systolic blood pressure, serum creatinine level, fasting blood glucose level, while protective factor was high density lipoprotein;in advanced age group, the risk factors were body weight index, systolic blood pressure, serum total cholesterol level, serum creatinine level, fasting blood glucose level, while protective factor was HDL-C. The area under the ROC curve (AUC) and 95%CI were 0.723 and 0.687 - 0.759 respectively. Discriminating power was good. All individual predictive ICVD cumulative incidence and actual incidence were analyzed using Hosmer-Lemeshow test, χ(2) = 1.43, P = 0.786, showing that the predictive veracity was good. The stratified Cox Hazards Regression model was used to establish prediction model of the aged male population under a certain health care program. The common prediction factor of the two age groups were: systolic blood pressure, serum creatinine level, fasting blood glucose level and HDL-C. The area under the ROC curve of the verification group was 0.723, showing that the distinguished ability was good and the predict ability at the individual level and at the group level were also satisfactory. It was feasible to using Cox Proportional Hazards Regression Model for predicting the population groups.

Polyfluorinated Compounds in Serum Linked to Indoor Air in Office Environments

PubMed Central

Fraser, Alicia J; Webster, Thomas F; Watkins, Deborah J; Nelson, Jessica W; Stapleton, Heather M; Calafat, Antonia M; Kato, Kayoko; Shoeib, Mahiba; Vieira, Verónica M; McClean, Michael D

2011-01-01

We aimed to investigate the role of indoor office air on exposure to polyfluorinated compounds (PFCs) among office workers. Week-long, active air sampling was conducted during the winter of 2009 in 31 offices in Boston, MA. Air samples were analyzed for fluorotelomer alcohols (FTOHs), sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs). Serum was collected from each participant (n=31) and analyzed for twelve PFCs including PFOA and PFOS. In air, FTOHs were present in the highest concentrations, particularly 8:2-FTOH (GM=9,920 pg/m3). FTOHs varied significantly by building with the highest levels observed in a newly constructed building. PFOA in serum was significantly correlated with air levels of 6:2-FTOH (r=0.43), 8:2-FTOH (r=0.60), and 10:2-FTOH (r=0.62). Collectively, FTOHs in air significantly predicted PFOA in serum (p < 0.001) and explained approximately 36% of the variation in serum PFOA concentrations. PFOS in serum was not associated with air levels of FOSAs/FOSEs. In conclusion, FTOH concentrations in office air significantly predict serum PFOA concentrations in office workers. Variation in PFC air concentrations by building is likely due to differences in the number, type, and age of potential sources such as carpeting, furniture and/or paint. PMID:22148395

Polyfluorinated compounds in serum linked to indoor air in office environments.

PubMed

Fraser, Alicia J; Webster, Thomas F; Watkins, Deborah J; Nelson, Jessica W; Stapleton, Heather M; Calafat, Antonia M; Kato, Kayoko; Shoeib, Mahiba; Vieira, Verónica M; McClean, Michael D

2012-01-17

We aimed to investigate the role of indoor office air on exposure to polyfluorinated compounds (PFCs) among office workers. Week-long, active air sampling was conducted during the winter of 2009 in 31 offices in Boston, MA. Air samples were analyzed for fluorotelomer alcohols (FTOHs), sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs). Serum was collected from each participant (n = 31) and analyzed for 12 PFCs including PFOA and PFOS. In air, FTOHs were present in the highest concentrations, particularly 8:2-FTOH (GM = 9920 pg/m(3)). FTOHs varied significantly by building with the highest levels observed in a newly constructed building. PFOA in serum was significantly correlated with air levels of 6:2-FTOH (r = 0.43), 8:2-FTOH (r = 0.60), and 10:2-FTOH (r = 0.62). Collectively, FTOHs in air significantly predicted PFOA in serum (p < 0.001) and explained approximately 36% of the variation in serum PFOA concentrations. PFOS in serum was not associated with air levels of FOSAs/FOSEs. In conclusion, FTOH concentrations in office air significantly predict serum PFOA concentrations in office workers. Variation in PFC air concentrations by building is likely due to differences in the number, type, and age of potential sources such as carpeting, furniture, and/or paint.

Clinical significance of serum decoy receptor 3 levels in patients with systemic sclerosis.

PubMed

Yamada, Daisuke; Asano, Yoshihide; Takahashi, Takehiro; Masui, Yuri; Aozasa, Naohiko; Akamata, Kaname; Noda, Shinji; Tamaki, Zenshiro; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

2012-01-01

Decoy receptor 3 (DcR3) is associated with autoimmunity and altered angiogenesis in certain pathological conditions. We herein measured serum DcR3 levels in 51 patients with systemic sclerosis (SSc) and 19 healthy controls and evaluated their clinical significance in this disorder. Serum DcR3 levels were significantly higher in diffuse cutaneous SSc (dcSSc) patients than in limited cutaneous SSc patients and in healthy controls. In dcSSc, serum DcR3 levels were significantly elevated in patients with disease duration of ≤6 years compared with healthy controls, but not in those with disease duration of >6 years. Serum DcR3 levels correlated negatively with the percentage of predicted diffusion lung capacity for carbon monoxide and positively with right ventricular systolic pressure. Furthermore, serum DcR3 levels positively correlated with C-reactive protein, erythrocyte sedimentation rate and immunoglobulin G. Collectively, the elevation of serum DcR3 levels is associated with the development of pulmonary arterial hypertension and systemic inflammation in SSc.

Serum Albumin and High-Sensitivity C-reactive Protein are Independent Risk Factors of Chronic Kidney Disease in Middle-Aged Japanese Individuals: the Circulatory Risk in Communities Study

PubMed Central

Kubo, Sachimi; Kitamura, Akihiko; Imano, Hironori; Cui, Renzhe; Yamagishi, Kazumasa; Umesawa, Mitsumasa; Muraki, Isao; Kiyama, Masahiko; Okada, Takeo

2016-01-01

Aim: It is important to explore predictive markers other than conventional cardiovascular risk factors for early detection and treatment of chronic kidney disease (CKD), a major risk factor for end-stage renal failure. We hypothesized that serum albumin and high-sensitivity C-reactive protein (hs-CRP) to be independent markers, and examined their associations with the risk of CKD. Methods: We examined the associations of serum albumin and hs-CRP levels with the risk of incident CKD, in 2535 Japanese adults aged 40–69 years without CKD at baseline during a median 9.0-year follow-up after adjustment for known cardiovascular risk factors. Results: During the follow-up period, 367 cases of CKD developed. In multivariable analyses adjusted for known risk factors, the CKD hazard ratios (95% confidence intervals) for the highest versus lowest quartiles of serum albumin levels were 0.69 (0.40–1.17) for men and 0.42 (0.28–0.64) for women. Corresponding values for hs-CRP were 0.95 (0.54–1.67) for men and 1.85 (1.25 -2.75) for women. The association of combined serum albumin and hs-CRP with the risk of CKD was examined for women. The hazard ratio was 1.72 (1.17–2.54) for low versus higher albumin levels at lower hs-CRP levels, but such an association was not observed at high hs-CRP level. The hazard ratio was 1.96 (1.44–2.66) for high versus lower hs-CRP levels at higher serum albumin levels, but such association was not observed at low serum albumin level. Conclusion: Both low serum albumin and high hs-CRP levels were predictive of CKD for women. PMID:26911856

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus.

PubMed

Lee, Chi Ho; Woo, Yu Cho; Chow, Wing Sun; Cheung, Chloe Yu Yan; Fong, Carol Ho Yi; Yuen, Michele Mae Ann; Xu, Aimin; Tse, Hung Fat; Lam, Karen Siu Ling

2017-06-06

Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases. Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; P <0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; P =0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors. We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C.

PubMed

Su, Tung-Hung; Liu, Chen-Hua; Liu, Chun-Jen; Chen, Chi-Ling; Ting, Te-Tien; Tseng, Tai-Chung; Chen, Pei-Jer; Kao, Jia-Horng; Chen, Ding-Shinn

2013-05-07

MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. Serum miR-122 has been implicated as a biomarker for various liver diseases; however, its role in chronic hepatitis C remains unclear. To address this issue, 126 patients with chronic hepatitis C who completed pegylated IFN plus ribavirin therapy with sustained virologic response (SVR) or nonresponse (NR) were retrospectively included, and their pretreatment clinical profiles and treatment responses were collected. Serum miR-122 was quantified before and during treatment. Another 51 patients in SVR and NR groups were prospectively enrolled for validation. Serum miR-122 was found to be a surrogate for hepatic miR-122 and positively correlated with hepatic necroinflammation. Patients who showed complete early virologic response and SVR had significantly higher pretreatment serum miR-122 levels than those with NR (P = 0.001 and P = 0.008, respectively), especially in subgroups of patients with hepatitis C virus genotype 2 and IL-28B rs8099917 TT genotype. Patients with IL-28B TT genotype had significantly better treatment responses and higher pretreatment serum miR-122 level than those with GT or GG genotypes. Univariate analysis showed that pretreatment body mass index, γ-glutamyl transpeptidase, triglyceride, IL-28B TT genotype, and serum miR-122 are predictors for SVR. Multivariate analysis specifically in IL-28B TT genotype demonstrated that pretreatment serum miR-122 independently predicted SVR. The validation cohort confirmed a significantly greater pretreatment serum miR-122 level in patients with SVR compared with NR (P = 0.025). In conclusion, serum miR-122 may serve as a surrogate of hepatic miR-122, and a higher pretreatment serum miR-122 level can help predict virologic responses to pegylated IFN plus ribavirin therapy.

Predictive value of serum sST2 in preschool wheezers for development of asthma with high FeNO.

PubMed

Ketelaar, M E; van de Kant, K D; Dijk, F N; Klaassen, E M; Grotenboer, N S; Nawijn, M C; Dompeling, E; Koppelman, G H

2017-11-01

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1 (IL1RL1 or ST2) is a well-replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3 years-old wheezers do not predict doctors' diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95% CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95% CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Job stress and agentic-communal personality traits related to serum cortisol levels of male workers in a Japanese medium-sized company: a cross-sectional study.

PubMed

Hirokawa, Kumi; Taniguchi, Toshiyo; Fujii, Yasuhito

2015-02-01

Although serum cortisol is a widely accepted index of stress levels, associations between job stress and cortisol levels have been inconsistent. Individual differences in personality traits were discussed as one compelling explanation for this discrepancy. Agentic-communal personality traits have been examined as possible predictive factors for psychological stress. This study investigated correlations among agentic-communal personality traits and serum cortisol levels. It was also investigated whether job stress levels modified correlations between agentic-communal personality and cortisol levels. Participants were 198 male workers (mean age = 52.2 years) employed by a shipbuilding company in Japan. Questionnaire data and blood samples were collected during an annual health checkup. Participants completed a self-report questionnaire that included the Job Content Questionnaire (JCQ) that assesses job control as job stress levels the Communion-Agency scale (CAS) and questions regarding health behaviors. Communion positively correlated with serum cortisol levels and unmitigated agency negatively correlated with serum cortisol levels. Stratified by job control, communion positively correlated with serum cortisol levels and agency negatively correlated with serum cortisol levels in participants with low levels of job control. Unmitigated agency negatively correlated with serum cortisol levels in participants with high levels of job control. Levels of job control may modify correlations of gender-related personality with serum cortisol levels. Especially with exposure to high job stress, male workers with high femininity (i.e., high communion and low agency) were more likely to have a high stress response as measured by serum cortisol levels.

Association between Serum Interleukin-17A Level and High-Altitude Deacclimatization Syndrome

PubMed Central

He, Binfeng; Li, Hongli; Hu, Mingdong; Dong, Weijie; Wei, Zhenghua; Li, Jin; Yao, Wei; Guo, Xiaolan

2016-01-01

High-altitude deacclimatization syndrome (HADAS) is emerging as a severe public health issue that threatens the quality of life of individuals who return to lower altitude from high altitude. In this study, we measured serum levels of SOD, MDA, IL-17A, IL-10, TNF-α, and HADAS score in HADAS subjects at baseline and 50th and 100th days and to evaluate the relationship between interleukins, including IL-17A, and HADAS. Our data showed that and the serum IL-17A levels and HADAS score decreased over time in the HADAS group, and serum IL-17A levels were significantly higher in the HADAS group at baseline and 50th day compared with controls (p < 0.05). Furthermore, baseline serum levels of MDA and TNF-α were significantly higher, while SOD and IL-10 levels were lower in HADAS subjects compared with controls (p < 0.05). It is interesting that serum levels of IL-17A were clearly interrelated with HADAS incidence and severity (p < 0.05). ROC curve analysis showed that combined serum IL-17A and IL-10 levels were a better predictor of HADAS incidence than serum levels of IL-17A or IL-10 alone. These data suggest that serum levels of IL-17A are a novel predictive index of HADAS. PMID:27190491

Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.

PubMed

Afarideh, Mohsen; Aryan, Zahra; Ghajar, Alireza; Noshad, Sina; Nakhjavani, Manouchehr; Baber, Usman; Mechanick, Jeffrey I; Esteghamati, Alireza

2016-11-01

We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], p for trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

"Anti-Mullerian Hormone: Marker for Ovarian Response in Controlled Ovarian Stimulation for IVF Patients": A First Pilot Study in the Indian Population.

PubMed

Singh, Neeta; Malik, Ekta; Banerjee, Ayan; Chosdol, Kunzang; Sreenivas, V; Mittal, Suneeta

2013-08-01

To measure the levels of early follicular phase Anti-Mullerian hormone (AMH) in Indian patients of IVF and to evaluate the AMH as a predictive marker of ovarian response in assisted reproductive technology outcome. Sixty women (age 25-40 years) selected for in vitro fertilization treatment were included in this study. Analysis of day-2 serum samples was done for the AMH, FSH, Inhibin B, and LH by ELISA kit methods. USG was done for the antral follicle count (AFC) and oocytes' retrieval. Hormone parameters were compared and correlated with the oocytes' retrieval count and the AFC. The discriminant analysis was done to compare relevance of different parameters for predicting ovarian response. The Anti-Mullerian hormone showed a significant correlation with the oocytes' retrieval after ovulation induction for IVF (r = 0.648, p < 0.0001) and no correlation was seen with serum FSH, LH, and Inhibin. Serum AMH levels show 80 % sensitivity and 80 % specificity in predicting poor ovarian response. There is a significant correlation between day-2 serum AMH levels and the oocytes' retrieval count in women undergoing ovulation induction for IVF, and the AMH is a good marker as the negative predictive values for the success of ART. There is no correlation found between other hormonal ovarian reserve markers and the oocytes' retrieval count.

Dynamics of postoperative serum cortisol after transsphenoidal surgery for Cushing's disease: implications for immediate reoperation and remission.

PubMed

Mayberg, Marc; Reintjes, Stephen; Patel, Anika; Moloney, Kelley; Mercado, Jennifer; Carlson, Alex; Scanlan, James; Broyles, Frances

2017-12-22

OBJECTIVE Successful transsphenoidal surgery for adrenocorticotropin hormone (ACTH)-producing pituitary tumors is associated with subnormal postoperative serum cortisol levels, which may guide decisions regarding immediate reoperation. However, little is known about the detailed temporal course of changes in serum cortisol in the immediate postoperative period, and the relationship of postoperative cortisol dynamics to remission and late recurrence. METHODS A single-center retrospective cohort analysis was performed for all patients undergoing pituitary surgery from 2007 through 2015. Standardized diagnostic and treatment algorithms were applied to all patients with potential Cushing's disease (CD), including microsurgical transsphenoidal adenomectomy (TSA) by a single surgeon. All patients had serum cortisol levels drawn at 6-hour intervals for 72 hours after surgery, and were offered reoperation within 3 days for normal or supranormal postoperative cortisol levels. Primary outcomes were 6-month remission and late recurrence; secondary outcomes were persistent postoperative hypocortisolism and surgical morbidity. Discriminatory levels of postoperative serum cortisol for predicting remission were calculated at various intervals after surgery using receiver operating characteristic (ROC) curves. RESULTS Among 89 patients diagnosed with CD, 81 underwent initial TSA for a potentially curable lesion; 23 patients (25.8%) underwent an immediate second TSA. For the entire cohort, 6-month remission was achieved in 77.8% and late recurrences occurred in 9.5%, at a mean of 43.5 months. Compared with patients with a single surgery, those with an immediate second TSA had similar rates of remission (78.3% vs 77.6%) and late recurrence (5.6% vs 11.1%). The rate of hypocortisolism for patients with 2 surgeries (12/23, 52.2%) was significantly greater than that for patients with single surgeries (13/58, 22.4%; p < 0.001). There was no difference in the incidence of CSF leaks between the first and second operations. Remission was achieved in 58 (92.1%) of 64 patients who completed the 2-surgery protocol. The temporal course of postoperative serum cortisol levels among patients varied considerably, with subnormal nadir levels < 2 μg/dl occurring between 12 hours and 66 hours. Patients achieving remission had significantly lower mean serum cortisol levels at every time point after surgery (p < 0.01). By ROC curve analysis, nadir cortisol levels < 2.1 μg/dl were predictive of 6-month remission for the entire cohort over 3 days (positive predictive value [PPV] = 94%); discriminating cortisol levels for predicting remission on postoperative day (POD) 2 were < 5.4 μg/dl (PPV = 97%), although patients with remission after postoperative cortisol levels of 2-5 μg/dl had a significantly higher rate of late recurrence. CONCLUSIONS There is substantial variation in the temporal course of serum cortisol levels over the first 72 hours after TSA for CD, with nadir levels predictive for remission occurring as late as POD 3. Although a cortisol level of 2.1 μg/dl at any point was an accurate predictor of 6-month remission, levels less than 5.4 μg/dl on POD 2 were reasonably accurate. These data may enable decisions regarding the efficacy of an immediate second surgical procedure performed during the same hospitalization; immediate reoperation is associated with excellent remission rates and low recurrence rates in patients otherwise unlikely to achieve remission, but carries a higher risk of permanent hypocortisolism.

Association between serum ligands and the skin toxicity of anti-epidermal growth factor receptor antibody in metastatic colorectal cancer.

PubMed

Takahashi, Naoki; Yamada, Yasuhide; Furuta, Koh; Nagashima, Kengo; Kubo, Akiko; Sasaki, Yusuke; Shoji, Hirokazu; Honma, Yoshitaka; Iwasa, Satoru; Okita, Natsuko; Takashima, Atsuo; Kato, Ken; Hamaguchi, Tetsuya; Shimada, Yasuhiro

2015-05-01

Skin toxicity is a known clinical signature used to predict the prognosis of anti-epidermal growth factor receptor (EGFR) antibody treatment in metastatic colorectal cancer (mCRC). There are no biological markers to predict skin toxicity before anti-EGFR antibody treatment in mCRC patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from KRAS wild-type (WT) patients who received anti-EGFR antibody treatment. Serum levels of ligands were measured by ELISA. A total of 103 KRAS WT patients were enrolled in the study. Progression-free survival and overall survival of patients with a high grade (grade 2-3) of skin toxicity were significantly longer than those with a low grade (grade 0-1) of skin toxicity (median progression-free survival, 6.4 months vs 2.4 months, P < 0.001; median overall survival, 14.6 months vs 7.1 months, P = 0.006). There were significant differences in distribution of serum levels of epiregulin (EREG), amphiregulin (AREG), and hepatocyte growth factor (HGF) between groups of low/high grade of skin toxicity (P < 0.048, P < 0.012, P < 0.012, respectively). In addition, serum levels of HGF, EREG, and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran-Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG, and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti-EGFR antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in mCRC patients. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Serum uric acid level predicts adverse outcomes after myocardial revascularization or cardiac valve surgery.

PubMed

Lazzeroni, Davide; Bini, Matteo; Camaiora, Umberto; Castiglioni, Paolo; Moderato, Luca; Bosi, Davide; Geroldi, Simone; Ugolotti, Pietro T; Brambilla, Lorenzo; Brambilla, Valerio; Coruzzi, Paolo

2018-01-01

Background High levels of serum uric acid have been associated with adverse outcomes in cardiovascular diseases such as myocardial infarction and heart failure. The aim of the current study was to evaluate the prognostic role of serum uric acid levels in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. Design We performed an observational prospective cohort study. Methods The study included 1440 patients with available serum uric acid levels, prospectively followed for 50 ± 17 months. Mean age was 67 ± 11 years; 781 patients (54%) underwent myocardial revascularization, 474 (33%) cardiac valve surgery and 185 (13%) valve-plus-coronary artery by-pass graft surgery. The primary endpoints were overall and cardiovascular mortality while secondary end-points were combined major adverse cardiac and cerebrovascular events. Results Serum uric acid level mean values were 286 ± 95 µmol/l and elevated serum uric acid levels (≥360 µmol/l or 6 mg/dl) were found in 275 patients (19%). Overall mortality (hazard ratio = 2.1; 95% confidence interval: 1.5-3.0; p < 0.001), cardiovascular mortality (hazard ratio = 2.0; 95% confidence interval: 1.2-3.2; p = 0.004) and major adverse cardiac and cerebrovascular events rate (hazard ratio = 1.5; 95% confidence interval: 1.0-2.0; p = 0.019) were significantly higher in patients with elevated serum uric acid levels, even after adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate, atrial fibrillation and medical therapy. Moreover, strong positive correlations between serum uric acid level and probability of overall mortality ( p < 0.001), cardiovascular mortality ( p < 0.001) and major adverse cardiac and cerebrovascular events ( p = 0.003) were found. Conclusions Serum uric acid levels predict mortality and adverse cardiovascular outcome in patients undergoing myocardial revascularization and/or cardiac valve surgery even after the adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate and medical therapy.

Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer.

PubMed

Guo, Suyang; Yang, Bo; Liu, Hongli; Li, Yuzhi; Li, Shengze; Ma, Ling; Liu, Jian; Guo, Wei

2017-01-01

The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21-33.20) mg/mL, 4.78 (0.22-175.20) mg/mL, and 11.56 (2.028-123.66) IU/mL for NRG and 5.64 (0.50-136.80) mg/mL, 22.41 (0.56-588.90) mg/mL, and 25.41 (3.658-3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= -0.13, P = 0.56) was found in the RG patients. Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.

Clinical Significance of Serum IL-6 and TNF-α Levels in Patients with Metabolic Syndrome.

PubMed

Mohammadi, Mojgan; Gozashti, Mohammad Hossein; Aghadavood, Majid; Mehdizadeh, Mohammad Reza; Hayatbakhsh, Mohammad Mahdi

2017-10-01

Several components of metabolic syndrome (MetS) facilitate its diagnosis, including abdominal obesity, hyperlipidemia, high blood pressure, and insulin resistance. The production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) seem to be associated with MetS components. The aim of this study was to evaluate the correlation between IL-6 and TNF-α serum levels with MetS and its components. This case-control study investigated 250 subjects, comprising 125 healthy controls from the Kerman Blood Transfusion Organization and 125 MetS patients. Serum IL-6 and TNF-α levels were measured using the enzyme-linked immunosorbent assay (ELISA). Serum IL-6 and TNF-α levels were greater in MetS patients than in controls. However, no correlation was observed between MetS components and IL-6 or TNF-α serum levels. Patients with MetS had significantly greater serum IL-6 and TNF-α levels than the controls, supporting the evidence that inflammation plays an important role in the immunopathogenesis of the disease. Additionally, IL-6 and TNF-α serum levels may predict MetS. The lack of association between IL-6 and TNF-α serum levels and MetS components remains to be investigated by further research.

Serum PTHrP level as a biomarker in assessing skeletal maturation during circumpubertal development.

PubMed

Hussain, Mohammed Zahid; Talapaneni, Ashok Kumar; Prasad, Mandava; Krishnan, Ramalingam

2013-04-01

Many investigators have studied the cellular organization and the local and systemic factors regulating endochondral bone growth in the growth plate and condylar cartilage. Parathyroid hormone-related protein (PTHrP) and Indian hedgehog protein have been reported to regulate multiple steps during such skeletal morphogenesis. The aims of this study were to quantify serum PTHrP levels at 6 cervical vertebral stages and to correlate serum PTHrP levels to the 6 skeletal maturation stages for use as a biologic indicator of skeletal maturation. Mean serum PTHrP levels were measured in 90 subjects categorized into 6 cervical vertebral stages. Mean serum PTHrP levels were significantly higher in the late pubertal stages than in the early pubertal stages. Pearson correlation showed that serum PTHrP levels had a positive correlation with cervical vertebral maturation stages from the prepubertal to the late pubertal stages, and a negative correlation from the late pubertal to the postpubertal stages. Peak serum PTHrP levels do not correlate with early pubertal stages characterized by maximum growth increments. Hence, the validity of using serum PTHrP levels to predict peak growth velocity is questionable. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Ferritin levels predict severe dengue.

PubMed

Soundravally, R; Agieshkumar, B; Daisy, M; Sherin, J; Cleetus, C C

2015-02-01

Currently, no tests are available to monitor and predict severity and outcome of dengue. To find potential markers that predict dengue severity, the present study validated the serum level of three acute-phase proteins α-1 antitrypsin, ceruloplasmin and ferritin in a pool of severe dengue cases compared to non-severe forms and other febrile illness controls. A total of 96 patients were divided into two equal groups with group 'A' comprising dengue-infected cases and group 'B' with other febrile illness cases negative for dengue. Out of 48 dengue-infected cases, 13 had severe dengue and the remaining 35 were classified as non-severe dengue. Immunoassays were performed to evaluate the serum levels of acute-phase proteins both on the day of admission and on the day of defervescence. The efficiency of individual proteins in predicting the disease severity was assessed using receiver operating characteristic curve. The study did not find any significant difference in the levels of α-1 antitrypsin between the clinical groups. A significant increase in the levels of ceruloplasmin around defervescence in severe cases compared to non-severe and other febrile controls was observed and this is the first report describing the potential association of ceruloplasmin and dengue severity. Interestingly, a steady increase in the level of serum ferritin was recorded throughout the course of illness. Among all the three proteins, the elevated ferritin level could predict the disease severity with highest sensitivity and specificity of 76.9 and 83.3 %, respectively, on the day of admission and the same was found to be 90 and 91.6 % around defervescence. On the basis of this diagnostic efficiency, we propose that ferritin may serve as a potential biomarker for an early prediction of disease severity.

Predictive values of semi-quantitative procalcitonin test and common biomarkers for the clinical outcomes of community-acquired pneumonia.

PubMed

Ugajin, Motoi; Yamaki, Kenichi; Hirasawa, Natsuko; Yagi, Takeo

2014-04-01

The semi-quantitative serum procalcitonin test (Brahms PCT-Q) is available conveniently in clinical practice. However, there are few data on the relationship between results for this semi-quantitative procalcitonin test and clinical outcomes of community-acquired pneumonia (CAP). We investigated the usefulness of this procalcitonin test for predicting the clinical outcomes of CAP in comparison with severity scoring systems and the blood urea nitrogen/serum albumin (B/A) ratio, which has been reported to be a simple but reliable prognostic indicator in our prior CAP study. This retrospective study included data from subjects who were hospitalized for CAP from August 2010 through October 2012 and who were administered the semi-quantitative serum procalcitonin test on admission. The demographic characteristics; laboratory biomarkers; microbiological test results; Pneumonia Severity Index scores; confusion, urea nitrogen, breathing frequency, blood pressure, ≥ 65 years of age (CURB-65) scale scores; and age, dehydration, respiratory failure, orientation disturbance, pressure (A-DROP) scale scores on hospital admission were retrieved from their medical charts. The outcomes were mortality within 28 days of hospital admission and the need for intensive care. Of the 213 subjects with CAP who were enrolled in the study, 20 died within 28 days of hospital admission, and 32 required intensive care. Mortality did not differ significantly among subjects with different semi-quantitative serum procalcitonin levels; however, subjects with serum procalcitonin levels ≥ 10.0 ng/mL were more likely to require intensive care than those with lower levels (P < .001). The elevation of semi-quantitative serum procalcitonin levels was more frequently observed in subjects with proven etiology, especially pneumococcal pneumonia. Using the receiver operating characteristic curves for mortality, the area under the curve was 0.86 for Pneumonia Severity Index class, 0.81 for B/A ratio, 0.81 for A-DROP, 0.80 for CURB-65, and 0.57 for semi-quantitative procalcitonin test. The semi-quantitative serum procalcitonin level on hospital admission was less predictive of mortality from CAP compared with the B/A ratio. However, the subjects with serum procalcitonin levels ≥ 10.0 ng/mL were more likely to require intensive care than those with lower levels.

Serum neutrophil gelatinase-associated lipocalin (NGAL) in predicting worsening renal function in acute decompensated heart failure.

PubMed

Aghel, Arash; Shrestha, Kevin; Mullens, Wilfried; Borowski, Allen; Tang, W H Wilson

2010-01-01

The development of worsening renal function (WRF, defined as creatinine rise >or=0.3mg/dL) occurs frequently in the setting of acute decompensated heart failure (ADHF) and strongly predicts adverse clinical outcomes. Neutrophil gelatinase-associated lipocalin (NGAL) is produced by the nephron in response to tubular epithelial damage and serves as an early marker for acute renal tubular injury. We sought to determine the relationship between admission serum NGAL levels and WRF in the setting of ADHF. We measured serum NGAL levels in 91 patients admitted to the hospital with ADHF. Patients were adjudicated by independent physician into those that did or did not develop WRF over the ensuing 5 days of in-hospital treatment. In our study cohort (68% male, mean age 61+/-15 years, mean left ventricular ejection fraction 31+/-14%), median admission serum NGAL level was 165 ng/mL (interquartile range [IQR] 108-235 ng/mL). Thirty-five patients (38%) developed WRF within the 5-day follow-up. Patients who developed WRF versus those without WRF had significantly higher median admission serum NGAL levels (194 [IQR 150-292] ng/mL vs. 128 [IQR 97-214] ng/mL, P=.001). High serum NGAL levels at admission were associated with greater likelihood of developing WRF (odds ratio: 1.92, 95% confidence interval 1.23-3.12, P=.004). In particular, admission NGAL >or=140 ng/mL had a 7.4-fold increase in risk of developing WRF, with a sensitivity and specificity of 86% and 54%, respectively. The presence of elevated admission serum NGAL levels is associated with heightened risk of subsequent development of WRF in patients admitted with ADHF.

Hyperandrogenemia Predicts Metabolic Phenotype in Polycystic Ovary Syndrome: The Utility of Serum Androstenedione

PubMed Central

O'Reilly, Michael W.; Taylor, Angela E.; Crabtree, Nicola J.; Hughes, Beverly A.; Capper, Farfia; Crowley, Rachel K.; Stewart, Paul M.; Tomlinson, Jeremy W.

2014-01-01

Context: Polycystic ovary syndrome (PCOS) is a triad of anovulation, insulin resistance, and hyperandrogenism. Androgen excess may correlate with metabolic risk and PCOS consensus criteria define androgen excess on the basis of serum T. Here we studied the utility of the androgen precursor serum androstenedione (A) in conjunction with serum T for predicting metabolic dysfunction in PCOS. Patients and Methods: Eighty-six PCOS patients fulfilling Rotterdam diagnostic consensus criteria and 43 age- and body mass index-matched controls underwent measurement of serum androgens by tandem mass spectrometry and an oral glucose tolerance test with homeostatic model assessment of insulin resistance and insulin sensitivity index calculation. We analyzed 24-hour urine androgen excretion by gas chromatography/mass spectrometry. Results: PCOS patients had higher levels of serum androgens and urinary androgen metabolites than controls (all P < .001). Within the PCOS cohort, both serum A and T were positively correlated with the free androgen index (T × 100/SHBG) and total androgen metabolite excretion (all P < .001). All subjects with T above the normal reference range [high T (HT)] also had high A (HA/HT group, n = 56). However, the remaining 30 patients had normal T levels, either in the presence of HA (HA/NT; n = 20) or normal A (NA/NT; n = 10). The groups did not differ in age or BMI. The HA/HT and HA/NT groups had higher total androgen excretion than NA/NT (P < .01 and P < .05, respectively). Multiple linear regression showed a strong negative association between serum androstenedione and insulin sensitivity. The incidence of dysglycemia according to an oral glucose tolerance test increased with the severity of androgen phenotype (NA/NT, 0%; HA/NT, 14%; HA/HT, 25%, P = .03). Conclusion: Simultaneous measurement of serum T and A represents a useful tool for predicting metabolic risk in PCOS women. HA levels are a sensitive indicator of PCOS-related androgen excess. PMID:24423344

Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione.

PubMed

O'Reilly, Michael W; Taylor, Angela E; Crabtree, Nicola J; Hughes, Beverly A; Capper, Farfia; Crowley, Rachel K; Stewart, Paul M; Tomlinson, Jeremy W; Arlt, Wiebke

2014-03-01

Polycystic ovary syndrome (PCOS) is a triad of anovulation, insulin resistance, and hyperandrogenism. Androgen excess may correlate with metabolic risk and PCOS consensus criteria define androgen excess on the basis of serum T. Here we studied the utility of the androgen precursor serum androstenedione (A) in conjunction with serum T for predicting metabolic dysfunction in PCOS. Eighty-six PCOS patients fulfilling Rotterdam diagnostic consensus criteria and 43 age- and body mass index-matched controls underwent measurement of serum androgens by tandem mass spectrometry and an oral glucose tolerance test with homeostatic model assessment of insulin resistance and insulin sensitivity index calculation. We analyzed 24-hour urine androgen excretion by gas chromatography/mass spectrometry. PCOS patients had higher levels of serum androgens and urinary androgen metabolites than controls (all P < .001). Within the PCOS cohort, both serum A and T were positively correlated with the free androgen index (T × 100/SHBG) and total androgen metabolite excretion (all P < .001). All subjects with T above the normal reference range [high T (HT)] also had high A (HA/HT group, n = 56). However, the remaining 30 patients had normal T levels, either in the presence of HA (HA/NT; n = 20) or normal A (NA/NT; n = 10). The groups did not differ in age or BMI. The HA/HT and HA/NT groups had higher total androgen excretion than NA/NT (P < .01 and P < .05, respectively). Multiple linear regression showed a strong negative association between serum androstenedione and insulin sensitivity. The incidence of dysglycemia according to an oral glucose tolerance test increased with the severity of androgen phenotype (NA/NT, 0%; HA/NT, 14%; HA/HT, 25%, P = .03). Simultaneous measurement of serum T and A represents a useful tool for predicting metabolic risk in PCOS women. HA levels are a sensitive indicator of PCOS-related androgen excess.

Predictive value of uterine contractility and the serum levels of progesterone and oestrogens with regard to preterm labour.

PubMed

Smit, D A; Essed, G G; de Haan, J

1984-01-01

A longitudinal investigation regarding the serum concentrations of oestradiol, oestriol and progesterone in relation to uterine activity has been performed in 80 healthy primigravid women during the course of pregnancy up to the 37th week of pregnancy. The frequency of uterine contractions was quantitatively objectivated by means of external toco-dynamometry; simultaneously the uterine activity has been recorded by the pregnant women qualitatively. It appears that there is a gradual increase of all the three mentioned hormones during the course of pregnancy. However, there is a large interindividual spread. There exists no relation between the hormonal serum levels and uterine activity (quantitatively as well as qualitatively recorded). Between these two latter there is a poor relation. It is impossible to predict the occurrence of preterm birth based on hormonal serum changes. This holds for the progesterone-oestradiol ratio.

Maternal c-reactive protein and oxidative stress markers as predictors of delivery latency in patients experiencing preterm premature rupture of membranes.

PubMed

Ryu, Hyun Kyung; Moon, Jong Ho; Heo, Hyun Ji; Kim, Jong Woon; Kim, Yoon Ha

2017-02-01

To evaluate the usefulness of maternal serum c-reactive protein (CRP), lipid peroxide, and oxygen radical absorbance capacity (ORAC), to predict the interval between membrane rupture and delivery in patients with preterm premature rupture of membranes (PPROM). The present prospective study included patients with singleton pregnancies experiencing PPROM at earlier than 34 weeks of pregnancy who underwent spontaneous vaginal delivery between August 1, 2010 and July 31, 2013 at Chonnam National University Hospital, Republic of Korea. Patients were categorized based on whether delivery occurred within 3 days of PPROM or after. CRP levels, lipid peroxide (using malondialdehyde levels), ORAC, protein carbonyl, and other potential risk factors were compared between the groups. There were 72 patients included. Maternal serum CRP levels, malondialdehyde levels, and Bishop Score were higher in patients who underwent delivery within 3 days (all P<0.05); ORAC levels were lower among these patients (P=0.002). A receiver operating characteristic curve analysis showed that CRP, malondialdehyde, and ORAC levels were predictive of delivery within 3 days after PPROM. Maternal serum CRP, malondialdehyde, and ORAC levels at admission were useful in predicting the latent period in patients with PPROM. © 2016 International Federation of Gynecology and Obstetrics.

Levels and Concentration Ratios of Polychlorinated Biphenyls and Polybrominated Diphenyl Ethers in Serum and Breast Milk in Japanese Mothers

PubMed Central

Inoue, Kayoko; Harada, Kouji; Takenaka, Katsunobu; Uehara, Shigeki; Kono, Makoto; Shimizu, Takashi; Takasuga, Takumi; Senthilkumar, Kurunthachalam; Yamashita, Fumiyoshi; Koizumi, Akio

2006-01-01

Blood and/or breast milk have been used to assess human exposure to various environmental contaminants. Few studies have been available to compare the concentrations in one matrix with those in another. The goals of this study were to determine the current levels of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in Japanese women, with analysis of the effects of lifestyle and dietary habits on these levels, and to develop a quantitative structure–activity relationship (QSAR) with which to predict the ratio of serum concentration to breast milk concentration. We measured PBDEs and PCBs in 89 paired samples of serum and breast milk collected in four regions of Japan in 2005. The geometric means of the total concentrations of PBDE (13 congeners) in milk and serum were 1.56 and 2.89 ng/g lipid, respectively, whereas those of total PCBs (15 congeners) were 63.9 and 37.5 ng/g lipid, respectively. The major determinant of total PBDE concentration in serum and milk was the geographic area within Japan, whereas nursing duration was the major determinant of PCB concentration. BDE-209 was the most predominant PBDE congener in serum but not in milk. The excretion of BDE 209 in milk was lower than that of BDE 47 and BDE 153. QSAR analysis revealed that two parameters, calculated octanol/water partition and number of hydrogen-bond acceptors, were significant descriptors. During the first weeks of lactation, the predicted partitioning of PBDE and PCB congeners from serum to milk agreed with the observed values. However, the prediction became weaker after 10 weeks of nursing. PMID:16882522

Relationship of Liver X Receptors α and Endoglin Levels in Serum and Placenta with Preeclampsia.

PubMed

Wang, Jing; Dong, Xing; Wu, Hong-Yan; Wu, Nan; Zhang, Xue-Jun; Wang, Xin; Shang, Li-Xin

2016-01-01

Liver X receptor alpha (LXRα) and endoglin have been postulated to play roles in trophoblast invasion and lipid metabolic disturbances. However, the relationship between LXRα and endoglin levels in serum and placenta of patients with preeclampsia remains poorly understood. The objective of this study was to identify correlations between LXRα, endoglin and preeclampsia and provide new feasible methods of clinical prediction and treatment for preeclampsia. We enrolled 45 patients with preeclampsia (24 with moderate preeclampsia and 21 with severe preeclampsia) and 15 normal pregnant women (control group) who were admitted to the Department of Obstetrics of the General Hospital of Beijing Command between October 2012 and July 2013 in this study. Serum and placental LXRα and endoglin levels were analyzed by enzyme-linked immunosorbent assay, real-time quantitative PCR, tissue microarray and immunohistochemistry. Serum and placental LXRα and endoglin levels were significantly higher in patients with preeclampsia than those in control group (P<0.05, each). Moreover, patients with severe preeclampsia displayed significantly higher LXRα and endoglin levels than those with moderate preeclampsia (P<0.05, each). The LXRα sensitivity, specificity and positive and negative predictive values were 66.00%, 80.00%, 89.19% and 48.48%, respectively, while those of endoglin levels were 62.00%, 85.00%, 91.18% and 47.22%, respectively. LXRα and endoglin levels in serum and placenta from patients with preeclampsia were positively correlated (serum: r = 0.486, P<0.01; placenta: r = 0.569, P<0.01). Elevated LXRα and endoglin levels may be associated with preeclampsia pathogenesis and development and could be used as potential predictors for this disorder.

Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma.

PubMed

Yao, Mingjie; Zhao, Jingmin; Lu, Fengmin

2016-01-26

Use of serum alpha-fetoprotein (AFP) in clinical practices has been challenged in recent years, due to the lack of specificity and sensitivity. Here we conducted a retrospective study to evaluate the diagnostic and prognostic value of serum AFP among hepatocellular carcinoma (HCC) patients with their pathogenic features taken into consideration. The cohort for this study comprised 318 cases of hepatitis and 731 cases of cirrhosis, as well as 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum hepatitis B surface antigen (HBsAg) positive HCC patients was significantly higher than that in those HBsAg negative HCC patients (79.55% vs 56.49%, P < 0.000). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml vs 40.82ng/ml, P < 0.000). In addition, Kaplan-Meier curve analysis revealed that lower preoperative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients etiologically irrelevant to HBV infection. We believe that serum AFP is of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and strongly suggest use of serum AFP as a biomarker in China and other HBV infection endemic area like Southeast Asia.

Low serum level of COMP, a cartilage turnover marker, predicts rapid and high ACR70 response to adalimumab therapy in rheumatoid arthritis.

PubMed

Morozzi, G; Fabbroni, M; Bellisai, F; Cucini, S; Simpatico, A; Galeazzi, M

2007-08-01

The aim of this study was to evaluate serum biomarkers, used in clinical routine, to predict the American College of Rheumatology (ACR) response to long-term anti-TNF alpha treatment (adalimumab). Sera from 29 consecutive rheumatoid arthritis patients were analysed for anti-cyclic citrullinated peptide (anti-CCP), cartilage oligomeric matrix protein (COMP) and IgM and IgA RFs (class-specific rheumatoid factors) at the start of treatment with adalimumab and after 3, 6 and 12 months. The response to the therapy was evaluated by ACR 20, 50, 70 and by DAS 28 scores. The mean serum COMP level of the population did not change after treatment. However, patients with low serum COMP levels (<10 U/l) at baseline showed a significant (p<0.02) higher ACR70 response (>50%) within 3 months, and also at 6 months, than patients with higher COMP values (ACR70<20%). This was also reflected by significantly higher decrease in DAS score at 3 (p<0.02) and 6 months (p<0.01) treatments. The IgM RF titre decreased significantly (p=0.02) after the therapy, but the percentage of serum positivity for anti-CCP and IgA/IgM RF did not change. No significant correlation was shown between serum COMP levels and C-reactive protein/erythrocyte sedimentation rate during the follow-up. Neither were any correlations shown between ACR/DAS 28 scores and anti-CCP, Ig M/IgA RFs. Our data indicate that low (<10 U/l) serum COMP before starting anti-TNF alpha treatment predicts a rapid (within 3 months) and high ACR70 response compared to RA patients with higher COMP values. This might reflect different mechanisms in the cartilage process in the RA disease at that time of treatment with different therapeutic sensitivity to anti-TNF alpha treatment.

Mid-infrared fibre evanescent wave spectroscopy of serum allows fingerprinting of the hepatic metabolic status in mice.

PubMed

Le Corvec, Maëna; Allain, Coralie; Lardjane, Salim; Cavey, Thibault; Turlin, Bruno; Fautrel, Alain; Begriche, Karima; Monbet, Valérie; Fromenty, Bernard; Leroyer, Patricia; Guggenbuhl, Pascal; Ropert, Martine; Sire, Olivier; Loréal, Olivier

2016-10-24

Non-alcoholic fatty liver disease is associated with obesity, diabetes, and metabolic syndrome. The detection of systemic metabolic changes associated with alterations in the liver status during non-alcoholic fatty liver disease could improve patient follow-up. The aim of the present study was to evaluate the potential of mid-infrared fibre evanescent wave spectroscopy as a minimum-invasive method for evaluating the liver status during non-alcoholic fatty liver disease. Seventy-five mice were subjected to a control, high-fat or high-fat-high carbohydrate diets. We analysed the serum biochemical parameters and mRNA levels of hepatic genes by quantitative RT-PCR. Steatosis was quantified by image analysis. The mid-infrared spectra were acquired from serum, and then analysed to develop a predictive model of the steatosis level. Animals subjected to enriched diets were obese. Hepatic steatosis was found in all animals. The relationship between the spectroscopy-predicted and observed levels of steatosis, expressed as percentages of the liver biopsy area, was not linear. A transition around 10% steatosis was observed, leading us to consider two distinct predictive models (<10% and >10%) based on two different sets of discriminative spectral variables. The model performance was evaluated using random cross-validation (10%). The hypothesis that additional metabolic changes occur beyond this transition was supported by the fact that it was associated with increased serum ALT levels, and Col1α1 chain mRNA levels. Our data suggest that mid-infrared spectroscopy combined with statistical analysis allows identifying serum mid-infrared signatures that reflect the liver status during non-alcoholic fatty liver disease.

Relationship between family history of type 2 diabetes and serum FGF21.

PubMed

Davis, Greggory R; Deville, Tiffany; Guillory, Joshua; Bellar, David; Nelson, Arnold G

2017-11-01

Determining predictive markers for the development of type 2 diabetes (T2D), particularly in young individuals, offers immense potential benefits in preventative medicine. Previous research examining serum fibroblast growth factor 21 (FGF21) in humans has revealed equivocal relationships with clinical markers of metabolic dysfunction. However, it is unknown to what extent, if any, first-degree family history of T2D (mother or father of the participant diagnosed with T2D) level affects serum FGF21 levels. The aim of this study was to determine whether in healthy individuals with FH+ (n = 18) and without FH- (n = 17) a family history of T2D affects serum FGF21. Fasting serum and clinical, metabolic and anthropometric measures were determined using a cross-sectional design. Differences between groups for FGF21 were not significant (FH+ = 266 pg/mL ± 51·4, FH = 180 pg/mL ± 29; Z = 0·97, P = 0·33). Adiponectin values were lower in FH+ (8·81 μg/mL ± 2·14) compared to FH- (10·65 μg/mL ± 1·44; F = 8·83, P = 0·01). Resistin was negatively correlated with FGF21 for all participants (r = -0·38, P = 0·03), but no other clinical, metabolic, or serum markers were predictive for serum FGF21 in FH+ or FH-. Serum FGF21 is not significantly different between FH+ and FH- in young, healthy individuals. Based upon the data of this pilot study, it is unclear whether serum FGF21 can be used as a stand-alone predictive marker for T2D in healthy subjects. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Circulating irisin and chemerin levels as predictors of seizure control in children with idiopathic epilepsy.

PubMed

Elhady, Marwa; Youness, Eman R; Gafar, Heba S; Abdel Aziz, Ali; Mostafa, Rehab S I

2018-06-02

Irisin and chemerin peptides expression are triggered by hypoxia and involved in activation of inflammatory cascades in various organs including the brain; however, their role in epilepsy is not fully illustrated. This study aims to explore the predictive role of irisin and chemerin for seizure control in children with idiopathic epilepsy. This cross-sectional comparative study included 50 children with idiopathic epilepsy; 25 of them had controlled seizures over the previous 6 months and 30 age- and sex-matched healthy children as controls. Epilepsy characteristics, seizure severity Chalfont score, and response to medications were assessed in relation to serum irisin and chemerin levels. In comparison to healthy controls, serum chemerin and irisin levels were significantly higher in children with idiopathic epilepsy especially those with uncontrolled seizures. Serum chemerin and irisin levels had significant positive correlation with seizure severity Chalfont score and the duration of epilepsy. Elevated Chalfont score (OR 3.19), serum chemerin (OR 2.01), and irisin (OR 2.03) are predictors of uncontrolled seizures. Circulating chemerin and irisin have 80% and 76% sensitivity and 88% and 92% specificity at cutoff point > 191.38 ng/ml and > 151.2 ng/ml respectively for prediction of uncontrolled seizures in children with idiopathic epilepsy. Elevated circulating level of irisin and chemerin may predict poor seizure control in children with idiopathic epilepsy suggesting the role of hypoxia-triggered neuroinflammation in the pathogenesis of childhood idiopathic epilepsy.

Lysophosphatidic Acid and Apolipoprotein A1 Predict Increased Risk of Developing World Trade Center Lung Injury: A Nested Case-Control Study

PubMed Central

Tsukiji, Jun; Cho, Soo Jung; Echevarria, Ghislaine C.; Kwon, Sophia; Joseph, Phillip; Schenck, Edward J.; Naveed, Bushra; Prezant, David J.; Rom, William N.; Schmidt, Ann Marie; Weiden, Michael D.; Nolan, Anna

2014-01-01

Rationale Metabolic syndrome, inflammatory and vascular injury markers measured in serum after WTC exposures predict abnormal FEV1. We hypothesized that elevated LPA levels predict FEV1

The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan

PubMed Central

Kogiso, Tomomi; Kobayashi, Mutsuki; Yamamoto, Kuniko; Ikarashi, Yuichi; Kodama, Kazuhisa; Taniai, Makiko; Torii, Nobuyuki; Hashimoto, Etsuko; Tokushige, Katsutoshi

2017-01-01

Objective Hyponatremia is frequently observed in patients with decompensated liver cirrhosis and it is also related to a poor prognosis. The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level. In this study, we investigated (i) whether or not correction of the Na level improves the prognosis of cirrhotic patients with ascites and (ii) predictors of normalization of the serum Na level after tolvaptan therapy. Methods This was a single-center retrospective study. A total of 95 Japanese cirrhotic patients (60 men, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites treatment. The serum Na level was monitored during the period of tolvaptan treatment. The laboratory data and survival rates of patients who achieved serum Na levels of <135 and ≥135 mEq/L after 1 week were compared. Results Patients showed serum Na levels of 136 (121-145) mEq/L, and 42.1% had a serum Na level of <135 mEq/L. Among patients with an initial serum Na level <135 mEq/L, 60.0% achieved a normal level after 1 week, and the survival rate was significantly higher in patients with a normalized serum Na level (p<0.01). The pretreatment brain natriuretic peptide (BNP) level was predictive of achieving a serum Na level of ≥135 mEq/L (odds ratio: 0.87, 95% confidence interval: 0.316-0.987, p<0.05). Conclusion Normalization of the Na level after one week was associated with a favorable outcome of tolvaptan therapy, and Na correction improved the prognosis. PMID:28943585

Predictive value of serum β-hCG for early pregnancy outcomes among women with recurrent spontaneous abortion.

PubMed

Liu, Yinglin; Liu, Yukun; Li, Xuejiao; Jiao, Xuedan; Zhang, Rui; Zhang, Jianping

2016-10-01

To examine peak serum levels of the β-subunit of human chorionic gonadotropin (β-hCG) for prediction of early pregnancy outcomes among women with recurrent spontaneous abortion (RSA). In a retrospective study, the medical records of pregnant women with a history of RSA treated at Sun Yat-sen Memorial Hospital, China, between January 2011 and July 2013 were reviewed. Serum β-hCG had been measured twice weekly from 5 to 13weeks of pregnancy, and pregnancy was monitored by transvaginal ultrasonography to 13(+6)weeks. Optimal cutoff for peak β-hCG level was determined by receiver operator characteristic curve analysis and Youden index. Women were divided into four groups on the basis of optimal peak β-hCG cutoff and pregnancy outcome (pregnancy at 13weeks or spontaneous abortion). Peak β-hCG levels and length of pregnancy at this peak were examined. Overall, 1240 patients were included. The optimal cutoff value of peak β-hCG was 88 468IU/L, with a sensitivity, specificity, positive predictive value, and negative predictive value for successful pregnancy of 95.6%, 88.0%, 95.6%, and 89.0%, respectively. A faster rise in β-hCG, higher peak β-hCG, and longer pregnancy length at peak β-hCG were associated with successful early pregnancy. A cutoff value of serum β-hCG of 88 000IU/L could be used to predict early pregnancy outcomes for women with a history of RSA. Copyright © 2016. Published by Elsevier Ireland Ltd.

Non-survivor septic patients have persistently higher serum sCD40L levels than survivors.

PubMed

Lorente, Leonardo; Martín, María M; Pérez-Cejas, Antonia; Ferreres, José; Solé-Violán, Jordi; Labarta, Lorenzo; Díaz, César; Jiménez, Alejandro

2017-10-01

Soluble CD40 ligand (sCD40L) is a protein with proinflammatory and prothrombotic effects. Previously we found higher circulating sCD40L levels in non-survivor than in survivor patients at sepsis diagnosis. Now some questions arise such as how are serum sCD40L levels during the first week of severe sepsis?, is there an association between serum sCD40L levels during the first week and mortality?, and serum sCD40L levels during the first week could be used as sepsis mortality biomarker?. This study was developed to answer these asks. Study from 6 Spanish Intensive Care Units with 291 severe septic patients. There were determined serum levels of sCD40L and tumor necrosis factor (TNF)-alpha during the first week. The end-point study was 30-day mortality. We found that serum sCD40L at days 1, 4, and 8 could predict mortality at 30days, and are associated with mortality. The novel findings of our study were that there were higher serum sCD40L levels persistently during the first week in non-survivor than in survivor patients, that there is an association between serum sCD40L levels during the first week and sepsis mortality, and that serum sCD40L levels during the first week could be used as sepsis mortality biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

Feasibility of Predicting MCI/AD Using Neuropsychological Tests and Serum β-Amyloid

PubMed Central

Luis, Cheryl A.; Abdullah, Laila; Ait-Ghezala, Ghania; Mouzon, Benoit; Keegan, Andrew P.; Crawford, Fiona; Mullan, Michael

2011-01-01

We examined the usefulness of brief neuropsychological tests and serum Aβ as a predictive test for detecting MCI/AD in older adults. Serum Aβ levels were measured from 208 subjects who were cognitively normal at enrollment and blood draw. Twenty-eight of the subjects subsequently developed MCI (n = 18) or AD (n = 10) over the follow-up period. Baseline measures of global cognition, memory, language fluency, and serum Aβ1–42 and the ratio of serum Aβ1–42/Aβ1–40 were significant predictors for future MCI/AD using Cox regression with demographic variables, APOE ε4, vascular risk factors, and specific medication as covariates. An optimal sensitivity of 85.2% and specificity of 86.5% for predicting MCI/AD was achieved using ROC analyses. Brief neuropsychological tests and measurements of Aβ1–42 obtained via blood warrants further study as a practical and cost effective method for wide-scale screening for identifying older adults who may be at-risk for pathological cognitive decline. PMID:21660215

The utility of serum CA-125 in predicting extra-uterine disease in apparent early-stage endometrial cancer.

PubMed

Nicklin, James; Janda, Monika; Gebski, Val; Jobling, Thomas; Land, Russell; Manolitsas, Tom; McCartney, Anthony; Nascimento, Marcelo; Perrin, Lewis; Baker, Jannah F; Obermair, Andreas

2012-08-15

Surgical staging in early-stage uterine cancer is controversial. Preoperative serum CA-125 may be of clinical value in predicting the presence of extra-uterine disease in patients with apparent early-stage endometrial cancer. Between October 6, 2005, and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. Of these, 657 patients with endometrial adenocarcinoma had a preoperative serum CA-125 value recorded. Multiple cross-validation analysis was undertaken to correlate preoperative serum CA-125 with stage of disease (Stage I vs. Stage II+) after surgery. Patients' median preoperative serum CA-125 was 14 U/ml. A cutoff point of 30 U/ml was associated with the smallest misclassification error, and using this cutoff, 98 patients (14.9%) had elevated CA-125 levels. Of those, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had an elevated CA-125 level. On univariate and multivariable logistic regression analysis, only preoperative CA-125 level, but no other preoperative clinical characteristics were found to be associated with extra-uterine spread of disease. Utilizing a cutoff point of 30 U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0, 88.5, 36.7 and 85.7%, respectively. Elevated CA-125 above 30 U/ml in patients with apparent early-stage disease is a risk factor for the presence of extra-uterine disease and may assist clinicians in the management of patients with clinical Stage I endometrial cancer. Copyright © 2011 UICC.

Serum ischemia modified albumin is a possible new marker of oxidative stress in phenylketonuria.

PubMed

Keshavarzi, Fatemeh; Rastegar, Mohsen; Vessal, Mahmood; Rafiei Dehbidi, Gholamreza; Khorsand, Marjan; Ganjkarimi, Amir Hossein; Takhshid, Mohammad Ali

2018-06-01

The role of oxidative stress in the pathogenesis of phenylketonuria (PKU)-associated disorders has been implicated. Ischemia modified albumin (IMA) is a modified form of serum albumin, which is produced under the conditions of oxidative stress. The aim of this study was to measure the serum level of IMA in the PKU patients and to investigate its ability in predicting the status of oxidative stress in these patients. Fifty treated-PKU patients and fifty age- and sex-matched healthy subjects were included in the study. The blood samples were obtained and the serum level of phenylalanine (Phe) was measured using reverse phase HPLC method. The levels of IMA, malondialdehyde (MDA), gamma-glutamyl transferase (GGT) activity, and uric acid (UA) were determined using colorimetric methods. The levels of serum Phe, IMA, and MDA were significantly higher (p < 0.001) and the level of UA (p < 0.05) was lower in the PKU patients compared to control group. Serum IMA level was positively correlated with MDA (r = 0.585, p < 0.001) and UA (r = 0.6, p < 0.001). An inverse relationship was observed between the serum level of IMA and Phe (r = - 0.410, p < 0. 01). Results of the present study suggest that serum IMA level could be used as a novel marker for the evaluation of oxidative stress in the PKU patients.

Serum decoy receptor 3 level: a predictive marker for nodal metastasis and survival among oral cavity cancer patients.

PubMed

Tu, Hsi-Feng; Liu, Chung-Ji; Liu, Shyun-Yeu; Chen, Yu-Ping; Yu, En-Hao; Lin, Shu-Chun; Chang, Kuo-Wei

2011-03-01

Validating markers for prediction of nodal metastasis could be beneficial in treatment of oral cavity cancer. Decoy receptor 3 (DcR3), locus on 20q13, functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor (TNFR) family. This study analyzed the serum level of DcR3 in relationship to the clinical parameters of oral cavity cancer patients together with detection of DcR3 genomic copy number in primary and recurrent tumors. Elevated serum DcR3 was associated with nodal metastasis and worse prognosis. Gain of DcR3 copy number was detected in 17% of primary tumor tissue but not found in healthy areca chewers. Tissue from recurrent tumors showed more frequent DcR3 copy number alteration (48%) than the paired primary tumor tissue. Serum DcR3 level is a predictor for the nodal metastasis and survival among oral cavity cancer patients and the DcR3 copy number alteration could underlie oral carcinogenesis progression. Copyright © 2010 Wiley Periodicals, Inc.

Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy.

PubMed

Tanaka, Shigeru; Ninomiya, Toshiharu; Masutani, Kosuke; Nagata, Masaharu; Tsuchimoto, Akihiro; Tsuruya, Kazuhiko; Kitazono, Takanari

2015-12-01

Serum bilirubin has been recognized as a novel endogenous antioxidant. The aim of our study was to evaluate the impact of serum bilirubin on kidney prognosis in IgA nephropathy (IgAN). We followed retrospectively 694 patients with IgAN diagnosed by renal biopsy between 1982 and 2010. The risk factors for developing end-stage renal disease (ESRD) were estimated using a Cox proportional hazard model. Predictive performance between models with or without serum bilirubin was evaluated by calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Seventy-seven patients developed ESRD during the median 4.9 years of follow-up. Estimated glomerular filtration rate, proteinuria and histological severity were inversely related to bilirubin levels. In multivariate analysis, serum bilirubin was an independent risk factor for ESRD (hazard ratio for every 0.1 mg/dL decrease in serum bilirubin, 1.18; 95 % CI, 1.04-1.33). The incidence rate of ESRD decreased linearly with the increases in bilirubin levels (P for trend <0.01). When bilirubin was incorporated into a model with conventional ESRD risk factors, the NRI and IDI were 0.281 (P = 0.02) and 0.019 (P = 0.01), respectively. We demonstrated that lower bilirubin levels were significantly associated with higher risk of ESRD in IgAN. In addition, bilirubin provided incremental predictive value in the risk assessment for progression of IgAN beyond that provided by standard risk factors.

The role of elevated serum procalcitonin in neuroendocrine neoplasms of digestive system.

PubMed

Chen, Luohai; Zhang, Yu; Lin, Yuan; Deng, Langhui; Feng, Shiting; Chen, Minhu; Chen, Jie

2017-12-01

Elevated serum procalcitonin (PCT) was reported in patients with certain type of neuroendocrine neoplasms (NENs). The aim of this study was to assess the role of elevated serum PCT in NENs from digestive system. Serum PCT and serum CgA level were measured in 155 patients with NENs from digestive system. Elevated serum PCT was found in 63 patients (40.6%). Grade 3 disease was a significant factor associated with elevated serum PCT (OR, 9.24; 95%CI, 3.04-28.08; P<0.001). Serum PCT level was significantly decreased after treatment both in patients with stable disease (P=0.003) and patients with partial remission (P=0.001). In these patients, serum PCT level significantly increased again at the time of progression disease (P=0.001). Elevated serum PCT was a significant factor of worse survival (HR, 2.86; 95%CI, 1.36-6.03; P=0.006). Compared with patients with normal serum PCT and CgA level, patients with either PCT or CgA elevated and patients with both PCT and CgA elevated had progressively worse survival. Additionally, PCT expression in tumor cells was found in 24.0% of patients but did not correlate with other clinicopathological factors, including serum PCT. Serum PCT is elevated in part of patients with NENs of digestive system, especially in patients with grade 3 disease. Serum PCT level can help evaluate treatment response and its elevation indicates poor prognosis. Combination of serum PCT and CgA can improve outcome prediction. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The timing of calcium measurements in helping to predict temporary and permanent hypocalcaemia in patients having completion and total thyroidectomies.

PubMed

Pfleiderer, A G; Ahmad, N; Draper, M R; Vrotsou, K; Smith, W K

2009-03-01

Postoperative hypocalaemia commonly occurs after extensive thyroid surgery and may require calcium and/or vitamin D supplements to alleviate or prevent the symptoms. In this study, we determined the risk factors for developing hypocalcaemia and whether early serum calcium levels can predict the development of or differentiate between temporary or permanent hypocalcaemia. A total of 162 patients who either had a completion or total thyroidectomy formed the basis of this prospective study. Serial serum calcium measurements were recorded as well as details of the operation, pathology, indications for surgery, number of parathyroids identified at operation and any complications. Eighty-four (52%) patients did not develop hypocalcaemia but 69 (43%) were found to have temporary hypocalcaemia and 9 (5%) had permanent hypocalcaemia. Hypocalcaemia was more common after total than completion thyroidectomies and the identification of parathyroids at operation appears to have a significant adverse effect on outcome. The calcium levels measured on day 1 postoperatively and the slope (serum calcium levels of day 1 postoperative minus day of operation) were statistically significant in predicting the development of hypocalcaemia and possibly to differentiate between temporary or permanent hypocalcaemia. Although almost half the patients having extensive thyroid surgery developed hypocalcaemia (as defined by any postoperative corrected serum calcium level of < 2.12 mmol/l) only 24% had a serum calcium of < 2.12 mmol/l associated with clinical symptoms of hypocalcaemia or a calcium level of < 2.0 mmol/l. Only 5% had persistent hypocalcaemia defined as requiring exogenous supplements at 6 months' postoperatively. Patients having a completion thyroidectomy appear to be less likely to develop hypocalcaemia perhaps as a result of any iatrogenic effects on the parathyroids at the first operation being reversed before the second operation. Identification and, therefore, exposure of parathyroids at operation may have an adverse effect on the blood supply to the glands affecting their function. Serum calcium levels measured 6 hours' post-surgery and on day 1 postoperatively can be useful in predicting if the patient will develop hypocalcaemia and the slope may indicate whether the hypocalcaemia will be temporary or permanent. Patients with toxic goitres and those having a one-stage total thyroidectomy are most at risk of developing hypocalcaemia.

The Timing of Calcium Measurements in Helping to Predict Temporary and Permanent Hypocalcaemia in Patients Having Completion and Total Thyroidectomies

PubMed Central

Pfleiderer, AG; Ahmad, N; Draper, MR; Vrotsou, K; Smith, WK

2009-01-01

INTRODUCTION Postoperative hypocalaemia commonly occurs after extensive thyroid surgery and may require calcium and/or vitamin D supplements to alleviate or prevent the symptoms. In this study, we determined the risk factors for developing hypocalcaemia and whether early serum calcium levels can predict the development of or differentiate between temporary or permanent hypocalcaemia. PATIENTS AND METHODS A total of 162 patients who either had a completion or total thyroidectomy formed the basis of this prospective study. Serial serum calcium measurements were recorded as well as details of the operation, pathology, indications for surgery, number of parathyroids identified at operation and any complications. RESULTS Eighty-four (52%) patients did not develop hypocalcaemia but 69 (43%) were found to have temporary hypocalcaemia and 9 (5%) had permanent hypocalcaemia. Hypocalcaemia was more common after total than completion thyroidectomies and the identification of parathyroids at operation appears to have a significant adverse effect on outcome. The calcium levels measured on day 1 postoperatively and the slope (serum calcium levels of day 1 postoperative minus day of operation) were statistically significant in predicting the development of hypocalcaemia and possibly to differentiate between temporary or permanent hypocalcaemia. DISCUSSION Although almost half the patients having extensive thyroid surgery developed hypocalcaemia (as defined by any postoperative corrected serum calcium level of < 2.12 mmol/l) only 24% had a serum calcium of < 2.12 mmol/l associated with clinical symptoms of hypocalcaemia or a calcium level of < 2.0 mmol/l. Only 5% had persistent hypocalcaemia defined as requiring exogenous supplements at 6 months' postoperatively. Patients having a completion thyroidectomy appear to be less likely to develop hypocalcaemia perhaps as a result of any iatrogenic effects on the parathyroids at the first operation being reversed before the second operation. Identification and, therefore, exposure of parathyroids at operation may have an adverse effect on the blood supply to the glands affecting their function. CONCLUSIONS Serum calcium levels measured 6 hours' post-surgery and on day 1 postoperatively can be useful in predicting if the patient will develop hypocalcaemia and the slope may indicate whether the hypocalcaemia will be temporary or permanent. Patients with toxic goitres and those having a one-stage total thyroidectomy are most at risk of developing hypocalcaemia. PMID:19317937

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

PubMed

Sanjay, Pandanaboyana; de Figueiredo, Rodrigo S; Leaver, Heather; Ogston, Simon; Kulli, Christoph; Polignano, Francesco M; Tait, Iain S

2012-03-10

There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Post-therapeutic recovery of serum interleukin-35 level might predict positive response to immunosuppressive therapy in pediatric aplastic anemia.

PubMed

Huang, Zhen; Tong, Hongfei; Li, Yuan; Zhou, Haixia; Qian, Jiangchao; Wang, Juxiang; Ruan, Jichen

2017-08-01

The predictive value of interleukin-35 (IL-35) on efficacy of immunosuppressive therapy (IST) in aplastic anemia (AA) has not been well investigated. The aim of the study was to evaluate the association between serum IL-35 level and response to IST in pediatric AA. A total of 154 children with AA and 154 controls were included between January 2012 and December 2013. Blood and bone marrow fluid specimens were collected. Serum level of IL-35 was determined by enzyme-linked immunosorbent assay. Patients were treated with IST, and response to therapy was evaluated during 180-day follow-up period after starting therapy. Serum levels of IL-35 at admission decreased significantly in patients compared with that in controls (10.9 ± 5.5 pg ml -1 and 45.3 ± 8.8 pg ml -1 , p < 0.001). After starting IST, serum levels of IL-35 in patients recovered 30.7 ± 9.7 pg ml -1 in the first 28 days (p < 0.001). During the follow-up period, increased range of serum IL-35 level ≥30.7 pg ml -1 in the first 28 days was associated with effective response to therapy (odds ratio 7.97, 95% confidence interval 3.82-16.79). In addition, Fas/FasL protein expression in bone marrow mononuclear cells dropped significantly in the same group of patients in the first 28 days (p < 0.05). The study revealed that post-therapeutic recovery of circulating IL-35 concentration might be an independent predictor for effective response to IST in pediatric AA. Moreover, apoptosis might be involved in such a forecasting process.

Sputum-to-serum hydrogen sulfide ratio as a novel biomarker of predicting future risks of asthma exacerbation.

PubMed

Suzuki, Yasuhito; Saito, Junpei; Kikuchi, Masami; Uematsu, Manabu; Fukuhara, Atsuro; Sato, Suguru; Munakata, Mitsuru

2018-05-14

Increased level of hydrogen sulfide (H 2 S) in sputum is reported to be a new biomarker of neutrophilic airway inflammation in chronic airway disorders. However, the relationship between H 2 S and disease activity remains unclear. We investigated whether H 2 S levels could vary during different conditions in asthma. H 2 S levels in sputum and serum were measured using a sulfide-sensitive electrode in 47 stable asthmatic subjects (S-BA), 21 uncontrolled asthmatic subjects (UC-BA), 26 asthmatic subjects with acute exacerbation (AE-BA), and 15 healthy subjects. Of these, H 2 S levels during stable, as well as exacerbation states were obtained in 13 asthmatic subjects. Sputum H 2 S levels were significantly higher in the AE-BA subjects compared to the UC-BA and healthy subjects (p<0.05). However, serum H 2 S levels in the AE-BA subjects were lower than in the S-BA subjects (p<0.001) and similar to those in healthy subjects. Thus, the sputum-to-serum ratio of H 2 S (H 2 S ratio) in the AE-BA subjects was significantly higher than in the S-BA, UC-BA and healthy subjects (p<0.05). Among all subjects, sputum H 2 S levels showed a trend to decrease with FEV 1% predicted, and significantly positive correlations with sputum neutrophils (%), sputum IL-8, and serum IL-8. A multiple linear regression analysis showed that sputum H 2 S was independently associated with increased sputum neutrophils (%) and decreased FEV 1% predicted (p<0.05) The cut-off level of H 2 S ratio to indicate an exacerbation was ≥0.34 (area under the curve; 0.88, with a sensitivity of 81.8% and specificity of 72.7%, p<0.001). Furthermore, half of the asthmatic subjects with H 2 S ratios higher than the cutoff level experienced asthma exacerbations over the following 3 months after enrollment. The H 2 S ratio may provide useful information on predicting future risks of asthma exacerbation, as well as on obstructive neutrophilic airway inflammation as one of the non-Th2 biomarkers, in asthma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Serum biological antioxidant potential predicts the prognosis of hemodialysis patients.

PubMed

Ishii, Tomoko; Ohtake, Takayasu; Okamoto, Koji; Mochida, Yasuhiro; Ishioka, Kunihiro; Oka, Machiko; Maesato, Kyoko; Ikee, Ryota; Moriya, Hidekazu; Hidaka, Sumi; Doi, Kent; Noiri, Eisei; Fujita, Toshiro; Kobayashi, Shuzo

2011-01-01

It is well known that oxidative stress is enhanced in patients with end-stage renal disease. However, little is known about the relationship between serum antioxidant capacity and clinical outcome in hemodialysis (HD) patients. We examined the relationship between serum biomarkers of oxidative stress and clinical outcomes including all-cause mortality, hospitalization rate and incidence of cardiovascular events in HD patients. As biomarkers of oxidative stress, we measured serum levels of coenzyme Q10 (CoQ10) and biological antioxidant potential (BAP). 108 patients were observed for 30 months as the follow-up periods. The survival group (n = 83) showed significantly higher BAP values compared with those in death groups (n = 25; p < 0.05). When serum BAP levels were divided into two groups by their median value, the group with higher BAP values had a better survival rate than that with lower BAP values on the Kaplan-Meier survival analysis (p = 0.05). Although serum levels of CoQ10 did not show any association with clinical outcomes, lower BAP was selected as an independent risk factor for all-cause mortality as well as the absence of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy by age-adjusted Cox regression analysis. This study indicated that BAP could predict the prognosis of HD patients. Copyright © 2010 S. Karger AG, Basel.

Serum titanium, niobium and aluminium levels two years following instrumented spinal fusion in children: does implant surface area predict serum metal ion levels?

PubMed

Cundy, Thomas P; Cundy, William J; Antoniou, Georgia; Sutherland, Leanne M; Freeman, Brian J C; Cundy, Peter J

2014-11-01

Measurement of serum metal ion levels is used to determine systemic exposure to implant-derived metal debris that may be generated by processes of wear and corrosion. The aim of this study is to investigate predictors of serum metal ion levels in children undergoing instrumented spinal arthrodesis using a titanium alloy, focusing on implant characteristics and instrumentation construct design variables. This prospective longitudinal cohort study involved 33 children. Serum samples were obtained preoperatively:and at five defined interval periods over the first:two post-operative years. Samples were analysed using high resolution:inductively coupled plasma mass spectrometry to measure titanium, niobium and aluminium concentrations. Instrumentation characteristics were catalogued and construct surface area (SA) measurements calculated using an implant-specific software algorithm tool. Significantly elevated levels of serum titanium and niobium were observed (p< 0.0001), with >95 % of post-operative levels abnormally elevated. Significant predictors of serum titanium and niobium levels included time since surgery, surgical procedure (posterior or anterior fusion), number of levels fused, number of pedicle screws inserted, total rod length, total metal SA, total exposed metal SA and total metal-on-metal SA. All significant instrumentation variables were highly correlated. There is a strong relationship between implant SA and both serum titanium and niobium levels. The direct clinical implications of these findings for patients are uncertain, but remain of concern. Surgeons should be aware of the strong correlation between implant surface area of the chosen construct and the subsequent serum metal ion levels.

Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

PubMed

Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

2016-03-01

It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p < 0.008 and p < 0.001, respectively). There was no statistically significant difference between the KL-6 levels in the healthy control group and the CTD without pulmonary involvement group (p = 0.289). The KL-6 levels did not differ significantly according to the connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

Biomarker-Based Prediction Models for Response to Treatment in Systemic Sclerosis-Related Interstitial Lung Disease

DTIC Science & Technology

2017-10-01

in the baseline samples of the Scleroderma Lung Study II (SLS II). We are currently analyzing whether these serum proteins have predictive...In this project, we use the valuable samples collected in the Scleroderma Lung Study II (SLSII) clinical trial and the observational cohort, GENISOS...determine key serum protein levels and transcript signatures in whole blood and skin samples collected in the SLSII study . The identified candidate

Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

PubMed

Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

2018-05-01

The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to the embryo transfer stage due to several reasons including cancelation of stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant predictor for cancelation of stimulation (AUC 0.774, P < 0.001). In women with diminished ovarian reserve, basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

Value of 18F-FDG PET/CT Combined With Tumor Markers in the Evaluation of Ascites.

PubMed

Han, Na; Sun, Xun; Qin, Chunxia; Hassan Bakari, Khamis; Wu, Zhijian; Zhang, Yongxue; Lan, Xiaoli

2018-05-01

The purpose of this study is to investigate the value of 18 F-FDG PET/CT combined with assessment of tumor markers in serum or ascites for the diagnosing and determining the prognosis of benign and malignant ascites. Patients with ascites of unknown cause who underwent evaluation with FDG PET/CT were included in this retrospective study. The maximum standardized uptake value (SUV max ) and levels of the tumor markers carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen (CEA) in serum and ascites were recorded. The diagnostic values of FDG PET/CT, CEA and CA-125 levels in serum or ascites, and the combination of imaging plus tumor marker assessment were evaluated. Factors that were predictive of survival were also analyzed. A total of 177 patients were included. Malignant ascites was eventually diagnosed in 104 patients, and benign ascites was diagnosed in the remaining 73 patients. With the use of FDG PET/CT, 44 patients (42.3%) were found to have primary tumors. The sensitivity, specificity, and accuracy of FDG PET/CT were 92.3%, 83.6%, and 88.7%, respectively. CA-125 levels in serum and ascites showed much better sensitivity than did CEA levels, but they showed significantly lower specificity. If the combination of tumor markers and FDG PET/CT was analyzed, the sensitivity, specificity, and accuracy of tumor markers in serum were 96.6%, 78.1%, and 88.7%, and those of tumor markers in ascites were 97.7%, 80.0%, and 90.4%, respectively. Sex may be an important factor affecting survival time (hazard ratio, 0.471; p = 0.004), but age, CEA level, and FDG PET/CT findings could not predict survival. FDG PET/CT combined with assessment of tumor markers, especially CEA, increased the efficacy of diagnosis of ascites of unknown causes. Male sex conferred a poorer prognosis, whereas age, CEA level, and FDG uptake had no predictive significance in patients with malignant ascites.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

PubMed

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H Irene

2014-02-01

To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions.

PubMed

Burns, Christine M; Chen, Kewei; Kaszniak, Alfred W; Lee, Wendy; Alexander, Gene E; Bandy, Daniel; Fleisher, Adam S; Caselli, Richard J; Reiman, Eric M

2013-04-23

To investigate whether higher fasting serum glucose levels in cognitively normal, nondiabetic adults were associated with lower regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer disease (AD). This is a cross-sectional study of 124 cognitively normal persons aged 64 ± 6 years with a first-degree family history of AD, including 61 APOEε4 noncarriers and 63 carriers. An automated brain mapping algorithm characterized and compared correlations between higher fasting serum glucose levels and lower [(18)F]-fluorodeoxyglucose-PET rCMRgl measurements. As predicted, higher fasting serum glucose levels were significantly correlated with lower rCMRgl and were confined to the vicinity of brain regions preferentially affected by AD. A similar pattern of regional correlations occurred in the APOEε4 noncarriers and carriers. Higher fasting serum glucose levels in cognitively normal, nondiabetic adults may be associated with AD pathophysiology. Findings suggest that the risk imparted by higher serum glucose levels may be independent of APOEε4 status. This study raises additional questions about the role of the metabolic process in the predisposition to AD and supports the possibility of targeting these processes in presymptomatic AD trials.

Prognostic value of high sensitivity C-reaction protein in non-insulin dependent diabetes mellitus patients with non-alcoholic fatty liver disease.

PubMed

Bi, Yiliang; Min, Min; Shen, Wei; Deng, Pei; Du, Qiupeng; Dong, Mingjie; Liu, Yan

2015-01-01

High sensitivity C-reaction protein (hsCRP) has been used as a significant predictive factor of cardiovascular events in patients with non-insulin dependent diabetes mellitus (NIDDM). However, existing reports in regards to the significance of hsCRP in predicting the progression of hepatic complications in NIDDM patients are too sparse to deliver clear results. This study is aimed at investigating the prognostic value of hsCRP in NIDDM patients with non-alcoholic fatty liver disease (NAFLD). 1128 NIDDM patients with a definite diagnosis of NAFLD were enrolled and followed for one year. The baseline body mass index (BMI), waist-hip circumference ratio (WHR), serum aspartate aminotransferase (AST), presence of hypertension, alanine aminotransferase (ALT), serum hsCRP, total cholesterol (Tch), fasting blood glucose (FBG), triglycerine (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and hepatitis B surface antigen (HBsAg) were recorded to analyze the significance of hsCRP in predicting the short-term progression from NAFLD to non-alcoholic steatohepatitis (NASH). One year after baseline, 32% of the NAFLD patients suffered progression to NASH and the percentages of NASH were respectively 8.2%, 12.5%, 33.8% and 72.6% in 4 groups with quartered baseline serum level of hsCRP; there was significant difference among the 4 groups in percentage of NASH (P<0.001). With sex, age, WHR, BMI, hypertension, TG, TCH, HDL-C, LDL-C, FBG and HBsAg included, the calibrated regression model gave the OR values of 1.000, 1.669, 6.635 and 32.131 in in 4 quartered baseline serum levels of hsCRP. High serum level of hsCRP is an independent risk factor of short-term progression to NASH in patients with NIDDM and NAFLD. Those NIDDM patients with NAFLD that present with high serum level of hsCRP should be subjected to regular monitoring, lifestyle intervention and medication.

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

PubMed

Sung, Nayoung; Kwak-Kim, Joanne; Koo, H S; Yang, K M

2016-09-01

To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-β level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-β level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-β was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-β level and fold increase of hCG-β significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies.

Serum N-terminal-pro-brain natriuretic peptide level and its clinical implications in patients with atrial fibrillation.

PubMed

Bai, Mei; Yang, Jiefu; Li, Yingying

2009-12-01

Brain natriuretic peptide (BNP) is increasingly being used for screening and monitoring of congestive heart failure. However, the role of BNP in patients with atrial fibrillation (AF) and normal left ventricular function has not been determined. This study investigates serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and its clinical implications in patients with AF. Serum NT-proBNP levels were measured by enzyme-linked immunosorbent assay (ELISA) and transthoracic echocardiography was performed in 136 subjects (90 cases with AF and 46 cases with sinus rhythm [SR]). Subjects were excluded if they had a history of myocardial infarction, cardiomyopathy, rheumatic heart disease, or hyperthyroidism that preceded the onset of AF. Controls (n = 30) were from a healthy outpatient primary care population. Potential determinants of serum NT-proBNP levels were identified by univariate and multivariate analyses. Individuals with AF had higher serum NT-proBNP levels (689.56 +/- 251.87 fmol/ml) than those with SR (456.11 +/- 148.14 fmol/ml, P < 0.01) and control subjects (415.83 +/- 62.02 fmol/ml, P < 0.01). Individuals with SR and control subjects did not show significant difference at serum NT-proBNP levels (P > 0.05). The regression model of serum NT-proBNP levels and clinical predictors showed that presence of AF, older age, and larger right atrial diameter were independently predictive of higher serum NT-proBNP values. Patients with AF were associated with increased serum NT-proBNP levels. Examining the change of serum NT-proBNP levels is helpful to evaluate the cardiac function in patients with AF. Copyright 2009 Wiley Periodicals, Inc.

Serum decoy receptor 3 is a biomarker for disease severity in nonatopic asthma patients.

PubMed

Chen, Ming-Han; Kan, Hung-Tsai; Liu, Chun-Yu; Yu, Wen-Kuang; Lee, Shinn-Shing; Wang, Jia-Horng; Hsieh, Shie-Liang

2017-01-01

Decoy receptor 3 (DcR3), a soluble receptor of the tumor necrosis factor receptor superfamily, is a pleiotropic immunomodulator. The aim of this study was to investigate serum DcR3 levels in atopic and nonatopic asthma patients. The serum DcR3 levels of 70 adults with asthma and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). The asthma patients were divided into atopic and nonatopic subgroups, based on the presence or absence of immunoglobulin E (IgE) specific to allergen. Correlations between serum DcR3 levels and blood total-eosinophil counts, forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and Asthma Control Test (ACT) scores were analyzed. The mean serum DcR3 level was significantly higher in asthma patients than in healthy controls (266.1 ± 60.6 pg/mL vs. 63.7 ± 21.9 pg/mL, p = 0.003), but there was no significant difference between the mean serum DcR3 level of asthma patients with atopy (37 patients) and patients without atopy (33 patients; 298.7 ± 111.2 pg/mL vs. 230.6 ± 38.5 pg/mL, p = 0.064). However, the serum DcR3 level was positively correlated with the total eosinophil count (r = 0.448, p = 0.012) and inversely correlated with the percentages of predicted FEV1, FEV1/FVC, and ACT score (r = 0.409, p = 0.018; r = -0.399, p = 0.021; and r = -0.505, p = 0.003, respectively) in nonatopic asthma patients, but not in atopic patients. High serum DcR3 levels are associated with disease severity in nonatopic asthma patients, which suggests that DcR3 is a potential biomarker that can be used to predict the severity of nonatopic asthma. Copyright © 2016. Published by Elsevier B.V.

Predictive value of IL-35 and IL-17 in diagnosis of childhood asthma.

PubMed

Mansour, Amira Ibrahim; Abd Almonaem, Eman Rateb; Behairy, Ola Galal; Gouda, Tahany Mahmoud

2017-09-01

This study aimed to evaluate the correlation between serum levels of IL-17 and IL-35 and the presence and severity of childhood asthma. The study was performed on 60 diagnosed asthmatic children, who were further classified into four groups according to the Global Initiative for Asthma Guidelines for Asthma Severity and Control (GINA) 2016, plus 30 age- and sex-matched apparently healthy children. All participants were subjected to full medical history, clinical examination, pulmonary function tests and laboratory evaluation in the form of complete blood count (CBC), serum total IgE, IL-17 and IL-35 by ELISA. Our results revealed that eosinophils count, IgE and IL-17 were significantly higher in the asthmatic group than the control group (p < .001), while IL-35 levels were significantly lower in asthmatics than control (p < .001). A strong negative correlation was found between serum IL-17 and serum IL-35; a positive correlation was found between serum IL-17 and both of serum total IgE and eosinophils counts in atopic asthmatic patients, and serum IL-35 showed significant negative correlations with both. ROC analysis of the data showed that the cut-off value of IL-35 level was <189.5 pg/mL and for IL-17 level, it was >13.1 pg/mL; this value could predict childhood asthma with sensitivity of 81.7% and 83.3%, and specificity of 76.7% and 70%, respectively. A combination of both cytokines yielded an increase in sensitivity to 95%. In conclusion, in the current study, IL-17 is upregulated while IL-35 is downregulated in childhood asthma with a significant negative correlation between both. These results suggest that both may play an important role in the pathogenesis of childhood asthma.

Elevated Serum Brain-Derived Neurotrophic Factor (BDNF) but not BDNF Gene Val66Met Polymorphism Is Associated with Autism Spectrum Disorders.

PubMed

Meng, Wei-Dong; Sun, Shao-Jun; Yang, Jie; Chu, Rui-Xue; Tu, Wenjun; Liu, Qiang

2017-03-01

The aim of our study was to illuminate the potential role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder (ASD). We measured the circulating levels of BDNF in serum and BDNF gene (Val66Met) polymorphisms, in which two indicators were then compared between ASD and normal controls. A total of 82 drug-naïve ASD children and 82 age- and gender-matched normal controls were enrolled in the study. Their serum BDNF levels were detected by the ELISA. BDNF Val66Met polymorphism genotyping was conducted as according to the laboratory's standard protocol in laboratory. The ASD severity assessment was mainly determined by the score of the Childhood Autism Rating Scale (CARS). ELISA assay showed that the mean serum BDNF level of children with ASD was significantly (P < 0.0001) higher than that of the control cases (17.75 ± 5.43 vs. 11.49 ± 2.85 ng/ml; t = 9.236). Besides, the serum BDNF levels and CARS scores (P < 0.0001) were positively related. And, the BDNF genotyping results showed that there was no difference between the ASD cases and the control. Among the children with ASD, the mean serum BDNF level of Met/Met group was lower than other groups. According to the ROC curve generated from our clinical data, the optimal cutoff value of serum BDNF levels, an indicator for diagnosis of ASD, was projected to be 12.50 ng/ml. Thus, it yielded a corresponding sensitivity of 81.7 % and the specificity of 66.9 %. Accordingly, area value under the curve was 0.836 (95 % CI, 0.774-0.897); the positive predictive value (PPV) and the negative predictive value (NPV) were 70.1 and 79.1 %, respectively. These results suggested that rather than Val66Met polymorphism, BDNF was more possible to impact the pathogenesis of ASD.

Association between serum levels of caspase-cleaved cytokeratin-18 and early mortality in patients with severe spontaneous intracerebral hemorrhage.

PubMed

Lorente, Leonardo; Martín, María M; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Solé-Violán, Jordi; Cáceres, Juan J; Jiménez, Alejandro; García-Marín, Victor

2018-04-16

Apoptotic changes after cerebral hemorrhage in brain samples of humans have been found. Caspase-cleaved cytokeratin (CCCK)-18 could be detected in the bloodstream during apoptosis. Higher circulating CCCK-18 levels have been associated with 6-month mortality in patients with basal ganglia hemorrhage. The aim of our study was to determine whether there is an association between serum CCCK-18 levels and early mortality of spontaneous intracerebral hemorrhage (SIH) patients. We performed an observational, prospective and multicentre study. There were included patients with severe SIH defined as Glasgow Coma Scale (GCS) lower than 9. We determined serum CCCK-18 levels at the severe SIH diagnosis moment. We found that non-surviving SIH patients (n = 46) showed lower GCS, and higher serum CCCK-18 levels and APACHE-II score than survivor ones (n = 54). In ROC analysis was found that the area under the curve of serum CCCK-18 levels for 30-day mortality prediction was 90% (95% CI 82-95%; p < 0.001). In the multiple logistic regression analysis, we found an association between serum CCCK-18 levels and 30-day mortality (OR 1.034; 95% CI 1.013-1.055; p = 0.002). The novel finding of our study was that there is an association between high serum CCCK-18 levels and 30-day mortality in severe SIH patients.

A decline of LAMP- 2 predicts ursodeoxycholic acid response in primary biliary cirrhosis

PubMed Central

Wang, Lu; Guo, Guan-ya; Wang, Jing-bo; Zhou, Xin-min; Yang, Qiong; Han, Zhe-yi; Li, Qiang; Zhang, Jing-wen; Cai, Yun; Ren, Xiao-li; Zhou, Xia; Chen, Rui-rui; Shi, Yong-quan; Han, Ying; Fan, Dai-ming

2015-01-01

Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA. The efficiency of serum LAMP-2 to predict biochemical response was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014). Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and specificity of 75.0% by Paris criteria. Meanwhile the specificity and sensitivity were identified as 63.5% and 64.1% by Barcelona criteria. Together, a decline in LAMP-2 might help to predict the response to UDCA. PMID:25894308

Value of combining serum carcinoembryonic antigen and PET/CT in predicting EGFR mutation in non-small cell lung cancer.

PubMed

Gu, Jincui; Xu, Siqi; Huang, Lixia; Li, Shaoli; Wu, Jian; Xu, Junwen; Feng, Jinlun; Liu, Baomo; Zhou, Yanbin

2018-02-01

We sought to investigate the associations between pretreatment serum Carcinoembryonic antigen (CEA) level, 18 F-Fluoro-2-deoxyglucose ( 18 F-FDG) uptake value of primary tumor and epidermal growth factor receptor ( EGFR ) mutation status in non-small cell lung cancer (NSCLC). We retrospectively reviewed medical records of 210 NSCLC patients who underwent EGFR mutation test and 18 F-FDG positron emission tomography/computed tomography (PET/CT) scan before anti-tumor therapy. The associations between EGFR mutations and patients' characteristics, serum CEA, PET/CT imaging characteristics maximal standard uptake value (SUVmax) of the primary tumor were analyzed. Receiver-operating characteristic (ROC) curve was used to assess the predictive value of these factors. EGFR mutations were found in 70 patients (33.3%). EGFR mutations were more common in high CEA group (CEA ≥7.0 ng/mL) than in low CEA group (CEA <7.0 ng/mL) (40.4% vs . 27.6%; P=0.05). Females (P<0.001), non-smokers (P<0.001), patients with adenocarcinoma (P<0.001) and SUVmax <9.0 (P=0.001) were more likely to be EGFR mutation-positive. Multivariate analysis revealed that gender, tumor histology, pretreatment serum CEA level, and SUVmax were the most significant predictors for EGFR mutations. The ROC curve revealed that combining these four factors yielded a higher calculated AUC (0.80). Gender, histology, pretreatment serum CEA level and SUVmax are significant predictors for EGFR mutations in NSCLC. Combining these factors in predicting EGFR mutations has a moderate diagnostic accuracy, and is helpful in guiding anti-tumor treatment.

Polychlorinated biphenyls and polybrominated biphenyl ethers in adipose tissue and matched serum from an E-waste recycling area (Wenling, China).

PubMed

Lv, Quan-Xia; Wang, Wenyue; Li, Xing-Hong; Yu, Lianlian; Zhang, Yun; Tian, Yuan

2015-04-01

To Date, the knowledge on relationship between PCBs/PBDEs exposure and thyroid hormones (THs) levels during pregnancy still needs to be extended. Meanwhile, studies on congener-specific adipose-serum ratios for PCBs/PBDEs were limited. This study reports the levels of PCBs/PBDEs in serum-adipose tissue samples (n = 64) from expectant women living surrounding e-waste recycling sites in Wenling, China. Their concentrations varied from several to hundreds of ng g(-1) lipid. Maternal exposure to PCBs was associated with lower TSH during pregnancy, suggesting possible implication for maternal health and fetal development. The compound levels between the adipose tissue and matched serum samples were highly correlated (p < 0.001), generating a predicted adipose-serum partitioning relationship for individual PCB congener and PBDE congener. Molecular characteristics, such as Kow value, molecular weight and molecular volume, may play a key role in the variable partitioning of some compounds between serum and adipose tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma?

PubMed

Wang, Jun-Ke; Hu, Hai-Jie; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Liu, Fei; Cheng, Nan-Sheng; Li, Fu-Yu

2017-07-11

To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P < 0.001). Preoperative to postoperative increase in CA19-9 level was also correlated with poor survival outcome (P < 0.001). In multivariate analysis, preoperative CA19-9 level > 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216-9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391-28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107-14.459; P = 0.034). Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence.

Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy.

PubMed

Janbaziroudsari, Hamid; Mirzaei, Arezoo; Maleki, Nasrollah

2016-09-01

To investigate the relationship of serum prostate-specific antigen (PSA) levels with outcomes of prostate needle biopsy in men 50 or more years old. We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level (≥4ng/mL) or abnormal digital rectal examination, a transrectal ultrasound-guided prostate biopsy was performed. The mean serum total PSA level was 13.73±11.44ng/mL, and the mean serum free PSA level was 4.99±0.97ng/mL. Of the 260 men who had serum total PSA levels of≥4ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4%) had prostate cancer. Benign prostatic hyperplasia with or without prostatitis was diagnosed in 94 patients (67.6%). There was no significant correlation between age and histologic results of prostate needle biopsy (P-value=0.469). The serum free PSA showed no significant correlation with histologic results of prostate needle biopsy, whereas the serum total PSA level had a significant correlation in patients with adenocarcinoma compared with other diagnosis. The overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

PubMed

Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing

2008-03-01

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p < 0.001). Serum NO(x) were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO(x) level defined as mean +/- 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients.

PubMed

Singh, Prashant K; Preus, Leah; Hu, Qiang; Yan, Li; Long, Mark D; Morrison, Carl D; Nesline, Mary; Johnson, Candace S; Koochekpour, Shahriar; Kohli, Manish; Liu, Song; Trump, Donald L; Sucheston-Campbell, Lara E; Campbell, Moray J

2014-02-15

We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p<.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.

Preclinical screening for retinopathy of prematurity risk using IGF1 levels at 3 weeks post-partum.

PubMed

Pérez-Muñuzuri, Alejandro; Couce-Pico, Maria Luz; Baña-Souto, Ana; López-Suárez, Olalla; Iglesias-Deus, Alicia; Blanco-Teijeiro, José; Fernández-Lorenzo, José Ramón; Fraga-Bermúdez, José María

2014-01-01

Following current recommendations for preventing retinopathy of prematurity (ROP) involves screening a large number of patients. We performed a prospective study to establish a useful screening system for ROP prediction and we have determined that measuring serum levels of IGF1 at week three and the presence of sepsis have a high predictive value for the subsequent development of ROP. A total of 145 premature newborn, with birthweight <1500 g and/or <32 weeks gestational age, were enrolled. 26.9% of them showed some form of retinopathy. A significant association was found between the development of retinopathy and each of the following variables: early gestational age, low birthweight, requiring mechanical ventilation, oxygen treatment, intracranial haemorrhage, sepsis during the first three weeks, bronchopulmonary dysplasia, the need for erythrocyte transfusion, erythropoietin treatment, and low levels of serum IGF1 in the third week. A multiple logistic regression analysis was used to obtain curves for the probability of developing ROP, based on the main factors linked with ROP, namely serum levels of IGF1 and presence of sepsis. Such preclinical screening has the ability to identify patients with high-risk of developing retinopathy and should lead to better prediction for ROP, while at the same time optimising the use of clinical resources, both human and material.

Relation between serum creatinine and postoperative results of open-heart surgery.

PubMed

Ezeldin, Tamer H

2013-10-01

To determine the impact of preoperative serum creatinine level in non-dialyzable patients on postoperative morbidity and mortality. This is a prospective study, where serum creatinine was used to give primary assessment on renal function status preoperatively. This study includes 1,033 patients, who underwent coronary artery bypass grafting, or valve(s) operations. The study took place at Al-Hada Military Hospital, Taif, Kingdom of Saudi between May 2008 and January 2012. Data were statistically analyzed using Chi square (x2) test and multivariable logistic regression, to evaluate the postoperative morbidity and mortality risks associated with low serum creatinine levels. Postoperative mortality increased with high serum creatinine level >1.8 mg/dL (p

Elevated levels of serum nidogen-2 in esophageal squamous cell carcinoma.

PubMed

Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Lee, Nikki Pui Yue; Chan, Kin Tak; Law, Simon Ying-Kit; Lung, Maria Li

2018-02-14

Nidogen-2 (NID2), a secretory basement membrane protein, has been implicated as a potential biomarker in ovarian cancer and hepatocellular carcinoma. In this study, we aimed to investigate the utility of detecting serum NID2 levels for identification of esophageal squamous cell carcinoma (ESCC) patients and prediction of poor survival outcome. Using an in-house NID2 enzyme-linked immunosorbent assay (ELISA), serum samples from 101 ESCC patients and 50 healthy controls were screened for their NID2 levels. The serum NID2 levels in ESCC patients (median 24.4 μg/L) are significantly higher (p= 4.3e-09) than that of the healthy controls (median 15.85 μg/L). The receiver operating characteristic (ROC) curve demonstrated an area under the curve of 0.756. At the threshold of 17.95 μg/L, the sensitivity and specificity achieved are 0.76 and 0.63, respectively. Kaplan-Meier survival analysis revealed that patients with high serum NID2 levels (⩾ 32.6 μg/L) have significantly higher risk of death (HR = 1.984, 95% CI: 1.175-3.349; log-rank p-value = 0.012) compared to those with low serum NID2 levels (< 20.0 μg/L). In conclusion, we show that detecting the elevation of serum NID2 levels has potential diagnostic and prognostic value for ESCC patients.

Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance.

PubMed

Guler, Ismail; Himmetoglu, Ozdemir; Turp, Ahmet; Erdem, Ahmet; Erdem, Mehmet; Onan, M Anıl; Taskiran, Cagatay; Taslipinar, Mine Yavuz; Guner, Haldun

2014-06-01

In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study.

PubMed

Jacobs, Esther M G; Hendriks, Jan C M; van Deursen, Cees Th B M; Kreeftenberg, Herman G; de Vries, Richard A; Marx, Joannes J M; Stalenhoef, Anton F H; Verbeek, André L M; Swinkels, Dorine W

2009-01-01

In families of patients with clinically detected hereditary hemochromatosis (HH) early screening has been suggested to prevent morbidity and mortality. Here, we aim to identify determinants for iron overload in first-degree family members of C282Y homozygous probands with clinically detected HH. Data on HFE-genotype, iron parameters, demographics, lifestyle factors and health, were collected from 224 Dutch C282Y homozygous patients with clinically diagnosed HH and 735 of their first-degree family members (FDFM), all participating in the HEmochromatosis FAmily Study (HEFAS). The best predictive multivariable model forecasted 45% of variation of the serum ferritin levels. In this model severity of iron overload in the proband significantly predicted serum ferritin levels in FDFM. Other significant determinants in this model consisted of C282Y homozygosity, compound heterozygosity, age at testing for serum ferritin and supplemental iron intake, whereas a low body mass index showed a protective effect. This study provides a model to assess the risk of development of iron overload for relatives of probands with HH. These results might be instrumental in the development of an optimal strategy for future family screening programs.

Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome

PubMed Central

Plée, Julie; Le Jan, Sébastien; Giustiniani, Jérôme; Barbe, Coralie; Joly, Pascal; Bedane, Christophe; Vabres, Pierre; Truchetet, François; Aubin, François; Antonicelli, Frank; Bernard, Philippe

2015-01-01

Bullous pemphigoid (BP) is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation. Recently, IL-17 and IL-23 were evidenced in lesional skin and serum of BP patients at time of diagnosis, but their involvement in disease outcome has still not been investigated yet. We then analysed IL-17 and IL-23 serum levels during the first months of follow-up upon treatment. Compared with age- and sex- matched controls, high levels of IL-23 were observed at baseline in BP patients serum (P < 0.01), while IL-17 levels was not. However, some BP patients expressed high IL-17 serum level, independently of disease severity. In these patients, those with ongoing remission reduced IL-17 concentration upon treatment (P < 0.001), whereas IL-17 level remained elevated in patients who relapsed. Meanwhile, IL-23 serum levels increased during the first month of treatment in BP patients who later relapsed (P < 0.01) and MMP-9 serum level was not controlled. Accordingly, we found that both IL-17 and IL-23 increased MMP-9 secretion from leukocytes in-vitro. Then, we showed that elevated IL-17/IL-23 serum concentrations helped to discriminate BP patients who later relapsed. Such uncontrolled inflammatory response raises the question whether these molecules could become biological target for BP patients resistant to steroid treatment. PMID:26656739

The value of serum pro-oxidant/antioxidant balance in the assessment of asphyxia in term neonates.

PubMed

Boskabadi, Hassan; Zakerihamidi, Maryam; Heidarzadeh, Mohammad; Avan, Amir; Ghayour-Mobarhan, Majid; Ferns, Gordon A

2017-07-01

Asphyxia is a major cause of disabilities in term-born infants. Here we have explored the value in HIE (hypoxic-ischemic-encephalopathy) of using a combination of serum pro-oxidant/antioxidant balance (PAB) assay for predicting the prognosis of asphyxia. Ninety term neonates with asphyxia were enrolled and followed up for two years. Serum PAB, demographic/biochemical characteristics of mothers, and their neonates were determined. The Denver II test was used to assess outcomes. Of the 90 asphyxiated neonates, 47 (52.2%) had a normal outcome and 43 babies (47.8%) had abnormal outcome. Serum PAB levels in neonates with normal and abnormal outcomes were 17.1 ± 9.23 and 48.27 ± 41.30 HK, respectively. A combination of HIE intensity and PAB, compared to other indicators, had a higher predictive-value (95.2%) for outcomes in asphyxiated babies. We demonstrate that PAB in combination with HIE grade may have a better predictive value for the prognosis of asphyxiated babies and predicting future neurologic problems in asphyxiated term infants.

[Correlation between serum uric acid level and acute renal injury after coronary artery bypass grafting].

PubMed

Xu, D Q; Du, J; Zheng, Z; Tang, Y; Zou, L; Zhang, Y H; Zhang, H T

2017-07-11

Objective: To evaluate whether early postoperative serum uric acid level can predict postoperative acute renal injury (AKI) among patients undergoing coronary artery bypass grafting (CABG). Methods: The study retrospectively enrolled 1 306 patients undergoing CABG in Fuwai Hospital between September 2012 and December 2013. The patients were divided into 5 groups by the concentrations of serum uric acid measured on the morning of the first postoperative day, and uric acid categories were as follow: less than 195 μmol/L (Q1 group, 262 cases), 195-236 μmol/L (Q2 group, 263 cases), 237-280 μmol/L (Q3 group, 260 cases), 281-336 μmol/L (Q4 group, 261 cases), more than 336 μmol/L (Q5 group, 260 cases). The primary end points were AKI (RIFLE criteria), severe AKI (AKI≥stage Ⅰ), postoperative continuous renal replacement therapy (CRRT) requirement, in-hospital death, length of stay in hospital and intensive care unit(ICU). The area under the receiver-operating characteristic (ROC) curve (AUC) was used to determine the ability of the early postoperative serum uric acid level as a risk factor for postoperative AKI prediction. Results: Among the 1 306 patients enrolled in the study, AKI was found in 335 patients (25.65%). After adjusting for variables that were different between the 5 groups, the Q5 group had significantly higher risk of AKI, AKI≥ stage Ⅰ and the requirement of CRRT ( P <0.01). The ROC for the outcome of postoperative AKI had an AUC of 0.648 (95% CI: 0.612-0.683) when serum creatinine levels alone were used and 0.722 (95% CI: 0.688-0.755) when serum uric acid levels alone were used (both P <0.001). Early postoperative serum uric acid was a better predictor than serum creatinine( P <0.001). Conclusion: The serum uric acid concentration within 12 hours after operation is an independent predictor of postoperative AKI in patients undergoing CABG, which could be used to identify patients at high risk for AKI.

Serum cortisol as a useful predictor of cardiac events in patients with chronic heart failure: the impact of oxidative stress.

PubMed

Yamaji, Masayuki; Tsutamoto, Takayoshi; Kawahara, Chiho; Nishiyama, Keizo; Yamamoto, Takashi; Fujii, Masanori; Horie, Minoru

2009-11-01

The pathophysiological role of cortisol, which binds to the mineralocorticoid receptor with an affinity equal to that of aldosterone (ALD), may be influenced by oxidative stress in patients with chronic heart failure. We evaluated cardiac event prediction using cortisol levels in chronic heart failure, in comparison with ALD, adrenocorticotropic hormone, and brain natriuretic peptide (BNP), and the impact of oxidative stress. We measured the plasma levels of biomarkers such as BNP, ALD, adrenocorticotropic hormone, serum cortisol, and oxidized low-density lipoprotein (oxLDL), a biomarker of oxidative stress, in 319 consecutive symptomatic patients with chronic heart failure, and we followed these patients for a mean period of 33 months. During the follow-up period, 29 patients had cardiac events (death or hospitalization). Plasma levels of BNP, ALD, adrenocorticotropic hormone, oxLDL, and serum cortisol (16.8+/-1.8 microg/dL versus 12.4+/-0.3 microg/dL, P=0.01) were significantly higher in patients with cardiac events than in those without cardiac events. On stepwise multivariate analyses, high levels of BNP (P=0.0003), renin (P=0.002), cortisol (P=0.02), and oxLDL (P=0.002) were independent predictors of cardiac events, but ALD and adrenocorticotropic hormone levels were not. In patients with serum cortisol > or =12.5 microg/dL, the hazard ratio of cardiac events in patients with oxLDL > or =12 U/mL was 3.5 compared with that in patients with oxLDL <12 U/mL (P=0.008). These findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in combination with BNP in patients with chronic heart failure and that cardiac event prediction based on cortisol levels was influenced by oxidative stress.

Effects of Serum Albumin, Calcium Levels, Cancer Stage and Performance Status on Weight Loss in Parathyroid Hormone-Related Peptide Positive or Negative Patients with Cancer.

PubMed

Lee, Ji Yeon; Hong, Namki; Kim, Hye Ryun; Lee, Byung Wan; Kang, Eun Seok; Cha, Bong Soo; Lee, Yong Ho

2018-03-01

A recent animal study showed that parathyroid hormone-related peptide (PTHrP) is associated with cancer cachexia by promoting adipose tissue browning, and we previously demonstrated that PTHrP predicts weight loss (WL) in patients with cancer. In this study, we investigated whether prediction of WL by PTHrP is influenced by clinical factors such as serum albumin, corrected calcium levels, cancer stage, and performance status (PS). A cohort of 219 patients with cancer whose PTHrP level was measured was enrolled and followed for body weight (BW) changes. Subjects were divided into two groups by serum albumin (cutoff value, 3.7 g/dL), corrected calcium (cutoff value, 10.5 mg/dL), cancer stage (stage 1 to 3 or 4), or PS (Eastern Cooperative Oncology Group 0 to 1 or 2 to 4), respectively. Clinically significant WL was defined as either percent of BW change (% BW) <-5% or % BW <-2% plus body mass index (BMI) <20 kg/m². After a median follow-up of 327 days, 74 patients (33.8%) experienced clinically significant WL. A positive PTHrP level was associated with a 2-fold increased risk of WL after adjusting for age, baseline BMI, serum albumin, corrected calcium level, cancer stage, and PS. The effect of PTHrP on WL remained significant in patients with low serum albumin, stage 4 cancer, and good PS. Regardless of calcium level, the effect of PTHrP on WL was maintained, although there was an additive effect of higher calcium and PTHrP levels. Early recognition of patients with advanced cancer who are PTHrP positive with hypercalcemia or hypoalbuminemia is needed for their clinical management. Copyright © 2018 Korean Endocrine Society.

Serum and cerebrospinal fluid levels of visinin-like protein-1 in acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Takahara, Midori; Kajimoto, Madoka; Momonaka, Hiroshi; Oka, Momoko; Isumi, Hiroshi; Emi, Sakie; Hayashi, Megumi; Ichiyama, Takashi

2014-08-01

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has recently been recognized as an encephalopathy subtype. Typical clinical symptoms of AESD are biphasic seizures, and MRI findings show reduced subcortical diffusion during clustering seizures with unconsciousness after the acute phase. Visinin-like protein-1 (VILIP-1) is a recently discovered protein that is abundant in the central nervous system, and some reports have shown that VILIP-1 may be a prognostic biomarker of conditions such as Alzheimer's disease, stroke, and brain injury. However, there have been no reports regarding serum and cerebrospinal fluid (CSF) levels of VILIP-1 in patients with AESD. We measured the serum and CSF levels of VILIP-1 in patients with AESD, and compared the levels to those in patients with prolonged febrile seizures (FS). Both serum and CSF levels of VILIP-1 were significantly higher in patients with AESD than in patients with prolonged FS. Serum and CSF VILIP-1 levels were normal on day 1 of AESD. Our results suggest that both serum and CSF levels of VILIP-1 may be one of predictive markers of AESD. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Serum chemerin level during the first trimester of pregnancy and the risk of gestational diabetes mellitus.

PubMed

Yang, Xuezhou; Quan, Xiaozhen; Lan, Yanli; Ye, Jinhai; Wei, Qipeng; Yin, Xiaofang; Fan, Fangfang; Xing, Hui

2017-10-01

To investigate the association between chemerin level in the first trimester of pregnancy and the risk of gestational diabetes mellitus. The blood samples of 212 women at 8-12 weeks of gestation were collected. After screening for gestational diabetes mellitus (GDM), 19 women with GDM and 20 women randomly selected from 144 women with normal glucose tolerance (NGT) were included in the study. Blood samples were collected from these women. Triglycerides, glucose, total cholesterol, and HDL cholesterol, LDL cholesterol, insulin and chemerin were measured. Gestational weight gain and body mass index was assessed. Serum levels of chemerin were significantly elevated during late gestation, and the risk of GDM was positively associated with maternal serum chemerin in the first trimester. Serum chemerin level during the first trimester of pregnancy has the potential to predict risk of GDM.

The Role of YKL-40 in Predicting Resistance to Docetaxel Chemotherapy in Prostate Cancer.

PubMed

Darr, Christopher; Krafft, Ulrich; Hadaschik, Boris; Tschirdewahn, Stephan; Sevcenco, Sabina; Csizmarik, Anita; Nyirady, Peter; Küronya, Zsófia; Reis, Henning; Maj-Hes, Agnieszka; Shariat, Shahrokh F; Kramer, Gero; Szarvas, Tibor

2018-06-27

High baseline YKL-40 serum levels are associated with drug resistance in several solid tumours. However, their role in predicting docetaxel (DOC) resistance in prostate cancer (PCa) is unknown. Pre-treatment serum levels of YKL-40 and prostate-specific antigen (PSA) were analyzed in 109 castration-resistant prostate cancer patients who underwent DOC-therapy. Responsive patients were retreated by repeated series of DOC. Results were compared with the clinical parameters as well as overall (OS) and disease-specific survival (DSS). YKL-40 but not PSA serum levels were significantly higher in patients with baseline resistance to DOC (p = 0.035). Higher YKL-40 and PSA levels were detected in patients with bone metastasis (p = 0.032; p = 0.010) and in those who were not pre-treated with radical prostatectomy (p = 0.011, p = 0.008). High YKL-40 levels were associated with shorter OS (p = 0.037) and DSS (p = 0.017) in patients who received DOC in the first-line setting. In multivariable analysis, ECOG performance status (p = 0.009), presence of any metastases (p = 0.016) and high PSA levels (p = 0.005) remained independent predictors for DSS. YKL-40 may help to identify patients with baseline resistance to DOC and therefore may help to optimize treatment decisions. In accordance, high pre-treatment YKL-40 serum levels were associated with shorter OS and DSS in patients who received DOC as first-line therapy. © 2018 S. Karger AG, Basel.

The use of serum anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) to predict the number of oocytes collected and availability of embryos for cryopreservation in IVF.

PubMed

Kotanidis, L; Nikolettos, K; Petousis, S; Asimakopoulos, B; Chatzimitrou, E; Kolios, G; Nikolettos, N

2016-12-01

To investigate the predictive value of anti-Mullerian hormone (AMH) and antral follicle count (AFC) on the final number of oocytes retrieved and the availability of embryos for cryopreservation in in vitro fertilization (IVF) cycles. In this prospective study, one hundred and twenty women in their first IVF treatment were enrolled. The short stimulation agonist protocol was used for controlled ovarian hyperstimulation in all cases. Serum AMH levels were measured during the menstrual cycle preceding treatment. AFC was measured in cycle day 2, just before starting ovarian stimulation. A strong, positive correlation between AMH, AFC and the number of collected oocytes was found. The patients with available and suitable supplementary embryos for cryopreservation had higher levels of AMH and larger numbers of AFC. AMH and AFC appear to be valuable markers mainly for ovarian reserve and response to IVF treatment. Serum AMH levels and AFC are significantly associated with the number of retrieved oocytes. Also, a positive correlation with the availability of supernumerary embryos suitable for cryopreservation was observed.

Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor.

PubMed

Leão, Ricardo; van Agthoven, Ton; Figueiredo, Arnaldo; Jewett, Michael A S; Fadaak, Kamel; Sweet, Joan; Ahmad, Ardalan E; Anson-Cartwright, Lynn; Chung, Peter; Hansen, Aaron; Warde, Padraig; Castelo-Branco, Pedro; O'Malley, Martin; Bedard, Philippe L; Looijenga, Leendert H J; Hamilton, Robert J

2018-02-21

Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently to our knowledge there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy. Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers. They correlated with the presence of a viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity. miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor maker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in post-chemotherapy retroperitoneal lymph node dissection specimens of patients harboring viable germ cell tumors. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02). To our knowledge our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Predictive value of serum HCG concentrations in pregnancies achieved after single fresh or vitrified-warmed blastocyst transfer.

PubMed

Oron, Galia; Shavit, Tal; Esh-Broder, Efrat; Weon-Young, Son; Tulandi, Togas; Holzer, Hananel

2017-09-01

Possible differences between serum HCG levels in pregnancies achieved after transfer of a single fresh or a vitrified-warmed blastocyst were evaluated. Out of 1130 single blastocyst transfers resulting in positive HCG results, 789 were single fresh blastocyst transfers and 341 single vitrified-warmed blastocyst transfers. The initial serum HCG levels of 869 clinical intrauterine pregnancies were evaluated, 638 after the transfer of a single fresh blastocysts and 231 after the transfer of a single vitrified-warmed blastocysts. The HCG levels from cycles resulting in a clinical intrauterine pregnancy were significantly higher after the transfer of a single vitrified-warmed blastocyst (383 ± 230 IU/l) versus a fresh transfer (334 ± 192 IU/l; P = 0.01). Threshold values for predicting a clinical pregnancy for a fresh blastocyst were 111 IU/l and for a vitrified-warmed blastocyst 137 IU/l. Our study shows that the overall beta-HCG levels are comparable after the transfer of a fresh or vitrified-warmed blastocyst, suggesting that vitrification most probably does not affect the ability of the embryos to produce beta-HCG. This study further shows that when clinicians counsel patients, they should take into account that higher HCG levels are needed after a vitrified-warmed blastocyst transfer to predict a clinical intrauterine pregnancy. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Posaconazole in Human Serum: a Greater Pharmacodynamic Effect than Predicted by the Non-Protein-Bound Serum Concentration ▿

PubMed Central

Lignell, Anders; Löwdin, Elisabeth; Cars, Otto; Chryssanthou, Erja; Sjölin, Jan

2011-01-01

It is generally accepted that only the unbound fraction of a drug is pharmacologically active. Posaconazole is an antifungal agent with a protein binding of 98 to 99%. Taking into account the degree of protein binding, plasma levels in patients, and MIC levels of susceptible strains, it can be assumed that the free concentration of posaconazole sometimes will be too low to exert the expected antifungal effect. The aim was therefore to test the activity of posaconazole in serum in comparison with that of the calculated unbound concentrations in protein-free media. Significant differences (P < 0.05) from the serum control were found at serum concentrations of posaconazole of 1.0 and 0.10 mg/liter, with calculated free concentrations corresponding to 1× MIC and 0.1× MIC, respectively, against one Candida lusitaniae strain selected for proof of principle. In RPMI 1640, the corresponding calculated unbound concentration of 0.015 mg/liter resulted in a significant effect, whereas that of 0.0015 mg/liter did not. Also, against seven additional Candida strains tested, there was an effect of the low posaconazole concentration in serum, in contrast to the results in RPMI 1640. Fluconazole, a low-grade-protein-bound antifungal, was used for comparison at corresponding concentrations in serum and RPMI 1640. No effect was observed at the serum concentration, resulting in a calculated unbound concentration of 0.1× MIC. In summary, there was a substantially greater pharmacodynamic effect of posaconazole in human serum than could be predicted by the non-protein-bound serum concentration. A flux from serum protein-bound to fungal lanosterol 14α-demethylase-bound posaconazole is suggested. PMID:21502622

Moderating Effects of Cortisol on Neural-Cognitive Association in Cognitively Normal Elderly Subjects

PubMed Central

Lau, Way K. W.; Leung, Mei Kei; Law, Andrew C. K.; Lee, Tatia M. C.

2017-01-01

Cortisol homeostasis is important for healthy brain and cognitive aging. The aim of the current study is to investigate the role of serum cortisol levels in the relationship between regional brain volumes and cognitive processing speed in a group of cognitively normal elderly subjects. Forty-one healthy elderly participants were from a parallel longitudinal study. The reported data in this study reflects baseline measurements. Whole-brain anatomical scanning was performed using a 3.0 Tesla Philips Medical Systems Achieva scanner. Cognitive processing speed was assessed by the digit-symbol and symbol search tests, from the Chinese version of the Wechsler Adult Intelligence Scale—third edition (WAIS-III). Serum cortisol levels (sampled in the late morning) were measured by ELISA kits. Whole-brain regression analysis revealed that serum cortisol levels positively predicted the white matter volumes (WMV) of the right thalamus, the gray matter volumes (GMV) of the left thalamus and right cerebellar tonsil, and negatively predicted the WMV and GMV of the left middle temporal gyrus (MTG) in 41 healthy elderly participants. Furthermore, serum cortisol significantly moderated the relationship between the GMV of the left MTG and processing speed, as well as the GMV of the left thalamus and processing speed. This study provided the first piece of evidence supporting serum cortisol levels in moderating the relationship between regional brain volumes and processing speed in healthy elderly subjects. This observation enriches our understanding of the role of cortisol in brain morphology and cognitive functioning. PMID:28596732

Serum Levels of Progranulin Do Not Reflect Cerebrospinal Fluid Levels in Neurodegenerative Disease.

PubMed

Wilke, Carlo; Gillardon, Frank; Deuschle, Christian; Dubois, Evelyn; Hobert, Markus A; Müller vom Hagen, Jennifer; Krüger, Stefanie; Biskup, Saskia; Blauwendraat, Cornelis; Hruscha, Michael; Kaeser, Stephan A; Heutink, Peter; Maetzler, Walter; Synofzik, Matthis

2016-01-01

Altered progranulin levels play a major role in neurodegenerative diseases, like Alzheimer's dementia (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), even in the absence of GRN mutations. Increasing progranulin levels could hereby provide a novel treatment strategy. However, knowledge on progranulin regulation in neurodegenerative diseases remains limited. We here demonstrate that cerebrospinal fluid progranulin levels do not correlate with its serum levels in AD, FTD and ALS, indicating a differential regulation of its central and peripheral levels in neurodegeneration. Blood progranulin levels thus do not reliably predict central nervous progranulin levels and their response to future progranulin-increasing therapeutics.

[Serum PTH levels as a predictive factor of hypocalcaemia after total thyroidectomy].

PubMed

Díez Alonso, Manuel; Sánchez López, José Daniel; Sánchez-Seco Peña, María Isabel; Ratia Jiménez, Tomás; Arribas Gómez, Ignacio; Rodríguez Pascual, Angel; Martín-Duce, Antonio; Guadalix Hidalgo, Gregorio; Hernández Domínguez, Sara; Granell Vicent, Javier

2009-02-01

Postoperative parathyroid hormone (PTH) levels as a predictor of hypocalcaemia in patients subjected to total thyroidectomy is analyzed. Prospective study involving 67 patients who underwent total thyroidectomy due to a benign disease. Serum PTH and ionised calcium were measured 20 h after surgery. Sensitivity, specificity and predictive values of PTH and ionised calcium levels were calculated to predict clinical and analytical hypocalcaemia. A total of 42 (62.7%) patients developed hypocalcaemia (ionised calcium<0.95 mmol/l), but only 20 (29.9%) presented with symptoms. PTH concentration the day after surgery was significantly lower in the group that developed symptomatic hypocalcaemia (5.57+/-6.4 pg/ml) than in the asymptomatic (21.5+/-15.3 pg/ml) or normocalcaemic (26.8+/-24.9 pg/ml) groups (p=0.001). Taking the value of 13 pg/ml as a cut-off point of PTH levels, sensitivity, specificity, positive predictive value and negative predictive value were 54%, 72%, 76% and 48%, respectively. On the other hand, sensitivity for predicting symptomatic hypocalcaemia was 95% and specificity was 76%. The test showed a high incidence of false positives (11/30, 36%). Negative predictive value was 97% and positive predictive value was 65%. In multivariate analysis, PTH and ionised calcium were the only perioperative factors that showed an independent predictive value as risk indicators of symptomatic hypocalcaemia. Normal PTH levels 20 h after surgery practically rule out the subsequent appearance of hypocalcaemia symptoms. On the other hand, low PTH levels are not necessarily associated to symptomatic hypocalcaemia due to the high number of false positives.

Exploration of potential biomarkers and related biological pathways for PCB exposure in maternal and cord serum: A pilot birth cohort study in Chiba, Japan.

PubMed

Eguchi, Akifumi; Sakurai, Kenichi; Watanabe, Masahiro; Mori, Chisato

2017-05-01

Polychlorinated biphenyls (PCBs) have been associated with adverse human reproductive and fetal developmental measures or outcomes because of their endocrine-disrupting effects; however, the biological mechanisms of adverse effects of PCB exposure in humans are not currently well established. In this study, we aimed to identify the biological pathways and potential biomarkers of PCB exposure in maternal and umbilical cord serum using a hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) metabolomics platform. The median concentration of total PCBs in maternal (n=93) and cord serum (n=93) were 350 and 70pgg -1 wet wt, respectively. PCB levels in maternal and fetal serum from the Chiba Study of Mother and Children's Health (C-MACH) cohort are comparable to those of earlier cohort studies conducted in Japan, the USA, and European countries. We used the random forest model with the metabolome profile to predict exposure levels of PCB (first quartile [Q1] and fourth quartile [Q4]) for pregnant women and fetuses. In the prediction model for classification of Q1 versus Q4 (area-under-curve [AUC]: pregnant women=0.812 and fetuses=0.919), citraconic acid level in maternal serum and ethanolamine, p-hydroxybenzoate, and purine levels in cord serum had >0.70 AUC values. These candidate biomarkers and metabolite included in composited models were related to glutathione and amino acid metabolism in maternal serum and the amino acid metabolism and ubiquinone and other terpenoid-quinone biosynthesis in cord serum (FDR <0.10), indicating disruption of metabolic pathways by PCB exposure in pregnant women and fetuses. These results showed that metabolome analysis might be useful to explore potential biomarkers and related biological pathways for PCB exposure. Thus, more detailed studies are needed to verify sensitivity of the biomarkers and clarify the biochemical changes resulting from PCB exposure. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

PubMed Central

Tang, W W; Kaptein, E M

1989-01-01

Hypothalamic-pituitary dysfunction and thyroid gland cytomegalovirus inclusions have been described in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). We evaluated 80 patients with AIDS or ARC for the frequency of hypothalamic-pituitary or thyroid gland failure and altered serum thyroid hormone levels due to nonthyroidal disorders. One patient had subclinical hypothyroidism. Of these patients, 60% had low free triiodothyronine (T3) index values and 4% had low free thyroxine (T4) indexes; none of the latter had hypothalamic-pituitary or thyroid gland failure, since all serum cortisol values were greater than or equal to 552 nmol per liter (greater than or equal to 20 micrograms per dl) and all thyrotropin levels were less than or equal to 3 mU per liter (less than or equal to 3 microU per ml), respectively. Those who died had lower total T4 and T3, free T3 index, and albumin levels than those discharged from hospital. Serum total T4 and T3 levels correlated with albumin levels and total T3 with serum sodium levels. Serum total T3 levels best predicted the outcome of the hospital stay (accuracy = 82%). Thus, abnormal serum thyroid hormone levels in AIDS or ARC patients are most frequently due to nonthyroidal disorders, but hypothalamic-pituitary or thyroid gland failure may occur. PMID:2618039

Serum beta-2 microglobulin level in sympathetic ophthalmitis.

PubMed

Sen, D K; Sarin, G S; Mathur, M D

1990-04-01

Serum beta-2 microglobulin (beta 2-m) levels were measured in 12 patients with sympathetic ophthalmitis, 34 with neglected traumatic uveitis following penetrating injury and 36 healthy subjects by ELISA technique. There was no significant alteration of its level in patients with traumatic uveitis. However, its levels were significantly increased in patients with sympathetic ophthalmitis. They were high even in the early stage of the disease. Serum beta 2-m levels paralleled the severity of disease. It decreased significantly at the remission stage. Four patients came back with relapse of the condition and the level of serum beta 2-m was again found to be elevated in them. It is proposed that estimation of beta 2-m can be used as a diagnostic aid when the diagnosis of sympathetic ophthalmitis remains doubtful on clinical grounds. It is also suggested that a rise in serum beta 2-m in patients with traumatic uveitis following perforating injuries may point to the onset of sympathetic ophthalmitis. The extent of rise in its level may be considered a good parameter of the degree of severity of sympathetic ophthalmitis. It may also act as a useful tool to evaluate the drug efficacy in this disease and predict relapse.

Concurrent and Predictive Relations between Hormone Levels and Social-Emotional Functioning in Early Adolescence.

ERIC Educational Resources Information Center

Nottelmann, Editha D.; And Others

Hormone levels and changes in hormone levels were evaluated three times across a 1-year period as concurrent and predictive correlates of the socio-emotional functioning of 56 boys 10- to 14-years-old and 52 girls 9- to 14-years-old who represented the five stages of Tanner's criteria of pubertal development. The hormone measures were serum levels…

How can we better predict the risk of spontaneous miscarriage among women experiencing threatened miscarriage?

PubMed

Ku, Chee Wai; Allen, John C; Malhotra, Rahul; Chong, Han Chung; Tan, Nguan Soon; Østbye, Truls; Lek, Sze Min; Lie, Desiree; Tan, Thiam Chye

2015-01-01

This study seeks to establish progesterone and progesterone-induced blocking factor (PIBF) levels as predictors of subsequent completed miscarriage among women presenting with threatened miscarriage between 6 and 10 weeks of gestation. Our secondary objective was to assess the known maternal risk factors, toward development of a parsimonious and clinician-friendly risk assessment model for predicting completed miscarriage. In this article, we present a prospective cohort study of 119 patients presenting with threatened miscarriage from gestation weeks 6 to 10 at a tertiary women's hospital emergency unit in Singapore. Thirty (25.2%) women had a spontaneous miscarriage. Low progesterone and PIBF levels are similarly predictive of subsequent completed miscarriage. Study results (OR, 95% CI) showed that higher levels of progesterone (0.91, 95% CI 0.88-0.94) and PIBF (0.99, 95% CI 0.98-0.99) were associated with lower risk of miscarriage. Low progesterone level was a very strong predictor of miscarriage risk in our study despite previous concerns about its pulsatile secretion. Low serum progesterone and PIBF levels predicted spontaneous miscarriage among women presenting with threatened miscarriage between gestation weeks 6 to 10. Predictive models to calculate probability of spontaneous miscarriage based on serum progesterone, together with maternal BMI and fetal heart are proposed.

Impact of laparoscopic ovarian drilling on serum anti-mullerian hormone levels in patients with anovulatory Polycystic Ovarian syndrome.

PubMed

Paramu, Sobhana

2016-12-01

Anti-mullerian hormone (AMH) is a marker of the activity of recruitable ovarian follicles. It is useful in the prediction of ovarian reserve. Women with polycystic ovarian syndrome (PCOS) have elevated circulating and intrafollicular AMH levels. Laparoscopic ovarian drilling (LOD) in patients with PCOS destroys ovarian androgen-producing tissue and reduces their peripheral conversion to estrogens. Identifying factors that determine the response of patients with PCOS to LOD will help in selecting the patients who would likely benefit from this treatment. AMH is one such marker that can predict the response to LOD. To evaluate the effect of LOD on serum AMH levels among PCOS responders and non-responders and the usefulness of AMH as a tool in predicting the response to LOD, and to whether there was loss of ovarian function after LOD. This is a prospective cohort study including 30 clomiphene-resistant women with anovulatory PCOS undergoing LOD. Statistical analysis was performed to evaluate the effect of LOD on serum levels of AMH on these women. A significant fall in the levels of AMH was observed after LOD in both responders and non-responders (p<0.001). Women with AMH >8.3 ng/mL showed a significantly lower ovulation rate (33.3%). LOD was not associated with a risk of diminished ovarian reserve. LOD is an effective first-line treatment for women with PCOS who are clomiphene resistant. LOD has no negative effect on ovarian reserve. AMH is a useful marker in predicting the outcome of LOD.

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure.

PubMed

Dekker, Rebecca L; Lennie, Terry A; Moser, Debra K; Miller, Craig S; Ebersole, Jeffrey L; Chung, Misook L; Campbell, Charles L; Bailey, Alison; Tovar, Elizabeth G

2017-03-01

To describe correlations and agreement between salivary and serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin (IL)-6, and IL-10 and determine which biomarkers predict worse functional class in patients with heart failure (HF). Serum and saliva were collected from 75 hospitalized patients with HF (57 ± 12 years, 43% female, New York Heart Association [NYHA] Classes I [4%], II [43%], and III [53%]). Oral inflammation was rated as good, fair, or poor. Spearman's ρ and Bland-Altman were used to determine correlations and agreement of the salivary and serum forms of each biomarker. Logistic regressions were used to determine which biomarkers predicted worse NYHA functional class, controlling for depression, body mass index, smoking, and oral inflammation. Median biomarker concentrations were as follows: BNP (serum 361 pg/ml, saliva 9 pg/ml), CRP (serum 13 ng/ml, saliva 25.6 ng/ml), IL-6 (serum 19.3 pg/ml, saliva 10.5 pg/ml), and IL-10 (serum 64.1 pg/ml, saliva 4.7 pg/ml). There was a moderate-to-strong correlation for serum-salivary CRP, weak correlation for serum-salivary IL-6, and no correlations for serum-salivary BNP and IL-10. The Bland-Altman test showed good salivary-serum agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. Visible oral inflammation was the only predictor of worse NYHA class.

Serum Liver Fibrosis Markers for Predicting the Presence of Gastroesophageal Varices in Liver Cirrhosis: A Retrospective Cross-Sectional Study

PubMed Central

Li, Hongyu; Chen, Jiang; Xia, Chunlian; Peng, Ying; Dai, Junna; Hou, Yue; Deng, Han; Li, Jing; Guo, Xiaozhong

2015-01-01

Background and Aims. A retrospective cross-sectional study was conducted to evaluate the role of hyaluronic acid (HA), laminin (LN), amino-terminal propeptide of type III procollagen (PIIINP), and collagen IV (CIV) in predicting the presence of gastroesophageal varices (GEVs) in patients with liver cirrhosis. Methods. We enrolled 118 patients with liver cirrhosis who underwent the tests for the four serum liver fibrosis markers and upper gastrointestinal endoscopy at the same admissions. The predictive values of the four serum liver fibrosis markers were evaluated by the areas under the receiving operator characteristics curves (AUROCs) with 95% confidence intervals (CIs). Results. The prevalence of GEVs was 88% (104/118). The AUROCs for HA, LN, PIIINP, and CIV levels in predicting the presence of GEVs were 0.553 (95% CI: 0.458 to 0.644, P = 0.5668), 0.490 (95% CI: 0.397 to 0.584, P = 0.9065), 0.622 (95% CI: 0.528 to 0.710, P = 0.1099), and 0.560 (95% CI: 0.466 to 0.652, P = 0.4909). The PIIINP level at a cut-off value of 31.25 had a sensitivity of 73.1% and a specificity of 57.1%. Conclusions. The present study did not recommend HA, LN, PIIINP, and CIV levels to evaluate the presence of GEVs in liver cirrhosis. PMID:26770190

Role of serum miRNAs in the prediction of ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

PubMed

Zhao, Chun; Liu, Xiaoguang; Shi, Zhonghua; Zhang, Jing; Zhang, Junqiang; Jia, Xuemei; Ling, Xiufeng

2015-01-01

Polycystic ovarian syndrome (PCOS) causes a significantly increased risk of ovarian hyperstimulation syndrome (OHSS). Here, we focused on the altered expression of serum miRNAs and their predictive value for OHSS in PCOS patients. We used the TaqMan low density array followed by individual quantitative reverse transcription-polymerase chain reaction to identify and validate the expression of serum miRNAs in PCOS patients likely to develop severe OHSS. The miR-16 and miR-223 expression levels were significantly reduced in the patients who were likely to develop severe OHSS than in the control subjects who were likely to develop mild or no OHSS. The sensitivity and specificity of the basal LH, basal LH/FSH, and body mass index (BMI) as OHSS predictors were also evaluated. miR-16 was the most efficient for OHSS prediction as it yielded the highest AUC. Logistic binary regression analyses revealed a positive association of miR-223 and BMI. Serum miRNAs are differentially expressed in PCOS patients likely to suffer from severe OHSS. We identified and validated two serum miRNAs that have potential for use as novel noninvasive biomarkers to accurately predict OHSS before controlled ovarian hyperstimulation (COH) for PCOS patients. © 2015 S. Karger AG, Basel.

Mortality indicators and risk factors for intra-abdominal hypertension in severe acute pancreatitis.

PubMed

Zhao, J G; Liao, Q; Zhao, Y P; Hu, Y

2014-01-01

This study assessed the risk factors associated with mortality and the development of intra-abdominal hypertension (IAH) in patients with severe acute pancreatitis (SAP). To identify significant risk factors, we assessed the following variables in 102 patients with SAP: age, gender, etiology, serum amylase level, white blood cell (WBC) count, serum calcium level, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, computed tomography severity index (CTSI) score, pancreatic necrosis, surgical interventions, and multiple organ dysfunction syndrome (MODS). Statistically significant differences were identified using the Student t test and the χ (2) test. Independent risk factors for survival were analyzed by Cox proportional hazards regression. The following variables were significantly related to both mortality and IAH: WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, pancreatic necrosis >50%, and MODS. However, it was found that surgical intervention had no significant association with mortality. MODS and pancreatic necrosis >50% were found to be independent risk factors for survival in patients with SAP. Mortality and IAH from SAP were significantly related to WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, and MODS. However, Surgical intervention did not result in higher mortality. Moreover, MODS and pancreatic necrosis >50% predicted a worse prognosis in SAP patients.

Study of adrenal function in patients with tuberculosis.

PubMed

Sarin, Bipan Chander; Sibia, Keerat; Kukreja, Sahiba

2018-07-01

Although subclinical adrenal insufficiency has been documented in tuberculosis but it has been neglected in mainstream management of TB due to inconclusive data on its prevalence in TB. The fact that adrenal insufficiency may result not only in poor general condition of the patient but also sudden death due to adrenal crisis, makes it all the more important to address this issue seriously. In this non-randomized interventional study comprising of 100 cases of TB, our aim was to assess the adreno-cortical functions in patients with pulmonary TB (50 cases) and extra-pulmonary TB (50 cases) in an attempt to determine if there is any compromise of adrenal function. In this study, 100 cases of active TB were investigated for adrenal insufficiency by measuring morning fasting basal serum cortisol levels, followed by low dose ACTH stimulation test using 1μg synacthen (synthetic ACTH analog). The post-stimulation serum cortisol levels were estimated. Basal serum cortisol levels<220nmol/L or post-stimulation test serum cortisol level increment<200nmol/L or post-stimulation serum cortisol levels<500nmol/L were suggestive of adrenal insufficiency. Basal serum cortisol level was low in 16% cases and after low dose ACTH stimulation test, cortisol response was subnormal in 76% cases. Incidence of adrenal insufficiency in pulmonary TB (74%) and extra-pulmonary TB (78%) were comparable. The number of females having adrenal insufficiency in both the groups was higher than the males (67.3% males and 83.3% females) but the difference was statistically significant only in extra-pulmonary TB group (p=0.011). On analysing the data, the sensitivity of basal serum cortisol level estimation in diagnosing adrenal insufficiency was observed to be 21.05% and its specificity was 100%. Positive predictive value was 100% and negative predictive value was 28.57%. Diagnostic accuracy of basal serum cortisol level estimation was observed to be 40%. The incidence of subclinical adrenal insufficiency in TB cases attending chest department at a tertiary care hospital was significantly high but comparable in both pulmonary and extra-pulmonary type of TB. Females in general and particularly those with extra-pulmonary TB were observed to be at increased risk of adrenal insufficiency. The low dose ACTH stimulation test was able to identify cases with adrenal insufficiency which had normal basal serum cortisol levels. Screening all TB cases for adrenal insufficiency by measuring both morning basal serum cortisol levels and low dose ACTH stimulation test can help identify cases at risk of fatal adrenal crisis and institute timely management, thus improving disease prognosis. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Serum uric acid level is an independent risk factor for presence of calcium in coronary arteries: an observational case-controlled study.

PubMed

Atar, Aslı Inci; Yılmaz, Omer Cağlar; Akın, Kayıhan; Selçoki, Yusuf; Er, Okan; Eryonucu, Beyhan

2013-03-01

A link between uric acid levels and cardiovascular diseases has been previously reported. Coronary artery calcium score (CACS) is a marker of atherosclerotic disease and a predictor of cardiovascular events. We sought to determine if serum uric acid level is an independent risk factor for the presence of calcium in coronary arteries. Four hundred and forty-two patients who were evaluated in the cardiology outpatient clinic for suspected coronary heart disease with a low-moderate risk for coronary artery disease were included in this observational case-controlled study. Serum uric acid levels were measured with colorimetric methods. CACS were performed using a 64-slice CT scanner. Patients were divided to 3 groups according to their CACS value (Group 1: CACS=0, Group 2: CACS 1-100, Group 3: CACS>100). The demographical characteristics and laboratory findings of 3 groups were similar, except age, fasting glucose levels and serum uric acid levels. Serum uric acid levels were found to increase significantly with increasing CACS (p=0.001). Patients were grouped according to presence CAC (CACS=0 and CACS≥1) and in the multiple regression analysis, age (OR, 1.11, 95% CI, 1.07-1.16), smoking (OR, 3.83, 95% CI, 2.06-7.09), serum uric acid levels (OR, 1.26, 95% CI, 1.04-1.54) and average 10-year total risk of Framingham risk score (OR, 1.13, 95% CI, 1.04-1.09) appeared as independent factors predictive of presence of CAC (p<0.05). Serum uric acid level is an independent risk factor for presence of coronary calcium. Moreover, increasing levels of serum uric acid are associated with increasing CACS.

Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease.

PubMed

Ramraj, Satish Kumar; Aravindan, Sheeja; Somasundaram, Dinesh Babu; Herman, Terence S; Natarajan, Mohan; Aravindan, Natarajan

2016-04-05

Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression.

Tumour necrosis factor-α/etanercept complexes in serum predict long-term efficacy of etanercept treatment in seronegative rheumatoid arthritis.

PubMed

Berthold, E; Månsson, B; Gullstrand, B; Geborek, P; Saxne, T; Bengtsson, A A; Kahn, R

2018-01-01

To study whether serum levels of tumour necrosis factor-α (TNF-α), free or bound to etanercept, in biological-naïve adults with rheumatoid arthritis (RA) could predict the long-term efficacy of etanercept, measured as drug survival. We identified 145 biological-naïve patients with RA starting treatment with etanercept at the Department of Rheumatology, Skåne University Hospital (1999-2008), of whom 16 had seronegative and 129 seropositive RA. TNF-α in serum was quantified using enzyme-linked immunosorbent assay in samples from the onset of treatment and at 6 week follow-up. Drug survival time was used to evaluate the long-term efficacy of etanercept. Levels of TNF-α were significantly increased at follow-up compared to at the start. At the 6 week follow-up, circulating TNF-α mainly comprised TNF-α in complex with etanercept. Longer drug survival time correlated with increased TNF-α at 6 week follow-up in the patients with seronegative RA, but not in the seropositive patients. We demonstrated that levels of circulating TNF-α increased in almost all individuals after initiation of treatment with etanercept and that this increase mainly comprised TNF-α in complex with etanercept. More importantly, this increase may predict drug survival in adults with seronegative, but not seropositive, RA and suggests that measuring TNF-α/etanercept complexes in serum may be relevant in patients with seronegative RA.

Predictive value of vascular disease biomarkers for digital ulcers in systemic sclerosis patients.

PubMed

Silva, Ivone; Teixeira, Andreia; Oliveira, José; Almeida, Isabel; Almeida, Rui; Vasconcelos, Carlos

2015-01-01

To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosis patients. Endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), endostatin and endoglin were measured in an observational prospective cohort of 77 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. After the 3-year follow-up, 40 patients developed new digital ulcers. Logistic regression confirmed VEGF (HR 1.128, 95% CI 1.010-1.260, p=0.033) and ADMA (HR 0.995, 95% CI 0.991-0.998, p=0.006) as independent predictors of new digital ulcers. Patients with serum levels of ET-1>11.9 pmol/ml (p<0.001) and VEGF<422.47 pg/ml (p=0.028) had significantly more DU in the 3-year follow-up. Although not significant, a trend towards increased serum levels of endoglin>4.215 ng/ml (p=0.053) was associated to a new DU episode. No predictive serum value was found for ADMA (p=0.075) and endostatin (p=0.130). Endothelial dysfunction and angiogenic vascular biomarkers have an important role in the underlying and in the progression of microvascular disease in systemic sclerosis. Increased serum levels of ET-1, ADMA and VEGF are strong predictors of severe microangiopathy complications, namely ischaemic digital ulcers.

Serum interleukin measurement may help identify thyroid cancer patients with active disease.

PubMed

Martins, Mariana Bonjiorno; Marcello, Marjory Alana; Batista, Fernando de Assis; Peres, Karina Colombera; Meneghetti, Murilo; Ward, Mirela Andrea Latham; Etchebehere, Elba Cristina Sá de Camargo; da Assumpção, Ligia Vera Montali; Ward, Laura Sterian

2018-02-01

Investigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease. We evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA. All ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p=0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p<0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p=0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p<0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness. We suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.

PubMed

Yokoyama, Jennifer S; Marx, Gabe; Brown, Jesse A; Bonham, Luke W; Wang, Dan; Coppola, Giovanni; Seeley, William W; Rosen, Howard J; Miller, Bruce L; Kramer, Joel H; Dubal, Dena B

2017-04-01

Cognitive decline is a major biomedical challenge as the global population ages. Elevated levels of the longevity factor klotho suppress aging, enhance cognition, and promote synaptic plasticity and neural resilience against aging and Alzheimer's disease (AD)-related pathogenic proteins. Here, we examined the relationship between human genetic variants of KLOTHO and systemic klotho levels - and assessed neuroanatomic correlates of serum klotho in a cohort of healthy older adults. Serum klotho levels were increased with KL-VS heterozygosity, as anticipated. We report, for the first time, that serum klotho levels were paradoxically decreased with KL-VS homozygosity. Further, we found that higher serum klotho levels were associated with measures of greater intrinsic connectivity in key functional networks of the brain vulnerable to aging and AD such as the fronto-parietal and default mode networks. Our findings suggest that elevated klotho promotes a resilient brain, possibly through increased network connectivity of critical brain regions.

Individual changes in clozapine levels after smoking cessation: results and a predictive model.

PubMed

Meyer, J M

2001-12-01

Published reports document 20-40% lower mean serum clozapine concentrations in smokers compared with nonsmokers due to enzyme induction. Despite the increase in nonsmoking psychiatric facilities in the United States, previous studies have not tracked individual changes in serum clozapine levels after smoking cessation. Clozapine level changes were analyzed in 11 patients at Oregon State Hospital who were on stable clozapine doses, before and after implementation of a hospital-wide nonsmoking policy. A mean increase in clozapine levels of 71.9% (442.4 ng/ml +/- 598.8 ng/ml) occurred upon smoking cessation (p < .034) from a baseline level of 550.2 ng/ml (+/- 160.18 ng/ml). One serious adverse event, aspiration pneumonia, was associated with a nonsmoking serum clozapine level of 3066 ng/ml. Elimination of statistically extreme results generated a mean increase of 57.4 % or 284.1 ng/ml (+/- 105.2 ng/ml) for the remaining cases (p < .001) and permitted construction of a linear model which explains 80.9% of changes in clozapine levels upon smoking cessation (F = 34.9;p = .001): clozapine level as nonsmoker = 45.3 + 1.474 (clozapine level as smoker). These findings suggest that significant increases in clozapine levels upon smoking cessation may be predicted by use of a model. Those with high baseline levels should be monitored for serious adverse events.

Financial strain, inflammatory factors, and haemoglobin A1c levels in African American women.

PubMed

Cutrona, Carolyn E; Abraham, William T; Russell, Daniel W; Beach, Steven R H; Gibbons, Frederick X; Gerrard, Meg; Monick, Martha; Philibert, Robert

2015-09-01

Type 2 diabetes disproportionately affects African American women, a population exposed to high levels of stress, including financial strain (Centers for Disease Control & Prevention, 2011, http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf). We tested a mediational model in which chronic financial strain among African American women contributes to elevated serum inflammation markers, which, in turn, lead to increased haemoglobin A1C (HbA1c) levels and risk for type 2 diabetes. We assessed level of financial strain four times over a 10-year period and tested its effect on two serum inflammation markers, C-reactive protein (CRP) and soluble interleukin-6 receptor (sIL-6R) in year 11 of the study. We tested the inflammation markers as mediators in the association between chronic financial strain and HbA1c, an index of average blood glucose level over several months. Data were from 312 non-diabetic African American women from the Family and Community Health Study (FACHS; Cutrona et al., 2000, J. Pers. Soc. Psychol., 79, 1088). Chronic financial strain predicted circulating sIL-6R after controlling for age, BMI, health behaviours, and physical health measures. In turn, sIL-6R significantly predicted HbA1c levels. The path between chronic financial strain and HbA1c was significantly mediated by sIL-6R. Contrary to prediction, CRP was not predicted by chronic financial strain. Results support the role of inflammatory factors in mediating the effects of psychosocial stressors on risk for type 2 diabetes. Findings have implications for interventions that boost economic security and foster effective coping as well as medical interventions that reduce serum inflammation to prevent the onset of type 2 diabetes. © 2014 The British Psychological Society.

Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma.

PubMed

Pham, Duy Le; Yoon, Moon-Guyng; Ban, Ga-Young; Kim, Seung-Hyun; Kim, Mi-Ae; Ye, Young-Min; Shin, Yoo Seob; Park, Hae-Sim

2015-01-01

S100A8 and S100A9 can be produced by lipopolysaccharide-stimulated granulocytes and provoke an innate immune-mediated airway inflammation. Involvement of S100A8 and S100A9 has been implicated in asthma. To further understand the role of S100A8 and S100A9 during innate immune responses in baker's asthma, we investigated the associations of serum S100A8 and S100A9 with exposure to bakery allergens and polymorphisms of the Toll-like receptor 4 (TLR4) gene. Totally, 381 bakery workers and 100 unexposed healthy controls were recruited. Skin prick tests for bakery allergens were performed. Serum levels of S100A8, S100A9, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, and interleukin (IL)-8 were measured using ELISA. Predictive values of serum S100A8 and S100A9 in bakery workers were evaluated by receiver-operating characteristic (ROC) curves. Polymorphisms of TLR4 -2027Ax2192;G and -1608Tx2192;C were genotyped. Higher serum levels of S100A8 and S100A9 were noted in bakery workers compared to the normal controls (p < 0.001); however, no significant differences were noted according to work-related symptoms. The area under the ROC curve of serum S100A8 was 0.886 for occupational exposure (p < 0.001). The TLR4 -1608CC genotype was significantly associated with a higher serum S100A8 level (p = 0.025). Serum S100A8 and S100A9 levels were correlated with serum levels of MPO (r = 0.396 and 0.189, respectively), TNF-α (r = 0.536 and 0.280, respectively), and IL-8 (r = 0.540 and 0.205, respectively; p < 0.001 for all). S100A8 and S100A9 are involved in innate immune responses under the regulation of TLR4 polymorphisms in baker's asthma pathogenesis. Serum S100A8 could be a potential biomarker for predicting occupational exposure to wheat flour in bakery workers. © 2016 S. Karger AG, Basel.

Excess adiposity, inflammation, and iron-deficiency in female adolescents.

PubMed

Tussing-Humphreys, Lisa M; Liang, Huifang; Nemeth, Elizabeta; Freels, Sally; Braunschweig, Carol A

2009-02-01

Iron deficiency is more prevalent in overweight children and adolescents but the mechanisms that underlie this condition remain unclear. The purpose of this cross-sectional study was to assess the relationship between iron status and excess adiposity, inflammation, menarche, diet, physical activity, and poverty status in female adolescents included in the National Health and Nutrition Examination Survey 2003-2004 dataset. Descriptive and simple comparative statistics (t test, chi(2)) were used to assess differences between normal-weight (5th < or = body mass index [BMI] percentile <85th) and heavier-weight girls (< or = 85th percentile for BMI) for demographic, biochemical, dietary, and physical activity variables. In addition, logistic regression analyses predicting iron deficiency and linear regression predicting serum iron levels were performed. Heavier-weight girls had an increased prevalence of iron deficiency compared to those with normal weight. Dietary iron, age of and time since first menarche, poverty status, and physical activity were similar between the two groups and were not independent predictors of iron deficiency or log serum iron levels. Logistic modeling predicting iron deficiency revealed having a BMI > or = 85th percentile and for each 1 mg/dL increase in C-reactive protein the odds ratio for iron deficiency more than doubled. The best-fit linear model to predict serum iron levels included both serum transferrin receptor and C-reactive protein following log-transformation for normalization of these variables. Findings indicate that heavier-weight female adolescents are at greater risk for iron deficiency and that inflammation stemming from excess adipose tissue contributes to this phenomenon. Food and nutrition professionals should consider elevated BMI as an additional risk factor for iron deficiency in female adolescents.

Meningitis in adult patients with a negative direct cerebrospinal fluid examination: value of cytochemical markers for differential diagnosis

PubMed Central

2011-01-01

Introduction The objective of this study was to determine the ability of various parameters commonly used for the diagnosis of acute meningitis to differentiate between bacterial and viral meningitis, in adult patients with a negative direct cerebrospinal fluid (CSF) examination. Methods This was a prospective study, started in 1997, including all patients admitted to the emergency unit with acute meningitis and a negative direct CSF examination. Serum and CSF samples were taken immediately on admission. The patients were divided into two groups according to the type of meningitis: bacterial (BM; group I) or viral (VM; group II). The CSF parameters investigated were cytology, protein, glucose, and lactate; the serum parameters evaluated were C-reactive protein and procalcitonin. CSF/serum glucose and lactate ratios were also assessed. Results Of the 254 patients with meningitis with a negative direct CSF examination, 35 had BM and 181, VM. The most highly discriminative parameters for the differential diagnosis of BM proved to be CSF lactate, with a sensitivity of 94%, a specificity of 92%, a negative predictive value of 99%, a positive predictive value of 82% at a diagnostic cut-off level of 3.8 mmol/L (area under the curve (AUC), 0.96; 95% confidence interval (CI), 0.95 to 1), and serum procalcitonin, with a sensitivity of 95%, a specificity of 100%, a negative predictive value of 100%, and a positive predictive value of 97% at a diagnostic cut-off level of 0.28 ng/ml (AUC, 0.99; 95% CI, 0.99 to 1). Conclusions Serum procalcitonin and CSF lactate concentrations appear to be the most highly discriminative parameters for the differential diagnosis of BM and VM. PMID:21645387

Anti-signal recognition particle autoantibody ELISA validation and clinical associations.

PubMed

Aggarwal, Rohit; Oddis, Chester V; Goudeau, Danielle; Fertig, Noreen; Metes, Ilinca; Stephens, Chad; Qi, Zengbiao; Koontz, Diane; Levesque, Marc C

2015-07-01

The aim of this study was to develop and validate a quantitative anti-signal recognition particle (SRP) autoantibody serum ELISA in patients with myositis and longitudinal association with myositis disease activity. We developed a serum ELISA using recombinant purified full-length human SRP coated on ELISA plates and a secondary antibody that bound human IgG to detect anti-SRP binding. Protein immunoprecipitation was used as the gold standard for the presence of anti-SRP. Serum samples from three groups were analysed: SRP(+) myositis subjects by immunoprecipitation, SRP(-) myositis subjects by immunoprecipitation and non-myositis controls. The ELISA's sensitivity, specificity, positive predictive value and negative predictive value were evaluated. Percentage agreement and test-retest reliability were assessed. Serial samples from seven SRP immunoprecipitation-positive subjects were also tested, along with serum muscle enzymes and manual muscle testing. Using immunoprecipitation, we identified 26 SRP(+) myositis patients and 77 SRP(-) controls (including 38 patients with necrotizing myopathy). Non-myositis control patients included SLE (n = 4) and SSc (n = 7) patients. Anti-SRP positivity by ELISA showed strong agreement (97.1%) with immunoprecipitation (κ = 0.94). The sensitivity, specificity, positive predictive value, and negative predictive value of the anti-SRP ELISA were 88, 100, 100 and 96, respectively. The area under the curve was 0.94, and test-retest reliability was strong (r = 0.91, P < 0.001). Serial samples showed that anti-SRP levels paralleled changes in muscle enzymes and manual muscle testing. We developed a quantitative ELISA for detecting serum anti-SRP autoantibodies and validated the assay in myositis. Longitudinal assessment of SRP levels by ELISA may be a useful biomarker for disease activity. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Serum cystatin C is an independent biomarker associated with the renal resistive index in patients with chronic kidney disease.

PubMed

Ogawa-Akiyama, Ayu; Sugiyama, Hitoshi; Kitagawa, Masashi; Tanaka, Keiko; Onishi, Akifumi; Yamanari, Toshio; Morinaga, Hiroshi; Uchida, Haruhito Adam; Nakamura, Kazufumi; Ito, Hiroshi; Wada, Jun

2018-01-01

Cystatin C is a cysteine protease inhibitor that is produced by nearly all human cells. The serum level of cystatin C is a stronger predictor of the renal outcome and the risk of cardiovascular events than the creatinine level. The resistive index (RI) on renal Doppler ultrasonography is a good indicator of vascular resistance as well as the renal outcomes in patients with chronic kidney disease (CKD). However, it is unclear whether serum cystatin C is associated with signs of vascular dysfunction, such as the renal RI. We measured the serum cystatin C levels in 101 CKD patients and investigated the relationships between cystatin C and markers of vascular dysfunction, including the renal RI, ankle-brachial pulse wave velocity (baPWV), intima-media thickness (IMT), and cardiac function. The renal RI was significantly correlated with the serum cystatin C level (p < 0.0001, r = 0.6920). The serum cystatin C level was found to be a significant determinant of the renal RI (p < 0.0001), but not the baPWV, in a multivariate regression analysis. The multivariate odds ratio of the serum cystatin C level for a renal RI of more than 0.66 was statistically significant (2.92, p = 0.0106). The area under the receiver-operating characteristic curve comparing the sensitivity and specificity of cystatin C for predicting an RI of more than 0.66 was 0.882 (cutoff value: 2.04 mg/L). In conclusion, the serum cystatin C level is an independent biomarker associated with the renal RI in patients with CKD.

ERBB3: A potential serum biomarker for early detection and therapeutic target for devil facial tumour 1 (DFT1)

PubMed Central

Kunde, Dale A.; Taylor, Robyn L.; Pyecroft, Stephen B.; Sohal, Sukhwinder Singh; Snow, Elizabeth T.

2017-01-01

Devil Facial Tumour 1 (DFT1) is one of two transmissible neoplasms of Tasmanian devils (Sarcophilus harrisii) predominantly affecting their facial regions. DFT1’s cellular origin is that of Schwann cell lineage where lesions are evident macroscopically late in the disease. Conversely, the pre-clinical timeframe from cellular transmission to appearance of DFT1 remains uncertain demonstrating the importance of an effective pre-clinical biomarker. We show that ERBB3, a marker expressed normally by the developing neural crest and Schwann cells, is immunohistohemically expressed by DFT1, therefore the potential of ERBB3 as a biomarker was explored. Under the hypothesis that serum ERBB3 levels may increase as DFT1 invades local and distant tissues our pilot study determined serum ERBB3 levels in normal Tasmanian devils and Tasmanian devils with DFT1. Compared to the baseline serum ERBB3 levels in unaffected Tasmanian devils, Tasmanian devils with DFT1 showed significant elevation of serum ERBB3 levels. Interestingly Tasmanian devils with cutaneous lymphoma (CL) also showed elevation of serum ERBB3 levels when compared to the baseline serum levels of Tasmanian devils without DFT1. Thus, elevated serum ERBB3 levels in otherwise healthy looking devils could predict possible DFT1 or CL in captive or wild devil populations and would have implications on the management, welfare and survival of Tasmanian devils. ERBB3 is also a therapeutic target and therefore the potential exists to consider modes of administration that may eradicate DFT1 from the wild. PMID:28591206

Stress and serum TNF-alpha levels may predict disease outcome in patients with pemphigus: a preliminary study.

PubMed

Ragab, Nader; Abdallah, Marwa; El-Gohary, Eman; Elewa, Rana

2011-04-01

The aim of the current preliminary case-control study was to estimate the initial serum levels of tumor necrosis factor alpha (TNF-alpha) in case patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) and correlate them with history of stress, body surface area (BSA) affected, disease severity, and disease outcome. Ten PV and 4 PF case patients as well as 7 healthy matched controls had their serum levels of TNF-alpha measured by an enzyme-linked immunosorbent assay. Case patients were treated and followed up for 2 months. A statistically significant elevation in serum levels of TNF-alpha in PV case patients compared with controls and in PV case patients compared with PF case patients was detected (P < .05), with no significant difference between PF case patients and controls (P > .05). No significant correlation was detected between the serum levels of TNF-alpha and the BSA affected (P > .05). Four PV case patients had a bad disease outcome, of which 3 had severe emotional stress a month prior to the onset of the attack. All 4 showed significantly elevated initial serum levels of TNF-alpha compared with those who had a good disease outcome (P < .05). Emotional stress is a factor affecting prognosis of the disease. Pretreatment assessment of serum TNF-alpha levels in patients with pemphigus may be a guide to the expected prognosis and selection of the proper treatment regimen.

Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis

PubMed Central

Baruah, Manash P.; Bhattacharya, Bhaskar

2012-01-01

Background: C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT). Aim: This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT. Materials and Methods: Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves’ disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens’ method. Either Tc99 nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves’ disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients. Results: Serum CRP level was high in 61% of SAT patients but in none of the Graves′patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P <0.0004) in the SAT group [27.55 (5.76) (15.72-39.38)], than in the Graves’ group [4.09 (0.12) (3.81-4.36)]. The sensitivity of serum CRP was 73.33%, specificity 53.85%, positive predictive value (PPV) 64.71%, and negative predictive value (NPV) 63.64% as compared to the sensitivity (53.57%), specificity (15.38%), PPV (57.69 %), and NPV (13.33%) of ESR. Conclusion: There is significantly higher rise in serum CRP level in patients with SAT is compared to patients with Graves’ disease. It correlates well with the rise in ESR. Such findings of this pilot study highlight the scope of using serum CRP as a diagnostic marker of SAT specially in situations when it may be confused with Graves’ disease, another common cause of thyrotoxicosis. It is logical to carry out studies to find a particular cut-off for serum CRP which can serve as an objective parameter for grading the inflammation in patients with SAT. PMID:23226645

Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis.

PubMed

Baruah, Manash P; Bhattacharya, Bhaskar

2012-11-01

C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT). This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT. Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves' disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens' method. Either Tc(99) nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves' disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients. Serum CRP level was high in 61% of SAT patients but in none of the Graves'patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P <0.0004) in the SAT group [27.55 (5.76) (15.72-39.38)], than in the Graves' group [4.09 (0.12) (3.81-4.36)]. The sensitivity of serum CRP was 73.33%, specificity 53.85%, positive predictive value (PPV) 64.71%, and negative predictive value (NPV) 63.64% as compared to the sensitivity (53.57%), specificity (15.38%), PPV (57.69 %), and NPV (13.33%) of ESR. There is significantly higher rise in serum CRP level in patients with SAT is compared to patients with Graves' disease. It correlates well with the rise in ESR. Such findings of this pilot study highlight the scope of using serum CRP as a diagnostic marker of SAT specially in situations when it may be confused with Graves' disease, another common cause of thyrotoxicosis. It is logical to carry out studies to find a particular cut-off for serum CRP which can serve as an objective parameter for grading the inflammation in patients with SAT.

Magnetic Resonance Imaging Predicts Adverse Local Tissue Reaction Histologic Severity in Modular Neck Total Hip Arthroplasty.

PubMed

Barlow, Brian T; Ortiz, Philippe A; Fields, Kara G; Burge, Alissa J; Potter, Hollis G; Westrich, Geoffrey H

2016-10-01

The association between advanced imaging, serum metal ion levels, and histologic adverse local tissue reaction (ALTR) severity has not been previously reported for Rejuvenate modular neck femoral stems. A cohort of 90 patients with 98 Rejuvenate modular neck femoral stems was revised by a single surgeon from July 2011 to December 2014. Before revision, patients underwent multiacquisition variable resonance image combination sequence magnetic resonance imaging (MRI), and serum cobalt and chromium ion levels were measured. Histologic samples from the revision surgery were scored for synovial lining, inflammatory infiltrate, and tissue organization as proposed by Campbell. Regression based on the generalized estimating equations approach was used to assess the univariate association between each MRI, demographic, and metal ion measure and ALTR severity while accounting for the correlation between bilateral hips. Random forest analysis was then used to determine the relative importance of MRI characteristics, demographics, and metal ion levels in predicting ALTR severity. Synovial thickness as measured on MRI was found to be the strongest predictor of ALTR histologic severity in a recalled modular neck femoral stem. MRI can accurately describe ALTR in modular femoral neck total hip arthroplasty. MRI characteristics, particularly maximal synovial thickness and synovitis volume, predicted histologic severity. Serum metal ion levels do not correlate with histologic severity in Rejuvenate modular neck total hip arthroplasty. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic Value of Serum Caspase-Cleaved Cytokeratin-18 Levels before Liver Transplantation for One-Year Survival of Patients with Hepatocellular Carcinoma

PubMed Central

Lorente, Leonardo; Rodriguez, Sergio T.; Sanz, Pablo; Pérez-Cejas, Antonia; Padilla, Javier; Díaz, Dácil; González, Antonio; Martín, María M.; Jiménez, Alejandro; Barrera, Manuel A.

2016-01-01

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301–73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%–84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival. PMID:27618033

Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease.

PubMed

Sin, Don D; Miller, Bruce E; Duvoix, Annelyse; Man, S F Paul; Zhang, Xuekui; Silverman, Edwin K; Connett, John E; Anthonisen, Nicholas A; Wise, Robert A; Tashkin, Donald; Celli, Bartolome R; Edwards, Lisa D; Locantore, Nicholas; Macnee, William; Tal-Singer, Ruth; Lomas, David A

2011-05-01

There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD.

Alpha-fetoprotein and (18)F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation.

PubMed

Hong, Geun; Suh, Kyung-Suk; Suh, Suk-Won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Paeng, Jin Chul; Yi, Nam-Joon; Lee, Kwang-Woong

2016-04-01

Given the organ shortage for liver transplantation (LT) and the limitations of the current morphology-based selection criteria, improved criteria are needed to achieve the maximum benefit of LT for hepatocellular carcinoma (HCC). We hypothesized that a combination of biological markers may better predict the prognosis than the Milan criteria. HCC patients (n=123) with preoperative data on serum alpha-fetoprotein (AFP) levels and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) positivity underwent live-donor LT between January 2003 and December 2009. The cut-off values for serum AFP levels (200 ng/ml) and (18)F-FDG PET positivity (1.10) for tumor recurrence were determined by c-statistics using receiver operating characteristic curves. Univariate and multivariate analyses with preoperative variables were performed to find pre-transplant prognostic factors. Disease-free survival rates and overall survival rates were analysed with regard to serum AFP levels and (18)F-FDG PET positivity. The 5-year disease-free survival rates and overall survival rates were 80.3% and 81.6% respectively. (18)F-FDG PET positivity (hazard ratio (HR) 9.766, 95% CI 3.557-26.816; p<0.001) and serum AFP level (HR 6.234, 95% CI 2.643-14.707; p<0.001) were the only significant pre-transplant prognostic factors in the multivariate analysis; tumor number and size were not significant. A combination of criteria showed that the biologically high-risk group (AFP level ⩾200 ng/ml and PET-positive) had an HR of 29.069 (95% CI 8.797-96.053; p<0.001) compared with the double-negative group. Use of the Milan criteria yielded an HR of 1.351 (95% CI 0.500-3.652; p=0.553). The combination of the serum AFP level and (18)F-FDG PET data predicted better outcomes than those using the Milan criteria, improving objectivity when adult-to-adult living donor LT is contemplated. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients.

PubMed

Yalin, G Y; Tanrikulu, S; Gul, N; Uzum, A K; Aral, F; Tanakol, R

2017-08-01

High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (<1 mcg/dl) at least 3 months after initial treatment. Serum P levels decreased significantly after treatment in both groups (p < 0.001). There was a significant correlation between baseline phosphorus levels and remission rates, nadir GH in OGTT, pituitary adenoma size and Ki-67 scores (p = 0.001, r: -0.51; p = 0.01, r: 0.44; p = 0.001, r: 0.52; p = 0.02, r: 0.71, respectively). Mean baseline P levels were significantly higher in patients with non-remission (4.8 vs 4.2, P < 0.001). Logistic regression analysis did not reveal an independent effect on remission with any of these risk factors. High serum P levels may be an indicator for a low likelihood of onset of remission in acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.

TNF Receptor 1/2 Predict Heart Failure Risk in Type 2 Diabetes Mellitus Patients.

PubMed

Ping, Zhang; Aiqun, Ma; Jiwu, Li; Liang, Shao

2017-04-06

Inflammation plays an important role in heart failure and diabetes mellitus. Traditional serum markers have limited predictive value in heart failure and diabetes. TNFR1 and TNFR2 (TNFR1/2) have been proven to be strongly associated with heart failure and diabetes complications. This study aimed to assess the association of sTNFR1 and sTNFR2 levels and incidental HF risk in diabetes patients.We detected the mRNA, protein, and serum expression of TNFR1/2, their downstream signaling pathway protein NF-kB, and JNK expression and some traditional serum inflammatory markers in a heart failure group without diabetes mellitus or abnormal glucose tolerance (n = 84), a diabetes mellitus group without heart failure (n = 86), and a heart failure with diabetes mellitus group (n = 86).TNFR1/2 were significantly higher in patients with heart failure and diabetes mellitus based on mRNA expression to protein expression and serum expression. However, there were no differences in mRNA, protein, and serum levels of TNFR1/2 between the HF group and DM group. Furthermore, there were no differences between the groups in some traditional serum inflammatory markers.This study demonstrated higher expressions of TNFR, NF-kB, and JNK in patients with heart failure and diabetes mellitus. Compared with traditional serum markers, TNFR1 and TNFR2 are associated with heart failure risk in type 2 diabetes mellitus patients.

Utility of the combination of serum highly-sensitive C-reactive protein level at discharge and a risk index in predicting readmission for acute exacerbation of COPD*,**

PubMed Central

Chang, Chun; Zhu, Hong; Shen, Ning; Han, Xiang; Chen, Yahong; He, Bei

2014-01-01

OBJECTIVE: Frequent readmissions for acute exacerbations of COPD (AECOPD) are an independent risk factor for increased mortality and use of health-care resources. Disease severity and C-reactive protein (CRP) level are validated predictors of long-term prognosis in such patients. This study investigated the utility of combining serum CRP level with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) exacerbation risk classification for predicting readmission for AECOPD. METHODS: This was a prospective observational study of consecutive patients hospitalized for AECOPD at Peking University Third Hospital, in Beijing, China. We assessed patient age; gender; smoking status and history (pack-years); lung function; AECOPD frequency during the last year; quality of life; GOLD risk category (A-D; D indicating the greatest risk); and serum level of high-sensitivity CRP at discharge (hsCRP-D). RESULTS: The final sample comprised 135 patients. Of those, 71 (52.6%) were readmitted at least once during the 12-month follow-up period. The median (interquartile) time to readmission was 78 days (42-178 days). Multivariate analysis revealed that serum hsCRP-D ≥ 3 mg/L and GOLD category D were independent predictors of readmission (hazard ratio = 3.486; 95% CI: 1.968-6.175; p < 0.001 and hazard ratio = 2.201; 95% CI: 1.342-3.610; p = 0.002, respectively). The ordering of the factor combinations by cumulative readmission risk, from highest to lowest, was as follows: hsCRP-D ≥ 3 mg/L and GOLD category D; hsCRP-D ≥ 3 mg/L and GOLD categories A-C; hsCRP-D < 3 mg/L and GOLD category D; hsCRP-D < 3 mg/L and GOLD categories A-C. CONCLUSIONS: Serum hsCRP-D and GOLD classification are independent predictors of readmission for AECOPD, and their predictive value increases when they are used in combination. PMID:25410837

Serum creatinine and bilirubin predict renal failure and mortality in patients with spontaneous bacterial peritonitis: a retrospective study.

PubMed

Terg, Rubén; Gadano, Adrian; Cartier, Mariano; Casciato, Paola; Lucero, Romina; Muñoz, Alberto; Romero, Gustavo; Levi, Diana; Terg, Gonzalo; Miguez, Carlos; Abecasis, Raquel

2009-03-01

Patients with spontaneous bacterial peritonitis (SBP) are at a high risk for renal failure and death despite successful treatment of infection. Intravenous (IV) albumin administration combined with antibiotic treatment has been shown to significantly decrease these risks. Clinical evidence is lacking on which patients are appropriate candidates for albumin treatment. To retrospectively analyse the usefulness of serum creatinine and bilirubin levels in predicting renal failure and mortality of patients hospitalized for SBP. Between March 1995 and September 1998, 127 cirrhotic patients with SBP who had not received plasma expansion were evaluated. Eighty-one patients (64%) were classified as having a high risk for renal failure and mortality (serum bilirubin >4 mg/dl or serum creatinine >1 mg/dl) and 46 (36%) as having a low risk. At admission, 36.3% of all patients presented renal failure. Mortality during their hospitalization was 23% among those with a high risk and 6.5% among those with a low risk (P=0.01). Renal failure occurred in 23% of the high-risk patients, compared with 2.6% of the low-risk patients (P=0.006). The presence of hyponatraemia was significantly associated with higher mortality and renal failure in the high-risk group. Our retrospective review of patients with SBP suggests that serum bilirubin levels >4 mg and serum creatinine levels >1 mg/dl at the time of diagnosis represent significant risk factors for the clinical outcomes of patients with SBP. Patients without these risk factors may have a very low likelihood of death or renal failure.

Plasma and serum L-selectin and clinical and subclinical the Multi-Ethnic Study of Atherosclerosis (MESA)cardiovascular disease

PubMed Central

BERARDI, CECILIA; DECKER, PAUL A.; KIRSCH, PHILLIP S.; DE ANDRADE, MARIZA; TSAI, MICHAEL Y.; PANKOW, JAMES S.; SALE, MICHELE M.; SICOTTE, HUGUES; TANG, WEIHONG; HANSON, NAOMI; POLAK, JOSEPH F.; BIELINSKI, SUZETTE J.

2014-01-01

L-selectin has been suggested to play a role in atherosclerosis. Previous studies on cardiovascular disease (CVD) and serum or plasma L-selectin are inconsistent. The association of serum L-selectin (sL-selectin) with carotid intima-media thickness, coronary artery calcium, ankle-brachial index (subclinical CVD) and incident CVD was assessed within 2403 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Regression analysis and the Tobit model were used to study subclinical disease; Cox Proportional Hazards regression for incident CVD. Mean age was 63 ± 10, 47% were males; mean sL-selectin was significantly different across ethnicities. Within each race/ethnicity, sL-selectin was associated with age and sex; among Caucasians and African Americans, it was associated with smoking status and current alcohol use. sL-selectin levels did not predict subclinical or clinical CVD after correction for multiple comparisons. Conditional logistic regression models were used to study plasma L-selectin and CVD within 154 incident CVD cases, occurred in a median follow up of 8.5 years, and 306 age-, sex-, and ethnicity-matched controls. L-selectin levels in plasma were significantly lower than in serum and the overall concordance was low. Plasma levels were not associated with CVD. In conclusion, this large multi-ethnic population, soluble L-selectin levels did not predict clinical or subclinical CVD. PMID:24631064

Procalcitonin as a Diagnostic and Prognostic Factor for Tuberculosis Meningitis

PubMed Central

Kim, Jinseung; Kim, Si Eun; Park, Bong Soo; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Kim, Sung Eun

2016-01-01

Background and Purpose We investigated the potential role of serum procalcitonin in differentiating tuberculosis meningitis from bacterial and viral meningitis, and in predicting the prognosis of tuberculosis meningitis. Methods This was a retrospective study of 26 patients with tuberculosis meningitis. In addition, 70 patients with bacterial meningitis and 49 patients with viral meningitis were included as the disease control groups for comparison. The serum procalcitonin level was measured in all patients at admission. Differences in demographic and laboratory data, including the procalcitonin level, were analyzed among the three groups. In addition, we analyzed the predictive factors for a prognosis of tuberculosis meningitis using the Glasgow Coma Scale (GCS) at discharge, and the correlation between the level of procalcitonin and the GCS score at discharge. Results Multiple logistic regression analysis showed that a low level of procalcitonin (≤1.27 ng/mL) independently distinguished tuberculosis meningitis from bacterial meningitis. The sensitivity and specificity for distinguishing tuberculosis meningitis from bacterial meningitis were 96.2% and 62.9%, respectively. However, the level of procalcitonin in patients with tuberculosis meningitis did not differ significantly from that in patients with viral meningitis. In patients with tuberculosis meningitis, a high level of procalcitonin (>0.4 ng/mL) was a predictor of a poor prognosis, and the level of procalcitonin was negatively correlated with the GCS score at discharge (r=-0.437, p=0.026). Conclusions We found that serum procalcitonin is a useful marker for differentiating tuberculosis meningitis from bacterial meningitis and is also valuable for predicting the prognosis of tuberculosis meningitis. PMID:27165424

Leptin levels in patients with anorexia nervosa following day/inpatient treatment do not predict weight 1 year post-referral.

PubMed

Seitz, Jochen; Bühren, Katharina; Biemann, Ronald; Timmesfeld, Nina; Dempfle, Astrid; Winter, Sibylle Maria; Egberts, Karin; Fleischhaker, Christian; Wewetzer, Christoph; Herpertz-Dahlmann, Beate; Hebebrand, Johannes; Föcker, Manuel

2016-09-01

Elevated serum leptin levels following rapid therapeutically induced weight gain in anorexia nervosa (AN) patients are discussed as a potential biomarker for renewed weight loss as a result of leptin-related suppression of appetite and increased energy expenditure. This study aims to analyze the predictive value of leptin levels at discharge as well as the average rate of weight gain during inpatient or day patient treatment for body weight at 1-year follow-up. 121 patients were recruited from the longitudinal Anorexia Nervosa Day patient versus Inpatient (ANDI) trial. Serum leptin levels were analyzed at referral and discharge. A multiple linear regression analysis to predict age-adjusted body mass index (BMI-SDS) at 1-year follow-up was performed. Leptin levels, the average rate of weight gain, premorbid BMI-SDS, BMI-SDS at referral, age and illness duration were included as independent variables. Neither leptin levels at discharge nor rate of weight gain significantly predicted BMI-SDS at 1-year follow-up explaining only 1.8 and 0.4 % of the variance, respectively. According to our results, leptin levels at discharge and average rate of weight gain did not exhibit any value in predicting weight at 1-year follow-up in our longitudinal observation study of adolescent patients with AN. Thus, research should focus on other potential factors to predict weight at follow-up. As elevated leptin levels and average rate of weight gain did not pose a risk for reduced weight, we found no evidence for the beneficial effect of slow refeeding in patients with acute AN.

Selected Adnexal Cystic Masses in Postmenopausal Women Can be Safely Managed by Laparoscopy

PubMed Central

Lee, Jeong-Won; Kim, Chul Jung; Lee, Ji Eun; Lee, Sun-Joo; Kim, Byoung-Gie; Lee, Je-Ho; Bae, Duk-Soo

2005-01-01

The aim of this study was to assess the efficacy and safety of laparoscopic treatment for adnexal cystic masses that were predicted to be benign in postmenopausal women. Postmenopausal women found to have an adnexal cystic mass were retrospectively evaluated with transvaginal ultrasonography, and serum CA-125 levels. The selection criteria were adnexal cystic masses greater than 3 cm but less than 10 cm, the masses were in the benign range (4-8) of Sassone's scoring system for transvaginal ultrasonography, and the patients had serum CA-125 levels less than 65 IU/mL. Two hundred nineteen women fulfilled the criteria and underwent operative laparoscopy. Almost all the masses (99.5%) were accurately predicted to be benign except for one borderline ovarian tumor. Two hundreds thirteen (97.3%) women were successfully managed by operative laparoscopy and six (2.7%) required laparotomy. For the patients managed by laparoscopy, the mean operative time was 51.3 min; the mean hospital stay was 2.5 days. There was no significant morbidity and surgery-related mortality. The combination of the Sassone's scoring system for transvaginal ultrasonography and serum CA-125 level can accurately predict benign cystic masses, and operative laparoscopy is technically feasible and safe for the management of adnexal mass in postmenopausal women. PMID:15953871

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study.

PubMed

Wu, Jianwei; Chen, Shengyun; Liu, Liping; Gao, Xiang; Zhou, Yong; Wang, Chunxue; Zhang, Qian; Wang, Anxin; Hussain, Mohammed; Sun, Baoying; Wu, Shouling; Zhao, Xingquan

2013-06-01

To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population. We performed a four-year cohort study of 95 778 men and women, aged 18-98 years, selected from the Kailuan study (2006-2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared. During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01-1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24-1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference). Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumonia.

PubMed

de Brito, Rita de Cássia Coelho Moraes; Lucena-Silva, Norma; Torres, Leuridan Cavalcante; Luna, Carlos Feitosa; Correia, Jaílson de Barros; da Silva, Giselia Alves Pontes

2016-12-01

To identify markers for earlier diagnosis of severe pneumonia, we assess the correlation between serum cytokine profile of children with different pneumonia severity. In 25 hospitalized children, 7 with mild pneumonia and 18 with severe pneumonia, the serum concentration of 11 cytokines in three sampling times were dosed. Statistical analysis included parametric and non-parametric tests, Pearson correlation and ROC curve for cut-off definition of cytokines. At admission, IL-6 serum levels were high in mild or severe pneumonia, and was associated to vomiting (P = 0.019) in both groups; and also to dyspnea (P = 0.012) and white blood cell count (P = 0.045) in patients with severe pneumonia. IL-10 levels were also high in patients with pneumonia and were associated to lymphocytosis (P = 0.025). The ROC curve of the IL-6:IL-10 serum levels ratio discriminated severe pneumonia cases at admission, and persistence of infection in the third day of antibiotic therapy, with positive predictive values of 93% and 89%, respectively. The balance between IL-6 and IL-10 serum levels showed to be a more discriminative marker for severity definition and evaluation of recovery in patients with pneumonia.

Evaluation of Serum Calcium as a Predictor of Biochemical Recurrence following Salvage Radiation Therapy for Prostate Cancer

PubMed Central

Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Parker, Alexander S.; Diehl, Nancy N.; Tzou, Katherine S.; Paryani, Nitesh N.; Ko, Stephen J.; Daugherty, Larry C.; Vallow, Laura A.; Pisansky, Thomas M.

2013-01-01

Background. Previous reports have shown a positive association between serum calcium level and prostate cancer mortality. However, there is no data regarding whether higher serum calcium levels are associated with increased risk of biochemical recurrence (BCR) following salvage radiation therapy (SRT) for prostate cancer. Herein, we evaluate the association between pretreatment serum calcium levels and BCR in a cohort of men who underwent SRT. Methods. We evaluated 165 patients who underwent SRT at our institution. Median dose was 65.0 Gy (range: 54.0–72.4 Gy). We considered serum calcium as both a continuous variable and a 3-level categorical variable (low [≤9.0 mg/dL], moderate [>9.0 mg/dL and ≤9.35 mg/dL], and high [>9.35 mg/dL]) based on sample tertiles. Results. We observed no evidence of a linear association between serum calcium and BCR (relative risk (RR): 0.96, P = 0.76). Compared to men with low calcium, there was no significantly increased risk of BCR for men with moderate (RR: 0.94, P = 0.79) or high (RR: 1.08, P = 0.76) serum calcium levels. Adjustment for clinical, pathological, and SRT characteristics in multivariable analyses did not alter these findings. Conclusion. Our results provide evidence that pretreatment serum calcium is unlikely to be a useful tool in predicting BCR risk following SRT. PMID:23606986

Circulating C1q complement/TNF-related protein (CTRP) 1, CTRP9, CTRP12 and CTRP13 concentrations in Type 2 diabetes mellitus: In vivo regulation by glucose

PubMed Central

Zhang, Man Man; Tan, Bee Kang; Chen, Jing

2017-01-01

Objectives The C1q complement/TNF-related protein (CTRP) superfamily, which includes the adipokine adiponectin, has been shown in animal models to have positive metabolic and cardiovascular effects. We sought to investigate circulating CTRP1, CTRP9, CTRP12 and CTRP13 concentrations in persons with type 2 diabetes mellitus (T2DM), with age and BMI matched controls, and to examine the effects of a 2 hour 75g oral glucose tolerance test (OGTT) on serum CTRP1, CTRP9, CTRP12 and CTRP13 levels in persons with T2DM. Design Cross-sectional study [newly diagnosed T2DM (n = 124) and control (n = 139) participants]. Serum CTRP1, CTRP9, CTRP12 and CTRP13 were measured by ELISA. Results Systolic and diastolic blood pressure, total cholesterol (TCH), Low-density lipoprotein (LDL)-cholesterol, triglycerides, TCH/High-density lipoprotein (HDL) ratio, triglycerides/HDL ratio, glucose, insulin, homeostatic model assessment–insulin resistance (HOMA-IR), C-reactive protein and endothelial lipase were significantly higher, whereas leptin and adiponectin were significantly lower in T2DM participants. Serum CTRP1 were significantly higher and CTRP12 significantly lower in T2DM participants. Age, diastolic blood pressure, glucose and CTRP12 were predictive of serum CTRP1; leptin was predictive of serum CTRP9; glucose and CTRP1 were predictive of serum CTRP12; endothelial lipase was predictive of serum CTRP13. Finally, serum CTRP1 were significantly higher and CTRP12 significantly lower in T2DM participants after a 2 hour 75g OGTT. Conclusions Our data supports CTRP1 and CTRP12 as potential novel biomarkers for the prediction and early diagnosis of T2DM. Furthermore, pharmacological agents that target CTRP1 and CTRP12 could represent a new strategy in the treatment of T2DM. PMID:28207876

Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers

PubMed Central

Chen, Qiuying; Deeb, Ruba S.; Ma, Yuliang; Staudt, Michelle R.; Crystal, Ronald G.; Gross, Steven S.

2015-01-01

COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US. Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease. Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD. A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentially-expressed in COPD-smokers vs. healthy-smokers. These 23 putative biomarkers were differentially-correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8% sensitivity and 86.5% specificity. In an independent validation set, this model correctly predicted COPD in 8/10 individuals. These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels. Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways. Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD. PMID:26674646

Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.

PubMed

Vondran, Florian W R; Timrott, Kai; Kollrich, Sonja; Steinhoff, Ann-Kristin; Kaltenborn, Alexander; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank; Schwinzer, Reinhard

2014-09-01

Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF < BL < AR. Relying on serum analysis only, multivariate logistic regression (logit link function) yielded a prognostic score for prediction of rejection with 75.0% sensitivity and 69.2% specificity. Patients with rejection showed markedly higher pre-transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combined panel of serum human tissue kallikreins and CA-125 for the detection of epithelial ovarian cancer.

PubMed

Koh, Stephen Chee Liang; Huak, Chan Yiong; Lutan, Delfi; Marpuang, Johny; Ketut, Suwiyoga; Budiana, Nyoma Gede; Saleh, Agustria Zainu; Aziz, Mohamad Farid; Winarto, Hariyono; Pradjatmo, Heru; Hoan, Nguyen Khac Han; Thanh, Pham Viet; Choolani, Mahesh

2012-07-01

To determine the predictive accuracy of the combined panels of serum human tissue kallikreins (hKs) and CA-125 for the detection of epithelial ovarian cancer. Serum specimens collected from 5 Indonesian centers and 1 Vietnamese center were analyzed for CA-125, hK6, and hK10 levels. A total of 375 specimens from patients presenting with ovarian tumors, which include 156 benign cysts, 172 epithelial ovarian cancers (stage I/II, n=72; stage III/IV, n=100), 36 germ cell tumors and 11 borderline tumors, were included in the study analysis. Receiver operating characteristic analysis were performed to determine the cutoffs for age, CA-125, hK6, and hK10. Sensitivity, specificity, negative, and positive predictive values were determined for various combinations of the biomarkers. The levels of hK6 and hK10 were significantly elevated in ovarian cancer cases compared to benign cysts. Combination of 3 markers, age/CA-125/hk6 or CA-125/hk6/hk10, showed improved specificity (100%) and positive predictive value (100%) for prediction of ovarian cancer, when compared to the performance of single markers having 80-92% specificity and 74-87% positive predictive value. Four-marker combination, age/CA-125/hK6/hK10 also showed 100% specificity and 100% positive predictive value, although it demonstrated low sensitivity (11.9%) and negative predictive value (52.8%). The combination of human tissue kallikreins and CA-125 showed potential for improving prediction of epithelial ovarian cancer in patients presenting with ovarian tumors.

Developing strategies for predicting hyperkalemia in potassium-increasing drug-drug interactions.

PubMed

Eschmann, Emmanuel; Beeler, Patrick Emanuel; Schneemann, Markus; Blaser, Jürg

2017-01-01

To compare different strategies predicting hyperkalemia (serum potassium level ≥5.5 mEq/l) in hospitalized patients for whom medications triggering potassium-increasing drug-drug interactions (DDIs) were ordered. We investigated 5 strategies that combined prediction triggered at onset of DDI versus continuous monitoring and taking into account an increasing number of patient parameters. The considered patient parameters were identified using generalized additive models, and the thresholds of the prediction strategies were calculated by applying Youden's J statistic to receiver operation characteristic curves. Half of the data served as the calibration set, half as the validation set. We identified 132 incidences of hyperkalemia induced by 8413 potentially severe potassium-increasing DDIs among 76 467 patients. The positive predictive value (PPV) of those strategies predicting hyperkalemia at the onset of DDI ranged from 1.79% (undifferentiated anticipation of hyperkalemia due to the DDI) to 3.02% (additionally considering the baseline serum potassium) and 3.10% (including further patient parameters). Continuous monitoring significantly increased the PPV to 8.25% (considering the current serum potassium) and 9.34% (additional patient parameters). Continuous monitoring of the risk for hyperkalemia based on current potassium level shows a better predictive power than predictions triggered at the onset of DDI. This contrasts with efforts to improve DDI alerts by taking into account more patient parameters at the time of ordering. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Alpha-amylase serum levels in professional soccer players are not related with physical fitness.

PubMed

Sanchis-Gomar, Fabian; Alis, Rafael; Rampinini, Ermanno; Bosio, Andrea; Romagnoli, Marco; Lombardi, Giovanni; Lippi, Giuseppe

2017-03-01

Recent evidence has showed that serum or salivary values of α-amylase predict endurance running performance. In this study we investigate whether serum α-amylase concentration may be associated with training status during a competitive season and after a detraining period in professional soccer players. The study population consisted in 15 male professional soccer players from an Italian major league team (age [mean±SD] 27±5 years, weight 76.9±4.1 kg, height 1.82±0.05 m). Serum α-amylase levels were measured 3 times during the last part of a competitive season (January, March and May) and just before preseason training (July). Metabolic and cardiovascular fitness of soccer players was improved during the last part of the season. The levels of α-amylase did not change significantly throughout the study period (χ2=7.331, P=0.062), nor they were found to be associated with variation of physical fitness and training status. The α-amylase fluctuations throughout a competitive season and after vacation time were meaningless in professional soccer players. No significant associations with physical fitness variations could be observed. These results suggest that α-amylase concentration may be a useful parameter for identifying individual inclination to endurance exercise, but not for predicting actual training status.

Soluble CD30 in renal transplant recipients: is it a good biomarker to predict rejection?

PubMed

Azarpira, Negar; Aghdaie, Mahdokht Hosein; Malekpour, Zahra

2010-01-01

It has been suggested that the serum soluble CD30 (sCD30) level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years) had higher sCD30 levels (P= 0.02). There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre transplant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

Correlations between serum assays of human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) and pre-eclampsia or intrauterine growth restriction (IUGR) among nulliparas younger than 38 years.

PubMed

Merviel, P; Müller, F; Guibourdenche, J; Berkane, N; Gaudet, R; Bréart, G; Uzan, S

2001-03-01

To study the relation between serum human chorionic gonadotrophin (hCG) levels measured at 15-18 weeks and gestational disorders, assess their correlation with the artery uteroplacental Doppler (AUD) at 24 weeks among nulliparas, and assess the predictivity of the hCG/hPL (human placental lactogen) ratio for pre-eclampsia. Retrospective study of two groups of women younger than 38 years old: one with an elevated serum hCG level (2 MoM (multiples of the median) or more) and a normal fetal karyotype (group A), and the other with a lower hCG level (group B). Within each group, we studied the nulliparas separately (respectively groups AO and BO). We analyzed the double screening, elevated hCG levels with abnormal AUD, for the predicting of hypertensive disorders. Elevated hCG levels were significantly (p<0.05) more prevalent among women who developed gestational diabetes (groups A and AO) and among nulliparas with pregnancy-induced hypertension and pre-eclampsia (AO). Among nulliparas, the combination of the hCG assay and a subsequent Doppler increased the positive predictive value (PPV) of the assay from 19 to 75%, without reducing its negative predictive value (NPV) for gestational vascular disorders. The hCG/hPL ratio did not improve the predictivity of the hCG assay alone for pre-eclampsia. An hCG level of 2 MoM or more at 15-18 weeks identifies a group of women at risk of gestational vascular disorders; it therefore ought to lead to an AUD at 24 weeks. This double screening should be able to define a population of women at risk of developing a hypertensive disorder, who could thus benefit from a preventive treatment, as aspirin.

Serum Oxytocin Levels and an Oxytocin Receptor Gene Polymorphism (rs2254298) Indicate Social Deficits in Children and Adolescents with Autism Spectrum Disorders

PubMed Central

Yang, Shuhan; Dong, Xiaopeng; Guo, Xuan; Han, Yu; Song, Hanbing; Gao, Lei; Dai, Wei; Su, Yuanyuan; Zhang, Xin

2017-01-01

The neuropeptide oxytocin (OT) and its receptor (OXTR) have been predicted to be involved in the regulation of social functioning in autism spectrum disorders (ASD). Objective of the study was to investigate serum OT levels and the OXTR rs2254298 polymorphism in Chinese Han children and adolescents with ASD as well as to identify their social deficits relevant to the oxytocinergic system. We tested serum OT levels using ELISA in 55 ASD subjects and 110 typically developing (TD) controls as well as genotyped the OXTR rs2254298 polymorphism using PCR-RFLP in 100 ASD subjects and 232 TD controls. Autistic symptoms were assessed by the Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS). There were no significant associations between OXTR rs2254298 polymorphism and ASD, serum OT levels and age, as well as serum OT levels and intelligent quotient (IQ) in both ASD and TD groups. However, ASD subjects exhibited elevated serum OT levels compared to TD controls and positive correlations between serum OT levels and “adaptation to change score” in the CARS and CARS total scores. Moreover, in the ASD group, significant relationships were revealed between the single-nucleotide polymorphism (SNP) rs2254298 and serum OT levels, the category “stereotypes and object use” in the ABC and the category “adaptation to change” in the CARS. These findings indicated that individuals with ASD may exhibit a dysregulation in OT on the basis of changes in OXTR gene expression as well as environmentally induced alterations of the oxytocinergic system to determine their social deficits. PMID:28484366

Prediction of therapeutic response in steroid-treated pulmonary sarcoidosis. Evaluation of clinical parameters, bronchoalveolar lavage, gallium-67 lung scanning, and serum angiotensin-converting enzyme levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hollinger, W.M.; Staton, G.W. Jr.; Fajman, W.A.

1985-07-01

To find a pretreatment predictor of steroid responsiveness in pulmonary sarcoidosis the authors studied 21 patients before and after steroid treatment by clinical evaluation, pulmonary function tests, bronchoalveolar lavage (BAL), gallium-67 lung scan, and serum angiotensin-converting enzyme (SACE) level. Although clinical score, forced vital capacity (FVC), BAL percent lymphocytes (% lymphs), quantitated gallium-67 lung uptake, and SACE levels all improved with therapy, only the pretreatment BAL % lymphs correlated with the improvement in FVC (r = 0.47, p less than 0.05). Pretreatment BAL % lymphs of greater than or equal to 35% predicted improvement in FVC of 10/11 patients, whereasmore » among 10 patients with BAL % lymphs less than 35%, 5 patients improved and 5 deteriorated. Clinical score, pulmonary function parameters, quantitated gallium-67 lung uptake, and SACE level used alone, in combination with BAL % lymphs or in combination with each other, did not improve this predictive value. The authors conclude that steroid therapy improves a number of clinical and laboratory parameters in sarcoidosis, but only the pretreatment BAL % lymphs are useful in predicting therapeutic responsiveness.« less

Novel adipokines WISP1 and betatrophin in PCOS: relationship to AMH levels, atherogenic and metabolic profile.

PubMed

Sahin Ersoy, Gulcin; Altun Ensari, Tugba; Vatansever, Dogan; Emirdar, Volkan; Cevik, Ozge

2017-02-01

To determine the levels of WISP1 and betatrophin in normal weight and obese women with polycystic ovary syndrome (PCOS) and to assess their relationship with anti-Müllerian hormone (AMH) levels, atherogenic profile and metabolic parameters Methods: In this prospective cross-sectional study, the study group was composed of 49 normal weighed and 34 obese women with PCOS diagnosed based on the Rotterdam criteria; 36 normal weight and 26 obese age matched non-hyperandrogenemic women with regular menstrual cycle. Serum WISP1, betatrophin, homeostasis model assessment of insulin resistance (HOMA-IR) and AMH levels were evaluated. Univariate and multivariate analyses were performed between betatrophin, WISP1 levels and AMH levels, metabolic and atherogenic parameters. Serum WISP1 and betatrophin values were elevated in the PCOS group than in the control group. Moreover, serum WISP1 and betatrophin levels were higher in the obese PCOS subgroup than in normal weight and obese control subgroups. Multivariate analyses revealed that Body mass index, HOMA-IR, AMH independently and positively predicted WISP1 levels. Serum betatrophin level variability was explained by homocysteine, HOMA-IR and androstenedione levels. WISP1 and betatrophin may play a key role on the pathogenesis of PCOS.

The role of serum C-reactive protein in women with lower urinary tract symptoms.

PubMed

Hsiao, Sheng-Mou; Lin, Ho-Hsiung; Kuo, Hann-Chorng

2012-07-01

Some lower urinary tract dysfunction (LUTD) subtypes may be associated with low-grade inflammation. This study aimed to investigate the role of serum C-reactive protein (CRP) levels in women with lower urinary tract symptoms (LUTS). A total of 197 consecutive women with non-stress urinary incontinence (non-SUI) LUTS and 18 healthy women without LUTS (normal controls) were enrolled. LUTS include urinary storage, voiding, and post-micturition symptoms. Patients with previous bladder or urethral surgery, active urinary tract infections, or possible neurogenic lesions were excluded. Serum CRP levels were measured before any treatment was given. Patients were stratified to LUTD subgroups based on a 3-day voiding diary, uroflowmetry, and selective videourodynamic studies. Median CRP levels were significantly higher in women with overactive bladder (OAB) wet (i.e., with urgency incontinence, n = 30, 0.12 mg/dl) than those in women with bladder oversensitivity (n = 68, 0.075 mg/dl, P = 0.008) and the control group (0.055 mg/dl, P = 0.032). Further analysis revealed that body mass index and maximum flow rate were two independent factors that affected CRP levels. The area under the receiver-operating characteristic curve for using CRP to predict OAB wet was 0.55, and the most predictive cutoff point for CRP was 0.15 mg/dl (sensitivity 43.5 %, specificity 72.7 %). High serum CRP levels were found in women with OAB wet, and they were related to lower maximum urinary flow rates and higher body mass indices in non-SUI LUTD. However, serum CRP is not a suitable biomarker for discriminating between subtypes of non-SUI LUTD.

Significance of change in serum bilirubin in predicting left ventricular reverse remodeling and outcomes in heart failure patients with cardiac resynchronization therapy.

PubMed

Hosoda, Junya; Ishikawa, Toshiyuki; Matsumoto, Katsumi; Iguchi, Kohei; Matsushita, Hirooki; Ogino, Yutaka; Taguchi, Yuka; Sugano, Teruyasu; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi

2017-11-01

Research on the correlation of serum bilirubin level with cardiac function as well as outcomes in heart failure patients with cardiac resynchronization therapy (CRT) has not yet been reported. The aim of this study was to analyze the relationship between change in serum bilirubin level and left ventricular reverse remodeling, and also to clarify the impact of bilirubin change on clinical outcomes in CRT patients. We evaluated 105 consecutive patients who underwent CRT. Patients who had no serum total-bilirubin data at both baseline and 3-9 months' follow-up or had died less than 3 months after CRT implantation were excluded. Accordingly, a total of 69 patients were included in the present analysis. The patients were divided into two groups: decreased bilirubin group (serum total-bilirubin level at follow-up≤that at baseline; n=48) and increased bilirubin group (serum total-bilirubin level at follow-up>that at baseline; n=21). Mean follow-up period was 39.3 months. In the decreased bilirubin group, mean left ventricular end-systolic diameter decreased from 54.5mm to 50.2mm (p=0.001) and mean left ventricular ejection fraction increased significantly from 29.8% to 37.0% (p=0.001). In the increased bilirubin group, there was no significant change in echocardiographic parameters from baseline to follow-up. In Kaplan-Meyer analysis, cardiac mortality combined with heart failure hospitalization in the increased bilirubin group was significantly higher than that in the decreased bilirubin group (log-rank p=0.018). Multivariate Cox regression analysis revealed that increased bilirubin was an independent predictor of cardiac mortality combined with heart failure hospitalization (OR=2.66, p=0.023). The change in serum bilirubin is useful for assessment of left ventricular reverse remodeling and prediction of outcomes in heart failure patients with CRT. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

High serum levels of caspase-cleaved cytokeratin-18 are associated with malignant middle cerebral artery infarction patient mortality.

PubMed

Lorente, Leonardo; Martín, María M; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Solé-Violán, Jordi; Cáceres, Juan J; Jiménez, Alejandro; García-Marín, Victor

2018-03-24

There have been found apoptotic changes in brain tissue samples from humans after cerebral ischemia. Caspase-cleaved cytokeratin (CCCK)-18 could appears in blood during apoptosis. High circulating levels of CCCK-18 have been associated with a poor prognosis in patients with cerebral process, such as traumatic brain injury and spontaneous cerebral hemorrhage. However, they have not been explored in patients with ischemic stroke. Thus, the aim of this study was to determine whether there is an association between serum CCCK-18 levels and mortality in patients with severe malignant middle cerebral artery infarction (MMCAI). This was an observational, prospective and multicentre study. We included patients with severe MMCAI. We considered MMCAI as severe when Glasgow Coma Scale (GCS) was lower than 9. We measured serum CCCK-18 levels at the diagnosis moment of the severe MMCAI. We found that non-surviving severe MMCAI patients (n = 33) showed lower GCS and platelet count, and higher serum CCCK-18 levels than survivor ones (n = 33). We found an area under the curve (AUC) of serum CCCK-18 levels to predict 30-day mortality of 82% (95% CI = 71%-91%; p < 0.001). In the multiple logistic regression analysis was found that serum CCCK-18 levels were associated with 30-day mortality (OR = 1.023; 95% CI = 1.010-1.037; p = 0.001) after to control for platelet count and GCS. To our knowledge, this is the first series reporting data on serum CCCK-18 levels in ischemic stroke patients. The novel findings of our study were that non-surviving severe MMCAI patients had higher serum CCCK-18 levels than surviving patients, and that there is an association between high serum CCCK-18 levels and MMCAI patients mortality.

The Clinical Significance of the MIF Homolog D-Dopachrome Tautomerase (MIF-2) and its Circulating Receptor (sCD74) in Burn Injury

PubMed Central

Kim, Bong-Sung; Stoppe, Christian; Grieb, Gerrit; Leng, Lin; Sauler, Maor; Assis, David; Simons, David; Boecker, Arne Hendrick; Schulte, Wibke; Piecychna, Marta; Hager, Stephan; Bernhagen, Jürgen; Pallua, Norbert; Bucala, Richard

2016-01-01

Background We reported earlier that the cytokine macrophage migration inhibitory factor (MIF) is a potential biomarker in burn injury. In the present study, we investigated the clinical significance in severely burned patients of expression levels the newly discovered MIF family member D-dopachrome tautomerase (DDT or MIF-2) and their common soluble receptor CD74 (sCD74). Methods DDT and sCD74 serum levels were measured 20 severely burned patients and 20 controls. Serum levels were correlated to the abbreviated burn severity index (ABSI) and TBSA followed by receiver operating characteristic (ROC) analysis. Data were supported by gene expression dataset analysis of 31 burn patients and 28 healthy controls. Results CD74 and DDT were increased in burn patients. Furthermore, CD74 and DDT also were elevated in septic non-survivors when compared to survivors. Serum levels of DDT showed a positive correlation with the ABSI and TBSA in the early stage after burn injury, and the predictive character of DDT was strongest at 24 hrs. Serum levels of CD74 only correlated with the ABSI five days post-injury. Conclusions DDT may assist in the monitoring of clinical outcome and prediction of sepsis during the early post-burn period. sCD74 and MIF, by contrast, have limited value as an early predictor of death due to their delayed response to burn injury. PMID:27209369

C-reactive protein as a prognostic indicator for rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

PubMed

Lee, Han Hee; Park, Jae Myung; Lee, Soon-Wook; Kang, Seung Hun; Lim, Chul-Hyun; Cho, Yu Kyung; Lee, Bo-In; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gyu

2015-05-01

In patients with acute nonvariceal upper gastrointestinal bleeding, rebleeding after an initial treatment is observed in 10-20% and is associated with mortality. To investigate whether the initial serum C-reactive protein level could predict the risk of rebleeding in patients with acute nonvariceal upper gastrointestinal bleeding. This was a retrospective study using prospectively collected data for upper gastrointestinal bleeding. Initial clinical characteristics, endoscopic features, and C-reactive protein levels were compared between those with and without 30-day rebleeding. A total of 453 patients were included (mean age, 62 years; male, 70.9%). The incidence of 30-day rebleeding was 15.9%. The mean serum C-reactive protein level was significantly higher in these patients than in those without rebleeding (P<0.001). The area under the receiver operating characteristics curve with a cutoff value of 0.5mg/dL was 0.689 (P<0.001). High serum C-reactive protein level (odds ratio, 2.98; confidence interval, 1.65-5.40) was independently associated with the 30-day rebleeding risk after adjustment for the main confounding risk factors, including age, blood pressure, and initial haemoglobin level. The serum C-reactive protein was an independent risk factor for 30-day rebleeding in patients with acute nonvariceal upper gastrointestinal bleeding, indicating a possible role as a useful screening indicator for predicting the risk of rebleeding. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Prediction of Neonatal Hyperbilirubinemia Using 1st Day Serum Bilirubin Levels.

PubMed

Spoorthi, S M; Dandinavar, Siddappa F; Ratageri, Vinod H; Wari, Prakash K

2018-02-15

The study was conducted on Full term neonates with birth weight > 2.5 kg born in KIMS, Hubballi with an objective to determine the first day Total Serum Bilirubin (TSB) value so as to predict subsequent development of significant hyperbilirubinemia in term neonates. All enrolled neonates were sampled for TSB and blood group on Day 1 at 20 ± 4 h and then followed up clinically by Kramer's rule and when the clinical jaundice by Kramer's rule was >10 mg/dl, TSB levels were repeated. A total of 180 newborns were enrolled for the study and 165 babies completed the study. Out of these, 17(10.3%) babies had significant hyperbilirubinemia by day 5 of life. Using Receiver Operating Characteristic (ROC) Curve, a cut off TSB value of 6.15 mg/dl was determined with sensitivity of 82.4%, specificity of 81.8%, positive predictive value of 32.8%, negative predictive value 97.6%. In term neonates, the first day total bilirubin level at 20 ± 4 h of life <6.15 predicts the low risk of subsequent significant hyperbilirubinemia with high probability.

Predictive Factors for Beneficial Response to Interferon-alfa Therapy in Chronic Hepatitis C

PubMed Central

Yoon, Seung-Kew; Kim, Sung Soo; Park, Young Min; Shim, Kyu Sik; Lee, Chang Don; Sun, Hee Sik; Park, Doo Ho; Kim, Boo Sung; Ryu, Wang Shick; Cho, Joong Myung

1995-01-01

Objectives: Interferon is the only established teatment for chronic hepatitis C but the host-dependent or virus-related factors affecting the response rate to interferon therapy are not yet dear. The purpose of this study was to investigate the factors predictive of response to interferon-alfa therapy in chronic hepatitis C. Methods: Twenty-five consecutive patients with chronic hepatitis C were randomized to three regimens of interferon-alfa: group A (n=7, 3MU every day for 3 months), group B (n=8, 3MU every other day for 3 months) and group C (n=10, 3MU every other day for 6 months), We quantified serum HC RNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR)and performed HCV genotyping using type-specific primers deduced from the NS5 region of the HCV genome. We also attempted to identify which demographic, biochemical and histologic factors in addition to virus-related factors would significantly predict beneficial response to interferon by multivariate analysis. Results: Sustained responders were 8 (36.4%), nonsustained responders were 2 (9.1%) and nonresponders were 12 (54.5%) of 22 patients who had received complete therapy. The initial HCV RNA level (logarithmic transformed copy numbers per ml of serum)in sustained responders (5.75±0.39) was significantly lower than that of nonsustained responders (6.80±0.71)and nonresponders (6.70±0.52) (p<0.05). In multivariate multiple logistic regression analysis, the serum HCV RNA level before therapy was only the independent predictor of a sustained response to interferon-alfa therapy (p=0.001). Conclusions: Serum HCV RNA level before therapy was the most useful predictor of a sustained response to interferon-alfa therapy for chronic hepatitis C. PMID:7495780

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

PubMed Central

Unger, Sofia; Corte, Tamera J.; Keller, Michael; Wolters, Paul J.; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M.; Hansbro, Philip M.; Argraves, William Scott; Oliver, Rema A.; Oliver, Brian G.; Black, Judith L.; Burgess, Janette K.

2014-01-01

BACKGROUND: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. METHODS: Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. RESULTS: Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = −0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). CONCLUSIONS: Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments. PMID:24832167

Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

PubMed

Jaffar, Jade; Unger, Sofia; Corte, Tamera J; Keller, Michael; Wolters, Paul J; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M; Hansbro, Philip M; Argraves, William Scott; Oliver, Rema A; Oliver, Brian G; Black, Judith L; Burgess, Janette K

2014-10-01

The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = -0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments.

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

PubMed Central

Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

2015-01-01

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy. PMID:26640716

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

PubMed

Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

2015-01-01

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

Increased plasma asymmetric dimethylarginine level is associated with ascending aorta dilatation: a case-control study.

PubMed

Satılmışoğlu, Muhammet Hulusi; Örnek Diker, Vesile; Taşbulak, Ömer; Diker, Mustafa; Birand, Ali; Kaya, Mehmet; İyigün, Taner; Eksik, Abdurrahman

2017-01-01

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. We aimed to determine plasma ADMA levels in patients with ascending aorta dilatation in comparison to those without aorta dilatation, and to evaluate the diagnostic, predictive, and prognostic value of serum ADMA level for aorta dilatation. This was a cross-sectional case-control study. A total of 104 consecutive patients (female/male, 35/69; mean age, 62.75 ± 13.11 years) diagnosed with ascending aorta dilatation (≥ 4.5 cm) on echocardiography (case group), and 52 age-and gender-matched patients (female/male, 17/35; mean age, 63.44 ± 7.56 years) with normal aorta dimensions (≤ 3.8 cm) (control group) were included. Routine biochemical and haematological analysis in addition to measurement of serum ADMA level were performed. The mean diameter of ascending aorta measured on echocardiography was 4.95 ± 0.57 cm and 3.34 ± 0.36 cm in patients with aorta dilatation and those without aorta dilatation, respectively (p < 0.001). Serum ADMA level was significantly higher in patients with aorta dilatation than in the control group (1.70 ± 1.12 μmol/L vs. 0.79 ± 0.76 μmol/L, respectively, p < 0.001). There was significant positive correlation between ADMA level and aortic diameter in Spearman correlation analysis (r = 0.317, p < 0.001). In linear regression analysis, ADMA was found to be a significant independent predictor of aorta diameter (Beta = 0.26, p < 0.001). Receiver-operator characteristic curve analysis also revealed that serum ADMA cut-off level over 0.29 μmol/L predicts aorta dilatation (≥ 4.5 cm) with 94% sensitivity and 92% specificity and with high ac-curacy (area under curve: 0.786; 95% confidence interval: 0.709-0.863, p < 0.001). Serum ADMA level is diagnostic for ascending aorta dilatation with high sensitivity and specificity, and should be considered for use in clinical diagnosis of aorta dilatation.

Tetanus toxoid IgE may be useful in predicting allergy during childhood.

PubMed

Ciprandi, G; De Amici, M; Quaglini, S; Labò, E; Castellazzi, A M; Miraglia Del Giudice, M; Marseglia, A; Bianchi, L; Moratti, R; Marseglia, G L

2012-01-01

Hypersensitivity reactions after immunization with tetanus toxoid are occasionally observed in atopic and non-atopic individuals. High IgE levels in infancy may predict subsequent allergy. The aims of this study were: i) to evaluate the role of specific IgE to tetanus toxoid in children in response to tetanus immunization and the possible factors associated with specific IgE levels, and ii) to investigate the correlation between specific IgE levels to tetanus toxoid and the late development of allergy (up to 12 years). Initially, 278 healthy infants (152 males and 126 females, aged 12 months) living in an urban city were screened for serum total IgE and specific IgE to tetanus toxoid, after having obtained informed consent from parents. After 12 years, 151 children could be evaluated. Total IgE summed with tetanus specific IgE were significantly associated with allergy at 12 years. In conclusion, this study demonstrates that serum total IgE and tetanus specific IgE may be predictive of subsequent allergy onset.

Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone.

PubMed

Ikeda, Kimiyuki; Shiratori, Masanori; Chiba, Hirofumi; Nishikiori, Hirotaka; Yokoo, Keiki; Saito, Atsushi; Hasegawa, Yoshihiro; Kuronuma, Koji; Otsuka, Mitsuo; Yamada, Gen; Takahashi, Hiroki

2017-10-01

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease with poor prognosis. Pirfenidone, the first antifibrotic drug, suppresses the decline in forced vital capacity (FVC) and improves prognosis in some, but not all, patients with IPF; therefore, an indicator for identifying improved outcomes in pirfenidone therapy is desirable. This study aims to clarify whether baseline parameters can be predictors of disease progression and prognosis in patients with IPF treated with pirfenidone. We retrospectively investigated patients with IPF who started treatment with pirfenidone between December 2008 and November 2014 at the Sapporo Medical University Hospital. Patients treated with pirfenidone for ≥6 months were enrolled in this study and were observed until November 2015. We investigated the association of clinical characteristics, pulmonary function test results, and blood examination results at the start of pirfenidone with the outcome of patients. Sixty patients were included in this study. In multivariate logistic regression analysis, % predicted FVC and serum surfactant protein (SP)-D levels were predictors of a ≥10% decline in FVC in the initial 12 months. In the Cox proportional hazards model, these two factors predicted progression-free survival. Pack-years, % predicted diffusing capacity for carbon monoxide, and SP-D levels predicted overall survival. The serum SP-D level was a predictor of disease progression and prognosis in patients with IPF treated with pirfenidone. In addition, this analysis describes the relative usefulness of other clinical parameters at baseline in estimating the prognosis of patients with IPF who are candidates for pirfenidone therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria.

PubMed

Bilir, Filiz; Akdemir, Nermin; Ozden, Selcuk; Cevrioglu, A Serhan; Bilir, Cemil

2013-09-05

Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p < 0.001). Serum procalcitonin levels were negative in all of the controls. In ASB group, 9 (30%) patients had procalcitonin levels greater than >0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p < 0.001). The sensitivity and specificity of procalcitonin assay for ASB was calculated as 30% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 65%. The most frequent microorganisms in the urine culture were Escherichia coli (26 patients, 87%), Proteus mirabilis (3 patients, 10%) and Klebsiella (1 patient, 3%) in the ASB group. We experienced four (44%) recurrences among nine positive procalcitonin in ASB patients after completion of treatment of the first ASB diagnosis. Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can predict the further urinary tract infection risk. Finally, serum procalcitonin levels were normal in healthy pregnant women while other inflammatory markers such as WBC, ESR and CRP levels were higher.

Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria

PubMed Central

2013-01-01

Background Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. Methods The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. Results Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p < 0.001). Serum procalcitonin levels were negative in all of the controls. In ASB group, 9 (30%) patients had procalcitonin levels greater than >0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p < 0.001). The sensitivity and specificity of procalcitonin assay for ASB was calculated as 30% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 65%. The most frequent microorganisms in the urine culture were Escherichia coli (26 patients, 87%), Proteus mirabilis (3 patients, 10%) and Klebsiella (1 patient, 3%) in the ASB group. We experienced four (44%) recurrences among nine positive procalcitonin in ASB patients after completion of treatment of the first ASB diagnosis. Discussion Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can predict the further urinary tract infection risk. Finally, serum procalcitonin levels were normal in healthy pregnant women while other inflammatory markers such as WBC, ESR and CRP levels were higher. PMID:24006912

Increased leptin levels in preeclampsia: associations with BMI, estrogen and SHBG levels.

PubMed

Acromite, Michael; Ziotopoulou, Mary; Orlova, Christine; Mantzoros, Christos

2004-01-01

Leptin is secreted mainly by the white adipose tissue but is also synthesized in several non-adipose tissue organs including the placenta. Serum leptin levels are increased in normal pregnancies and are higher in preeclamptic than normal pregnant women. There is, however, a lack of empirical evidence of an independent association of serum leptin levels and preeclamsia. We have studied cross-sectionally 18 3rd trimester preeclamptic women, 28 3rd trimester and 30 2nd trimester control women to confirm the reported increase of serum leptin in preeclampsia and to assess whether elevated leptin levels in preeclampsia increase the variance explained by body mass index (BMI), androgens, estrogens and/or sex hormone binding globulin (SHBG). Anthropometric, demographic and hormonal data were analyzed using linear and logistic regression models. Leptin is significantly increased in preeclampsia by univariate analysis, but use of multivariate analysis indicates that the elevated leptin levels are not associated with preeclampsia independently from BMI, estrogens and SHBG. This study confirms that leptin levels are higher in women with preeclampsia than in controls and demonstrates that serum leptin levels do not add to the prediction of preeclampsia after accounting for BMI, estrogen and SHBG levels of preeclamptic women.

Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: trends and biomarker correlations.

PubMed

Gifford, A H; Nymon, A B; Ashare, A

2014-04-01

Cystic fibrosis (CF) is characterized by low circulating levels of insulin-like growth factor-1 (IGF-1), a hormone produced by the liver that governs anabolism and influences immune cell function. Because treatment of CF pulmonary exacerbation (CFPE) often improves body weight and lung function, we questioned whether serum IGF-1 trends were emblematic of these responses. Initially, we compared serum levels between healthy adults with CF and controls of similar age. We then measured serum IGF-1 throughout the CFPE cycle. We also investigated correlations among IGF-1 and other serum biomarkers during CFPE. Anthopometric, spirometric, and demographic data were collected. Serum IGF-1 concentrations were measured by ELISA. CF subjects in their usual state of health had lower serum IGF-1 levels than controls. Serum IGF-1 concentrations fell significantly from baseline at the beginning of CFPE. Treatment with intravenous antibiotics was associated with significant improvement in serum IGF-1 levels, body mass index (BMI), and percent-predicted forced expiratory volume in 1 sec (FEV1 %). At early and late CFPE, serum IGF-1 was directly correlated with FEV1 %, serum iron, hemoglobin concentration, and transferrin saturation (TSAT) and indirectly correlated with alpha-1-antitrypsin. This study not only supports the paradigm that CF is characterized by IGF-1 deficiency but also that trends in lung function, nutritional status, and serum IGF-1 are related. Improvements in all three parameters after antibiotics for CFPE likely highlight the connection between lung function and nutritional status in CF. Close correlations among IGF-1 and iron-related hematologic parameters suggest that IGF-1 may participate in CF iron homeostasis, another process that is known to be influenced by CFPE. © 2013 Wiley Periodicals, Inc.

Pubertal Onset in Apparently Healthy Indian Boys and Impact of Obesity.

PubMed

Surana, Vineet; Dabas, Aashima; Khadgawat, Rajesh; Marwaha, Raman Kumar; Sreenivas, V; Ganie, M Ashraf; Gupta, Nandita; Mehan, Neena

2017-01-01

Primary - to determine the age of pubertal onset in Indian boys. Secondary - (a) to assess the impact of obesity on pubertal timing, (b) to assess the relationship between gonadotropins and puberty. Cross-sectional. General community-seven schools across New Delhi. Random sample of 1306 school boys, aged 6-17 years. Anthropometric measurement for weight and height and pubertal staging was performed for all subjects. Body mass index (BMI) was calculated to define overweight/obesity. Serum luteinizing hormone (LH), follicle stimulating hormone, and serum testosterone were measured in every sixth subject. Age at pubertal onset-testicular volume ≥4 mL (gonadarche) and pubic hair Stage II. Median age of attaining gonadarche and pubarche was 10.41 years (95% confidence interval [CI]: 10.2-10.6 years) and 13.60 (95% CI: 13.3-14.0 years), respectively. No significant difference in the age of attainment of gonadarche was observed in boys with normal or raised BMI, though pubarche occurred 8 months earlier in the latter group. Serum gonadotropins and testosterone increased with increasing stages of puberty but were unaffected by BMI. Serum LH level of 1.02 mIU/mL and testosterone level of >0.14 ng/mL showed the best prediction for pubertal onset. The study establishes a secular trend of the age of onset of puberty in Indian boys. Pubarche occurred earlier in overweight/obese boys. The cutoff levels of serum LH and testosterone for prediction of pubertal onset have been established.

Delayed clearance of triglyceride‐rich lipoproteins in young, healthy obese subjects†

PubMed Central

Goll, R.; Lekahl, S.; Moen, O. S.; Florholmen, J.

2015-01-01

Summary Obesity is associated with the metabolic syndrome. The aims were, first, to study the postprandial triglyceride clearance in young, healthy obese subjects and, second, to investigate if fasting triglycerides can predict delayed postprandial triglyceride clearance. Eighteen apparently healthy, obese subjects with no clinical signs of metabolic disturbances participated. Controls were age‐ and sex‐matched, healthy, normal weight subjects. Subclinical markers of metabolic disturbances were assessed by measuring postprandial triglycerides in serum and in chylomicrons by oral fat tolerance test. Postprandial triglyceride clearance for 8 h was assessed indirectly as removal of the lipid from serum during the oral fat tolerance test. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA‐IR). Twelve (66%) of the apparently healthy obese individuals had insulin resistance measured by HOMA‐IR. There was a delayed clearance of serum triglycerides and chylomicron triglycerides at 6 h when compared with the control group, while, at 8 h, the differences were only detected for the chylomicron triglyceride clearance. Triglyceride response was significantly greater in the obese subjects. Fasting triglycerides in upper normal level predicted a delayed postprandial triglyceride clearance and insulin resistance. In young, apparently healthy obese subjects early metabolic disturbances including insulin resistance and delayed postprandial triglyceride clearance can be detected. Fasting serum triglyceride in upper normal level predicted delayed postprandial triglyceride clearance and insulin resistance. PMID:26469529

Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

PubMed

Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

2016-03-01

Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.

Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension

PubMed Central

Condliffe, Robin; Pickworth, Josephine A.; Hopkinson, Kay; Walker, Sara J.; Hameed, Abdul G.; Suntharaligam, Jay; Soon, Elaine; Treacy, Carmen; Pepke-Zaba, Joanna; Francis, Sheila E.; Crossman, David C.; Newman, Christopher M. H.; Elliot, Charles A.; Morton, Allison C.; Morrell, Nicholas W.; Kiely, David G.; Lawrie, Allan

2012-01-01

We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation. PMID:22558516

Elevation of Plasmin-α2-plasmin Inhibitor Complex Predicts the Diagnosis of Systemic AL Amyloidosis in Patients with Monoclonal Protein.

PubMed

Ishiguro, Kazuya; Hayashi, Toshiaki; Yokoyama, Yoshihiro; Aoki, Yuka; Onodera, Kei; Ikeda, Hiroshi; Ishida, Tadao; Nakase, Hiroshi

2018-03-15

Objective The complication of systemic immunoglobulin light chain (AL) amyloidosis in patients with monoclonal immunoglobulin affects the prognosis, but amyloid deposition in tissues is sometimes difficult to detect due to bleeding tendencies and preferential distributions. However, fibrinolysis is known to be exacerbated in patients with systemic AL amyloidosis specifically. We therefore explored new biomarkers for predicting a diagnosis of systemic AL amyloidosis focusing on coagulation and fibrinolysis markers. Methods We reviewed the clinical features and treatment outcomes of patients with serum monoclonal protein, including primary systemic AL amyloidosis and multiple myeloma (MM), treated at our hospital between January 2008 and December 2014. Results Among several biomarkers, only the serum level of plasmin-α2-plasmin inhibitor complex (PIC) in patients with systemic AL amyloidosis (n=26) at the diagnosis was significantly higher than in patients with MM without AL amyloidosis (n=26) (mean±standard deviation, 3.69±2.82 μg/mL vs. 1.23±0.97 μg/mL, p<0.01). The cut-off for predicting a diagnosis of systemic AL amyloidosis in patients with serum monoclonal protein was 1.72 μg/mL with 84.6% sensitivity and 80.8% specificity. Hepatic involvement resulted in a significantly higher PIC level than no involvement in patients with systemic AL amyloidosis. The serum PIC level was also associated with the hematological response of systemic AL amyloidosis. Conclusion PIC is a useful biomarker for the diagnosis and management of patients with systemic AL amyloidosis.

The prognostic significance of prostate specific antigen in metastatic hormone-resistant prostate cancer.

PubMed Central

Fosså, S. D.; Waehre, H.; Paus, E.

1992-01-01

Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate cancer had normal serum levels of prostate specific antigen (PSA less than or equal to 10 micrograms l-1), when referred for secondary treatment. PSA was significantly correlated with the extent of skeletal metastases (R: 0.35) and the levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a multivariate Cox regression analysis the survival of the 152 patients was not correlated with the PSA level but with the patients performance status, the level of hemoglobin, and the time between primary hormone treatment and relapse. The lack of serum PSA to predict survival may be explained by a heterogenous composition of hormone resistant prostate cancer as regards differentiated and/or PSA producing vs undifferentiated and/or PSA non-producing cells. PMID:1379059

Evaluation of a Pharmacokinetic-Pharmacodynamic Model for Hypouricemic Effects of Febuxostat Using Datasets Obtained from Real-world Patients.

PubMed

Hirai, Toshinori; Itoh, Toshimasa; Kimura, Toshimi; Echizen, Hirotoshi

2018-06-06

Febuxostat is an active xanthine oxidase (XO) inhibitor that is widely used in the hyperuricemia treatment. We aimed to evaluate the predictive performance of a pharmacokinetic-pharmacodynamic (PK-PD) model for hypouricemic effects of febuxostat. Previously, we have formulated a PK--PD model for predicting hypouricemic effects of febuxostat as a function of baseline serum urate levels, body weight, renal function, and drug dose using datasets reported in preapproval studies (Hirai T et al., Biol Pharm Bull 2016; 39: 1013-21). Using an updated model with sensitivity analysis, we examined the predictive performance of the PK-PD model using datasets obtained from the medical records of patients who received febuxostat from March 2011 to December 2015 at Tokyo Women's Medical University Hospital. Multivariate regression analysis was performed to explore clinical variables to improve the predictive performance of the model. A total of 1,199 serum urate data were retrieved from 168 patients (age: 60.5 ±17.7 years, 71.4% males) who received febuxostat as hyperuricemia treatment. There was a significant correlation (r=0.68, p<0.01) between serum urate levels observed and those predicted by the modified PK-PD model. A multivariate regression analysis revealed that the predictive performance of the model may be improved further by considering comorbidities, such as diabetes mellitus, estimated glomerular filtration rate (eGFR), and co-administration of loop diuretics (r = 0.77, p<0.01). The PK-PD model may be useful for predicting individualized maintenance doses of febuxostat in real-world patients. This article is protected by copyright. All rights reserved.

Prognostic Significance of Tumor Size of Small Lung Adenocarcinomas Evaluated with Mediastinal Window Settings on Computed Tomography

PubMed Central

Sakao, Yukinori; Kuroda, Hiroaki; Mun, Mingyon; Uehara, Hirofumi; Motoi, Noriko; Ishikawa, Yuichi; Nakagawa, Ken; Okumura, Sakae

2014-01-01

Background We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. Methods We evaluated 176 patients with small lung adenocarcinomas (diameter, 1–3 cm) who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution computed tomography) with tumour dimensions evaluated under two settings: lung window and mediastinal window. We also determined the patient age, gender, preoperative nodal status, tumour size, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and pathological status (lymphatic vessel, vascular vessel or pleural invasion). Recurrence-free survival was used for prognosis. Results Lung window, mediastinal window, tumour disappearance ratio and preoperative nodal status were significant predictive factors for recurrence-free survival in univariate analyses. Areas under the receiver operator curves for recurrence were 0.76, 0.73 and 0.65 for mediastinal window, tumour disappearance ratio and lung window, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant predictive factors for lymph node metastasis in univariate analyses; areas under the receiver operator curves were 0.61, 0.76, 0.72 and 0.66, for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant factors for lymphatic vessel, vascular vessel or pleural invasion in univariate analyses; areas under the receiver operator curves were 0.60, 0.81, 0.81 and 0.65 for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Conclusions According to the univariate analyses including a logistic regression and ROCs performed for variables with p-values of <0.05 on univariate analyses, our results suggest that measuring tumour size using mediastinal window on high-resolution computed tomography is a simple and useful preoperative prognosis modality in small adenocarcinoma. PMID:25365326

Transcutaneous measurement of hyperbilirubinaemia: comparison of the Minolta jaundice meter and the Ingram icterometer.

PubMed

Bilgen, H; Ince, Z; Ozek, E; Bekiroglu, N; Ors, R

1998-12-01

The effectiveness of two different non-invasive transcutaneous bilirubin measurement devices was compared with serum bilirubin levels in 96 healthy newborns. Transcutaneous measurements were obtained with the Minolta Air Shields jaundice meter and the Ingram icterometer and serum bilirubin levels were determined by a direct spectrophotometric method (Bilitron 444). A linear correlation existed between serum bilirubin values and the readings on both the Minolta jaundice meter (r = 0.83) and the Ingram icterometer (r = 0.78). The Kappa coefficient was 0.66. the sensitivity, specificity and positive and negative predictive values were 100%, 56%, 33% and 100% for the Minolta jaundice meter and 100%, 48%, 29% and 100% for the Ingram icterometer, respectively. The high sensitivity and negative predictive value of both devices render them suitable for screening neonatal hyperbilirubinaemia. However, because of its low cost, the Ingram icterometer is preferable to the more complex and expensive Minolta jaundice meter, especially in countries with a high birth rate, such as Turkey.

Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.

PubMed

Huang, Hao; Wang, Xue-Ping; Li, Xiao-Hui; Chen, Hao; Zheng, Xin; Lin, Jian-Hua; Kang, Ting; Zhang, Lin; Chen, Pei-Song

2017-08-14

The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup). Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.

Predictive value of serum bradykinin and desArg9-bradykinin levels for chemotherapeutic responses in active tuberculosis patients: A retrospective case series.

PubMed

Qian, Xu; Nguyen, Duc T M; Li, Yaojun; Lyu, Jianxin; Graviss, Edward A; Hu, Tony Y

2016-12-01

There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg 9 -bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases. Nanotrap Mass-Spectrometry (MS) was used to analyze serial blood specimens from 13 HIV-negative adults with microbiologically confirmed active TB who were treated with first-line anti-TB chemotherapy. MS signal for BK (m/z 1060.5) and DABK (m/z 904.5) serum peptides were evaluated at multiple time-points (before, during, and after treatment) to evaluate how BK and DABK levels corresponded with disease status. Serum BK levels declined from pretreatment baseline levels during the early stage anti-TB therapy (induction phase) and tended to remain below baseline levels during extended treatment (consolidation phase) and after therapy completion. BK levels were consistent with induction phase sputum culture conversions indicative of decreased Mtb burden reflecting good treatment responses. Serum DABK levels tended to increase during the induction phase and decrease at consolidation and post-therapy time points, which may indicate a shift from active disease to chronic inflammation to a disease free state. Elevated BK and DABK levels after treatment completion in one patient may be related to the subsequent recurrent TB disease. Our pilot data suggests that changes in the circulating BK and DABK levels in adult TB patients can be used as potential surrogate markers of the host response both early and late in anti-TB treatment for both pulmonary and extrapulmonary TB patients. We will further exploit these host-response signatures in the future as biomarkers in combination with other clinical and microbiologic tools which may improve treatment efficacy and facilitate the development of host-directed therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum protein profiling using an aptamer array predicts clinical outcomes of stage IIA colon cancer: A leave-one-out crossvalidation

PubMed Central

Huh, Jung Wook; Kim, Sung Chun; Sohn, Insuk; Jung, Sin-Ho; Kim, Hee Cheol

2016-01-01

Background In this study, we established and validated a model for predicting prognosis of stage IIA colon cancer patients based on expression profiles of aptamers in serum. Methods Bloods samples were collected from 227 consecutive patients with pathologic T3N0M0 (stage IIA) colon cancer. We incubated 1,149 serum molecule-binding aptamer pools of clinical significance with serum from patients to obtain aptamers bound to serum molecules, which were then amplified and marked. Oligonucleotide arrays were constructed with the base sequences of the 1,149 aptamers, and the marked products identified above were reacted with one another to produce profiles of the aptamers bound to serum molecules. These profiles were organized into low- and high-risk groups of colon cancer patients based on clinical information for the serum samples. Cox proportional hazards model and leave-one-out cross-validation (LOOCV) were used to evaluate predictive performance. Results During a median follow-up period of 5 years, 29 of the 227 patients (11.9%) experienced recurrence. There were 212 patients (93.4%) in the low-risk group and 15 patients (6.6%) in the high-risk group in our aptamer prognosis model. Postoperative recurrence significantly correlated with age and aptamer risk stratification (p = 0.046 and p = 0.001, respectively). In multivariate analysis, aptamer risk stratification (p < 0.001) was an independent predictor of recurrence. Disease-free survival curves calculated according to aptamer risk level predicted through a LOOCV procedure and age showed significant differences (p < 0.001 from permutations). Conclusion Aptamer risk stratification can be a valuable prognostic factor in stage II colon cancer patients. PMID:26908450

Pharmacokinetic/pharmacodynamic integration and modelling of oxytetracycline for the porcine pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida.

PubMed

Dorey, L; Pelligand, L; Cheng, Z; Lees, P

2017-10-01

Pharmacokinetic-pharmacodynamic (PK/PD) integration and modelling were used to predict dosage schedules of oxytetracycline for two pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in broth and porcine serum. PK/PD integration established ratios of average concentration over 48 h (C av0-48 h )/MIC of 5.87 and 0.27 μg/mL (P. multocida) and 0.70 and 0.85 μg/mL (A. pleuropneumoniae) for broth and serum MICs, respectively. PK/PD modelling of in vitro time-kill curves established broth and serum breakpoint values for area under curve (AUC 0-24 h )/MIC for three levels of inhibition of growth, bacteriostasis and 3 and 4 log 10 reductions in bacterial count. Doses were then predicted for each pathogen, based on Monte Carlo simulations, for: (i) bacteriostatic and bactericidal levels of kill; (ii) 50% and 90% target attainment rates (TAR); and (iii) single dosing and daily dosing at steady-state. For 90% TAR, predicted daily doses at steady-state for bactericidal actions were 1123 mg/kg (P. multocida) and 43 mg/kg (A. pleuropneumoniae) based on serum MICs. Lower TARs were predicted from broth MIC data; corresponding dose estimates were 95 mg/kg (P. multocida) and 34 mg/kg (A. pleuropneumoniae). © 2017 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Correlation of serum KL-6 and CC16 levels with neurodevelopmental outcome in premature infants at 12 months corrected age

PubMed Central

Zhang, Zhiqun; Lu, Hui; Zhu, Yunxia; Xiang, Junhua; Huang, Xianmei

2015-01-01

The aim of this study was to evaluate KL-6 and CC16 levels and their correlation with neurodevelopmental outcome among very low birth weight pre-term infants at 12 months corrected age. This prospective cohort study was performed from 2011 to 2013 by enrolling pre-term neonates of gestational age ≤ 32 weeks and birth weight ≤ 1500 g. Serum KL-6 and CC16 levels were determined 7 days after birth and their correlation with neurodevelopment was evaluated using Gesell Mental Developmental Scales. Of the 86 eligible pre-term infants, 63 completed follow-up, of which 15 had bronchopulmonary dysplasia. At 12 months corrected age, 49 infants had favorable outcomes and 14 infants had poor neurodevelopmental outcome. KL-6 levels were higher and CC16 levels were lower in infants with poor neurodevelopmental outcome compared with those infants who had favourable neurodevelopmental outcome. Serum KL-6 levels less than 90.0 ng/ml and CC16 levels greater than 320.0 pg/ml at 7 days of life were found to be predictive of a favourable outcome at 12 months corrected age. These biological markers could predict neurodevelopmental outcome at 12 months corrected age in very low birth weight premature infants, and help the clinician plan early therapeutic interventions to minimize or avoid poor neurodevelopmental outcome. PMID:25631862

Suppression of homocysteine levels by vitamin B12 and folates: age and gender dependency in the Jackson Heart Study.

PubMed

Henry, Olivia R; Benghuzzi, Hamed; Taylor, Herman A; Tucci, Michelle; Butler, Kenneth; Jones, Lynne

2012-08-01

To examine factors potentially contributing to premature cardiovascular disease mortality in African Americans (40% versus 20% all other populations), plasma homocysteine, serum vitamin B12 and folate levels were examined for African American participants in the Jackson Heart Study. Of 5192 African American Jackson Heart Study participants (21-94 years), 5064 (mean age, 55 ± 13 years; 63% female) had homocysteine levels measured via fasting blood samples, with further assessments of participants' vitamin B12 (n = 1790) and folate (n = 1788) levels. Regression analyses were used to examine age, gender, vitamin B12 and folate with homocysteine levels. Homocysteine levels, a purported surrogate risk factor for cardiovascular disease, increased with age, were inversely proportional to folate and vitamin B12 levels (P < 0.001) and were higher for men of all ages. The results show that, as with other populations, age, gender, vitamin B12 and folate may predict homocysteine levels for African Americans. Diet may be an important predictive factor as well, given the relationships that were observed between plasma homocysteine and serum B vitamin levels.

Serum IgE levels are associated with coronary artery disease severity.

PubMed

Guo, Xiaoxiao; Yuan, Su; Liu, Yongtai; Zeng, Yong; Xie, Hongzhi; Liu, Zhenyu; Zhang, Shuyang; Fang, Quan; Wang, Jing; Shen, Zhujun

2016-08-01

Immunoglobulin E (IgE), a key element of allergic reactions, was considered to be involved in the development of atherosclerosis and the pathogenesis of myocardial ischemia. This study was designed to test whether total serum IgE levels were associated with the atherosclerosis severity of coronary artery disease (CAD). Total serum IgE concentrations were measured in 708 consecutive patients who were presented to our center for coronary angiography. Atherosclerosis severity of CAD was assessed by the number of diseased vessels showing ≥50% diameter stenosis and quantified by Gensini score. Patients with CAD (N = 562) had higher serum IgE levels than those without CAD (N = 146) [55.90 (19.10-156.00) vs. 26.90 (11.80-62.10) KU/L, p = 0.003]. Furthermore, the serum IgE levels were significantly increased in patients with multivessel disease (MVD) compared to those with single-vessel disease [61.80 (23.20-159.00) vs. 32.45(14.15-94.38) KU/L, p = 0.003]. After adjustment for traditional cardiovascular risk factors, a high serum IgE level was an independent predictor for an increased risk of MVD (OR 1.003; 95% CI 1.001-1.004; p = 0.041). Receiver-operating characteristic curve analysis demonstrated that serum IgE levels improved the predictive capability of traditional risk factors for MVD (area under the curve with and without IgE: 0.734 and 0.713, respectively, p < 0.001). Meanwhile, there was a significant linear relationship between Gensini score and the serum IgE level quartiles (p for linear trend <0.001). Increased total serum IgE levels are associated with MVD and contribute to discriminating CAD severity independently of traditional cardiovascular risk factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Serum antioxidant vitamins and the risk of oral cancer in patients seen at a tertiary institution in Nigeria.

PubMed

Lawal, A O; Kolude, B; Adeyemi, B F; Lawoyin, J O; Akang, E E

2012-01-01

Tobacco and alcohol are major risk factors of oral cancer, but nutritional deficiency may also contribute to development of oral cancer. This study compared serum antioxidant vitamin levels in oral cancer patients and controls in order to validate the role of vitamin deficiencies in the etiology of oral cancer. Serum vitamin A, C, and E levels of 33 oral cancer patients and 30 controls at University College Hospital, Ibadan, Nigeria, were determined using standard methods. The data obtained were analyzed using the Student t-test, odds ratio, and logistic regression. Mean vitamin A, C, and E levels were significantly lower in oral cancer patients (P=0.022, P=0.000, and P=0.013 respectively). Risk of oral cancer was 10.89, 11.35, and 5.6 times more in patients with low serum vitamins A, C, and E, respectively. However, on logistic regression analysis, only low serum vitamin E independently predicted occurrence of oral cancer. The lower serum vitamin A, C, and E levels in oral cancer patients could be either a cause or an effect of the oral cancer. Further studies using a larger sample size and cohort studies with long-term follow-up of subjects are desirable.

Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction.

PubMed

Larsson, Susanna C; Burgess, Stephen; Michaëlsson, Karl

2017-07-25

Serum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction. To evaluate the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease (CAD) and myocardial infarction using mendelian randomization. The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs) identified from a genome-wide association meta-analysis of serum calcium levels (N = up to 61 079 individuals) and from the Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000 genomes-based genome-wide association meta-analysis (N = up to 184 305 individuals) that included cases (individuals with CAD and myocardial infarction) and noncases, with baseline data collected from 1948 and populations derived from across the globe. The association of each SNP with CAD and myocardial infarction was weighted by its association with serum calcium, and estimates were combined using an inverse-variance weighted meta-analysis. Genetic risk score based on genetic variants related to elevated serum calcium levels. Co-primary outcomes were the odds of CAD and myocardial infarction. Among the mendelian randomized analytic sample of 184 305 individuals (60 801 CAD cases [approximately 70% with myocardial infarction] and 123 504 noncases), the 6 SNPs related to serum calcium levels and without pleiotropic associations with potential confounders were estimated to explain about 0.8% of the variation in serum calcium levels. In the inverse-variance weighted meta-analysis (combining the estimates of the 6 SNPs), the odds ratios per 0.5-mg/dL increase (about 1 SD) in genetically predicted serum calcium levels were 1.25 (95% CI, 1.08-1.45; P = .003) for CAD and 1.24 (95% CI, 1.05-1.46; P = .009) for myocardial infarction. A genetic predisposition to higher serum calcium levels was associated with increased risk of CAD and myocardial infarction. Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown.

Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

PubMed Central

Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

2016-01-01

Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

Serum 8-Oxo-dG as a Predictor of Sensitivity and Outcome of Radiotherapy and Chemotherapy of Upper Gastrointestinal Tumours.

PubMed

Pour Khavari, Ali; Liu, Yongping; He, Ellen; Skog, Sven; Haghdoost, Siamak

2018-01-01

The level of oxidative stress is important in the initiation and progression of various age-related diseases, such as cancer. The level of oxidative stress may also play a significant role in cancer patients' response to treatment. We aimed to investigate whether serum 8-oxo-dG as a marker of oxidative stress is a predictor of tumour response. We used modified ELISA with a two-step filtration to analyse 8-oxo-dG in serum. The relationship between 8-oxo-dG levels, tumour response, and toxicity was studied in 19 oesophageal cancer patients who received radiotherapy and 16 gastric cancer patients who received chemotherapy. In the radiotherapy and the merged radio- and chemotherapy groups, the baseline levels of 8-oxo-dG were significantly lower in responder patients than in nonresponder patients and the increments after treatment were greater. In comparison with patients whose serum 8-oxo-dG levels decrease after treatment, patients with increasing levels had a longer median "progression-free survival." Our results, although preliminary, suggest that serum levels of 8-oxo-dG may potentially be used to predict the sensitivity and outcome of radiotherapy and chemotherapy of upper gastrointestinal tumours. Patients with 8-oxo-dG levels that are low prior to treatment and subsequently increase after treatment may be more likely to benefit from the therapy.

Serum tryptase level is a better predictor of systemic side effects than prostaglandin D2 metabolites during venom immunotherapy in children.

PubMed

Cichocka-Jarosz, E; Sanak, M; Szczeklik, A; Brzyski, P; Gielicz, A; Pietrzyk, J J

2011-01-01

We performed a prospective study to analyze mast cell mediators as predictors of systemic adverse reactions during rush venom-specific immunotherapy (VIT) in children. Nineteen children aged 5-17 years received VIT with Venomenhal (HALAllergy). We analyzed serum tryptase (CAP, Phadia), plasma prostaglandin (PG) D2 metabolites (9alpha, 11beta-PGF2), and urine PGD2 metabolites (9alpha, 11beta-PGF2, tetranor-PGD-M) using gas chromatography mass spectrometry before and after the rush protocol. Three boys with high baseline serum tryptase values (>7.76 g/L) (P < .001) and low 9alpha, 11beta-PGF2 concentrations developed grade III systemic adverse reactions during VIT. Baseline serum tryptase was lowest in children who had a Mueller grade II reaction (1.93 [0.36]) before VIT and highest in children with a Mueller grade III reaction (6.31 [4.80]) (P = .029). Repeated measures analysis of variance confirmed that, in children who developed systemic adverse reactions during VIT, serum tryptase was higher both before and after desensitization and increased significantly following the procedure. Analysis of PGD2 metabolites in the prediction of systemic adverse reactions during VIT was inadequate (sensitivity 67% and specificity 0.53%), whilst prediction based on serum tryptase was accurate. In children with severe systemic adverse reactions to Hymenoptera sting, the evaluation of baseline tryptase levels should be a standard procedure. Children with Apis mellifera venom allergy and baseline tryptase levels higher than 7.75 g/L are at risk of anaphylaxis during buildup. Lower baseline values of plasma and urinary PGD2 metabolite concentration in patients with systemic adverse reaction during VIT suggest that prostaglandin catabolism is altered.

Insulin and Metformin Regulate Circulating and Adipose Tissue Chemerin

PubMed Central

Tan, Bee K.; Chen, Jing; Farhatullah, Syed; Adya, Raghu; Kaur, Jaspreet; Heutling, Dennis; Lewandowski, Krzysztof C.; O'Hare, J. Paul; Lehnert, Hendrik; Randeva, Harpal S.

2009-01-01

OBJECTIVE To assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects. RESEARCH DESIGN AND METHODS Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of chemerin. Serum chemerin was measured by enzyme-linked immunosorbent assay. We investigated the in vivo effects of insulin on serum chemerin levels via a prolonged insulin-glucose infusion. Ex vivo effects of insulin, metformin, and steroid hormones on adipose tissue chemerin protein production and secretion into conditioned media were assessed by Western blotting and enzyme-linked immunosorbent assay, respectively. RESULTS Serum chemerin, subcutaneous, and omental adipose tissue chemerin were significantly higher in women with PCOS (n = 14; P < 0.05, P < 0.01). Hyperinsulinemic induction in human subjects significantly increased serum chemerin levels (n = 6; P < 0.05, P < 0.01). In adipose tissue explants, insulin significantly increased (n = 6; P < 0.05, P < 0.01) whereas metformin significantly decreased (n = 6; P < 0.05, P < 0.01) chemerin protein production and secretion into conditioned media, respectively. After 6 months of metformin treatment, there was a significant decrease in serum chemerin (n = 21; P < 0.01). Importantly, changes in homeostasis model assessment–insulin resistance were predictive of changes in serum chemerin (P = 0.046). CONCLUSIONS Serum and adipose tissue chemerin levels are increased in women with PCOS and are upregulated by insulin. Metformin treatment decreases serum chemerin in these women. PMID:19502420

Changes in the Serum Urate Level Can Predict the Development of Parkinsonism in the 6-Hydroxydopamine Animal Model.

PubMed

Sarukhani, Mohammad Reza; Haghdoost-Yazdi, Hashem; Khandan-Chelarci, Gilda

2018-05-01

Epidemiological studies indicate that a higher plasma level of uric acid (UA) associates with the reduced risk of Parkinson's disease (PD). To confirm the role of UA as a biomarker for PD, we evaluated changes in the serum UA level in the 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonism in rat. For this purpose, 6-OHDA was administered in the medial forebrain bundle by stereotaxic surgery. According to the apomorphine-induced rotational test, the increased intensity of behavioral symptoms as a function of time was associated with the further reduction of UA level. On the other hand, the level of UA increased in the midbrain of the injured hemisphere. The level of reduction in the serum UA level of rats with severe and moderate symptoms was significantly higher than that of rats with mild symptoms. The immunohistofluorescence and biochemical analyses showed that the serum UA level was also correlated with the death of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc), reduced level of striatal dopamine, and severity of oxidative stress in the midbrain. The rats with mild symptoms also showed a significant decrease in TH-positive neurons and striatal dopamine level. These findings suggest a positive correlation between the level of reduction in the serum urate level and severity of 6-OHDA-induced Parkinsonism. In addition, our findings indicated that UA had no marked neuroprotective effects, at least at concentrations obtained in this study. On the other hand, UA was introduced as a biomarker for PD, as a significant decline was observed in the serum UA level of rats with mild behavioral symptoms but with significant dopaminergic cell death in the SNc.

Is Serum Bicarbonate Level Associated With Negative Outcomes in Pediatric Patients?: A Retrospective Cohort Study.

PubMed

Poonai, Naveen; Mainprize, David; Travers, Carolyn; Vivas, Lilian Lee Yan; Tryphonopoulos, Peter; Sangha, Gurinder; Arbeau, Ryan; Seabrook, Jamie; Miller, Michael; Sarpal, Amrita; Lim, Rodrick

2017-11-01

Early identification of children at risk for adverse outcomes is important. Serum bicarbonate is easily collected and widely available. We described the relationship between bicarbonate and adverse outcomes in children presenting to the emergency department (ED). We conducted a retrospective cohort study of children aged 0 to 17 years from January 1, 2007, to December 31, 2011, who had a serum bicarbonate measured in the ED. Primary outcome was the predictive ability of bicarbonate for the individual components of the composite outcome that included at least one of the following: intensive care unit admission, assisted ventilation, inotropic support, cardiopulmonary resuscitation, or death. Secondary outcome was the relationship between bicarbonate level of greater and less than 13 mEq/L and the composite outcome. We reviewed 16,989 charts, of which 432 had an adverse outcome. Receiver operating characteristic curve analysis showed that a bicarbonate level of less than 18.5 mEq/L predicted inotropic support with an area under the curve of 0.69 (95% confidence interval [CI], 0.60-0.77; P < 0.001) and death with an area under the curve of 0.75 (CI, 0.66-0.85; P < 0.001). Significantly more patients with bicarbonate level of less than 13 mEq/L had at least 1 adverse outcome compared with those with bicarbonate level of greater than 13 mEq/L (4.4% vs 2.5%, P = 0.001), odds ratio 1.96 (95% CI, 1.3-2.97). Among children presenting to the ED, bicarbonate level of 18.5 mEq/L had fair specificity in predicting inotropic support and death. Negative outcomes are significantly associated with bicarbonate level of less than 13 mEq/L. Bicarbonate should routinely be measured in children at risk of clinical deterioration.

The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure.

PubMed

Rössig, Lothar; Fichtlscherer, Stephan; Heeschen, Christopher; Berger, Jürgen; Dimmeler, Stefanie; Zeiher, Andreas M

2004-09-01

Systemic inflammation with elevated serum levels of circulating pro-inflammatory cytokines is a major determinant of prognosis in heart failure (HF). Since serum of patients with HF induces apoptosis of endothelial cells (EC), we aimed to determine whether the pro-apoptotic activity in the serum may predict prognosis of patients with HF. We measured the pro-apoptotic activity in the serum of 48 patients with HF of different aetiology by an ex vivo cell culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During follow-up, 16 patients died and 11 patients received a heart transplant. Survivors had a lower pro-apoptotic serum activity (P=0.007). By univariate analysis, pro-apoptotic serum activity, NYHA class, pro-BNP, low blood pressure, and creatinine levels were significantly associated with mortality. In a multivariable stepwise Cox-regression model, the pro-apoptotic serum activity (adjusted hazard ratio, HR=1.85 per %, P=0.008), elevated pro-BNP levels (HR=9.35 per log[pro-BNP], P=0.001), and low blood pressure (HR=0.96 per mmHg, P=0.041) remained as independent predictors of death. In this exploratory study, the pro-apoptotic serum capacity is independently associated with a worse prognosis in patients with HF, suggesting that the assessment of serum-induced EC apoptosis could provide an integrative estimate of the deleterious effects of various pro-inflammatory cytokines and other cytotoxic factors in HF.

Prognostic implication of serum hepatocyte growth factor in stage II/III breast cancer patients who received neoadjuvant chemotherapy.

PubMed

Kim, Hyori; Youk, Jeonghwan; Yang, Yaewon; Kim, Tae-Yong; Min, Ahrum; Ham, Hye-Seon; Cho, Seongcheol; Lee, Kyung-Hun; Keam, Bhumsuk; Han, Sae-Won; Oh, Do-Youn; Ryu, Han Suk; Han, Wonshik; Park, In Ae; Kim, Tae-You; Noh, Dong-Young; Im, Seock-Ah

2016-03-01

In stage II/III breast cancer, neoadjuvant chemotherapy (NAC) is a standard treatment. Although several biomarkers are used to predict prognosis in breast cancer, there is no reliable predictive biomarker for NAC success. Recently, the hepatocyte growth factor (HGF) and cMet signaling pathway demonstrated to be involved in breast cancer tumor progression, and its potential as a biomarker is under active investigation. In this study, we assessed the potential of serum HGF as a prognostic biomarker for NAC efficacy. Venous blood samples were drawn from patients diagnosed with stage II/III breast cancer and treated with NAC in Seoul National University Hospital from August 2004 to November 2009. Serum HGF level was determined using an ELISA system. We reviewed the medical records of the patients and investigated the association of HGF level with patients' clinicopathologic characteristics. A total of 121 female patients (median age = 45 years old) were included. Median level of HGF was 934 pg/ml (lower quartile: 772, upper quartile: 1145 pg/ml). Patients with higher HGF level than median value were significantly more likely to have clinically detectable regional node metastasis (p = 0.017, Fisher's exact test). Patients with complete and partial response according to the American Joint Committee on Cancer 7th Edition criteria tended to have higher HGF level (p = 0.105 by t test). Patients with an HGF level higher than the upper quartile value had longer relapse-free survival than the other patients (106 vs. 85 months, p = 0.008). High serum HGF levels in breast cancer patients are associated with clinically detectable regional node metastasis and, paradoxically, with longer relapse-free survival in stage II/III breast cancer.

Low serum osteocalcin concentration is associated with incident type 2 diabetes mellitus in Japanese women.

PubMed

Urano, Tomohiko; Shiraki, Masataka; Kuroda, Tatsuhiko; Tanaka, Shiro; Urano, Fumihiko; Uenishi, Kazuhiro; Inoue, Satoshi

2017-08-01

Increasing evidence suggests that osteocalcin is involved in the regulation of glucose homeostasis. However, the relationship between serum osteocalcin levels and risk of incident type 2 diabetes mellitus is not clear. The objective of this study is to investigate whether serum osteocalcin levels are associated with the risk of incident type 2 diabetes mellitus. This study included 1691 Japanese postmenopausal women, 61 incident diabetes cases, and 1630 non-diabetic control subjects in the observation period. Baseline concentrations of intact osteocalcin, HbA1c, bone-specific alkaline phosphatase, adiponectin, leptin, urinary N-telopeptides were assessed. Serum osteocalcin levels were significantly correlated with HbA1c levels among 1691 Japanese postmenopausal women (R = -0.12, P < 0.0001). In receiver operating characteristic curve analysis, the optimal cut-off levels for serum osteocalcin to predict the development of type 2 diabetes mellitus was 6.1 ng/mL. The group with baseline osteocalcin levels <6.1 ng/mL showed a significantly higher risk for developing diabetes than the group with baseline osteocalcin levels >6.1 ng/mL (log-rank test, P  <  0.0001) during the mean observation period (7.6 ± 6.1 years; mean ± SD). In multiple Cox proportional hazard analysis, osteocalcin levels were significantly associated with development of type 2 diabetes mellitus during the observation period. Our results indicate that a decrease in serum osteocalcin levels is associated with future development of type 2 diabetes mellitus independent of conventional risk factors in Japanese postmenopausal women.

Prognostic significance of preimmunotherapy serum CA27.29 (MUC-1) mucin level after active specific immunotherapy of metastatic adenocarcinoma patients.

PubMed

MacLean, G D; Reddish, M A; Longenecker, B M

1997-01-01

The TRUQUANT BR radioimmunoassay, which uses monoclonal antibody B27.29 to quantitate CA27.29 mucin antigen (MUC-1 gene product) in serum, has recently received Food and Drug Administration approval for predicting recurrent breast cancer in patients with stage II and III disease. The purpose of this study was to determine whether the new radioimmunoassay for serum MUC-1 has prognostic significance for patients with metastatic adenocarcinoma receiving active specific immunotherapy (ASI). Using 40 U/ml as the upper limit of "normal," patients with metastatic breast and ovarian cancer with a preimmunotherapy serum CA27.29 mucin > 40 U/ml (CA27.29 Hi patients) had a poorer survival than CA27.29 Lo patients (< or = 40 U/ml) after ASI. There was no significant correlation between preimmunotherapy CA27.29 serum levels and measurable tumor burden. The preimmunotherapy CA27.29 serum level was a predictor of poor survival of metastatic colorectal and pancreatic cancer patients independent of other prognostic factors. There seemed to be two populations of pancreatic cancer patients, separated at 60 U/ml serum CA27.29 (CA27.29 Hi versus Lo patients). A CA27.29 serum level of 22 U/ml separated patients with CA27.29 Hi vs. Lo colorectal cancer. Patients with CA27.29 Lo colorectal and pancreatic cancer survived longer after ASI compared with patients with CA27.29 Hi colorectal and pancreatic cancer, respectively. We suggest that various CA27.29 serum levels define poor prognosis patients (CA27.29 Hi secretors) versus good prognosis patients (CA27.29 Lo secretors) for different cancer types.

Identification of novel serum autoantibodies against EID3 in non-functional pancreatic neuroendocrine tumors

PubMed Central

Hontani, Koji; Tsuchikawa, Takahiro; Hiwasa, Takaki; Nakamura, Toru; Ueno, Takashi; Kushibiki, Toshihiro; Takahashi, Mizuna; Inoko, Kazuho; Takano, Hironobu; Takeuchi, Satoshi; Dosaka-Akita, Hirotoshi; Kuwatani, Masaki; Sakamoto, Naoya; Hatanaka, Yutaka; Mitsuhashi, Tomoko; Shimada, Hideaki; Shichinohe, Toshiaki; Hirano, Satoshi

2017-01-01

Pancreatic neuroendocrine tumors (pNETs) are relatively rare heterogenous tumors, comprising only 1–2% of all pancreatic neoplasms. The majority of pNETs are non-functional tumors (NF-pNETs) that do not produce hormones, and as such, do not cause any hormone-related symptoms. As a result, these tumors are often diagnosed at an advanced stage because patients do not present with specific symptoms. Although tumor markers are used to help diagnosis and predict some types of cancers, chromogranin A, a widely used tumor marker of pNETs, has significant limitations. To identify novel NF-pNET-associated antigens, we performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified five tumor antigens (phosphatase and tensin homolog, EP300-interacting inhibitor of differentiation 3 [EID3], EH domain-containing protein 1, galactoside-binding soluble 9, and BRCA1-associated protein). Further analysis using the AlphaLISA® immunoassay to compare serum antibody levels revealed that antibody levels against the EID3 antigen was significantly higher in the patient group than in the healthy donor group (n = 25, both groups). In addition, higher serum anti-EID3 antibody levels in NF-pNET patients correlated with shorter disease-free survival. The AUC calculated by ROC analysis was 0.784 with moderate diagnostic accuracy. In conclusion, serum anti-EID3 antibody levels may be useful as a tumor marker for prediction of tumor recurrence in NF-pNETs. PMID:29290942

Pro-Gastrin Releasing Peptide: A New Serum Marker for Endometrioid Adenocarcinoma.

PubMed

Kiseli, Mine; Caglar, Gamze Sinem; Yarci Gursoy, Asli; Tasci, Tolga; Candar, Tuba; Akincioglu, Egemen; Pabuccu, Emre Goksan; Boran, Nurettin; Tulunay, Gokhan; Umudum, Haldun

2018-06-13

Gastrin-releasing peptide (GRP) is thought to play a role in the metastatic process of various malignancies. The more stable precursor of GRP, pro-GRP (ProGRP), has been shown to be secreted by neuroendocrine tumors. This study was designed to assess the validity of ProGRP as a diagnostic marker in endometrioid adenocarcinomas (EAs) of the endometrium. Thirty-seven patients with a diagnosis of EA, 23 patients with endometrial hyperplasia, and 32 age-matched controls with normal endometrial histology were recruited for this study. Serum ProGRP and cancer antigen 125 (CA125) values were compared between groups. Median serum ProGRP levels were significantly higher in the cancer group compared to corresponding levels in both the hyperplasia and control groups (p = 0.008 and p < 0.001 respectively; endometrial cancer: 27.5 pg/mL; hyperplasia: 16.1 pg/mL; controls: 12.9 pg/mL). Age and endometrial thickness were positively correlated with ProGRP levels (r = 0.322, p = 0.006 and r = 0.269, p = 0.023, respectively). Receiver Operating Characteristic curve analyses for EA revealed a threshold of 20.81 pg/mL, with a sensitivity of 60.7% and specificity of 81.4%, positive predictive value of 68% and negative predictive value of 76.1%. Significantly higher ProGRP levels were observed in patients with EA than in controls. Serum ProGRP has good diagnostic sensitivity and specificity for EA. © 2018 S. Karger AG, Basel.

Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India

PubMed Central

2012-01-01

Background Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. Methods Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. Results Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. Conclusions Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk. PMID:22883023

Comparisons of Serum Total IgE, IgG, and IgG1 Levels in Patients with and without Echinococcosis-Induced Anaphylactic Shock

PubMed Central

Li, Yimei; Zheng, Hong; Gu, Meilin; Cao, Xinghua; Wen, Hao; Liu, Zaoling; Liu, Tao

2012-01-01

We investigated serum total immunoglobulin E (IgE), IgG, and IgG1 levels in patients with and without echinococcosis-induced anaphylactic shock. This was a case-control study of 11 patients with echinococcosis-induced anaphylactic shock and 22 echinococcosis patients with cyst rupture but without anaphylactic shock. Blood was collected before surgery (T0), at the time of cyst rupture (T1), and shock (Tx), 1 h (T2), 1 day (T3), and 1 week (T4) after cyst rupture. Serum IgE, IgG, and IgG1 were determined by enzyme-linked immunosorbent assay. Serum IgE, IgG, and IgG1 levels were significantly higher in patients who developed anaphylactic shock at all time points. Increased pre-surgical IgG and IgG1 levels were identified to be a significant risk factors for developing anaphylactic shock. The results showed that a serum IgG concentration of 312.25 μg/mL could be used as a cut-off point to predict whether an echinococcosis patient would develop anaphylactic shock. PMID:22764299

Serum PARC/CCL-18 Concentrations and Health Outcomes in Chronic Obstructive Pulmonary Disease

PubMed Central

Sin, Don D.; Miller, Bruce E.; Duvoix, Annelyse; Man, S. F. Paul; Zhang, Xuekui; Silverman, Edwin K.; Connett, John E.; Anthonisen, Nicholas A.; Wise, Robert A.; Tashkin, Donald; Celli, Bartolome R.; Edwards, Lisa D.; Locantore, Nicholas; MacNee, William; Tal-Singer, Ruth; Lomas, David A.

2011-01-01

Rationale: There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. Objectives: To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. Methods: PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. Measurements and Main Results: Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. Conclusions: Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID:21216880

Allergen cross reactions: a problem greater than ever thought?

PubMed

Pfiffner, P; Truffer, R; Matsson, P; Rasi, C; Mari, A; Stadler, B M

2010-12-01

Cross reactions are an often observed phenomenon in patients with allergy. Sensitization against some allergens may cause reactions against other seemingly unrelated allergens. Today, cross reactions are being investigated on a per-case basis, analyzing blood serum specific IgE (sIgE) levels and clinical features of patients suffering from cross reactions. In this study, we evaluated the level of sIgE compared to patients' total IgE assuming epitope specificity is a consequence of sequence similarity. Our objective was to evaluate our recently published model of molecular sequence similarities underlying cross reactivity using serum-derived data from IgE determinations of standard laboratory tests. We calculated the probabilities of protein cross reactivity based on conserved sequence motifs and compared these in silico predictions to a database consisting of 5362 sera with sIgE determinations. Cumulating sIgE values of a patient resulted in a median of 25-30% total IgE. Comparing motif cross reactivity predictions to sIgE levels showed that on average three times fewer motifs than extracts were recognized in a given serum (correlation coefficient: 0.967). Extracts belonging to the same motif group co-reacted in a high percentage of sera (up to 80% for some motifs). Cumulated sIgE levels are exaggerated because of a high level of observed cross reactions. Thus, not only bioinformatic prediction of allergenic motifs, but also serological routine testing of allergic patients implies that the immune system may recognize only a small number of allergenic structures. © 2010 John Wiley & Sons A/S.

Methods for measuring serum activity levels of the 192 Q and R isoenzymes of paraoxonase 1 in QR heterozygous individuals.

PubMed

Teiber, John F; Kramer, Gerald L; Haley, Robert W

2013-08-01

Paraoxonase 1 (PON1), an esterase that hydrolyzes toxic organophosphates and has antioxidative and antiatherogenic properties, contains a common polymorphism at position 192: glutamine (Q) or arginine (R). The Q and R isoenzymes exhibit different physical and protective properties. We describe 2 methods for quantifying their serum activity levels. We measured serum hydrolytic activity with paraoxon [paraoxonase (PXN) activity], phenylacetate [arylesterase (AE) activity], and diazoxon [diazoxonase (DZN) activity] with standard automated assays. We determined PON1 Q192R genotypes with PCR and Q192R phenotypes using the PXN/AE and PXN/DZN ratios. Interpolation equations were empirically derived to predict the percentage of total PON1 hydrolytic activity due to the Q isoenzyme (%Q) from the PXN/AE and PXN/DZN ratios; %R is 100 - %Q. We estimated Q and R isoenzyme activity levels in sera from 2095 veterans by multiplying AE activity, a measure of total PON1 hydrolytic activity, by %Q and %R. In all 2095 samples, the PXN/AE and PXN/DZN ratios predicted Q192R phenotypes with nearly identical accuracy (κ = 0.997). In the 925 QR heterozygotes, the 2 interpolation methods predicted Q and R isoenzyme activity levels with excellent agreement (intraclass correlation 0.94). After excluding a few genotype/phenotype-discordant samples, the percentage of total PON1 activity due to the Q isoenzyme ranged from 22% to 70%. These new interpolation methods allow accurate estimation of PON1 192 Q and R isoenzyme activity levels, increasing specificity and power for studying susceptibility to disease.

Predictors of variation in serum IGF1 and IGFBP3 levels in healthy African American and white men.

PubMed

Hoyo, Cathrine; Grubber, Janet; Demark-Wahnefried, Wendy; Lobaugh, Bruce; Jeffreys, Amy S; Grambow, Steven C; Marks, Jeffrey R; Keku, Temitope O; Walther, Phillip J; Schildkraut, Joellen M

2009-07-01

Individual variation in circulating insulinlike growth factor-1 (IGF1) and its major binding protein, insulinlike growth factor binding protein-3 (IGFBP3), have been etiologically linked to several chronic diseases, including some cancers. Factors associated with variation in circulating levels of these peptide hormones remain unclear. Multiple linear regression models were used to determine the extent to which sociodemographic characteristics, lifestyle factors, personal and family history of chronic disease, and common genetic variants, the (CA)n repeat polymorphism in the IGF1 promoter and the IGFBP3-202 A/C polymorphism (rs2854744) predict variation in IGF1 or IGFBP3 serum levels in 33 otherwise healthy African American and 37 white males recruited from Durham Veterans Administration Medical Center. Predictors of serum IGF1, IGFBP3, and the IGF1:IGFBP3 molar ratio varied by race. In African Americans, 17% and 28% of the variation in serum IGF1 and the IGF1:IGFBP3 molar ratio, were explained by cigarette smoking and carrying the IGF1 (CA)19 repeat allele, respectively. Not carrying at least 1 IGF1 (CA)19 repeat allele and a high body mass index explained 8% and 14%, respectively, of the variation IGFBP3 levels. These factors did not predict variation of these peptides in whites. If successfully replicated in larger studies, these findings would add to recent evidence, suggesting known genetic and lifestyle chronic disease risk factors influence IGF1 and IGFBP3 circulating levels differently in African Americans and whites.

Predictors of variation in serum IGFI and IGFBP3 levels in healthy African-American and white men

PubMed Central

Grubber, Janet; Demark-Wahnefried, Wendy; Lobaugh, Bruce; Jeffreys, Amy S.; Grambow, Steven C.; Marks, Jeffrey R.; Keku, Temitope O.; Walther, Phillip J.; Schildkraut, Joellen M.

2010-01-01

Background Individual variation in circulating insulin-like growth factor-I (IGF1) and its major binding protein, insulin-like growth factor binding protein-3 (IGFBP3) have been etiologically linked to several chronic diseases, including some cancers. Factors associated with variation in circulating levels of these peptide hormones remain unclear. Methods Multiple linear regression models were used to determine the extent to which socio-demographic characteristics, lifestyle factors, personal and family history of chronic disease, and common genetic variants, the (CA)n repeat polymorphism in the IGF1 promoter and the IGFBP3 -202 A/C polymorphism (rs2854744) predict variation in IGF1 or IGFBP3 serum levels in 33 otherwise healthy African American and 37 white males recruited from Durham Veterans Administration Medical Center. Results Predictors of serum IGF1, IGFBP3 and the IGF1:IGFBP3 molar ratio varied by race. In African Americans, 17% and 28% of the variation in serum IGF1 and the IGF1:IGFBP3 molar ratio, respectively, was explained by cigarette smoking and carrying the IGF1 (CA)19 repeat allele, respectively. Not carrying at least one IGF1 (CA)19 repeat allele and a high BMI explained 8% and 14%, respectively, of the variation IGFBP3 levels. These factors did not predict variation of these peptides in whites. Conclusion If successfully replicated in larger studies, these findings add to recent evidence suggesting known genetic and lifestyle chronic disease risk factors influence IGF1 and IGFBP3 circulating levels differently in African Americans and whites. PMID:19634593

Detecting tau in serum of transgenic animal models after tau immunotherapy treatment.

PubMed

d'Abramo, Cristina; Acker, Christopher M; Schachter, Joel B; Terracina, Giuseppe; Wang, Xiaohai; Forest, Stefanie K; Davies, Peter

2016-01-01

In the attempt to elucidate if the "peripheral sink hypothesis" could be a potential mechanism of action for tau removal in passive immunotherapy experiments, we have examined tau levels in serum of chronically injected JNPL3 and Tg4510 transgenic animals. Measurement of tau in serum of mice treated with tau antibodies is challenging because of the antibody interference in sandwich enzyme-linked immunosorbent assays. To address this issue, we have developed a heat-treatment protocol at acidic pH to remove interfering molecules from serum, with excellent recovery of tau. The present data show that pan-tau and conformational antibodies do increase tau in mouse sera. However, these concentrations in serum do not consistently correlate with reductions of tau pathology in brain, suggesting that large elevations of tau species measured in serum are not predictive of efficacy. Here, we describe a reliable method to detect tau in serum of transgenic animals that have undergone tau immunotherapy. Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely. Copyright © 2016 Elsevier Inc. All rights reserved.

Measurement of intraoperative parathyroid hormone predicts long-term operative success.

PubMed

Westerdahl, Johan; Lindblom, Pia; Bergenfelz, Anders

2002-02-01

A decrease in the intraoperative parathyroid hormone (PTH) level predicts long-term operative success. A case series of consecutive patients undergoing parathyroidectomy with intraoperative PTH measurement. A university hospital. One hundred two patients with sporadic primary hyperparathyroidism underwent parathyroidectomy according to the principles of unilateral exploration with intraoperative PTH measurement. Longitudinal effects on levels of serum calcium and PTH. In 94 of 98 patients who underwent primary exploration because of a solitary adenoma, intraoperative PTH decreased at least 60% 15 minutes after gland excision. The 4 cases in which PTH fell to less than 60% were classified as false negatives. Patients examined for multiglandular disease (n = 4) were correctly predicted not to have an adenoma. Twenty-two patients (22%) were unavailable for 5-year follow-up. These patients were followed up for 2 months to 48 months (median, 24 months), and none developed recurrent primary hyperparathyroidism. Of the remaining 80 patients (78%), all but 1 patient had normal or slightly decreased serum calcium levels (mean +/- SD, 9.24 +/- 0.4 mg/dL [2.31 +/- 0.10 mmol/L]) at 5-year follow-up. One patient with hypercalcemia (10.6 mg/dL [2.65 mmol/L]) was interpreted to have developed renal failure with secondary hyperparathyroidism. Thirty-four patients had elevated serum PTH levels at least once during the postoperative study period, with normal or slightly decreased calcium concentrations. The prediction of late postoperative normocalcemia by means of intraoperative PTH measurement had an overall accuracy of 95%. The measurement of intraoperative PTH during surgery for primary hyperparathyroidism accurately differentiates between single- and multiple-gland disease and ensures good long-term results.

High Serum sTREM-1 Correlates With Myocardial Dysfunction and Predicts Prognosis in Septic Patients.

PubMed

Li, Zhenyu; Zhang, Enyuan; Hu, Yipeng; Liu, Yi; Chen, Bing

2016-06-01

This study aimed to evaluate the predictive and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with myocardial dysfunction induced by severe sepsis and septic shock. A total of 84 patients with severe sepsis and septic shock were enrolled between May 2013 and December 2014.The patients were monitored by pulse indicator continuous cardiac output system and divided into myocardial depression group (cardiac function index [CFI] < 4.1/minute, n = 37) and nonmyocardial depression group (CFI ≥ 4.1/minute, n = 47 ). Additionally, the patients were divided into survival group (n = 40) and nonsurvival group (n = 44) based on 28-day mortality. Hemodynamic parameters and serum sTREM-1, B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels were collected on days 1, 3 and 5 after admission to intensive care unit. (1) The serum values of sTREM-1, BNP and cTnI in myocardial depression group were higher than those in nonmyocardial depression group (P < 0.01); and CFI, cardiac index, stroke volume, global ejection fraction and left ventricular contractility index (dpmax) in myocardial depression group were lower than those in nonmyocardial depression group on day 1 (P < 0.05); (2) serum sTREM-1 negatively correlated with left ventricular ejection fraction, CFI, cardiac index, global ejection fraction and dpmax, and it positively correlated with BNP and cTnI (P < 0.01); (3) the area under the receiver operating characteristics curve for sTREM-1 in the prediction of myocardial depression was 0.671 with a sensitivity of 83.8% and a specificity of 46.8% when cutoff point was 174.5ng/mL, the power of predicting septic depression for sTREM-1 was lower than that of BNP; logistic regression analysis showed that serum sTREM-1 was not an independent predictor of septic myocardial depression; the area under the receiver operating characteristics curve was 0.773 for sTREM-1 in predicting outcome with a sensitivity of 86.4% and a specificity of 80% when cutoff point was 182.3ng/mL, the power of predicting prognosis for sTREM-1 was superior to those of BNP and cTnI; (4) there was a decrease trend for sTREM-1 levels and an increasing trend for CFI in the survival group (P < 0.05). Myocardial dysfunction is common in patients with severe sepsis and septic shock and high serum levels of sTREM-1 correlates with myocardial dysfunction to some extent but is not an independent predictor, which more importantly showed prognostic value for septic shock outcome. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Relationship between T2* magnetic resonance imaging-derived liver and heart iron content and serum ferritin levels in transfusion-dependent thalassemic children

PubMed Central

Suthar, Kiran; Goyal, Vishnu Kumar; Sharma, Pramod; Deopa, Bindu; Rathore, Pradeep Singh; Bishnoi, Rama Krishan

2018-01-01

CONTEXT: T2* magnetic resonance imaging (MRI) is being increasingly used for the assessment of organ iron content in thalassemics, but cost is a major prohibitive factor for repeated measurements. If serum ferritin correlates well with the T2* MRI liver and heart, it will be economical and more simple tool to assess organ iron deposition. AIMS: The aim of this study was to find out the relationship between serum ferritin level and T2* MRI-derived liver and heart iron content in transfusion-dependent thalassemic children SETTINGS: Thalassemia day-care center of a teaching hospital DESIGN: This was a cross-sectional study SUBJECTS AND METHODS: Seventy-three transfusion-dependent beta thalassemic children belonging to 2–18 years of age were subjected to T2* MRI of heart and liver to assess their iron content. Values obtained here were related to serum ferritin. STATISTICAL ANALYSIS USED: Keeping the correlation between serum ferritin and T2* MRI as primary outcome, spearman's correlation coefficient was calculated. RESULTS: We found poor (negative) correlation between serum ferritin level and T2* MRI liver (r = -0.448, P = 0.000) but no correlation between serum ferritin and T2*MRI heart (r = -0.221, P = 0.060). Conclusions: Serum ferritin cannot reliably predict the liver and heart iron content in Indian children with β thalassemia. PMID:29563679

Differentiation of pancreatobiliary cancer from benign biliary strictures using neutrophil gelatinase-associated lipocalin.

PubMed

Budzynska, A; Nowakowska-Dulawa, E; Marek, T; Boldys, H; Nowak, A; Hartleb, M

2013-02-01

Aim of the study was to investigate the value of serum and bile neutrophil gelatinase-associated lipocalin (NGAL) for distinguishing malignant strictures caused by cholangiocarcinoma (CCA) or pancreatic cancer from benign biliary strictures. The study was performed prospectively on patients admitted for endoscopic or radiologic biliary decompression. Forty patients with dilated biliary ducts, including 16 cases of CCA, 6 cases of pancreatic cancer, and 18 cases of benign biliary stricture were enrolled. Their sera and bile were collected to measure NGAL. Routine biochemistry including measurement of serum levels of carbohydrate antigens (CA) 19-9 and carcinoembryonic antigen (CEA) was also performed. The serum CA19-9, serum CEA, and bile NGAL levels were significantly increased in patients with malignant strictures as compared with patients with benign biliary diseases. Serum NGAL had no significant value for discriminating between malignant and benign biliary strictures. Bile NGAL levels had a receiver characteristic area under the curve of 0.74, sensitivity 77.3, and specificity 72.2% for discriminating between pancreatobiliary cancer and benign biliary diseases. Bile NGAL and serum CA19-9 were independent parameters and their combined use improved diagnostic accuracy (sensitivity 91%, negative predictive value 85.7%). We conclude that measurement of biliary, but not serum NGAL, may differentiate malignant pancreatobiliary from benign biliary strictures, serving as a complementary biomarker for serum CA19-9.

The Investigation of Serum Vaspin Level in Atherosclerotic Coronary Artery Disease

PubMed Central

Kobat, Mehmet Ali; Celik, Ahmet; Balin, Mehmet; Altas, Yakup; Baydas, Adil; Bulut, Musa; Aydin, Suleyman; Dagli, Necati; Yavuzkir, Mustafa Ferzeyn; Ilhan, Selcuk

2012-01-01

Background It was speculated that fatty tissue originated adipocytokines may play role in pathogenesis of atherosclerosis. These adipocytokines may alter vascular homeostasis by effecting endothelial cells, arterial smooth muscle cells and macrophages. Vaspin is a newly described member of adipocytokines family. We aimed to investigate whether plasma vaspin level has any predictive value in coronary artery disease (CAD). Methods Forty patients who have at least single vessel ≥ 70 % stenosis demostrated angiographically and 40 subjects with normal coronary anatomy were included to the study. The vaspin levels were measured from serum that is obtained by centrifigation of blood and stored at -20 oC by ELISA method. The length, weight and body mass index of patients were measured. Biochemical parameters including total cholesterol, low density lipoprotein, high density lipoprotein, creatinine, sodium, potassium, hemoglobine, uric acid and fasting glucose were also measured. Results Biochemical markers levels were similar in both groups. Serum vaspin levels were significantly lower in CAD patients than control group (respectively; 256 ± 219 pg/ml vs. 472 ( 564 pg/ml, P < 0.02). Beside this serum vaspin level was lower in control group with high systolic blood pressure. Conclusion Serum vaspin levels were found significantly lower in patients with CAD than age-matched subjects with normal coronary anatomy. Vaspin may be used as a predictor of CAD. Keywords Coronary artery disease; Vaspin; Adipokine PMID:22505983

The investigation of serum vaspin level in atherosclerotic coronary artery disease.

PubMed

Kobat, Mehmet Ali; Celik, Ahmet; Balin, Mehmet; Altas, Yakup; Baydas, Adil; Bulut, Musa; Aydin, Suleyman; Dagli, Necati; Yavuzkir, Mustafa Ferzeyn; Ilhan, Selcuk

2012-04-01

It was speculated that fatty tissue originated adipocytokines may play role in pathogenesis of atherosclerosis. These adipocytokines may alter vascular homeostasis by effecting endothelial cells, arterial smooth muscle cells and macrophages. Vaspin is a newly described member of adipocytokines family. We aimed to investigate whether plasma vaspin level has any predictive value in coronary artery disease (CAD). Forty patients who have at least single vessel ≥ 70 % stenosis demostrated angiographically and 40 subjects with normal coronary anatomy were included to the study. The vaspin levels were measured from serum that is obtained by centrifigation of blood and stored at -20 (o)C by ELISA method. The length, weight and body mass index of patients were measured. Biochemical parameters including total cholesterol, low density lipoprotein, high density lipoprotein, creatinine, sodium, potassium, hemoglobine, uric acid and fasting glucose were also measured. Biochemical markers levels were similar in both groups. Serum vaspin levels were significantly lower in CAD patients than control group (respectively; 256 ± 219 pg/ml vs. 472 ( 564 pg/ml, P < 0.02). Beside this serum vaspin level was lower in control group with high systolic blood pressure. Serum vaspin levels were found significantly lower in patients with CAD than age-matched subjects with normal coronary anatomy. Vaspin may be used as a predictor of CAD. Coronary artery disease; Vaspin; Adipokine.

Changes in serum growth factors in stroke rehabilitation patients and their relation to hemiparesis improvement.

PubMed

Okazaki, Hideto; Beppu, Hidehiko; Mizutani, Kenmei; Okamoto, Sayaka; Sonoda, Shigeru

2014-07-01

Predicting recovery from hemiparesis after stroke is important for rehabilitation. A few recent studies reported that the levels of some growth factors shortly after stroke were positively correlated with the clinical outcomes during the chronic phase. The aim of this study was to examine the relationships between the serum levels of growth factors (vascular endothelial growth factor [VEGF], insulin-like growth factor-I [IGF-I], and hepatocyte growth factor [HGF]) and improvement in hemiparesis in stroke patients who received rehabilitation in a postacute rehabilitation hospital. Subjects were 32 stroke patients (cerebral infarction: 21 and intracerebral hemorrhage [ICH]: 11). We measured serum levels of VEGF, IGF-I, and HGF and 5 items of the Stroke Impairment Assessment Set (SIAS) for hemiparesis on admission and at discharge. Age-matched healthy subjects (n=15) served as controls. Serum levels of VEGF and HGF in cerebral infarct patients on admission were higher than those in control subjects, and the serum levels of IGF-I in stroke patients were lower than those in controls. The level of HGF in ICH patients on admission was negatively correlated with gains in SIAS, and higher outliers in HGF concentration were correlated with lower gains in SIAS. Focusing on the extremely high levels of these factors may be a predictor of the low recovery from hemiparesis after stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Utility of Serum Creatinine, Creatine Kinase and Urinary Myoglobin in Detecting Acute Renal Failure due to Rhabdomyolysis in Trauma and Electrical Burns Patients.

PubMed

Bhavsar, Preetish; Rathod, Kirtikumar Jagdish; Rathod, Darshana; Chamania, C S

2013-02-01

Rhabdomyolysis due to trauma and burns is an important cause of acute renal failure (ARF) secondary to myoglobinuria. To prevent morbidity and mortality from ARF due to rhabdomyolysis, early detection of ARF by monitoring the biochemical parameters such as serum creatinine, serum creatine kinase (CK), and urinary myoglobin (UM) can be helpful. The aims of the study were (1) to detect ARF due to rhabdomyolysis using serum creatinine, serum CK, and UM in trauma and electrical burn patients (2) to compare utility of these parameters in early prediction of ARF in patients of rhabdomyolysis. A total of 50 patients with trauma and electrical burns were included in the study. Serum creatinine, serum CK, and UM measurements were done at the time of admission and after 48 h. Diagnosis of ARF was made in the patients by Rifle's criteria. The presence of significant elevation of creatinine, serum CK, and UM at the time of admission and after 48 h was compared in patients developing ARF by Fisher's exact test. Fifteen of the 50 patients developed ARF as per the defined criteria. Of these, 9 patients (60 %) had raised level of serum creatinine above 1.4 mg% at admission and 14 patients (93.33 %) had CK level >1250 U/L at admission, whereas UM was positive in 6 (40 %) patients. Serum creatinine was significantly raised in all of the 15 ARF patients (100 %) after 48 h of admission and serum CK was raised in 14 of the 15 ARF patients (93.33 %). UM was negative in all the patients after 48 h of admission. Statistical analysis showed that rise in serum CK on admission was significantly increased in patients developing ARF as compared with serum creatinine and UM (P < 0.0001). On admission, CK is a better predictor of ARF due to rhabdomyolysis than creatinine and UM. Initial creatinine is a better predictor of ARF due to rhabdomyolysis than UM. UM assay is not a good investigation for early prediction of ARF in rhabdomyolysis.

Serum Human Chorionic Gonadotropin (β- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study

PubMed Central

Helmy, Samir; Mavrelos, Dimitrios; Sawyer, Elinor; Ben-Nagi, Jara; Koch, Marianne; Day, Andrea; Jurkovic, Davor

2015-01-01

Objective To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies. Design Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative. Setting Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). Patients We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. Main outcome measure Serum β hCG level. Results Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05). Conclusion We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management. PMID:26135923

Parathyroid hormone measurement in prediction of hypocalcaemia following thyroidectomy.

PubMed

Mehrvarz, Shaban; Mohebbi, Hassan Ali; Kalantar Motamedi, Mohammad Hosein; Khatami, Seyed Masoud; Rezaie, Ramzanali; Rasouli, Hamid Reza

2014-02-01

To determine the risk of postthyroidectomy hypocalcaemia by measuring parathyroid hormone (PTH) level after thyroidectomy. Cross-sectional study. Baqiyatallah Hospital, Tehran, Iran, from March 2008 to July 2010. All included patients were referred for total or near bilateral thyroidectomy. Serum Calcium (Ca) and PTH levels were measured before and 24 hours after surgery. In low Ca cases or development of hypocalcaemia symptoms, daily monitoring of Ca levels were continued. Data were analyzed using SPSS 20 software (SPSS, Chicago, IL, USA). A p-value less than 0.05 were considered statistically significant. To assess the standard value of useful predictive factors, we used receiver operating characteristic (ROC) curves. Of total 99 patients who underwent bilateral thyroidectomy, 47 patients (47.5%) developed hypocalcaemia, out of them, 12 (25.5%) became symptomatic while 2 patients developed permanent hypoparathyroidism. After surgery, mean rank of PTH level within the normocalcaemic and hypocalcaemic patients was 55.34 and 44.1 respectively, p=0.052. Twenty four hours after surgery, 62% drop in PTH was associated with 83.3% of symptomatic hypocalcaemic. For diagnosis of symptomatic hypocalcaemia, 62% PTH drop had sensitivity and specificity were 83.3% and 90.80%. The area under the ROC curve for the PTH postoperative and PTH drop for diagnostic symptomatic hypocalcaemia were 0.835 and 0.873 respectively. Measuring PTH levels after 24 hours postthyroidectomy is not reliable factor for predicting hypocalcaemia itself. For predicting the risk of hypocalcaemia after thyroidectomy it is more reliable to measure the serum PTH level before and after operation and compare the reduction level of percentage of PTH drop for predicting the risk of hypocalcaemia.

Knowledge-based identification of soluble biomarkers: hepatic fibrosis in NAFLD as an example.

PubMed

Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Petricoin, Emanuel; Younossi, Zobair; Chandhoke, Vikas; Baranova, Ancha

2013-01-01

The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.

Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example

PubMed Central

Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Petricoin, Emanuel; Younossi, Zobair; Chandhoke, Vikas; Baranova, Ancha

2013-01-01

The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases. PMID:23405244

Second Trimester Maternal Serum Screening for Fetal Down Syndrome: as a Screening Test for Hemoglobin Bart's Disease: A Prospective Population-based Study.

PubMed

Wanapirak, Chanane; Piyamomgkol, Wirawit; Sirichotiyakul, Supatra; Tongprasert, Fuanglada; Srisupundit, Kasemsri; Luewan, Suchaya; Traisrisilp, Kuntharee; Jatavan, Phudit; Tongsong, Theera

2018-06-21

To determine the effectiveness of second-trimester maternal serum screening (MSS) for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20,254 pregnancies) was conducted to compare the levels of MSS, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses, (1.96 vs. 1.12 multiple of the median (MoM); p<0.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cut-off value of 1.5 MoM. The serum free b-hCG levels were slightly, but significantly, higher in the affected pregnancies, while the serum uE3 levels were minimally, but significantly, lower among the affected pregnancies. Second trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis. This article is protected by copyright. All rights reserved.

Expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells, follicular fluid, and serum of women with polycystic ovary syndrome (PCOS).

PubMed

Naji, Mohammad; Nekoonam, Saeid; Aleyasin, Ashraf; Arefian, Ehsan; Mahdian, Reza; Azizi, Elham; Shabani Nashtaei, Maryam; Amidi, Fardin

2018-01-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies that affects women in reproductive age. MicroRNAs (miRNAs) play crucial roles in normal function of female reproductive system and folliculogenesis. Deregulated expression of miRNAs in PCOS condition may be significantly implicated in the pathogenesis of PCOS. We determined relative expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells (GLCs), follicular fluid (FF), and serum of PCOS patients. Human subjects were divided into PCOS (n = 20) and control (n = 21) groups. GLCs, FF, and serum were isolated and stored. RNA isolation was performed and cDNA was reversely transcribed using specific stem-loop RT primers. Relative expression of miRNAs was calculated after normalization against U6 expression. Correlation of miRNAs' expression level with basic clinical features and predictive value of miRNAs in FF and serum were appraised. Relative expression of miR-145 and miR-182 in GLCs was significantly decreased in PCOS, but miR-182 in FF of PCOS patients revealed up-regulated levels. Significant correlations between level of miRNAs in FF and serum and hormonal profile of subjects were observed. MiR-182 in FF showed a significant predictive value with AUC of 0.73, 76.4% sensitivity, and 70.5% specificity which was improved after combination of miR-182 and miR-145. A significant dysregulation of miR-145 and miR-182 in GLCs of PCOS may indicate their involvement in pathogenesis of PCOS. Differential up-regulation of miR-182 in FF of PCOS patients with its promising predictive values for discrimination of PCOS reinforced the importance of studying miRNAs' profile in FF.

Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models.

PubMed

Gomes, Anna; van der Wijk, Lars; Proost, Johannes H; Sinha, Bhanu; Touw, Daan J

2017-01-01

Gentamicin shows large variations in half-life and volume of distribution (Vd) within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1) creating an optimal model for endocarditis patients; and 2) assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE) and Median Absolute Prediction Error (MDAPE) were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients) with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358) renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076) L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68%) as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37%) and standard (MDPE -0.90%, MDAPE 4.82%) models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to avoid potential underdosing of gentamicin in endocarditis patients.

Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models

PubMed Central

van der Wijk, Lars; Proost, Johannes H.; Sinha, Bhanu; Touw, Daan J.

2017-01-01

Gentamicin shows large variations in half-life and volume of distribution (Vd) within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1) creating an optimal model for endocarditis patients; and 2) assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE) and Median Absolute Prediction Error (MDAPE) were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients) with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358) renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076) L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68%) as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37%) and standard (MDPE -0.90%, MDAPE 4.82%) models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to avoid potential underdosing of gentamicin in endocarditis patients. PMID:28475651

The prediction of self-care behaviors in end-stage renal disease patients using Leventhal's Self-Regulatory Model.

PubMed

O'Connor, Susan M; Jardine, Alan G; Millar, Keith

2008-08-01

To assess the utility of Leventhal's Self-Regulatory Model (SRM) to predict self-care behavior with regard to dietary, medication, and fluid regimes in end-stage renal disease (ESRD) patients. In a prospective study, ESRD patients treated via hospital-based haemodialysis (N=73) were screened for cognitive deficits and completed questionnaires that enquired about illness perceptions, coping strategies, knowledge of kidney disease, and psychological distress at Time 1. Physiological proxy measures of self-care behaviors regarding diet (serum potassium levels), fluid intake (mean and standard deviation of interdialytic weight gain), and medication (serum phosphate levels) regimes were collected 3 weeks later at Time 2. Illness representations (emotional and timeline perceptions) predicted self-care behaviors with regard to diet and medication. Emotion-focused coping strategies predicted higher levels of variation in adherence to fluid restrictions. Younger males were less likely to adhere to the fluid restrictions. The SRM has predictive utility. Psychological interventions should focus on alleviating disease-specific distress and challenging erroneous timeline perceptions in order to increase adherence to dietary and medication regimes in ESRD patients. A more specific measure of coping for ESRD is required to clarify the role of coping strategies in this population. Younger, male patients should be targeted for extra support with fluid restrictions.

Portable visible and near-infrared spectrophotometer for triglyceride measurements.

PubMed

Kobayashi, Takanori; Kato, Yukiko Hakariya; Tsukamoto, Megumi; Ikuta, Kazuyoshi; Sakudo, Akikazu

2009-01-01

An affordable and portable machine is required for the practical use of visible and near-infrared (Vis-NIR) spectroscopy. A portable fruit tester comprising a Vis-NIR spectrophotometer was modified for use in the transmittance mode and employed to quantify triglyceride levels in serum in combination with a chemometric analysis. Transmittance spectra collected in the 600- to 1100-nm region were subjected to a partial least-squares regression analysis and leave-out cross-validation to develop a chemometrics model for predicting triglyceride concentrations in serum. The model yielded a coefficient of determination in cross-validation (R2VAL) of 0.7831 with a standard error of cross-validation (SECV) of 43.68 mg/dl. The detection limit of the model was 148.79 mg/dl. Furthermore, masked samples predicted by the model yielded a coefficient of determination in prediction (R2PRED) of 0.6856 with a standard error of prediction (SEP) and detection limit of 61.54 and 159.38 mg/dl, respectively. The portable Vis-NIR spectrophotometer may prove convenient for the measurement of triglyceride concentrations in serum, although before practical use there remain obstacles, which are discussed.

Interferon-γ-inducible protein-10 in chronic hepatitis C: Correlations with insulin resistance, histological features & sustained virological response.

PubMed

Crisan, Dana; Grigorescu, Mircea Dan; Radu, Corina; Suciu, Alina; Grigorescu, Mircea

2017-04-01

One of the multiple factors contributing to virological response in chronic hepatitis C (CHC) is interferon-gamma-inducible protein-10 (IP-10). Its level reflects the status of interferon-stimulated genes, which in turn is associated with virological response to antiviral therapy. The aim of this study was to evaluate the role of serum IP-10 levels on sustained virological response (SVR) and the association of this parameter with insulin resistance (IR) and liver histology. Two hundred and three consecutive biopsy proven CHC patients were included in the study. Serum levels of IP-10 were determined using ELISA method. IR was evaluated by homeostasis model assessment-IR (HOMA-IR). Histological features were assessed invasively by liver biopsy and noninvasively using FibroTest, ActiTest and SteatoTest. Predictive factors for SVR and their interrelations were assessed. A cut-off value for IP-10 of 392 pg/ml was obtained to discriminate between responders and non-responders. SVR was obtained in 107 patients (52.70%). Area under the receiver operating characteristic curve for SVR was 0.875 with a sensitivity of 91.6 per cent, specificity 74.7 per cent, positive predictive value 80.3 per cent and negative predictive value 88.7 per cent. Higher values of IP-10 were associated with increasing stages of fibrosis (P<0.01) and higher grades of inflammation (P=0.02, P=0.07) assessed morphologically and noninvasively through FibroTest and ActiTest. Significant steatosis and IR were also associated with increased levels of IP-10 (P=0.01 and P=0.02). In multivariate analysis, IP-10 levels and fibrosis stages were independently associated with SVR. Our findings showed that the assessment of serum IP-10 level could be a predictive factor for SVR and it was associated with fibrosis, necroinflammatory activity, significant steatosis and IR in patients with chronic HCV infection.

Serum leptin level and waist-to-hip ratio (WHR) predict the overall survival of metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs).

PubMed

Artac, Mehmet; Bozcuk, Hakan; Kiyici, Aysel; Eren, Orhan Onder; Boruban, Melih Cem; Ozdogan, Mustafa

2013-04-01

Our objective was to determine whether serum leptin levels and obesity-related factors could affect outcome for metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs). Sixty MBC patients treated with first line hormonal therapy were enrolled in this study. Median age was 51 years (range 28-75). Median leptin level was 19400 pg/ml (1970-91900) and estradiol level 29.6 pg/ml (4.0-181.9). Factors associated with overall survival in univariate analysis were age and waist-to-hip ratio (WHR), whereas only WHR retained significance in the multivariate analysis. However, no factor was associated with progression-free survival. However, WHR was found to be a significant prognostic marker only if the leptin level was ≥19400 pg/ml (HR = 0.38; 95% CI: 0.16-0.91). This study suggests that serum leptin levels and WHR together may serve as potential prognostic markers in MBC patients treated with AIs.

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome.

PubMed

Yaron, Yuval; Heifetz, Sigal; Ochshorn, Yifat; Lehavi, Ofer; Orr-Urtreger, Avi

2002-09-01

Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome. Copyright 2002 John Wiley & Sons, Ltd.

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure

PubMed Central

Dekker, Rebecca L.; Lennie, Terry A.; Moser, Debra K.; Miller, Craig S.; Ebersole, Jeffrey L.; Chung, Misook L.; Campbell, Charles L.; Bailey, Alison; Tovar, Elizabeth G.

2016-01-01

Aims: To describe correlations and agreement between salivary and serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin (IL)-6, and IL-10 and determine which biomarkers predict worse functional class in patients with heart failure (HF). Methods: Serum and saliva were collected from 75 hospitalized patients with HF (57 ± 12 years, 43% female, New York Heart Association [NYHA] Classes I [4%], II [43%], and III [53%]). Oral inflammation was rated as good, fair, or poor. Spearman’s ρ and Bland–Altman were used to determine correlations and agreement of the salivary and serum forms of each biomarker. Logistic regressions were used to determine which biomarkers predicted worse NYHA functional class, controlling for depression, body mass index, smoking, and oral inflammation. Results: Median biomarker concentrations were as follows: BNP (serum 361 pg/ml, saliva 9 pg/ml), CRP (serum 13 ng/ml, saliva 25.6 ng/ml), IL-6 (serum 19.3 pg/ml, saliva 10.5 pg/ml), and IL-10 (serum 64.1 pg/ml, saliva 4.7 pg/ml). There was a moderate-to-strong correlation for serum–salivary CRP, weak correlation for serum–salivary IL-6, and no correlations for serum–salivary BNP and IL-10. The Bland–Altman test showed good salivary–serum agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. Visible oral inflammation was the only predictor of worse NYHA class. PMID:27605566

Hyperbilirubinemia as a Diagnostic Tool for the Prediction of Appendicular Perforation: A Prospective Study.

PubMed

Saxena, Divish; Tandon, Mrinal; Shah, Yunus; Gedam, B S

2015-01-01

The certainty of diagnosing acute appendicitis in patients presenting with right iliac fossa pain still remains a mystery though acute appendicitis being the commonest surgical procedure done in emergency. In acute appendicitis, serum bilirubin levels are raised due to hepatocellular damage as a result of direct insult caused by Gram-negative bacterial endotoxemia. The need for the study is to conclude whether the serum bilirubin can be considered as a new laboratory marker to aid in the diagnosis of acute appendicitis and if so, does it have the predictive capacity to warn us about appendicular perforation. This is a prospective study carried out at rural tertiary healthcare center and includes 213 patients clinically diagnosed as acute appendicitis. Out of 213 patients, raised serum bilirubin ≥1.2 mg/dl was present in 195 (91.5%) patients, out of which 194 (99.4%) patients had histopathologically inflamed appendix and this difference was statistically highly significant with p-value < 0.0001. In this study, 32 patients had perforated appendix. Out of those, 30 patients had bilirubin ≥ 4 mg/dl and 2 patients had bilirubin level between 1.2 and < 4 mg/dl. Raised serum bilirubin (≥4 mg/dl) was present in 35 (17.9%) patients, out of which 30 (87.7%) patients had perforated appendix. Saxena D, Tandon M, Shah Y, Gedam BS. Hyperbilirubinemia as a Diagnostic Tool for the Prediction of Appendicular Perforation: A Prospective Study. Euroasian J Hepato-Gastroenterol 2015;5(2):87-89.

Plasma fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus.

PubMed

Ning, Hui; Tao, Hong; Weng, Zhanping; Zhao, Xingbo

2016-12-01

Fatty acid-binding protein 4 (FABP4) is mainly expressed in adipocytes and macrophages and is demonstrated to be elevated in diabetes patients. The aim of this study was to evaluate the possible role of FABP4 in the diagnosis of GDM and to investigate the relationship between FABP4 and overweight, insulin resistance and inflammatory marker TNF-α. A total of 46 women with GDM and 55 age-matched pregnant women without GDM (non-GDM) were eligible for the study. Demographic and biochemical parameters and fasting venous blood samples of two groups were collected from all cases. Serum concentrations of FABP4 were determined using enzyme-linked immunosorbent assay (ELISA). The predictive value of Serum FABP4 level was evaluated using receiver operating characteristic curve (ROC curve) analysis. We found that the serum FABP4 levels were significantly higher in GDM compared to the non-GDM group. The area under the ROC curve assay yielded a satisfactory result of 0.94 (95 % confidence interval 0.90-0.98; p < 0.001). The best compromise between 86.96 % specificity and 89.09 % sensitivity was obtained with a cutoff value of 1.96 ng/mL for GDM diagnosis. Moreover, a significant positive correlation was observed between FABP4 and overweight, insulin resistance and TNF-α in pregnant women with GDM. These results suggest that serum FABP4 may potentially serve as a novel biomarker for the prediction of GDM.

Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaoxia, E-mail: xiaoxia.yang@fda.hhs.gov; Doerge, Daniel R.; Teeguarden, Justin G.

A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA (d{sub 6}-BPA) delivered in cookies to adult humans after overnight fasting. The availability of the serum concentration time course of unconjugated d{sub 6}-BPA offered direct empirical evidence for the calibration of BPA model parameters. The recalibrated PBPK adult humanmore » model for BPA was then evaluated against published human pharmacokinetic studies with BPA. A hypothesis of decreased oral uptake was needed to account for the reduced peak levels observed in adult humans, where d{sub 6}-BPA was delivered in soup and food was provided prior to BPA ingestion, suggesting the potential impact of dosing vehicles and/or fasting on BPA disposition. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U.S. general population. Model-predicted peak BPA serum levels were in the range of pM, with 95% of human variability falling within an order of magnitude. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in adult humans. • Serum concentrations of aglycone BPA are available for model calibration. • Model predicted peak BPA serum levels for adult humans were in the range of pM. • Model predicted 95% of human variability fell within an order of magnitude.« less

Septic acute kidney injury patients in emergency department: The risk factors and its correlation to serum lactate.

PubMed

Hsu, Yin-Chou; Hsu, Chih-Wei

2018-05-15

Acute kidney injury (AKI) is a common complication in septic patients, imposing a heavy burden of illness in terms of morbidity and mortality. Serum lactate is a widely used marker predicting the severity of sepsis. A paucity of research has investigated septic AKI in emergency departments (EDs) and its correlation with initial serum lactate level. This study aimed at identifying risk factors for septic AKI and clarifying the link between initial serum lactate level and septic AKI in ED patients. A retrospective cohort study was conducted at a single tertiary referral medical center. The medical records of all adult ED patients with measurement of serum lactate and creatinine between January 2012 and December 2016 were reviewed. A total of 696 septic patients were stratified into AKI and non-AKI groups according to Acute Kidney Injury Network (AKIN) criteria for further statistical analysis. Ninety-nine septic patients (14.2%) had AKI, with AKIN-I, AKIN-II, and AKIN-III in 71.7%, 11.1%, and 17.2% of patients, respectively. Compared with the non-AKI group, the AKI group had a significantly higher mortality rate (71.7% vs. 21.3%, p < 0.001). Independent risk factors for septic AKI included liver disease (adjusted odds ratio [AOR] = 2.02, 95% confidence interval [CI] = 1.16-3.52), diabetes mellitus (AOR = 1.73, 95% CI = 1.11-2.69), chronic kidney disease (AOR = 1.68, 95% CI = 1.06-2.66), and initial serum lactate (AOR = 1.08, 95% CI = 1.02-1.14). Patients with septic AKI had an overwhelmingly higher mortality rate. The comorbidities of liver disease, diabetes mellitus, and chronic kidney disease were correlated with septic AKI and in combination with an elevated initial serum lactate level had predictive regarding AKI and further mortality in ED septic patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Correlation of total serum immunoglobulin E level, sputum, and peripheral eosinophil count in assessing the clinical severity in bronchial asthma.

PubMed

Kumar, Roshan M; Pajanivel, R; Koteeswaran, G; Menon, Surendra K; Charles, Pravin Mv

2017-01-01

Asthma is a chronic inflammatory disorder of the airway with involvement of various cellular populations and release of many inflammatory mediators. Eosinophils and serum immunoglobulin E (IgE) are considered a good marker of airway inflammation in asthma. The correlation of clinical assessment with various markers of airway inflammation in asthma is not well established in the Indian population. This study aims to study the correlation of serum IgE, sputum eosinophil count, and peripheral eosinophil count with clinical severity of Asthma. This is a cross-sectional study involving 76 stable asthmatic patients of 18-60 years of age attending the pulmonary medicine OPD. Spirometry measured at baseline. Participants were categorized according to the GINA criteria based on clinical symptoms and pulmonary function test. Blood samples were collected for peripheral eosinophil count, serum IgE levels, and sputum samples for eosinophil count. All three parameters were compared with severity of asthma. The correlation of sputum eosinophil count, peripheral eosinophil count, and serum IgE with severity of asthma was analyzed by Pearson's Chi-square test, Fisher's exact test, and the correlation coefficient was reported together with standard error of the estimate. The mean age of patients in our study was 37.42 years and 56.6% were male. There was a significant inverse correlation between serum IgE levels and predicted forced expiratory volume 1 s (FEV1). Sputum eosinophilia was significantly seen in severe persistent asthma patients (19.7%). There was a significant inverse correlation between sputum eosinophil count and predicted FEV1and forced vital capacity. We also found there was a significant association between peripheral eosinophil count, sputum eosinophil count, and elevated serum IgE (g100 IU/mL) with severe persistent asthma. The assessment of sputum eosinophil count is simple, inexpensive, noninvasive, and direct measurement of airway inflammation. It could be the preferred method in monitoring airway inflammation and guided management in day-to-day practice.

Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation.

PubMed

Park, Yune-Jung; Yoo, Seung-Ah; Kim, Ga-Ram; Cho, Chul-Soo; Kim, Wan-Uk

2016-10-12

Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA) reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2 (CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and prognosis. One hundred seventy-three RA patients and 62 non-RA controls were recruited. Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity. Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High urinary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP. Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radiographic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold greater risk of radiographic progression. Conclusively, high urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA, reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA prognosis.

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis.

PubMed

Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie

2015-12-01

♦ As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 - 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 - 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 - 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 - 0.94) and 0.39 (95% CI 0.20 - 0.75), respectively. ♦ Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. Copyright © 2015 International Society for Peritoneal Dialysis.

Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial.

PubMed

Steinberg, William M; Buse, John B; Ghorbani, Marie Louise Muus; Ørsted, David D; Nauck, Michael A

2017-07-01

To evaluate serum amylase and lipase levels and the rate of acute pancreatitis in patients with type 2 diabetes and high cardiovascular risk randomized to liraglutide or placebo and observed for 3.5-5.0 years. A total of 9,340 patients with type 2 diabetes were randomized to either liraglutide or placebo (median observation time 3.84 years). Fasting serum lipase and amylase were monitored. Acute pancreatitis was adjudicated in a blinded manner. Compared with the placebo group, liraglutide-treated patients had increases in serum lipase and amylase of 28.0% and 7.0%, respectively. Levels were increased at 6 months and then remained stable. During the study, 18 (0.4% [1.1 events/1,000 patient-years of observation] [PYO]) liraglutide-treated and 23 (0.5% [1.7 events/1,000 PYO]) placebo patients had acute pancreatitis confirmed by adjudication. Most acute pancreatitis cases occurred ≥12 months after randomization. Liraglutide-treated patients with prior history of pancreatitis ( n = 147) were not more likely to develop acute pancreatitis than similar patients in the placebo group ( n = 120). Elevations of amylase and lipase levels did not predict future risk of acute pancreatitis (positive predictive value <1.0%) in patients treated with liraglutide. In a population with type 2 diabetes at high cardiovascular risk, there were numerically fewer events of acute pancreatitis among liraglutide-treated patients (regardless of previous history of pancreatitis) compared with the placebo group. Liraglutide was associated with increases in serum lipase and amylase, which were not predictive of an event of subsequent acute pancreatitis. © 2017 by the American Diabetes Association.

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis

PubMed Central

Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie

2015-01-01

♦ Background: As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ Methods: We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ Results: The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 – 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 – 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 – 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 – 0.94) and 0.39 (95% CI 0.20 – 0.75), respectively. ♦ Conclusions: Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. PMID:26224791

Abnormally high levels of anti-collagen type IV IgG antibodies in the serum of patients with a clinically isolated syndrome correlate with an increased risk of conversion to MS.

PubMed

Sadarzanska-Terzieva, Behidhe; Tzvetanov, Plamen; Hegde, Vishwajit; Al-Hashel, Jasem Y; Rousseff, Rossen Т; Haralanov, Lubomir; Stamenov, Boyko; Atanassova, Milena; Marinova, Iveta; Marinova, Anna; Rousseva, Adelaida

2015-06-01

To investigate anti-collagen-type-IV serum antibodies (ACIVAbs) levels in patients with clinically isolated syndrome (CIS), and to determine their predictive value for conversion into multiple sclerosis (MS). Serum levels of IgM and IgG ACIVAbs in 40 untreated patients with CIS (13 male, mean age 34.85±11.4 years, range 16-58 years) were compared to those of 27 gender- and age-matched healthy controls. ACIVAbs were quantified using ELISA. Patients were followed for 5 years by clinical examination and MRI studies. Thirty two patients (80%) converted to MS (converted CIS, C-CIS group) while the rest 8 (20%) did not (non-converted CIS, NC-CIS). The C-CIS patients had significantly higher levels of IgG ACIVAb compared to NC-CIS while the IgM levels did not differ between C-CIS and NC-CIS. Conversion to MS occurred in 66% of patients with IgG ACIVAbs levels exceeding the 95th percentile found in controls. IgG ACIVAbs levels correlated positively with the serum levels of matrix metalloproteinases type 9 (r = 0.37; p = 0.003) and inversely with those of tissue inhibitor of metalloproteinases type 1 (r = -0.43; p = 0.0008). High serum levels of IgG ACIVAbs in patients with CIS correlate strongly with increased risk of conversion to MS. Copyright © 2015 Elsevier B.V. All rights reserved.

The predictive value of mean serum uric acid levels for developing prediabetes.

PubMed

Zhang, Qing; Bao, Xue; Meng, Ge; Liu, Li; Wu, Hongmei; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Li, Chunlei; Su, Qian; Gu, Yeqing; Fang, Liyun; Yu, Fei; Yang, Huijun; Yu, Bin; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Huang, Guowei; Song, Kun; Niu, Kaijun

2016-08-01

We aimed to assess the predictive value of mean serum uric acid (SUA) levels for incident prediabetes. Normoglycemic adults (n=39,353) were followed for a median of 3.0years. Prediabetes is defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired HbA1c (IA1c), based on the American Diabetes Association criteria. Serum SUA levels were measured annually. Four diagnostic strategies were used to detect prediabetes in four separate analyses (Analysis 1: IFG. Analysis 2: IFG+IGT. Analysis 3: IFG+IA1c. Analysis 4: IFG+IGT+IA1c). Cox proportional hazards regression models were used to assess the relationship between SUA quintiles and prediabetes. C-statistic was additionally used in the final analysis to assess the accuracy of predictions based upon baseline SUA and mean SUA, respectively. After adjustment for potential confounders, the hazard ratios (95% confidence interval) of prediabetes for the highest versus lowest quintile of mean SUA were 1.22 (1.10, 1.36) in analysis 1; 1.59 (1.23, 2.05) in analysis 2; 1.62 (1.34, 1.95) in analysis 3 and 1.67 (1.31, 2.13) in analysis 4. In contrast, for baseline SUA, significance was only reached in analyses 3 and 4. Moreover, compared with baseline SUA, mean SUA value was associated with a significant increase in the C-statistic (P<0.001). Mean SUA value was strongly and positively related to prediabetes risk, and showed better predictive ability for prediabetes than baseline SUA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prediction of insufficient serum vitamin D status in older women: a validated model.

PubMed

Merlijn, T; Swart, K M A; Lips, P; Heymans, M W; Sohl, E; Van Schoor, N M; Netelenbos, C J; Elders, P J M

2018-05-28

We developed an externally validated simple prediction model to predict serum 25(OH)D levels < 30, < 40, < 50 and 60 nmol/L in older women with risk factors for fractures. The benefit of the model reduces when a higher 25(OH)D threshold is chosen. Vitamin D deficiency is associated with increased fracture risk in older persons. General supplementation of all older women with vitamin D could cause medicalization and costs. We developed a clinical model to identify insufficient serum 25-hydroxyvitamin D (25(OH)D) status in older women at risk for fractures. In a sample of 2689 women ≥ 65 years selected from general practices, with at least one risk factor for fractures, a questionnaire was administered and serum 25(OH)D was measured. Multivariable logistic regression models with backward selection were developed to select predictors for insufficient serum 25(OH)D status, using separate thresholds 30, 40, 50 and 60 nmol/L. Internal and external model validations were performed. Predictors in the models were as follows: age, BMI, vitamin D supplementation, multivitamin supplementation, calcium supplementation, daily use of margarine, fatty fish ≥ 2×/week, ≥ 1 hours/day outdoors in summer, season of blood sampling, the use of a walking aid and smoking. The AUC was 0.77 for the model using a 30 nmol/L threshold and decreased in the models with higher thresholds to 0.72 for 60 nmol/L. We demonstrate that the model can help to distinguish patients with or without insufficient serum 25(OH)D levels at thresholds of 30 and 40 nmol/L, but not when a threshold of 50 nmol/L is demanded. This externally validated model can predict the presence of vitamin D insufficiency in women at risk for fractures. The potential clinical benefit of this tool is highly dependent of the chosen 25(OH)D threshold and decreases when a higher threshold is used.

HYPERGLYCOSYLATED HUMAN CHORIONIC GONADOTROPIN AS AN EARLY PREDICTOR OF PREGNANCY OUTCOMES AFTER IN VITRO FERTILIZATION

PubMed Central

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H. Irene

2014-01-01

Objective To determine if hyperglycosylated hCG (hhCG), produced by invasive trophoblasts, measured as early as 9 days after egg retrieval can predict ongoing pregnancies (OP) after in vitro fertilization and fresh embryo transfer (IVF-ET). Design Cohort Setting Academic ART center Patients Consecutive patients undergoing IVF-ET Interventions Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Outcome Ongoing pregnancy (OP) beyond 9 weeks of gestation Results OP (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. D9 hhCG levels >110 pg/mL was 96% specific for OP, yielding a positive predictive value of 95%. Compared to D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67). Diagnostic test characteristics were similar between D16 hhCG and hCG levels. Conclusions In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable. HhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. At this early assessment, hhCG is superior to traditional hCG and highly predictive of ongoing pregnancies. PMID:24355054

Early Predictors of Hypocalcemia After Total Thyroidectomy

PubMed Central

Noureldine, Salem I.; Genther, Dane J.; Lopez, Michael; Agrawal, Nishant; Tufano, Ralph P.

2015-01-01

IMPORTANCE Postoperative hypocalcemia is common after total thyroidectomy, and perioperative monitoring of serum calcium levels is arguably the primary reason for overnight hospitalization. Confidently predicting which patients will not develop significant hypocalcemia may allow for a safe earlier discharge. OBJECTIVE To examine associations of patient characteristics with hypocalcemia, duration of hospitalization, and postoperative intact parathyroid hormone (IPTH) level after total thyroidectomy. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of consecutive patients who underwent total thyroidectomy by a single high-volume surgeon between February 1, 2010, and November 30, 2012. Postoperative serum 25-hydroxyvitamin D (vitamin D), calcium, and IPTH levels were tested within 6 to 8 hours after surgery. Mild hypocalcemia was defined as any postoperative serum calcium level of less than 8.4 to 8.0 mg/dL. Significant hypocalcemia was defined as any postoperative serum calcium level of less than 8.0 mg/dL or the development of hypocalcemia-related symptoms. INTERVENTIONS Total thyroidectomy. MAIN OUTCOMES AND MEASURES Associations of patient demographic and clinical characteristics and laboratory values with postoperative mild and significant hypocalcemia were examined using univariate analysis, and independent predictors of hypocalcemia, duration of hospitalization, and IPTH level were determined using multivariate analysis. RESULTS Overall, 304 total thyroidectomies were performed. Mild and significant hypocalcemia occurred in 68 (22.4%) and 91 (29.9%) patients, respectively, of which the majority were female (P = .003). The development of significant hypocalcemia was associated with postoperative IPTH level (P < .001). On multivariate analysis, males had a decreased risk of developing mild (odds ratio, 0.37 [95% CI, 0.16–0.85]) and significant (odds ratio, 0.57 [95% CI, 0.09–0.78]) hypocalcemia. Every 10-pg/mL increase in postoperative IPTH level predicted a 43% decreased risk of significant hypocalcemia (P < .001) and an 18% decreased risk of hospitalization beyond 24 hours (P = .03). Presence of malignant neoplasm carried a 27% risk of mild hypocalcemia (P = .02). There was a progressively increasing risk of lower IPTH levels for each parathyroid gland inadvertently resected or autotransplanted. Male sex and African American race were independently predictive of higher IPTH levels. CONCLUSIONS AND RELEVANCE Low postoperative IPTH level, female sex, and presence of malignant neoplasm are all significant, independent predictors of hypocalcemia after total thyroidectomy. Clinicians should consider these variables when deciding how to best manage or prevent postoperative hypocalcemia. PMID:25321339

Serum Bilirubin Concentrations in Patients With Takayasu Arteritis.

PubMed

Peng, You-Fan; Deng, Yi-Bin

2017-06-01

- Bilirubin has strong anti-inflammatory and antioxidative stress action. Progression of inflammation involving arteries is a crucial activator in pathogenesis of Takayasu arteritis (TA). - To investigate the relationship between serum bilirubin and TA. - Our study involved 115 consecutive TA patients. Patients with active-phase disease were followed and received prednisone therapy. - Lower concentrations of serum bilirubin were detected in TA patients compared with healthy subjects (0.6 ± 0.31 versus 0.7 ± 0.22 mg/dL, P = .02). Serum bilirubin concentrations in active TA patients were lower than those in inactive patients (0.5 ± 0.20 versus 0.8 ± 0.32 mg/dL, P < .001). In all patients with TA, serum bilirubin correlated positively with total protein (r = 0.193, P = .04) and negatively with C-reactive protein and erythrocyte sedimentation rate (r = -0.213, P = .03, and r = -0.532, P < .001, respectively). Multiple logistic regression analysis showed that each decrease of 1 mg/dL in serum bilirubin was associated with a 1.10 times increase in the odds for TA compared with the controls (odds ratio = 0.913, 95% CI, 0.856-0.974; P = .006). Serum bilirubin was correlated with erythrocyte sedimentation rate (β = -0.170, P < .001) in multiple linear regression analysis. The area under the curve for serum bilirubin in predicting active TA patients was 0.802. Serum bilirubin levels were found to be significantly increased after prednisone treatment (0.5 ± 0.20 versus 0.7 ± 0.15 mg/dL, P = .002). - Lower serum bilirubin levels are associated with TA, and serum bilirubin may be influenced by prednisone therapy in active TA patients. Serum bilirubin levels in TA patients correlate negatively with erythrocyte sedimentation rate.

Early Prediction of Persistent Organ Failure by Serum Angiopoietin-2 in Patients with Acute Pancreatitis.

PubMed

Zhang, Yu-Ping; Liu, Chang; Ye, Lei; Yu, Na; Ye, Yuan-Ning; Sun, Wen-Rong; Wu, Lin; Wang, Fang-Yu

2016-12-01

Biomarkers for the early prediction of the severity of acute pancreatitis (AP) are urgently needed for clinical management of the disease. Angiopoietin-2 (Ang-2), one of the autocrine peptides that reduce endothelial permeability, has been found to be associated with various diseases, including inflammatory disorders. This study aimed to determine whether serum Ang-2 could serve as a noninvasive biomarker for the early prediction of persistent organ failure (POF) in acute pancreatitis. A total of 120 AP patients were prospectively enrolled at Jinling Hospital. Serum samples were collected on admission. Clinical and laboratory data were recorded. Ang-2 levels were measured by enzyme-linked immunosorbent assay. A total of 37 patients developed POF and were classified as having severe AP (SAP). Ang-2 was significantly higher on admission in patients who developed POF than in those who did not (p < 0.001 for all). Furthermore, receiver operating characteristic (ROC) curve analysis revealed that Ang-2 could distinguish patients who developed POF from mild AP (MAP, area under ROC curve [AUC] = 0.88, 95 % CI 0.78-0.94) and moderately severe AP patients (MSAP, AUC = 0.74, 95 % CI 0.63-0.83). In addition, multivariate logistic regression showed that increased Ang-2 was an independent predictor of developing POF between subgroups with MSAP and SAP (OR 7.2, 95 % CI 2.7-19.4) and among all AP patients (OR 12.1, 95 % CI 4.8-30.3). Elevated serum Ang-2 levels on admission may be a promising biomarker for the prediction of POF in AP.

Quantification of bovine immunoglobulin G using transmission and attenuated total reflectance infrared spectroscopy.

PubMed

Elsohaby, Ibrahim; McClure, J Trenton; Riley, Christopher B; Shaw, R Anthony; Keefe, Gregory P

2016-01-01

In this study, we evaluated and compared the performance of transmission and attenuated total reflectance (ATR) infrared (IR) spectroscopic methods (in combination with quantification algorithms previously developed using partial least squares regression) for the rapid measurement of bovine serum immunoglobulin G (IgG) concentration, and detection of failure of transfer of passive immunity (FTPI) in dairy calves. Serum samples (n = 200) were collected from Holstein calves 1-11 days of age. Serum IgG concentrations were measured by the reference method of radial immunodiffusion (RID) assay, transmission IR (TIR) and ATR-IR spectroscopy-based assays. The mean IgG concentration measured by RID was 17.22 g/L (SD ±9.60). The mean IgG concentrations predicted by TIR and ATR-IR spectroscopy methods were 15.60 g/L (SD ±8.15) and 15.94 g/L (SD ±8.66), respectively. RID IgG concentrations were positively correlated with IgG levels predicted by TIR (r = 0.94) and ATR-IR (r = 0.92). The correlation between 2 IR spectroscopic methods was 0.94. Using an IgG concentration <10 g/L as the cut-point for FTPI cases, the overall agreement between TIR and ATR-IR methods was 94%, with a corresponding kappa value of 0.84. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for identifying FTPI by TIR were 0.87, 0.97, 0.91, 0.95, and 0.94, respectively. Corresponding values for ATR-IR were 0.87, 0.95, 0.86, 0.95, and 0.93, respectively. Both TIR and ATR-IR spectroscopic approaches can be used for rapid quantification of IgG level in neonatal bovine serum and for diagnosis of FTPI in dairy calves. © 2015 The Author(s).

Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity.

PubMed

Park, So Young; Hong, Gyong Hwa; Park, Sunjoo; Shin, Bomi; Yoon, Sun-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

2016-12-01

Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. To investigate the association between serum progranulin levels and various clinical features in patients with asthma. Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma. Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P < .001) after adjustment for other variables, such as age, sex, smoking status, blood neutrophil count, and current use of systemic corticosteroids. Although the exact mechanism of the anti-inflammatory action of progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Cardiovascular disease delay in centenarian offspring: role of heat shock proteins.

PubMed

Terry, Dellara F; McCormick, Maegan; Andersen, Stacy; Pennington, Jaemi; Schoenhofen, Emily; Palaima, Elizabeth; Bausero, Maria; Ogawa, Kishiko; Perls, Thomas T; Asea, Alexzander

2004-06-01

Cardiovascular disease is a major cause of morbidity and mortality of older Americans. We have demonstrated recently that centenarian offspring, when compared with age-matched controls, avoid and/or delay cardiovascular disease and cardiovascular risk factors. Given recent evidence suggesting that higher circulating levels of HSP70 predict the future development of cardiovascular disease in established hypertensives and a recent study demonstrating a decrease in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be lower in centenarian offspring compared with controls. The circulating serum concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was analyzed using a modified HSP70 ELISA method. Centenarian offspring showed approximately 10-fold lower levels of circulating serum HSP70 compared with spousal controls (P <.001). The exact biological significance of the extremely low levels of circulating serum HSP70 observed in centenarian offspring thus far is not clear. However, circulating HSP has been shown to correlate in diseases or disorders in which there is destruction or damage to target tissues or organs, including cardiovascular diseases and numerous autoimmune disorders. We hypothesize that low levels of circulating serum HSP70 may be an indicator of a healthy state and point to longevity of the host; therefore, our results suggest that levels of circulating serum HSP70 may be a marker for longevity.

Cardiovascular Disease Delay in Centenarian Offspring: Role of Heat Shock Proteins

PubMed Central

TERRY, DELLARA F.; McCORMICK, MAEGAN; ANDERSEN, STACY; PENNINGTON, JAEMI; SCHOENHOFEN, EMILY; PALAIMA, ELIZABETH; BAUSERO, MARIA; OGAWA, KISHIKO; PERLS, THOMAS T.; ASEA, ALEXZANDER

2006-01-01

Cardiovascular disease is a major cause of morbidity and mortality of older Americans. We have demonstrated recently that centenarian offspring, when compared with age-matched controls, avoid and/or delay cardiovascular disease and cardiovascular risk factors. Given recent evidence suggesting that higher circulating levels of HSP70 predict the future development of cardiovascular disease in established hypertensives and a recent study demonstrating a decrease in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be lower in centenarian offspring compared with controls. The circulating serum concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was analyzed using a modified HSP70 ELISA method. Centenarian offspring showed approximately 10-fold lower levels of circulating serum HSP70 compared with spousal controls (P < .001). The exact biological significance of the extremely low levels of circulating serum HSP70 observed in centenarian offspring thus far is not clear. However, circulating HSP has been shown to correlate in diseases or disorders in which there is destruction or damage to target tissues or organs, including cardiovascular diseases and numerous autoimmune disorders. We hypothesize that low levels of circulating serum HSP70 may be an indicator of a healthy state and point to longevity of the host; therefore, our results suggest that levels of circulating serum HSP70 may be a marker for longevity. PMID:15247074

[IPTH dosage as a prognosis predictor of postoperatory hypocalcemia in patients submitted to total thyroidectomy].

PubMed

Paliogiannis, Panagiotis; Attene, Federico; Torre, Carlo; Denti, Salvatore; Trignano, Emilio; Scognamillo, Fabrizio; Trignano, Mario

2011-01-01

Hypocalcemia is the most frequent complication after total thyroidectomy (TT) and represents the main cause of prolonged hospital stay because of the need to monitor the calcemic status of the patients. The aim of this study is to evaluate the role of serum iPTH as a predictor of post-thyroidectomy hypocalcemia in order to allow patients' early and safe discharge. Fifty patients who underwent TT without autotransplantation of parathyroid tissue were prospectively included in the study The mean age was 52 years and the male/female ratio was 1/6. The iPTH serum level were determined 1 hour after the operation and the calcium serum values after 24 and 48 hours. The cut-off value assumed for testing the sensitivity, specificity, PPV and NPV was 16 pg/ml. Nineteen patients (38%) presented hypocalcemia within 48 hours after TT and 16 of them (84.2%) had iPTH serum levels lower than 16 pg/ml. The normocalcemic patients were 31 (62%) and only 4 of them had iPTH serum levels inferior to the cut-off value. Postoperative iPTH serum level determined 1 hour after the operation had a sensibility of 84.2%, specificity of 87.1%, PPV and NPV of 90% and 80% respectively. The dosage of iPTH serum levels after total thyroidectomy reliably predicts patients who are likely to develop hypocalcaemia. It may be useful in clinical practice in order to reduce the number of postoperative blood tests and the hospital length of stay for the patients who are not at risk of postoperative hypocalcemia.

Hypervitaminosis A is prevalent in children with CKD and contributes to hypercalcemia.

PubMed

Manickavasagar, Baheerathi; McArdle, Andrew J; Yadav, Pallavi; Shaw, Vanessa; Dixon, Marjorie; Blomhoff, Rune; Connor, Graeme O'; Rees, Lesley; Ledermann, Sarah; Van't Hoff, William; Shroff, Rukshana

2015-02-01

Vitamin A accumulates in renal failure, but the prevalence of hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is not known. Hypervitaminosis A has been associated with hypercalcemia. In this study we compared dietary vitamin A intake with serum retinoid levels and their associations with hypercalcemia. We studied the relationship between vitamin A intake, serum retinoid levels, and serum calcium in 105 children with CKD stages 2-5 on dialysis and posttransplant. Serum retinoid measures included retinol (ROH), its active retinoic acid (RA) metabolites [all-trans RA (at-RA) and 13-cis RA] and carrier proteins [retinol-binding protein-4 (RBP4) and transthyretin (TTR)]. Dietary vitamin A intake was assessed using a food diary. Twenty-five children were in CKD 2-3, 35 in CKD 4-5, 23 on dialysis and 22 posttransplant; 53 % had vitamin A intake above the Reference Nutrient Intake (RNI) value. Children receiving supplemental feeds compared with diet alone had higher vitamin A intake (p = 0.02) and higher serum ROH (p < 0.001). Notably, increased ROH was seen as early as CKD stage 2. For every 10 ml/min/1.73 m(2) fall in estimated glomerular filtration rate (eGFR), there was a 13 % increase in ROH. RBP4 levels were increased in CKD 3-5 and dialysis patients. The lowest ratios of ROH:RBP4 were seen in dialysis compared with CKD 2-3 (p = 0.03), suggesting a relative increase in circulating RBP4. Serum ROH, RBP4 and at-RA were associated with serum calcium. On multivariable analysis RBP4 levels and alfacalcidol dose were significant predictors of serum calcium (model R (2) 32 %) in dialysis patients. Hypervitaminosis A is seen in early CKD, with highest levels in children on supplemental feeds compared with diet alone. Serum retinoid levels significantly predict hypercalcemia.

Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression.

PubMed

Matthews, Christine; Catherwood, Mark A; Morris, T C M; Kettle, Paul J; Drake, Mary B; Gilmore, William S; Alexander, H Denis

2006-10-01

Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients. Furthermore, the use of serum TK measurement to identify subcategories of disease within those defined by IgV(H) mutational status, gene usage and chromosomal aberrations was investigated. Ninety-one CLL patients were enrolled. Serum TK levels were measured using a radioenzyme assay. IgV(H) mutational status and V(H) gene usage were determined using BIOMED-2 primers and protocol. Recurring chromosomal abnormalities were detected by interphase fluorescent in situ hybridisation (FISH). Flow cytometry and reverse transcriptase polymerase chain reaction (RT-PCR) determined CD38 and Zap-70 expression, respectively. Significantly higher serum TK levels were found in IgV(H) unmutated, compared with IgV(H) mutated, patients (P < 0.001). Elevated TK levels were also found in patients with CD38 and Zap-70 positivity (P = 0.004, P < 0.001, respectively), short lymphocyte doubling time (LDT) (P = 0.044) and poor or intermediate prognosis chromosomal aberrations (P < 0.001). A TK level of >8.5 U/L best identified patients with progressive disease. Elevated TK levels could identify patients categorised, at diagnosis, into good prognosis subgroups by the various biological markers (mutated IgV(H), good prognosis chromosomal aberrations, Zap-70(-) and CD38(-)) who subsequently showed disease progression. Additionally, patients with V(H)3-21 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.

Serum Albumin and Disease Severity of Non-Cystic Fibrosis Bronchiectasis.

PubMed

Lee, Seung Jun; Kim, Hyo-Jung; Kim, Ju-Young; Ju, Sunmi; Lim, Sujin; Yoo, Jung Wan; Nam, Sung-Jin; Lee, Gi Dong; Cho, Hyun Seop; Kim, Rock Bum; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog

2017-08-01

A clinical classification system has been developed to define the severity and predict the prognosis of subjects with non-cystic fibrosis (CF) bronchiectasis. We aimed to identify laboratory parameters that are correlated with the bronchiectasis severity index (BSI) and FACED score. The medical records of 107 subjects with non-CF bronchiectasis for whom BSI and FACED scores could be calculated were retrospectively reviewed. The correlations between the laboratory parameters and BSI or FACED score were assessed, and multiple-linear regression analysis was performed to identify variables independently associated with BSI and FACED score. An additional subgroup analysis was performed according to sex. Among all of the enrolled subjects, 49 (45.8%) were male and 58 (54.2%) were female. The mean BSI and FACED scores were 9.43 ± 3.81 and 1.92 ± 1.59, respectively. The serum albumin level (r = -0.49), bilirubin level (r = -0.31), C-reactive protein level (r = 0.22), hemoglobin level (r = -0.2), and platelet/lymphocyte ratio (r = 0.31) were significantly correlated with BSI. Meanwhile, serum albumin (r = -0.37) and bilirubin level (r = -0.25) showed a significant correlation with the FACED score. Multiple-linear regression analysis showed that the serum bilirubin level was independently associated with BSI, and the serum albumin level was independently associated with both scoring systems. Subgroup analysis revealed that the level of uric acid was also a significant variable independently associated with the BSI in male bronchiectasis subjects. Several laboratory variables were identified as possible prognostic factors for non-CF bronchiectasis. Among them, the serum albumin level exhibited the strongest correlation and was identified as an independent variable associated with the BSI and FACED scores. Copyright © 2017 by Daedalus Enterprises.

Neurofilament Subunit L Levels in the Cerebrospinal Fluid and Serum of Patients with Amyotrophic Lateral Sclerosis.

PubMed

Gong, Zhong-Ying; Lv, Gao-Peng; Gao, Li-Na; Lu, Yi; Guo, Jie; Zang, Da-Wei

2018-06-13

There are no reliable biomarkers that could evaluate the disease burden in amyotrophic lateral sclerosis (ALS). The aim of our study is to evaluate the changes in cerebrospinal fluid (CSF) and serum neurofilament subunit L (NF-L) in patients with ALS and to analyze the correlations between the levels of NF-L and clinical parameters. CSF and serum samples were obtained from 80 ALS patients and 40 controls. The levels of NF-L in CSF and serum were assessed, and disease progression parameters including duration, revised ALS Functional Rating Scale (ALSFRS-r) score, disease progression rate (DPR), upper motor neuron (UMN) score, and survival were analyzed by registered neurologists. All samples were measured using a commercial enzyme-linked immunosorbent assay. Statistical analyses were performed using Prism software. Compared to the controls, the ALS patients displayed significantly increased levels of NF-L; these values were negatively correlated with the ALSFRS-r score and positively correlated with the decrease in ALSFRS-r score, DPR, and UMN score. There was no correlation between levels of NF-L and duration. In addition, the cumulative survival rate in ALS patients with a low level of NF-L was higher than in patients with a high level of NF-L. NF-L levels increased in CSF and serum of patients with ALS. NF-L may thus be a neurodegenerative biomarker for predicting ALS severity and progression, and the survival of patients with this disease. © 2018 S. Karger AG, Basel.

Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

PubMed

Pepper, Ruth J; Draibe, Juliana B; Caplin, Ben; Fervenza, Fernando C; Hoffman, Gary S; Kallenberg, Cees G M; Langford, Carol A; Monach, Paul A; Seo, Philip; Spiera, Robert; William St Clair, E; Tchao, Nadia K; Stone, John H; Specks, Ulrich; Merkel, Peter A; Salama, Alan D

2017-01-01

S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Patients were divided into 4 groups: proteinase 3 (PR3)-ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)-ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA-positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment. © 2016, American College of Rheumatology.

Clinical value of preoperative serum CA 19-9 and CA 125 levels in predicting the resectability of hilar cholangiocarcinoma.

PubMed

Hu, Hai-Jie; Mao, Hui; Tan, Yong-Qiong; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

2016-01-01

To examine the predictive value of tumor markers for evaluating tumor resectability in patients with hilar cholangiocarcinoma and to explore the prognostic effect of various preoperative factors on resectability in patients with potentially resectable tumors. Patients with potentially resectable tumors judged by radiologic examination were included. The receiver operating characteristic (ROC) analysis was conducted to evaluate serum carbohydrate antigenic determinant 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125) and carcino embryonie antigen levels on tumor resectability. Univariate and multivariate logistic regression models were also conducted to analysis the correlation of preoperative factors with resectability. In patients with normal bilirubin levels, ROC curve analysis calculated the ideal CA 19-9 cut-off value of 203.96 U/ml in prediction of resectability, with a sensitivity of 83.7 %, specificity of 80 %, positive predictive value of 91.1 % and negative predictive value of 66.7 %. Meanwhile, the optimal cut-off value for CA 125 to predict resectability was 25.905 U/ml (sensitivity, 78.6 %; specificity, 67.5 %). In a multivariate logistic regression model, tumor size ≤3 cm (OR 4.149, 95 % CI 1.326-12.981, P = 0.015), preoperative CA 19-9 level ≤200 U/ml (OR 20.324, 95 % CI 6.509-63.467, P < 0.001), preoperative CA 125 levels ≤26 U/ml (OR 8.209, 95 % CI 2.624-25.677, P < 0.001) were independent determinants of resectability in patients diagnosed as hilar cholangiocarcinoma. Preoperative CA 19-9 and CA 125 levels predict resectability in patients with radiological resectable hilar cholangiocarcinoma. Increased preoperative CA 19-9 levels and CA 125 levels are associated with poor resectability rate.

Serum Procalcitonin for Predicting Significant Infections and Mortality in Pediatric Oncology.

PubMed

Gunasekaran, Vinod; Radhakrishnan, Nita; Dinand, Veronique; Sachdeva, Anupam

2016-12-15

To evaluate the role of serum procalcitonin (PCT) level at admission in predicting significant infections and deaths among children on chemotherapy presenting with fever. Children with clinically significant (CSI) and microbiologically documented (MDI) infections were identified using standard definitions. Association of PCT with CSI, MDI and mortality was analyzed. We evaluated 821 febrile episodes in 316 children. CSI, MDI and deaths were seen in 40.9%, 20.1% and 2.9%, respectively. PCT levels ranged from 0.05-560ng/mL. Median PCT was higher in episodes with CSI (0.80 vs. 0.28) and MDI (0.71 vs. 0.34) (P<0.001). PCT ≥0.7ng/mL optimally predicted CSI (AUC-0.740) and MDI (AUC-0.636). Relative risk of mortality for PCT ≥5ng/mL was 7.1. PCT ≥0.7ng/mL had poor sensitivity (45-55%) but good specificity and NPV (70-90%). PCT was elevated in nearly half of documented viral and fungal infections. PCT predicts significant infections and mortality in pediatric oncology but it has poor sensitivity to guide clinical decisions.

High variation of individual soluble serum CD30 levels of pre-transplantation patients: sCD30 a feasible marker for prediction of kidney allograft rejection?

PubMed

Altermann, Wolfgang; Schlaf, Gerald; Rothhoff, Anita; Seliger, Barbara

2007-10-01

Previous studies have suggested that the pre-transplant levels of the soluble CD30 molecule (sCD30) represent a non-invasive tool which can be used as a biomarker for the prediction of kidney allograft rejections. In order to evaluate the feasibility of sCD30 for pre-transplantation monitoring the sera of potential kidney recipients (n = 652) were collected four times in a 3 months interval. Serum from healthy blood donors (n = 203) served as controls. The sCD30 concentrations of all samples were determined using a commercially available ELISA. This strategy allowed the detection of possible variations of individual sCD30 levels over time. Heterogeneous sCD30 concentrations were found in the samples obtained from individual putative kidney transplant recipients when quarterly measured over 1 year. Total 95% of serum samples obtained from healthy controls exhibited sCD30 values <30 U/ml, whereas most recipients displayed higher serum levels (>30 U/ml). Total 524 patients (80.4%) constantly exhibited serum concentrations of <100 U/ml during the period investigated, whereas 109 patients (16.7%) showed variations by exceeding the proposed 'cut off' of 100 U/ml for one to three times. The frequency of samples exhibiting sCD30 values >100 U/ml was significantly lower than that previously reported. The high degree of variation does not allow the stratification of patients into high and low immunological risk groups based on a single sCD30 value > 100 U/ml. Due to the heterogeneity of sCD30 levels during time course and the high values of SD, its implementation as a pre-transplant marker cannot be justified to generate special provisions for the organ allocation to patients with single sCD30 values > 100 U/ml.

Serum glycerophosphate levels are increased in Japanese men with type 2 diabetes.

PubMed

Daimon, Makoto; Soga, Tomoyoshi; Hozawa, Atsushi; Oizumi, Toshihide; Kaino, Wataru; Takase, Kaoru; Karasawa, Shigeru; Jimbu, Yumi; Wada, Kiriko; Kameda, Wataru; Susa, Shinji; Kayama, Takamasa; Saito, Kaori; Tomita, Masaru; Kato, Takeo

2012-01-01

To identify metabolites showing changes in serum levels among Japanese male with diabetes. We performed metabolite profiling by coupling capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry using fasting serum samples from Japanese male subjects with diabetes (n=17), impaired glucose tolerance (IGT; n=5) and normal glucose tolerance (NGT; n=14). Other than the expected differences in characteristics related to abnormal glucose metabolism, the percent body fat was significantly different among subjects with diabetes, IGT and NGT (27.3±6.2, 22.2±4.5 and 19.2±6.0%, respectively, p=0.0022). Therefore, percent body fat was considered as a possible confounding factor in subsequent analyses. Of 560 metabolites detected using our platform, the levels of 74 metabolites were quantified in all of the serum samples. Significant differences between diabetes and NGT were observed for 24 metabolites. The top-ranked metabolite was glycerol-3-phophate (glycerophosphate), which was significantly higher in subjects with diabetes than in those with NGT, even after Bonferroni correction for multiple testing (11.7±3.6 vs. 6.4±1.9 µM, respectively; corrected p=0.0222). Stepwise multiple regression analyses revealed that serum glycerophosphate levels were significantly correlated with 2-h plasma glucose after a 75-g oral glucose tolerance test (r=0.553, p=0.0005), independently of other characteristics, including FPG and HbA1c. Serum glycerophosphate levels were found to be elevated in Japanese men with diabetes, and correlated with 2-h PG, independent of FPG and HbA1c. Namely, serum glycerophosphate level at fasting condition can be a marker for predicting glucose intolerance. These results warrant further studies to evaluate the relevance of glycerophosphate in the pathophysiology of diabetes.

Probability of reduced renal function after contrast-enhanced CT: a model based on serum creatinine level, patient age, and estimated glomerular filtration rate.

PubMed

Herts, Brian R; Schneider, Erika; Obuchowski, Nancy; Poggio, Emilio; Jain, Anil; Baker, Mark E

2009-08-01

The objectives of our study were to develop a model to predict the probability of reduced renal function after outpatient contrast-enhanced CT (CECT)--based on patient age, sex, and race and on serum creatinine level before CT or directly based on estimated glomerular filtration rate (GFR) before CT--and to determine the relationship between patients with changes in creatinine level that characterize contrast-induced nephropathy and patients with reduced GFR after CECT. Of 5,187 outpatients who underwent CECT, 963 (18.6%) had serum creatinine levels obtained within 6 months before and 4 days after CECT. The estimated GFR was calculated before and after CT using the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. Pre-CT serum creatinine level, age, race, sex, and pre-CT estimated GFR were tested using multiple-variable logistic regression models to determine the probability of having an estimated GFR of < 60 and < 45 mL/min/1.73 m(2) after CECT. Two thirds of the patients were used to create and one third to test the models. We also determined discordance between patients who met standard definitions of contrast-induced nephropathy and those with a reduced estimated GFR after CECT. Significant (p < 0.002) predictors for a post-CT estimated GFR of < 60 mL/min/1.73 m(2) were age, race, sex, pre-CT serum creatinine level, and pre-CT estimated GFR. Sex, serum creatinine level, and pre-CT estimated GFR were significant factors (p < 0.001) for predicting a post-CT estimated GFR of < 45 mL/min/1.73 m(2). The probability is [exp(y) / (1 + exp(y))], where y = 6.21 - (0.10 x pre-CT estimated GFR) for an estimated GFR of < 60 mL/min/1.73 m(2), and y = 3.66 - (0.087 x pre-CT estimated GFR) for an estimated GFR of < 45 mL/min/1.73 m(2). A discrepancy between those who met contrast-induced nephropathy criteria by creatinine changes and those with a post-CT estimated GFR of < 60 mL/min/1.73 m(2) was detected in 208 of the 963 patients (21.6%). The probability of a reduced estimated GFR after CECT can be predicted by the pre-CT estimated GFR using the four-variable MDRD equation. Furthermore, standard criteria for contrast-induced nephropathy are poor predictors of poor renal function after CECT. Criteria need to be established for what is an acceptable risk to manage patients undergoing CECT.

Anti-Műllerian hormone – a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome

PubMed Central

Neagu, M; Cristescu, C

2012-01-01

Background: The anti- Műllerian hormone (AMH) is secreted in women exclusively by the granulosa cells of the ovarian follicles. The serum level of AMH is a precise marker of follicle pool size. In recent clinical studies of polycystic ovary syndrome (PCOS), the serum levels of AMH were elevated about two to threefold. The use of metformin in women with infertility and PCOS has proved to be efficient: restoring ovulation and reducing metabolic dysfunctions. The aim of our study is to assess AMH as a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome (PCOS). Methods: Eleven patients with infertility and PCOS were enrolled; PCOS was diagnosed according to the criteria of Androgen Excess and Polycystic Ovarian Syndrome Society 2006 (AE/PCOS). All patients have received metformin therapy. Serum AMH was recorded before and after 2 months of treatment; the normal laboratory values were 2.0-6.8 ng/ml. Results: The primary serum AMH level of all women in study was very high: 8.99±0.99 ng/ml. After 2 months of treatment with metformin ovulation was restored in all the patients and the serum AMH levels were significantly decreased. Conclusions: In clinical practice, serum AMH levels of women with infertility and PCOS receiving metformin are a useful predictive marker for the treatment efficiency. PMID:23346251

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects.

PubMed

Hagen, Imke; Schulte, Dominik M; Müller, Nike; Martinsen, Jessica; Türk, Kathrin; Hedderich, Jürgen; Schreiber, Stefan; Laudes, Matthias

2015-06-01

Obesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD). 22 severe obese subjects (Median Body Mass Index (BMI): 44.5kg/m(2)) were included in a dietary intervention study of 6month, consisting of a very low calorie formula diet phase (VLCD: 800kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR). Mean body weight reduction by VLCD accounted to 21.7kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (rS=-0.642, p=0.001) and HOMA (rS=-0.419, p=0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p=0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p=0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (rS=-0.650, p=0.022) during intervention. Anti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Suppression of Homocysteine Levels by Vitamin B12 and Folates: Age and Gender Dependency in the Jackson Heart Study

PubMed Central

Henry, Olivia R.; Benghuzzi, Hamed; Taylor, Herman A.; Tucci, Michelle; Butler, Kenneth; Jones, Lynne

2011-01-01

Objectives To examine factors potentially contributing to premature cardiovascular disease mortality in African Americans (40% versus 20% all other populations), plasma homocysteine, serum vitamin B12 and folate levels were examined for African American participants in the Jackson Heart Study. Methods Of 5,192 African American Jackson Heart Study participants (21–94 years), 5,064 (mean age, 55±13 years; 63% female) had homocysteine levels measured via fasting blood samples, with further assessments of participants’ vitamin B12 (n=1,790) and folate (n=1,788) levels. We used regression analyses to examine age, gender, vitamin B12, and folate with homocysteine levels. Results Homocysteine levels, a purported surrogate risk factor for cardiovascular disease, increased with age, were inversely proportional to folate and vitamin B12 levels (p<0.001), and higher for men of all ages. Conclusions Our results show that, as with other populations, age, gender, vitamin B12, and folate may predict homocysteine levels for African Americans. Diet may be an important predictive factor as well, given the relationships we observed between plasma homocysteine and serum B vitamin levels. PMID:22173042

A rapid field test for the measurement of bovine serum immunoglobulin G using attenuated total reflectance infrared spectroscopy.

PubMed

Elsohaby, Ibrahim; Hou, Siyuan; McClure, J Trenton; Riley, Christopher B; Shaw, R Anthony; Keefe, Gregory P

2015-08-20

Following the recent development of a new approach to quantitative analysis of IgG concentrations in bovine serum using transmission infrared spectroscopy, the potential to measure IgG levels using technology and a device better designed for field use was investigated. A method using attenuated total reflectance infrared (ATR) spectroscopy in combination with partial least squares (PLS) regression was developed to measure bovine serum IgG concentrations. ATR spectroscopy has a distinct ease-of-use advantage that may open the door to routine point-of-care testing. Serum samples were collected from calves and adult cows, tested by a reference RID method, and ATR spectra acquired. The spectra were linked to the RID-IgG concentrations and then randomly split into two sets: calibration and prediction. The calibration set was used to build a calibration model, while the prediction set was used to assess the predictive performance and accuracy of the final model. The procedure was repeated for various spectral data preprocessing approaches. For the prediction set, the Pearson's and concordance correlation coefficients between the IgG measured by RID and predicted by ATR spectroscopy were both 0.93. The Bland Altman plot revealed no obvious systematic bias between the two methods. ATR spectroscopy showed a sensitivity for detection of failure of transfer of passive immunity (FTPI) of 88 %, specificity of 100 % and accuracy of 94 % (with IgG <1000 mg/dL as the FTPI cut-off value). ATR spectroscopy in combination with multivariate data analysis shows potential as an alternative approach for rapid quantification of IgG concentrations in bovine serum and the diagnosis of FTPI in calves.

Identifying Malignant Pleural Effusion by A Cancer Ratio (Serum LDH: Pleural Fluid ADA Ratio).

PubMed

Verma, Akash; Abisheganaden, John; Light, R W

2016-02-01

We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.

Prospective evaluation of intra-operative quick parathyroid hormone assay as an early predictor of post thyroidectomy hypocalcaemia.

PubMed

Reddy, Ashwini C; Chand, Gyan; Sabaretnam, M; Mishra, Anjali; Agarwal, Gaurav; Agarwal, Amit; Verma, A K; Mishra, S K

2016-10-01

Hypocalcaemia following total thyroidectomy is a major contributing factor in delayed hospital discharge and dissuading surgeons from day care thyroidectomy. We prospectively evaluated the utility of Intra-operative serum quick parathyroid hormone level measurement twenty minutes after total thyroidectomy in predicting post-operative hypocalcemia. Prospective longitudinal study which included patients undergoing total thyroidectomy for benign or malignant thyroid disorders at SGPGIMS, Lucknow, India from November 2013 to February 2015. Patients who received calcium prophylaxis were excluded from the study. Intraoperative serum quick PTH level measurements were done twenty minutes after resection of thyroid. Serum calcium levels were estimated preoperatively and on three consecutive post operative days. Calcium supplementation was started in patients with symptomatic hypocalcemia. The study included 100 patients with a mean age of 41 years, range 17-72 years. 48 patients had Euthyroid multinodular goitre, 10 patients grave's disease and 42 patients had differentiated thyroid cancer. Total thyroidectomy was performed in 88 patients, total thyroidectomy with lymph node dissection in 12 patients. Post-operatively 23% patients experienced symptomatic hypocalcemia. The IOPTH level of 9 pmol/L, twenty minutes after total thyroidectomy, had the highest sensitivity and specificity of 92% and 83% respectively in predicting post-operative hypocalcemia. Parathyroid hormone assay twenty minutes after thyroidectomy is an accurate and reliable means of predicting clinically relevant hypocalcemia. Patients with PTH values greater than 9 pmol/L twenty minutes after thyroidectomy, can be safely discharged on the same postoperative day as the probability of life threatening hypocalcemia is unlikely. Copyright © 2016. Published by Elsevier Ltd.

A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH).

PubMed

Younossi, Zobair M; Jarrar, Mohammed; Nugent, Clare; Randhawa, Manpreet; Afendy, Mariam; Stepanova, Maria; Rafiq, Nila; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha

2008-11-01

Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH. The aim of this study was to develop a noninvasive diagnostic biomarker for NASH. The study included 101 patients with liver biopsies who were tested with enzyme-linked immunosorbent assay (ELISA)-based assays. Of these, 69 were included in the biomarker development set and 32 were included in the biomarker validation set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum samples were assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, cytokeratin CK-18 (M65 antigen), and caspase-cleaved CK-18 (M30 antigen). Data analysis revealed that the levels of M30 antigen (cleaved CK-18) predicted histological NASH with 70% sensitivity and 83.7% specificity and area under the curve (AUC) = 0.711, p < 10(-4), whereas the predictive value of the levels of intact CK-18 (M65) was higher (63.6% sensitivity and 89.4% specificity and AUC = 0.814, p < 10(-4)). Histological NASH could be predicted by a combination of Cleaved CK-18, a product of the subtraction of Cleaved CK-18 level from intact CK-18 level, serum adiponectin, and serum resistin with a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10(-4)). Blinded validation of this model confirmed its reliability for separating NASH from simple steatosis. Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.

Limitations of serum ferritin to predict liver iron concentration responses to deferasirox therapy in patients with transfusion-dependent thalassaemia.

PubMed

Porter, John B; Elalfy, Mohsen; Taher, Ali; Aydinok, Yesim; Lee, Szu-Hee; Sutcharitchan, Pranee; El-Ali, Ali; Han, Jackie; El-Beshlawy, Amal

2017-03-01

In transfusion-dependent anaemias, while absolute serum ferritin levels broadly correlate with liver iron concentration (LIC), relationships between trends in these variables are unclear. These relationships are important because serum ferritin changes are often used to adjust or switch chelation regimens when liver magnetic resonance imaging (MRI) is unavailable. This post hoc analysis of the EPIC study compared serum ferritin and LIC in 317 patients with transfusion-dependent thalassaemia before and after 1 yr of deferasirox. Serum ferritin responses (decreases) occurred in 73% of patients, 80% of whom also have decreased LIC. However, 52% of patients without a serum ferritin response did decrease LIC and by >1 mg Fe/g dw (median 3.9) in 77% of cases. Absolute serum ferritin and LIC values correlated significantly only when serum ferritin was <4000 ng/mL (r = 0.59; P < 0.0001) and not at higher levels (≥4000 ng/mL; r = 0.19). Serum ferritin response was accompanied by decreased LIC in 89% and 70% of cases when serum ferritin was <4000 or ≥4000 ng/mL, respectively. As serum ferritin non-response was associated with LIC decrease in over half of patients, use of liver MRI may be particularly useful for differentiating true from apparent non-responders to deferasirox based on serum ferritin trends alone. © 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy.

PubMed

Vorselaars, Adriane D M; van Moorsel, Coline H M; Zanen, Pieter; Ruven, Henk J T; Claessen, Anke M E; van Velzen-Blad, Heleen; Grutters, Jan C

2015-02-01

In sarcoidosis, the search for disease activity markers that correlate with treatment response is ongoing. The aim of this study was to investigate the pattern of two proposed markers, serum angiotensin-converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) during methotrexate (MTX) therapy in sarcoidosis patients. We analysed 114 sarcoidosis patients who used MTX for six months, consisting of a subgroup of 76 patients with a pulmonary indication for treatment and a subgroup of 38 patients with an extra-pulmonary indication. ACE and sIL-2R serum levels were measured at baseline and after six months of treatment. Correlation coefficients (R) and odds ratios (ORs) were calculated to study the correlation and predictive effect of serum ACE and sIL-2R levels for pulmonary improvement. High baseline levels of ACE correlated significantly with lung function improvement after treatment (R = 0.45, p < 0.0001; stronger in the pulmonary subgroup R 0.57, p < 0.0001). ACE baseline levels >90 U/l predicted a 10% improvement in overall lung function (OR 3.55; CI 1.34-9.38), with the highest prediction level for 10% improvement in DLCO (OR 4.63; CI 1.23-17.4). After six months of MTX, mean ACE decreased with 17.2 U/l (p < 0.0001) and sIL-2R with 1850 pg/ml (p < 0.0001). Decreases in both ACE and sIL-2R correlated with an increase in lung function. The strongest correlation was found with change in DLCO in the pulmonary subgroup (ACE R = 0.63, P < 0.0001; sIL-2R R = 0.56, P < 0.0001). Baseline and serial serum ACE and sIL-2R levels correlate well with lung function improvement during MTX treatment. Serial measurements of these biomarkers are helpful in monitoring treatment effects in sarcoidosis patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pregnancy-associated plasma protein-A (PAPP-A) levels in patients with severe allergic asthma are reduced by omalizumab.

PubMed

Bulut, Ismet; Ozseker, Zeynep F; Coskun, Abdurrahman; Serteser, Mustafa; Unsal, Ibrahim

2017-12-06

Remodeling is a crucial feature of severe asthma and may be associated with activation of the allergic cascade by immunoglobulin E (IgE). Omalizumab, an anti-IgE monoclonal antibody, effectively targets the severe allergic asthma phenotype. Pregnancy-associated plasma protein-A (PAPP-A) is an insulin-like growth factor binding protein-4 (IGFBP-4) protease, increasing local insulin-like growth factor (IGF)-1 concentrations, which in turn initiating a cascade involved in the regulation of cell growth, differentiation, and proliferation in various tissues. In the present study, we evaluated the effects of omalizumab on serum PAPP-A, IGFBP-4, and IGF-1 levels in subjects with severe allergic asthma. We studied 36 asthmatic subjects and 36 healthy controls. An ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit was used to measure serum PAPP-A levels, and routine commercial ELISA kits were employed to assess serum levels of IGF-1, IGFBP-4 in control subjects and asthmatic subjects before therapy (baseline) and after six months of omalizumab therapy in patients with severe asthma. Compared to control subjects, serum PAPP-A and IGFB-4 levels were significantly higher in asthmatic subjects (both p values < 0.001). However, the serum IGF-I levels of asthmatic subjects were similar to those of control subjects (p > 0.05). In asthma subjects, 6-month omalizumab treatment significantly decreased the serum PAPP-A (p < 0.001), IGF-I (p = 0.031), and IGFB4 (p = 0.025) levels. PAPP-A level may be a useful biomarker for predicting airway remodeling in patients with severe asthma receiving omalizumab, and may also reflect the response to treatment.

Serum oxidant and antioxidant levels in diesel exposed toll collectors.

PubMed

Arbak, Peri; Yavuz, Ozlem; Bukan, Neslihan; Balbay, Oner; Ulger, Füsun; Annakkaya, Ali Nihat

2004-07-01

It has been suggested that exposure to diesel exhaust may lead to adverse effects due to the generation of oxidants. To evaluate the end products of oxidative stress in DE exposure, toll collectors who are considered a high risk group in regard to occupational toxins were compared to controls who had office-based occupations in the same company in this cross sectional study. A total of 38 toll collectors constituted the study group. All subjects were male. The toll collectors and 29 controls were similar regarding age, smoking status and duration of work. All subjects underwent a clinical examination and an interviewer-administrated questionnaire regarding respiratory symptoms, past medical and occupational history, and pulmonary function tests were performed in all subjects. Serum malondialdehyde (MDA), nitrite+nitrate and vitamin E levels were measured. Toll collectors showed higher serum MDA (5.76 +/- 2.15 micromol/L vs. 3.07 +/- 0.76 micromol/L, p=0.0001) and nitrite+nitrate levels (96.50 +/- 45.54 micromol/L vs. 19.32 +/- 11.77 micromol/L, p=0.0001) than controls. Vitamin E levels were similar in toll collectors and controls (10.57 +/- 3.44 mg/L and 9.72 +/- 2.44 mg/L, respectively, p=0.267). There was no difference between groups in terms of the findings of clinical examinations and respiratory symptoms. In pulmonary function parameters, only peak expiratory flow (PEF) in toll collectors was significantly lower than that of controls (88.9% predicted and 104.2% predicted, respectively, p=0.012). In conclusion, we suggest that serum MDA and nitrite+nitrate levels may be used as biological markers of oxidative stress related to DE exposure, but prospective controlled clinical studies are necessary to clarify the possible association between concentrations of MDA and nitrite+nitrate and pulmonary diseases related to DE exposure.

Serum decoy receptor 3 is a useful predictor for the active status of chronic hepatitis B in hepatitis B e antigen-negative patients.

PubMed

Hou, Yanqiang; Xu, Ping; Lou, Xiaoli; Liang, Dongyu; Zhang, Mei; Zhang, Zhenhuan; Zhang, Lurong

2013-08-01

Hepatitis B virus (HBV) infection is a global public health problem, because patients with chronic hepatitis B (CHB) may progress to liver cirrhosis and eventually evolve into hepatocellular carcinoma. Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily, and has been implicated in anti-apoptotic and anti-inflammatory pathways. In this study, we explored the clinical value of serum DcR3 in predicting the active status of CHB in hepatitis B e antigen-negative patients (active HBeAg (-) CHB), which was determined with ELISA. The serum level of DcR3 in active HBeAg (-) CHB patients (1.92 ± 0.68 ng/ml) was higher than that in healthy controls (0.80 ± 0.25 ng/ml, p < 0.0001) and that in inactive status of HBeAg (-) CHB (inactive hepatitis B surface antigen carrier, HBsAg-IaC) patients (0.95 ± 0.26 ng/ml, p < 0.0001). DcR3 level was correlated with HBV DNA level (r = 0.819, p < 0.0001) and alanine transaminase level (ALT, r = 0.704, p < 0.0001) in active HBeAg (-) CHB patients. The area under the Receiver Operating Characteristics curve of DcR3 for detecting the active status of HBeAg (-) CHB patients was 0.914 (95% confidence interval, 0.851-0.977). The optimal cut-off value for DcR3 to predict active HBeAg (-) CHB was 1.22 ng/ml, which had a sensitivity of 87.5% and a specificity of 84.4%. These results suggest that serum DcR3 level may be useful for detecting HBeAg (-) CHB in the active stage, which requires medical treatment.

The Effects of Fetal Gender on Serum Human Chorionic Gonadotropin and Testosterone in Normotensive and Preeclamptic Pregnancies

PubMed Central

Lorzadeh, Nahid; Kazemirad, Sirous

2012-01-01

Introduction. The aim of the present study was to evaluate the effects of fetal sex on serum human chorionic gonadotropin (hCG) and testosterone in normotensive and preeclamptic pregnancies. Materials and Methods. This is a cross-sectional study and 139 women with singleton pregnancies in the third trimester were studied. Seventy-one pregnancies were uncomplicated; among those were 35 male and 36 female fetuses. Sixty-eight pregnancies were complicated by preeclampsia; among those were 35 male and 33 female fetuses. Human chorionic gonadotropin and total testosterone were measured in maternal peripheral blood. Data analyzed by SPSS software. Results. In male-bearing pregnancies, maternal hCG and testosterone serum levels were significantly higher in preeclamptic than normotensive mothers (P < 0.001 and P < 0.001, resp.) in female-bearing pregnancies testosterone levels were significantly higher in preeclamptic than normotensive mothers (P < 0.001). Total testosterone levels were significantly higher in pregnancies with either gender and significantly higher in mlae-bearing than in female-bearing pregnancies. Conclusion. According to our results, there is a correlation between maternal serum hCG and testosterone levels and preeclampsia. Therefore these tests can be used as routine during 30–38 weeks of gestation. High maternal serum concentrations of these markers can predict preeclampsia. PMID:22518314

Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy.

PubMed

de Groot, Stefanie; Gelderblom, Hans; Fiocco, Marta; Bovée, Judith Vmg; van der Hoeven, Jacobus Jm; Pijl, Hanno; Kroep, Judith R

2017-01-01

Activation of the insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3) can predict event-free survival (EFS) and overall survival (OS) in Ewing sarcoma patients treated with chemotherapy. Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE) chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t -tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O'Quigley procedure. Survival analyses were performed using Cox regression analysis. High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009-0.602 and HR 0.090, 95% CI 0.011-0.712, respectively) in univariate and multivariate analyses (HR 0.063, 95% CI 0.007-0.590 and HR 0.057, 95% CI 0.005-0.585, respectively). OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy ( P =0.055 and P =0.023, respectively). High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated with improved EFS and a trend for improved OS in Ewing sarcoma patients treated with VIDE chemotherapy. These findings suggest the need for further investigation of the IGF-1 pathway as a biomarker of disease progression in patients with Ewing sarcoma.

Inflammatory response in mixed viral-bacterial community-acquired pneumonia.

PubMed

Bello, Salvador; Mincholé, Elisa; Fandos, Sergio; Lasierra, Ana B; Ruiz, María A; Simon, Ana L; Panadero, Carolina; Lapresta, Carlos; Menendez, Rosario; Torres, Antoni

2014-07-29

The role of mixed pneumonia (virus+bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP.

Changes in serum magnesium and phosphate in older hospitalised patients--correlation with muscle strength and risk factors for refeeding syndrome.

PubMed

Henderson, S; Boyce, F; Sumukadas, D; Witham, M D

2010-12-01

To evaluate changes in serum magnesium and phosphate over time in hospitalised older patients, examine whether such changes were associated with changes in muscle strength, and assess whether risk factors for refeeding syndrome were associated with falls in serum magnesium and phosphate. Community dwelling patients aged 70 and over, admitted to a specialist Medicine for the Elderly assessment unit were included in a prospective study. Weight, height, triceps skinfold thickness and mid arm circumference were recorded at baseline. Serum magnesium and phosphate was measured on admission, and at days 1, 2, 3, 5, 7, 10, 14, 21, 28 after admission, along with handgrip and quadriceps strength measured in the non-dominant limbs using a portable dynamometer. 43 patients were recruited with a mean age of 83.8 years (SD 7.5). 58% were female. Mean baseline serum magnesium and phosphate levels were 0.89 mmol/L and 1.07 mmol/L respectively. 10/43 patients had a fall in serum magnesium of at least 0.2 mmol/l from baseline and 20/43 had a similar fall in phosphate. No correlation was shown between these changes in electrolytes and muscle strength. Regression analyses did not show that risk factors for refeeding syndrome were associated with falls in electrolyte levels. Changes in serum magnesium and phosphate levels do not correlate with changes in muscle strength in older hospitalised patients. Risk factors for refeeding syndrome did not predict falls in serum phosphate or magnesium.

MiR-300 Serves as Potential Biomarker to Screen Knee Osteoarthritis Patients by Targeting TNFα.

PubMed

Zhou, Zihao; Tian, Fengde; An, Ning; Zhang, Yao; Wang, Changcheng; Guo, Lin

2018-04-01

This study mainly explored the serum level of miR-300 with the risk of knee OA, thereby evaluating their diagnostic ability for treatment of knee osteoarthritis (KOA) patients. In the current study, we evaluated the level of TNFα in KOA patients and HCs. The serum was used to quantify the level of TNF-α by way of a sandwich enzyme-linked immunosorbent assay. Dual luciferase reporter assay was carried out to identify the possible target gene of miR-300. In line with previous studies, our data showed that serum TNFα level was increased along with K/L grades and WOMAC scoring, suggesting TNFα induced inflammatory responses correlating with the severity of KOA. We also showed that serum miR-300 level was increased with the severity of KOA according to X ray examination and K/L grades. Furthermore, we showed that serum miR-300 level positively correlated with K/L grades, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scoring and WOMAC function scoring. Bioinformatic predictions showed a conserved binding site of miR-300 in the 3'UTR of IκBα. We then carried out a dual luciferase reporter assay and found miR-300 significantly suppressed pmirGLO-IκBα-3'UTR luciferase activity. Serum miR-300 is increased with the severity of KOA according to X-ray examination and K/L grades, thereby reflecting the severity of KOA and the degree of cartilage damage. Therefore, it could be used as a potential biomarker to screen KOA patients from healthy controls.

Association between gamma-glutamyltransferase and coronary artery calcification.

PubMed

Atar, Asli I; Yilmaz, Omer C; Akin, Kayihan; Selcoki, Yusuf; Er, Okan; Eryonucu, Beyhan

2013-08-20

The exact mechanisms behind the association between atherosclerosis and gamma-glutamyltransferase (GGT) are unclear. Coronary artery calcification (CAC) detected by computerized tomography is an important marker of atherosclerosis and its severity correlates with coronary plaque burden. The aim of this study was to investigate if serum GGT levels are associated with CAC in patients without known coronary heart disease (CHD) who had low-intermediate risk for CHD. Two hundred and seventy two patients who had low-intermediate risk for coronary artery disease were included in the study. Serum GGT levels were measured spectrophotometrically. CACS (Agatston method) were performed using a 64-slice computerized tomography scanner. The patients were grouped according to their GGT values in four quartiles. Patients in higher GGT quartiles had elevated CAC score (P<0.001). Patients in higher GGT quartiles were predominantly males (P<0.001) and were more likely to be smoking (P=0.004), and have elevated uric acid (P<0.001), fasting blood glucose (P<0.001), CRP levels (P=0.003) and 10-year total cardiovascular risk (P=0.007) and low HDL levels (P<0.001). Positive correlations were found between log GGT and CAC (r=0.233, P<0.001). In the multivariate analysis GGT, age, smoking and serum uric acid levels appeared as independent factors predictive of presence of CAC. We demonstrated a significant correlation between serum GGT levels and CAC and CHD risk factors. Serum GGT level was an independent marker of CAC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Ability of sextant biopsies to predict radical prostatectomy stage.

PubMed

Wills, M L; Sauvageot, J; Partin, A W; Gurganus, R; Epstein, J I

1998-05-01

There are few studies evaluating multiple variables on sextant biopsies with the intent to predict stage in radical prostatectomy specimens. We studied 113 sextant biopsies with corresponding totally submitted radical prostatectomy specimens. Variables evaluated on sextant biopsies included total length and percent of cancer; maximum length and percent of cancer on one core; location (apex, mid, base); bilaterality; Gleason grade; number of cores involved; serum prostate-specific antigen (PSA) level; and serum PSA density (PSAD). Radical prostatectomy stage was classified as organ versus non-organ confined. The following variables individually correlated with radical prostatectomy stage: total cancer measured in millimeters (P <0.0001) or percent (P <0.0005); biopsy Gleason score (P <0.0001); number of involved cores (P <0.0001); maximum cancer on one core measured in millimeters (P = 0.0001); maximum percent of cancer on one core (P = 0.01); bilaterality (P = 0.01); PSA level (P = 0.03), and PSAD (P = 0.001). The most predictive sets of two variables that correlated with stage included high Gleason score (P <0.0001) combined with numbers of cores involved (P = 0.002). When biopsies had Gleason scores of 6 or less, two or fewer positive cores, and serum PSA of 0 to 4 ng/mL, 89% were organ confined. When biopsies had Gleason scores of 6 or less with two unilaterally positive cores, 87% were organ confined. In biopsies with Gleason scores of 7 or more and more than one positive core, only 10% were organ confined. The most important predictors of stage by sextant needle biopsy evaluation are numbers of cores involved with carcinoma and high Gleason score. Bilaterality and serum PSA values improved prediction in two small subgroups. In 37% of our population we were able to predict with a greater than 87% probability the organ-confined versus non-organ-confined status.

Prediction of Gut Wall Integrity Loss in Viral Gastroenteritis by Non-Invasive Marker

PubMed Central

Elnady, Hala G.; Sherif, Lobna S.; Saleh, Maysa T.; El-Alameey, Inas R.; Youssef, Mai M.; El Shafie, Amal I.; Helwa, Iman; Raouf, Haiam Abdel; EL-Taweel, Ahmed N.

2015-01-01

BACKGROUND: Intestinal fatty acid binding proteins (I-FABPs) are mainly expressed in the intestinal villi, which are the initial site of destruction in viral gastroenteritis. AIM: This study was designed to assess serum I-FABPs as a predictor of gut wall integrity loss in viral gastroenteritis. PATIENTS AND METHODS: This case-control cross-sectional study was conducted on 93 cases of acute viral gastroenteritis. Twenty-eight healthy children matching in age were recruited as control group. Serum I-FABPs were measured using ELISA technique. Viral detection and typing were done by PCR for adenovirus, and by Reverse transcriptase PCR for rotavirus, astrovirus and norovirus. RESULTS: Serum I-FABPs level was significantly higher in the cases compared to the controls and was also higher in the 46 rotavirus gastroenteritis cases compared to other viral gastroenteritis cases. Serum I- FABPs level was significantly higher in severely dehydrated cases as compared to mildly dehydrated ones (P=0.037). CONCLUSION: Serum I-FABPs could be used as an early and sensitive predictor marker of gut wall integrity loss in children with viral gastroenteritis and its level can indicate case severity. PMID:27275194

Investigative clinical study on prostate cancer part IV: exploring functional relationships of total testosterone predicting free testosterone and total prostate-specific antigen in operated prostate cancer patients.

PubMed

Porcaro, Antonio B; Petrozziello, Aldo; Migliorini, Filippo; Lacola, Vincenzo; Romano, Mario; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Zecchini Antoniolli, Stefano; Rubilotta, Emanuele; Monaco, Carmelo; Comunale, Luigi

2011-01-01

To explore, in operated prostate cancer patients, functional relationships of total testosterone (tt) predicting free testosterone (ft) and total PSA. 128 operated prostate cancer patients were simultaneously investigated for tt, ft and PSA before surgery. Patients were not receiving 5α-reductase inhibitors, LH-releasing hormone analogues and testosterone replacement treatment. Scatter plots including ft and PSA versus tt were computed in order to assess the functional relationship of the variables. Linear regression analysis of tt predicting ft and PSA was computed. tt was a significant predictor of the response variable (ft) and different subsets of the patient population were assessed according to the ft to tt ratio. PSA was related to tt according to a nonlinear law. tt was a significant predictor of PSA according to an inversely nonlinear law and different significant clusters of the patient population were assessed according to the different constant of proportionality computed from experimental data. In our prostate cancer population, ft was significantly predicted by tt according to a linear law, and the ft/tt ratio was a significant parameter for assessing the different clusters. Also, tt was a significant variable predicting PSA by a nonlinear law and different clusters of the patient population were assessed by the different constants of proportionality. As a theory, we explain the nonlinear relation of tt in predicting PSA as follows: (a) the number of androgen-independent prostate cancer cells increases as tumor volume and PSA serum levels rise, (b) the prevalence of androgen-independent cells producing a substance which inhibits serum LH, and (c) as a result lower levels of serum tt are detected. Copyright © 2011 S. Karger AG, Basel.

Innate immunity in renal transplantation: the role of mannose-binding lectin.

PubMed

Ibernon, Meritxell; Moreso, Francesc; Serón, Daniel

2014-01-01

Innate immune system plays an important role in the modulation of the inflammatory response during infection and tissue injury/repair. Mannose-binding lectin (MBL) is a component of the innate immune system that activates complement via the lectin pathway. Different polymorphisms of the MBL gene are associated with MBL levels and MBL function. The relationship between MBL and disease is rather complex because MBL behaves as a double-edged sword. In the general population, low serum MBL levels are associated with higher risk of infection, type 2 diabetes, autoimmune and cardiovascular disease. However, in patients with diabetes or autoimmune disease, high MBL levels are associated with more severe renal and cardiovascular comorbidities. In renal transplantation, low MBL serum levels constitute a risk factor for infection, low grade inflammation, new onset diabetes after transplantation and subclinical rejection. Despite these associations suggest that low MBL levels should be associated with poorer renal allograft outcome, epidemiological studies evaluating the predictive value of MBL levels on graft survival are controversial. Taken together, these observations suggest that low MBL serum levels modulate chronic inflammatory response that may influence transplant outcome. © 2013.

Serum Hepatocyte Growth Factor Is Probably Associated With 3-Month Prognosis of Acute Ischemic Stroke.

PubMed

Zhu, Zhengbao; Xu, Tan; Guo, Daoxia; Huangfu, Xinfeng; Zhong, Chongke; Yang, Jingyuan; Wang, Aili; Chen, Chung-Shiuan; Peng, Yanbo; Xu, Tian; Wang, Jinchao; Sun, Yingxian; Peng, Hao; Li, Qunwei; Ju, Zhong; Geng, Deqin; Chen, Jing; Zhang, Yonghong; He, Jiang

2018-02-01

Serum hepatocyte growth factor (HGF) is positively associated with poor prognosis of heart failure and myocardial infarction, and it can also predict the risk of ischemic stroke in population. The goal of this study was to investigate the association between serum HGF and prognosis of ischemic stroke. A total of 3027 acute ischemic stroke patients were included in this post hoc analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months. After multivariate adjustment, elevated HGF levels were associated with an increased risk of primary outcome (odds ratio, 1.50; 95% confidence interval, 1.10-2.03; P trend =0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed HGF was associated with 14% (95% confidence interval, 2%-27%) increased risk of primary outcome. Adding HGF quartiles to a model containing conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 17.50%, P <0.001; integrated discrimination index: 0.23%, P =0.022). The association between serum HGF and primary outcome could be modified by heparin pre-treatment ( P interaction =0.001), and a positive linear dose-response relationship between HGF and primary outcome was observed in patients without heparin pre-treatment ( P linearity <0.001) but not in those with heparin pre-treatment. Serum HGF levels were higher in the more severe stroke at baseline, and elevated HGF levels were probably associated with 3-month poor prognosis independently of stroke severity among ischemic stroke patients, especially in those without heparin pre-treatment. Further studies from other samples of ischemic stroke patients are needed to validate our findings. © 2018 American Heart Association, Inc.

Circulating anti-mullerian hormone as predictor of ovarian response to clomiphene citrate in women with polycystic ovary syndrome.

PubMed

Xi, Wenyan; Yang, Yongkang; Mao, Hui; Zhao, Xiuhua; Liu, Ming; Fu, Shengyu

2016-02-11

To investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. This prospective cohort observational study included 81 anovulatory women with PCOS who underwent 213 cycles of CC ovarian stimulation. Serum AMH concentrations were measured on cycle day 3 before the commencement of CC in the first cycle, which were compared between responders and CC-resistant anovulation (CRA). Logistic regression analysis was applied to study the value of serum AMH for the prediction of ovarian responsiveness to CC stimulation. The receiver-operating characteristic (ROC) curve was used to evaluate the prognostic value of circulating AMH. Serum AMH levels. Women who ovulated after CC therapy had a significantly lower AMH compared with the CRA (5.34 ± 1.97 vs.7.81 ± 3.49, P < 0.001). There was a significant gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation (P < 0.05). In multivariate logistic regression analysis, AMH was an independent predictor of ovulation induction by CC in PCOS patients. ROC curve analysis showed AMH to be a useful predictor of ovulation induction by CC in PCOS patients, having 92 % specificity and 65 % sensitivity when the threshold AMH concentration was 7.77 ng/ml. Serum AMH may be clinically useful to predict which PCOS women are more likely to respond to CC treatment and thus to direct the selection of protocols of ovulation induction.

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer

PubMed Central

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-01

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen–glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively. PMID:28134773

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer.

PubMed

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-26

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c -index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.

Changes in lactate dehydrogenase are associated with central gray matter lesions in newborns with hypoxic-ischemic encephalopathy.

PubMed

Yum, Sook Kyung; Moon, Cheong-Jun; Youn, Young-Ah; Sung, In Kyung

2017-05-01

Biomarkers may predict neurological prognosis in infants with hypoxic-ischemic encephalopathy (HIE). We evaluated the relationship between serum lactate dehydrogenase (LDH) and brain magnetic resonance imaging (MRI), which predicts neurodevelopmental outcomes, in order to assess whether LDH levels are similarly predictive. Medical records were reviewed for infants with HIE and LDH levels were assessed on the first (LDH 1 ) and third (LDH 3 ) days following birth. Receiver operating characteristic curves were obtained in relation to central gray matter hypoxic-ischemic lesions. Of 92 patients, 52 (56.5%) had hypoxic-ischemic lesions on brain MRI, and 21 of these infants (40.4%) had central gray matter lesions. LDH 1 and LDH 3 did not differ; however, the percentage change (ΔLDH%) was significantly higher in infants with central gray matter lesions (36.9% versus 6.6%, p = 0.006). With cutoffs of 187 (IU/L, ΔLDH) and 19.4 (%, ΔLDH%), the sensitivity, specificity, positive predictive value and negative predictive value were 71.4, 69.0, 40.5 and 89.1%, respectively. The relative risk was 5.57 (p = 0.001). Changes in serum LDH may be a useful biomarker for predicting future neurodevelopmental prognosis in infants with HIE.

Use of Metabolomics as a Complementary Omic Approach to Implement Risk Criteria for First-Degree Relatives of Gastric Cancer Patients

PubMed Central

Miolo, Gianmaria; Caggiari, Laura; De Zorzi, Mariangela; Steffan, Agostino

2018-01-01

A positive family history is a strong and consistently reported risk factor for gastric cancer (GC). So far, it has been demonstrated that serum pepsinogens (PGs), and gastrin 17 (G17) are useful for screening individuals at elevated risk to develop atrophic gastritis but they are suboptimal biomarkers to screen individuals for GC. The main purpose of this study was to investigate serum metabolomic profiles to find additional biomarkers that could be integrated with serum PGs and G17 to improve the diagnosis of GC and the selection of first-degree relatives (FDR) at higher risk of GC development. Serum metabolomic profiles included 188 serum metabolites, covering amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexoses. Serum metabolomic profiles were performed with tandem mass spectrometry using the Biocrates AbsoluteIDQ p180 kit. The initial cohort (training set) consisted of n = 49 GC patients and n = 37 FDR. Differential metabolomic signatures among the two groups were investigated by univariate and multivariate partial least square differential analysis. The most significant metabolites were further selected and validated in an independent group of n = 22 GC patients and n = 17 FDR (validation set). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic power and the optimal cut-off for each of the discriminant markers. Multivariate analysis was applied to associate the selected serum metabolites, PGs, G17 and risk factors such as age, gender and Helicobacter pylori (H. pylori) infection with the GC and FDR has been performed and an integrative risk prediction algorithm was developed. In the training set, 40 metabolites mainly belonging to phospholipids and acylcarnitines classes were differentially expressed between GC and FDR. Out of these 40 metabolites, 9 were further confirmed in the validation set. Compared with FDR, GC patients were characterized by lower levels of hydroxylated sphingomyelins (SM(OH)22:1, SM(OH)22:2, SM(OH)24:1) and phosphatidylcholines (PC ae 40:1, PC ae 42:2, PC ae 42:3) and by higher levels of acylcarnitines derivatives (C2, C16, C18:1). The specificity and sensitivity of the integrative risk prediction analysis of metabolites for GC was 73.47% and 83.78% respectively with an area under the curve of the ROC curve of 0.811 that improves to 0.90 when metabolites were integrated with the serum PGs. The predictive risk algorithm composed of the C16, SM(OH)22:1 and PG-II serum levels according to the age of individuals, could be used to stratify FDR at high risk of GC development, and then this can be addressed with diagnostic gastroscopy. PMID:29518896

Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor.

PubMed

Alanbay, Ibrahim; Akturk, Erhan; Coksuer, Hakan; Ercan, Mutlu; Karaşahin, Emre; Dede, Murat; Yenen, Mufit Cemal; Ozan, Hakan; Baser, Iskender

2012-06-01

The aim of this study was to assess the prognostic values of risk of malignancy index (RMI IV), ultrasound score, menopausal status, and serum CA125 and CA19-9 level in patients with borderline ovarian tumor (BOT). Fifty women having borderline ovarian tumor (BOT) and 5O individuals with benign adnexal mass were enrolled in this retrospective study. The sensitivity, specificity, positive predictive values, negative predictive values and diagnostic accuracy of preoperative serum levels of the CA125 and CA19-9, ultrasound findings and menopausal status, and RMI IV were calculated for prediction of discrimination between BOTs and benign adnexal masses and the results were compared. The RMI IV was the best method for discrimination between BOTs and benign adnexal masses and was more accurate than the other parameters. When Receiver Operator Characteristic area under the curves for menopausal status was analyzed, serum CA 125 and CA19-9 level, ultrasound score, RMI IV(CA125), and RMI IV(CA19-9) were, 0.580, 0.625, 0.548, 0.694, 0.734 and 0.711, respectively. The best RMI IV cut-off was found to be 200 for discrimination of benign and BOT lesions. In the RMI formulation, replacing CA125 with CA19-9 didn't affect RMI IV sensitivity and specificity for discrimination. Compared to ultrasound, menopausal status, CA-125, CA19-9, the RMI IV was found to be the best predictive method for differentiation of BOTs from benign adnexal masses. RMI IV cut-off value of 200 is suitable for differentiation of benign and BOT's.

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

PubMed

Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

2018-02-14

The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

CA 15-3 predicting breast cancer relapse: beware of vitamin B12 deficiency.

PubMed

Rassy, Elie El; Ghor, Maya Al; Kattan, Joseph

2018-05-10

A sustained increase of cancer antigen 15-3 serum levels was found in a 54-year-old woman treated 2 years ago for early stage breast cancer, without any evidence of cancer recurrence. The patient thereafter developed severe megaloblastic anemia secondary to vitamin B12 deficiency. Supplementation with B12 to reverse the anemia led to the normalization of the cancer antigen 15-3 serum levels. As such, with the limited understanding of molecular biology, the integrative approach of clinical history, physical examination, and diagnostic imaging remain pivotal in the management of cancer patients.

Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study.

PubMed

El-Ghamrawy, Mona Kamal; Hanna, Wagdi Maurice; Abdel-Salam, Amina; El-Sonbaty, Marwa M; Youness, Eman R; Adel, Ahmed

2014-01-01

the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia. the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls. mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r=-0.3, p=0.04). PON level was found to be positively correlated with patients' weight and BMI (r=-0.4, p=0.01; r=-0.7, p<0.001, respectively), but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p=0.006). Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes. children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

CCL11 (eotaxin-1): a new diagnostic serum marker for prostate cancer.

PubMed

Agarwal, Manisha; He, Chang; Siddiqui, Javed; Wei, John T; Macoska, Jill A

2013-05-01

The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer. Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of <10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA. Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (P < 0.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (P < 0.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status. Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values. Copyright © 2012 Wiley Periodicals, Inc.

CCL11 (Eotaxin-1): A New Diagnostic Serum Marker for Prostate Cancer

PubMed Central

Agarwal, Manisha; He, Chang; Siddiqui, Javed; Wei, John; Macoska, Jill A.

2012-01-01

Background The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer. Methods Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of < 10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA. Results Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (p<.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (p<.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status. Conclusions Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values. PMID:23059958

Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.

PubMed

Yashi, Masahiro; Nukui, Akinori; Kurokawa, Shinsuke; Ochi, Masanori; Ishikawa, Shinya; Goto, Kentaro; Kobayashi, Yutaka; Muraishi, Osamu; Tokue, Akihiko

2003-09-01

The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression. Copyright 2003 Wiley-Liss, Inc.

Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma.

PubMed

Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshifumi

2017-05-16

Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma

PubMed Central

Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshifumi

2017-01-01

Background Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Methods Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Results Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Conclusions Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients. PMID:28380419

Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients.

PubMed

He, Lian; He, Wan-Yu; A, La-Ta; Yang, Wen-Ling; Zhang, Ai-Hua

2018-01-01

Vascular calcification, which involves an active cellular transformation of vascular smooth muscle cells into bone forming cells, is prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that irisin, a newly identified myokine also may play roles in vascular calcification in hemodialysis patients. This study aims to evaluate serum irisin levels and establish their relation to vascular calcification and other parameters in hemodialysis patients. A total of 150 patients on maintenance hemodialysis treatment and 38 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentrations were measured by ELISA. Vascular calcification was evaluated by abdominal aortic calcification scores. Serum irisin concentrations were significantly lower in hemodialysis patients than in controls [52.8 (22.0, 100.0) vs. 460.8 (434.8, 483.4) ng/ml, P<0.01]. In addition, irisin was negatively correlated with the parathyroid hormone level (P=0.01). The HD patients with vascular calcification showed significantly lower serum irisin concentrations [39.0 (21.7, 86.2) vs.79.0 (39.5, 130.2) ng/mL, P<0.01]. Compared with the group without vascular calcification multivariate logistic regression analyses revealed that serum irisin, HD vintage and age were significant independent determinant factors for vascular calcification in HD patients. Our results are the first to provide a clinical evidence of the association between serum irisin and vascular calcification in HD patients. Lower irisin levels, long-term hemodialysis and old ages are independent risk factors in HD patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

A new model consists of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of prostate cancer.

PubMed

Xu, Ding; Yu, Yongjiang; Zhu, Yunkai; Huang, Tao; Chen, Yaqing; Qi, Jun

2014-04-01

The Prostate-specific antigen (PSA) level is largely used to diagnose prostate cancer (PCa) in last decades. However, its specificity is low in patients with a PSA level ranging from 4.0 to 10.0 ng/ml. This study aims to define the correlation between intravesical prostatic protrusion (IPP) and PSA and to establish a new model to predict PCa. A total of 339 patients order than 45 years examined between October 2010 and June 2012 were enrolled. Eligible patients were recommended for transrectal ultrasonography (TRUS)-guided prostate biopsies after measuring total prostate volume (TPV), tranzisional zone volume (TZV) and IPP. The levels of total PSA (tPSA), free PSA (fPSA) were analyzed by using Hybritech calibrated Access tPSA and fPSA assays. A new mathematical model, named IPP removed PCa predicting score (IRPPS), consists of tPSA, TZV and IPP was established. The predictive accuracy of IRPPS, PSA density (PSAD), %PSA and tPSA were compared using receiver-operator characteristic (ROC) analysis. Eighty-six patients had PSA levels of 4.0-10.0 ng/ml. Twenty of them were diagnosed as PCa. Using ROC curves, the areas under the curve for IRPPS, PSAD and %PSA and tPSA were 0.786, 0.768 and 0.664 and 0.585, respectively. We suggested IPP grade had a significant relationship with serum tPSA levels. The predictive accuracy of IRPPS was higher than the other 3 indictors.

Alarmins and Clinical Outcomes After Major Abdominal Surgery-A Prospective Study.

PubMed

Máca, Jan; Burša, Filip; Ševčík, Pavel; Sklienka, Peter; Burda, Michal; Holub, Michal

2017-06-01

Tissue injury causing immune response is an integral part of surgical procedure. Evaluation of the degree of surgical trauma could help to improve postoperative management and determine the clinical outcomes. We analyzed serum levels of alarmins, including S100A5, S100A6, S100A8, S100A9, S100A11, and S100A12; high-mobility group box 1; and heat-shock protein 70, after elective major abdominal surgery (n = 82). Blood samples were collected for three consecutive days after surgery. The goals were to evaluate the relationships among the serum levels of alarmins and selected surgical characteristics and to test potential of alarmins to predict the clinical outcomes. Significant, positive correlations were found for high-mobility group box 1 with the length of surgery, blood loss, and intraoperative fluid intake for all three days of blood sampling. The protein S100A8 serum levels showed positive correlations with intensive care unit length of stay, 28-day and in-hospital mortality. The protein S100A12 serum levels had significant, positive correlations with intensive care unit length of stay, 28-day mortality, and in-hospital mortality. We did not find significant differences in alarmin levels between cancer and noncancer subjects. The high-mobility group box 1 serum levels reflect the degree of surgical injury, whereas proteins S100A8 and S100A12 might be considered good predictors of major abdominal surgery morbidity and mortality.

Serum adipocyte-fatty acid binding protein (FABP4) levels in women from Mexico exposed to polycyclic aromatic hydrocarbons (PAHs).

PubMed

Ochoa-Martínez, Ángeles C; Ruíz-Vera, Tania; Pruneda-Álvarez, Lucia G; González-Palomo, Ana K; Almendarez-Reyna, Claudia I; Pérez-Vázquez, Francisco J; Pérez-Maldonado, Iván N

2017-01-01

Recent studies indicate that exposure to polycyclic aromatic hydrocarbons (PAHs) is a very important risk factor for the development of cardiovascular diseases (CVDs). Correspondingly, adipocyte-fatty acid binding protein (FABP4, also known as aP2 and AFABP) has been proposed as a new, meaningful and useful biomarker to predict metabolic and cardiovascular diseases. Therefore, the aim of this study was to evaluate serum FABP4 levels in Mexican women exposed to PAHs. Urinary 1-hydroxypyrene ((1-OHP), exposure biomarker for PAHs) levels were quantified using a high-performance liquid chromatography (HPLC) technique, and serum FABP4 concentrations were analyzed using a commercially available ELISA kit. The mean urinary 1-OHP level found in women participating in this study was 1.30 ± 1.10 μmol/mol creatinine (2.45 ± 2.10 μg/g creatinine). Regarding serum FABP4 concentrations, the levels ranged from 3.80 to 62.5 ng/mL in the assessed population. Moreover, a significant association (p < 0.001) was found between urinary 1-OHP levels and serum FABP4 concentrations in women after adjusting for potential confounding variables. The presented data in this study can be considered only as a starting point for further studies. Then, in order to elucidate whether FABP4 represents a risk factor for CVD disease in humans exposed to air contaminants (such as PAHs), large epidemiological studies are necessary.

Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis

PubMed Central

Dumlu, Ersin Gürkan; Tokaç, Mehmet; Bozkurt, Birkan; Yildirim, Murat Baki; Ergin, Merve; Yalçin, Abdussamed; Kiliç, Mehmet

2014-01-01

OBJECTIVES: To determine the serum and tissue levels of markers of impaired oxidative metabolism and correlate these levels with the histopathology and Alvarado score of acute appendicitis patients. METHOD: Sixty-five acute appendicitis patients (mean age, 31.4±12.06 years; male/female, 30/35) and 30 healthy control subjects were studied. The Alvarado score was recorded. Serum samples were obtained before surgery and 12 hours postoperatively to examine the total antioxidant status, total oxidant status, paraoxonase, stimulated paraoxonase, arylesterase, catalase, myeloperoxidase, ceruloplasmin, oxidative stress markers (advanced oxidized protein products and total thiol level) and ischemia-modified albumin. Surgical specimens were also evaluated. RESULTS: The diagnoses were acute appendicitis (n = 37), perforated appendicitis (n = 8), phlegmonous appendicitis (n = 12), perforated+phlegmonous appendicitis (n = 4), or no appendicitis (n = 4). The Alvarado score of the acute appendicitis group was significantly lower than that of the perforated+phlegmonous appendicitis group (p = 0.004). The serum total antioxidant status, total thiol level, advanced oxidized protein products, total oxidant status, catalase, arylesterase, and ischemia-modified albumin levels were significantly different between the acute appendicitis and control groups. There was no correlation between the pathological extent of acute appendicitis and the tissue levels of the markers; additionally, there was no correlation between the tissue and serum levels of any of the parameters. CONCLUSIONS: The imbalance of oxidant/antioxidant systems plays a role in the pathogenesis acute appendicitis. The Alvarado score can successfully predict the presence and extent of acute appendicitis. PMID:25518019

Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction

PubMed Central

Wang, Hao; Zhang, Xiao-Meng; Tomiyoshi, Go; Nakamura, Rika; Shinmen, Natsuko; Kuroda, Hideyuki; Kimura, Risa; Mine, Seiichiro; Kamitsukasa, Ikuo; Wada, Takeshi; Aotsuka, Akiyo; Yoshida, Yoichi; Kobayashi, Eiichi; Matsutani, Tomoo; Iwadate, Yasuo; Sugimoto, Kazuo; Mori, Masahiro; Uzawa, Akiyuki; Muto, Mayumi; Kuwabara, Satoshi; Takemoto, Minoru; Kobayashi, Kazuki; Kawamura, Harukiyo; Ishibashi, Ryoichi; Yokote, Koutaro; Ohno, Mikiko; Chen, Po-Min; Nishi, Eiichiro; Ono, Koh; Kimura, Takeshi; Machida, Toshio; Takizawa, Hirotaka; Kashiwado, Koichi; Shimada, Hideaki; Ito, Masaaki; Goto, Ken-Ichiro; Iwase, Katsuro; Ashino, Hiromi; Taira, Akiko; Arita, Emiko; Takiguchi, Masaki; Hiwasa, Takaki

2018-01-01

Transient ischemic attack (TIA) is a predictor for cerebral infarction (CI), and early diagnosis of TIA is extremely important for the prevention of CI. We set out to identify novel antibody biomarkers for TIA and CI, and detected matrix metalloproteinase 1 (MMP1), chromobox homolog 1 (CBX1), and chromobox homolog 5 (CBX5) as candidate antigens using serological identification of antigens by recombinant cDNA expression cloning (SEREX) and Western blotting to confirm the presence of serum antibodies against the antigens. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) revealed that serum antibody levels were significantly higher in patients with TIA or acute-phase CI (aCI) compared with healthy donors (P < 0.01). Spearman’s correlation analysis and multivariate logistic regression analysis demonstrated that levels of anti-MMP1, anti-CBX1, and anti-CBX5 antibodies were associated with age, cigarette-smoking habits, and blood pressure. Thus, serum levels of antibodies against MMP1, CBX1, and CBX5 could potentially serve as useful tools for diagnosing TIA and predicting the onset of aCI. PMID:29464021

Drug safety evaluation through biomarker analysis-A toxicity study in the cynomolgus monkey using an antibody-cytotoxic conjugate against ovarian cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, Frank Y.; Tengstrand, Elizabeth; Lee, J.-W.

2007-10-01

Antibody-cytotoxin conjugates are complex novel therapeutic agents whose toxicological properties are not presently well understood. The objective of this study was to identify serum biomarkers that correlate with MLN8866 (an Antibody-Cytotoxic Conjugate, mAb8866-CT) pathological events in monkeys and to predict the maximal tolerated dose (MTD) level using biomarkers. Cynomolgus monkeys were administered a single dose MLN8666 (5, 15 or 30 mg/kg) by intravenous infusion and evaluated over a 7-day period. Exposure levels were determined by quantifying MLN8866 levels (C{sub max} and AUC{sub 0-96h}) in serum. The increase in MLN8866 C{sub max} and AUC{sub 0-96h} was approximately dose proportional. Two biomarkersmore » in serum (m/z 316 and m/z 368) were identified to be correlated with MLN8866 toxicological outcomes. The predicted MTD, 11.4 mg/kg, was within the MTD range set by pathology results (5-15 mg/kg). Administration of MLN8866 at 15 mg/kg and 30 mg/kg dose levels resulted in changes in hematology parameters associated with impaired hematopoiesis and bone marrow toxicity. The projected MLN8866 MTD exposure level was integrated with toxicokinetic analysis and showed C{sub max} = 236 {mu}g/mL and AUC{sub 0-96h} = 7246 h mg/mL. The safety of three different MLN8866 dosing regimens with three dosing schedules was explored with pharmacokinetic modeling.« less

Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection.

PubMed

Song, L-W; Liu, P-G; Liu, C-J; Zhang, T-Y; Cheng, X-D; Wu, H-L; Yang, H-C; Hao, X-K; Yuan, Q; Zhang, J; Kao, J-H; Chen, D-S; Chen, P-J; Xia, N-S

2015-02-01

We previously demonstrated that pretreatment quantitative anti-hepatitis B core protein (qAnti-HBc) levels can predict the treatment response for both interferon and nucleoside analogue therapy, but the characteristics of qAnti-HBc during chronic hepatitis B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and hepatitis B e antigen (HBeAg)-negative hepatitis phase. Individuals with hepatitis B surface antigen (n = 598, 3.74 ± 0.90 log10 IU/mL) had significantly higher (p < 0.001, approximately 1000-fold) serum qAnti-HBc levels than those who had occult HBV, and serum qAnti-HBc levels were significantly higher in the occult HBV group than in the past HBV infection group (p < 0.001). qAnti-HBc levels were positively correlated with alanine aminotransferase levels (R = 0.663, p < 0.001), and subjects with an abnormal alanine aminotransferase level had a higher qAnti-HBc level (p < 0.001). Serum qAnti-HBc level varied in different phases of HBV infection, as determined by host immune status. Serum qAnti-HBc level is strongly associated with hepatitis activity in subjects with chronic HBV infection. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The EPOS-CC Score: An Integration of Independent, Tumor- and Patient-Associated Risk Factors to Predict 5-years Overall Survival Following Colorectal Cancer Surgery.

PubMed

Haga, Yoshio; Ikejiri, Koji; Wada, Yasuo; Ikenaga, Masakazu; Koike, Shoichiro; Nakamura, Seiji; Koseki, Masato

2015-06-01

Surgical audit is an essential task for the estimation of postoperative outcome and comparison of quality of care. Previous studies on surgical audits focused on short-term outcomes, such as postoperative mortality. We propose a surgical audit evaluating long-term outcome following colorectal cancer surgery. The predictive model for this audit is designated as 'Estimation of Postoperative Overall Survival for Colorectal Cancer (EPOS-CC)'. Thirty-one tumor-related and physiological variables were prospectively collected in 889 patients undergoing elective resection for colorectal cancer between April 2005 and April 2007 in 16 Japanese hospitals. Postoperative overall survival was assessed over a 5-years period. The EPOS-CC score was established by selecting significant variables in a uni- and multivariate analysis and allocating a risk-adjusted multiplication factor to each variable using Cox regression analysis. For validation, the EPOS-CC score was compared to the predictive power of UICC stage. Inter-hospital variability of the observed-to-estimated 5-years survival was assessed to estimate quality of care. Among the 889 patients, 804 (90%) completed the 5-years follow-up. Univariate analysis displayed a significant correlation with 5-years survival for 14 physiological and nine tumor-related variables (p < 0.005). Highly significant p-values below 0.0001 were found for age, ASA score, severe pulmonary disease, respiratory history, performance status, hypoalbuminemia, alteration of hemoglobin, serum sodium level, and for all histological variables except tumor location. Age, TNM stage, lymphatic invasion, performance status, and serum sodium level were independent variables in the multivariate analysis and were entered the EPOS-CC model for the prediction of survival. Risk-adjusted multiplication factors between 1.5 (distant metastasis) and 0.16 (serum sodium level) were accorded to the different variables. The predictive power of EPOS-CC was superior to the one of UICC stage; area under the curve 0.87, 95% CI 0.85-0.90 for EPOS-CC, and 0.80, 0.76-0.83 for UICC stage, p < 0.001. Quality of care did not differ between hospitals. The EPOS-CC score including the independent variables age, performance status, serum sodium level, TNM stage, and lymphatic invasion is superior to the UICC stage in the prediction of 5-years overall survival. This higher accuracy might be explained by the inclusion of physiological factors, thus also taking non-tumor-associated deaths into account. Furthermore, EPOS-CC score may compare quality of care among different institutions. Future studies are necessary to further evaluate this score and help improving the prediction of long-term survival following colorectal cancer surgery.

High serum soluble CD30 does not predict acute rejection in liver transplant patients.

PubMed

Matinlauri, I; Höckerstedt, K; Isoniemi, H

2006-12-01

Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.

Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis.

PubMed

Casoinic, F; Sampelean, D; Buzoianu, Anca D; Hancu, N; Baston, Dorina

2016-12-01

Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls. In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here. Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA). Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.

Serum gamma-glutamyl transferase activity is an independent predictor for cardiovascular disease in obstructive sleep apnea syndrome.

PubMed

Kanbay, Asiye; Kaya, Elif; Buyukoglan, Hakan; Ozdogan, Nezihe; Kaya, Mehmet Gungor; Oymak, Fatma Sema; Gulmez, Inci; Demir, Ramazan; Kokturk, Oguz

2011-04-01

Gamma glutamyl transferase (GGT) is a new marker for predicting myocardial infarction, stroke, cardiac death and inflammation. There is also a strong relationship between Obstructive Sleep Apnea Syndrome (OSAS) and cardiovascular disease. This study was designed to investigate the association between serum GGT levels and cardiovascular disease in patients with OSAS, and relationship between severity of OSAS and serum GGT level. We evaluated the medical records of 166 subjects who were admitted for sleep study. OSAS was diagnosed by polysomnography if Apnea-Hypopnea Index (AHI) > 5. According to AHI, individuals in whom AHI< 5 were recruited as group 1 (OSAS negative group), AHI = 5-15: group 2 (mild OSAS group), AHI = 15-30: group 3 (moderate OSAS group), AHI >30: group 4 (severe OSAS group). Cardiovascular disease was defined if the patients had heart failure, coronary artery disease or arrhythmia. Of the subjects, 112 (67.5%) were male and the mean age was 54.3 ± 12.2 years. There were 22 patients (13.2%), 17 patients (10.2%), 34 patients (20.4%) and 93 patients (56.2%) in group 1, 2, 3 and 4, respectively. There is a significant increase in serum GGT levels while AHI score increases (group 1 = 28.0 ± 10.1, group 2 = 33.8 ± 13.2, group 3 = 35.2 ± 8.5, group 4 = 40.0 ± 22.0; p for trend = 0.024). However, serum C-reactive protein (CRP), alanine aminotransferase and aspartate aminotransferase levels were similar in all groups (p > 0.05). There was a significant independent association between serum GGT levels and the severity of OSAS. Moreover, serum GGT levels were significantly high in patients with cardiovascular disease compared with patients without cardiovascular disease in severe-moderate-mild OSAS (p < 0.05) and OSAS negative groups while CRP levels were not. This was a significant independent association. The present study suggests that high serum GGT level, regardless of the other traditional risk factors, is an independent predictor of cardiovascular disease in patients with OSAS. The results should be confirmed with other randomized prospective studies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study

PubMed Central

Jorde, Rolf; Schirmer, Henrik; Wilsgaard, Tom; Joakimsen, Ragnar Martin; Mathiesen, Ellisiv Bøgeberg; Njølstad, Inger; Løchen, Maja-Lisa; Figenschau, Yngve; Berg, Jens Petter; Svartberg, Johan; Grimnes, Guri

2012-01-01

Objective Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health. Methods DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994–1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007–2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level. Results A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1)) there was a significant association with breast cancer (P<0.05). Conclusion Our results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency. Trial Registration ClinicalTrials.gov NCT01395303 PMID:22649517

Serum Aminotransferase Levels are Associated with Markers of Hypoxia in Patients with Obstructive Sleep Apnea

PubMed Central

Norman, Daniel; Bardwell, Wayne A.; Arosemena, Farah; Nelesen, Richard; Mills, Paul J.; Loredo, Jose S.; Lavine, Joel E.; Dimsdale, Joel E.

2008-01-01

Study Objectives: Nonalcoholic fatty liver disease (NAFLD) is a disorder that often presents with elevated serum aminotransferase levels. Although it has classically been linked with the metabolic syndrome, recent studies suggest NAFLD may also be associated with obstructive sleep apnea (OSA). This study evaluates the association between serum aminotransferase levels and factors connected with: either the metabolic syndrome (elevated body mass index [BMI], lipid profile, blood pressure, fasting glucose), or with OSA severity (apnea hypopnea index, lowest oxygen saturation level, oxygen desaturation index, percent of time below 90% saturation [%T<90]). Design: Retrospective case series. Patients and Setting: 109 adult patients with OSA at a university hospital general clinical research center. Measurements and Results: Markers of hypoxia (lowest oxygen saturation level and %T<90), correlated significantly with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (Pearson's r = −0.31 to −0.38, P <0.003), while apnea hypopnea index, body mass index, blood pressure, fasting glucose, triglyceride, and cholesterol levels did not. Hierarchical linear regression was then done to determine the best predictors of aminotransferase levels. Markers of metabolic syndrome were entered as one block and markers of sleep apnea as another. Regression analyses explained 16.3% of the variance in AST and 18.9% of the variance in ALT, with %T<90 playing the largest role. Conclusions: In patients with obstructive sleep apnea, serum aminotransferase levels are better predicted by markers of oxygen desaturation than by factors traditionally associated with the metabolic syndrome. Citation: Norman D; Bardwell WA; Arosemena F; Nelesen R; Mills PJ; Loredo JS; Lavine JE; Dimsdale JE. Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea. SLEEP 2008;31(1):-121-126. PMID:18220085

Serum Neutrophil Gelatinase-Associated Lipocalin: A Diagnostic Marker in Pediatric Sepsis.

PubMed

Saleh, Nagwan Yossery; Abo El Fotoh, Wafaa Moustafa M; El-Hawy, Mahmoud A

2017-06-01

Sepsis is a life-threatening condition that arises when the response of the body to infection injures its own tissues and organs. The early prediction of sepsis by current clinical and laboratory methods remains inadequate. Serum neutrophil gelatinase-associated lipocalin level is increased in sepsis irrespective of renal dysfunction. Therefore, we aimed to correlate the serum neutrophil gelatinase-associated lipocalin value determined at admission with clinical progression and severity of disease in critically ill children and to declare its role as a potential diagnostic and prognostic marker for sepsis in critically ill children in the emergency department. A prospective cohort study. The study carried out at the PICU of Menoufia University Hospital. We serially enrolled 120 critically ill children admitted to the PICU at 2 fixed days per week in addition to 40 healthy children served as controls. Clinical examination was performed including calculation of the Pediatric Risk of Mortality and Pediatric Index of Mortality 2. Serum neutrophil gelatinase-associated lipocalin measurement was performed for patients at admission and for the controls. Patients were followed up for 30 days. The discriminatory power of neutrophil gelatinase- associated lipocalin was determined using the receiver-operating characteristic and other predictive likelihood values. Serum neutrophil gelatinase-associated lipocalin level was significantly higher among the total patient cohort and those with sepsis than among the controls (p < 0.001), also in patients with systemic inflammatory response syndrome without sepsis and patients without systemic inflammatory response syndrome (p = 0.04 and <0.001). Furthermore, plasma level of neutrophil gelatinase-associated lipocalin was significantly elevated in nonsurvivors compared with survivors (p < 0. 001). Receiver-operating characteristic curve analysis exhibited an area under the curve of 0.84 for neutrophil gelatinase-associated lipocalin for diagnosis of sepsis, whereas C-reactive protein had an area under the curve of 0.79. Regarding the prognosis, neutrophil gelatinase-associated lipocalin had an area under the curve of 0.74 for prediction of mortality, whereas the area under the curve for Pediatric Risk of Mortality, Pediatric Index of Mortality 2, and C-reactive protein were 0.59, 0.58, and 0.62, respectively. Overall, the data support the view that measurement at admission, serum neutrophil gelatinase-associated lipocalin results in substantial added value for early diagnosis and prognostication of sepsis in critically sick children.

Venous glucose, serum lactate and base deficit as biochemical predictors of mortality in patients with polytrauma.

PubMed

Saad, Sameh; Mohamed, Naglaa; Moghazy, Amr; Ellabban, Gouda; El-Kamash, Soliman

2016-01-01

The trauma and injury severity score (TRISS) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) are accurate but complex. This study aimed to compare venous glucose, levels of serum lactate, and base deficit in polytraumatized patients as simple parameters to predict the mortality in these patients versus (TRISS) and (APACHE IV). This was a comparative cross-sectional study of 282 patients with polytrauma presented to the Emergency Department (ED). The best cut off value of TRISS probability of survival score for prediction of mortality among poly-traumatized patients was ≤90. APACHE IV demonstrated 67% sensitivity and 95% specificity at 95% CI at cut off point 99. The best cutoff value of Random Blood Sugar was >140 mg/dl, with 89% sensitivity, 49% specificity; base deficit was less than -5.6 with 64% sensitivity, 93% specificity; lactate was >2.6 mmol/L with 92%, sensitivity, 42% specificity. Venous glucose, serum lactate and base deficit are easy and rapid biochemical predictors of mortality in patients with polytrauma. These predictors could be used as TRISS and APACHE IV in predicting mortality.

Building and verifying a severity prediction model of acute pancreatitis (AP) based on BISAP, MEWS and routine test indexes.

PubMed

Ye, Jiang-Feng; Zhao, Yu-Xin; Ju, Jian; Wang, Wei

2017-10-01

To discuss the value of the Bedside Index for Severity in Acute Pancreatitis (BISAP), Modified Early Warning Score (MEWS), serum Ca2+, similarly hereinafter, and red cell distribution width (RDW) for predicting the severity grade of acute pancreatitis and to develop and verify a more accurate scoring system to predict the severity of AP. In 302 patients with AP, we calculated BISAP and MEWS scores and conducted regression analyses on the relationships of BISAP scoring, RDW, MEWS, and serum Ca2+ with the severity of AP using single-factor logistics. The variables with statistical significance in the single-factor logistic regression were used in a multi-factor logistic regression model; forward stepwise regression was used to screen variables and build a multi-factor prediction model. A receiver operating characteristic curve (ROC curve) was constructed, and the significance of multi- and single-factor prediction models in predicting the severity of AP using the area under the ROC curve (AUC) was evaluated. The internal validity of the model was verified through bootstrapping. Among 302 patients with AP, 209 had mild acute pancreatitis (MAP) and 93 had severe acute pancreatitis (SAP). According to single-factor logistic regression analysis, we found that BISAP, MEWS and serum Ca2+ are prediction indexes of the severity of AP (P-value<0.001), whereas RDW is not a prediction index of AP severity (P-value>0.05). The multi-factor logistic regression analysis showed that BISAP and serum Ca2+ are independent prediction indexes of AP severity (P-value<0.001), and MEWS is not an independent prediction index of AP severity (P-value>0.05); BISAP is negatively related to serum Ca2+ (r=-0.330, P-value<0.001). The constructed model is as follows: ln()=7.306+1.151*BISAP-4.516*serum Ca2+. The predictive ability of each model for SAP follows the order of the combined BISAP and serum Ca2+ prediction model>Ca2+>BISAP. There is no statistical significance for the predictive ability of BISAP and serum Ca2+ (P-value>0.05); however, there is remarkable statistical significance for the predictive ability using the newly built prediction model as well as BISAP and serum Ca2+ individually (P-value<0.01). Verification of the internal validity of the models by bootstrapping is favorable. BISAP and serum Ca2+ have high predictive value for the severity of AP. However, the model built by combining BISAP and serum Ca2+ is remarkably superior to those of BISAP and serum Ca2+ individually. Furthermore, this model is simple, practical and appropriate for clinical use. Copyright © 2016. Published by Elsevier Masson SAS.

Fibroblast growth factor-21 and omentin-1 hepatic mRNA expression and serum levels in morbidly obese women with non-alcoholic fatty liver disease.

PubMed

Waluga, M; Kukla, M; Zorniak, M; Kajor, M; Liszka, L; Dyaczynski, M; Kowalski, G; Zadlo, D; Waluga, E; Olczyk, P; Buldak, R J; Berdowska, A; Hartleb, M

2017-06-01

Fibroblast growth factor-21 (FGF21) and omentin-1 have been recognized as potent antidiabetic agents with potential hepatoprotective activity. The aim of this study was to evaluate hepatic FGF21 and omentin-1 mRNA expression as well as their serum levels as predictive markers of liver injury and insulin resistance in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). This study included 56 severely obese women who underwent intraoperative wedge liver biopsy during the bariatric surgery. Hepatic FGF21 and omentin-1 mRNA were assessed by quantitative real-time PCR, while their serum concentrations were measured with commercially available enzyme-linked immunosorbent assays. The FGF21 serum level was significantly higher in patients with a greater extent of steatosis (grade 2 and 3) compared to those without or with mild steatosis (grade 0 and 1) (P = 0.049). Receiver Operating Characteristic analysis, however, showed poor discriminant power for the FGF21 serum levels in differentiating between more and less extensive steatosis with an AUC = 0.666. There was a tendency towards higher levels of hepatic FGF21 mRNA in patients with lobular inflammation and fibrosis and towards lower levels in the case of hepatocyte ballooning and steatosis. There was a positive mutual correlation between hepatic FGF21 and omentin-1 mRNA levels (r = 0.78; P < 0.001). Fibrosis stage was associated with serum glucose and homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.03 and P = 0.02, respectively). Serum omentin-1 was not associated with histopathological features. The hepatic omentin-1 mRNA levels showed a tendency to be lower in patients with advanced steatosis and hepatocyte ballooning. In conclusion, our study, which focused on hepatic FGF21 and omentin-1 mRNA expression, confirmed marked expression of both molecules in the liver of morbidly obese patients with NAFLD. More extensive steatosis was associated with evident changes in the serum FGF21 concentration in morbidly obese women with NAFLD, but the difference did not reach statistical significance. The vast amount of fat, both visceral and subcutaneous, in severely obese patients may be the additional source and influence the FGF21 and omentin-1 serum levels.

Longitudinal association between eating frequency and HbA1c and serum lipids in diabetes in the SEARCH for Diabetes in Youth Study.

PubMed

Li, Chao; D'Agostino, Ralph B; Dabelea, Dana; Liese, Angela D; Mayer-Davis, Elizabeth J; Pate, Russell; Merchant, Anwar T

2018-04-30

Few studies have evaluated the prospective association of eating frequency with HbA1c levels and cardiovascular disease risk markers among youth with diabetes. To examine the 5-year longitudinal association of eating frequency with HbA1c and serum lipid levels among youth with type 1 diabetes (T1D) or type 2 diabetes (T2D). 1,049 youth (≥10 years old) with incident T1D (n=821) or T2D (n=228) who participated in the SEARCH for Diabetes in Youth Study were included. Eating frequency (≤3, 4-5 or 6-10 times/day) measured at baseline and follow-up visits was related to HbA1c and serum lipid levels measured repeatedly over 5 years. Increased eating frequency was associated with larger increases in HbA1c among youth T1D. For example, for youth with T1D who ate ≤ 3 times/day at the outset and ate 6-10 times/day 5 years later, the longitudinal model predicted greater absolute increases in HbA1c (2.77%); whereas for youth with T1D who ate 6-10 times/day at the outset and ate ≤3 times/day 5 years later, the model predicted lesser absolute increases in HbA1c (1.33%). Eating frequency was not associated with changes in serum lipid levels among youth with T1D or T2D. Youth with T1D who increased their eating frequency vs. those who decreased it had larger increases in HbA1c over 5 years. This article is protected by copyright. All rights reserved.

Development and validation of a Luminex assay for detection of a predictive biomarker for PROSTVAC-VF therapy

PubMed Central

Lucas, Julie L.; Tacheny, Erin A.; Ferris, Allison; Galusha, Michelle; Srivastava, Apurva K.; Ganguly, Aniruddha; Williams, P. Mickey; Sachs, Michael C.; Thurin, Magdalena; Tricoli, James V.; Ricker, Winnie; Gildersleeve, Jeffrey C.

2017-01-01

Cancer therapies can provide substantially improved survival in some patients while other seemingly similar patients receive little or no benefit. Strategies to identify patients likely to respond well to a given therapy could significantly improve health care outcomes by maximizing clinical benefits while reducing toxicities and adverse effects. Using a glycan microarray assay, we recently reported that pretreatment serum levels of IgM specific to blood group A trisaccharide (BG-Atri) correlate positively with overall survival of cancer patients on PROSTVAC-VF therapy. The results suggested anti-BG-Atri IgM measured prior to treatment could serve as a biomarker for identifying patients likely to benefit from PROSTVAC-VF. For continued development and clinical application of serum IgM specific to BG-Atri as a predictive biomarker, a clinical assay was needed. In this study, we developed and validated a Luminex-based clinical assay for measuring serum IgM specific to BG-Atri. IgM levels were measured with the Luminex assay and compared to levels measured using the microarray for 126 healthy individuals and 77 prostate cancer patients. This assay provided reproducible and consistent results with low %CVs, and tolerance ranges were established for the assay. IgM levels measured using the Luminex assay were found to be highly correlated to the microarray results with R values of 0.93–0.95. This assay is a Laboratory Developed Test (LDT) and is suitable for evaluating thousands of serum samples in CLIA certified laboratories that have validated the assay. In addition, the study demonstrates that discoveries made using neoglycoprotein-based microarrays can be readily migrated to a clinical assay. PMID:28771597

Serum Mac-2 binding protein glycosylation isomer predicts grade F4 liver fibrosis in patients with biliary atresia.

PubMed

Yamada, Naoya; Sanada, Yukihiro; Tashiro, Masahisa; Hirata, Yuta; Okada, Noriki; Ihara, Yoshiyuki; Urahashi, Taizen; Mizuta, Koichi

2017-02-01

Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) is a novel fibrosis marker. We examined the ability of M2BPGi to predict liver fibrosis in patients with biliary atresia. Sixty-four patients who underwent living donor liver transplantation (LDLT) were included [median age, 1.1 years (range 0.4-16.0), male 16 patients (25.0 %)]. We examined M2BPGi levels in serum obtained the day before LDLT, and we compared the value of the preoperative M2BPGi levels with the histological evaluation of fibrosis using the METAVIR fibrosis score. Subsequently, we assessed the ability of M2BPGi levels to predict fibrosis. The median M2BPGi level in patients with BA was 6.02 (range, 0.36-20.0), and 0, 1, 1, 11, and 51 patients had METAVIR fibrosis scores of F0, F1, F2, F3, and F4, respectively. In patients with F4 fibrosis, the median M2BPGi level was 6.88 (quartile; 5.235, 12.10), significantly higher than that in patients with F3 fibrosis who had a median level of 2.42 (quartile; 1.93, 2.895, p < 0.01). Area under the curve analysis for the ability of M2BPGi level to predict grade fibrosis was 0.917, with a specificity and sensitivity of 0.923 and 0.941, respectively. In comparison with other fibrosis markers such as hyaluronic acid, procollagen-III-peptide, type IV collagen 7 s, and aspartate aminotransferase platelet ratio index, M2BPGi showed the strongest ability to predict grade F4 fibrosis. M2BPGi is a novel fibrosis marker for evaluating the status of the liver in patients with BA, especially when predicting grade F4 fibrosis.

IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition.

PubMed

Reid, Tirissa J; Jin, Zhezhen; Shen, Wei; Reyes-Vidal, Carlos M; Fernandez, Jean Carlos; Bruce, Jeffrey N; Kostadinov, Jane; Post, Kalmon D; Freda, Pamela U

2015-12-01

Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly's excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly. In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA. Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SM(E)) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship. Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.

Preoperative serum alkaline phosphatase: a predictive factor for early hypocalcaemia following parathyroidectomy of primary hyperparathyroidism.

PubMed

Sun, Longhao; He, Xianghui; Liu, Tong

2014-01-01

Postoperative hypocalcemia is one of the most common complications following parathyroidectomy for primary hyperparathyroidism (PHPT). The aim of this study was to analyze the predictive value of biochemical parameters as indicators for episodes of hypocalcemia in patients undergoing parathyroidectomy for PHPT. The patients with PHPT who underwent parathyroidectomy between February 2004 and February 2014 were studied retrospectively at a single medical center. The patients were divided into biochemical, clinical, and no postoperative hypocalcemia groups, based on different clinical manifestations. Potential risk factors for postoperative hypocalcemia were identified and investigated by univariate and multivariate Logistic regression analysis. Of the 139 cases, 25 patients (18.0%) were diagnosed with postoperative hypocalcemia according to the traditional criterion. Univariate analysis revealed only alkaline phosphatase (ALP) and the small area under the curve (AUC) of receiver operating characteristics (ROC) curve for ALP demonstrates low accuracy in predicting the occurrence of postoperative hypocalcemia. Based on new criteria, 22 patients were added to the postoperative hypocalcemia group and similar biochemical parameters were compared. The serum ALP was a significant independent risk factor for postoperative hypocalcemia (P = 0.000) and its AUC of ROC curve was 0.783. The optimal cutoff point was 269 U/L and the sensitivity and specificity for prediction were 89.2% and 64.3%, respectively. The risk of postoperative hypocalcemia after parathyroidectomy should be emphasized for patients with typical symptoms of hypocalcemia despite their serum calcium level is in normal or a little higher range. Serum ALP is a predictive factor for the occurrence of postoperative hypocalcemia.

The prognostic significance of preoperative serum albumin in urothelial carcinoma: a systematic review and meta-analysis.

PubMed

Liu, Jing; Wang, Fang; Li, Shaohong; Huang, Wenhui; Jia, Yanjuan; Wei, Chaojun

2018-04-23

Preoperative serum albumin has been considered to be closely correlated with the prognosis of various cancers, including urothelial carcinoma (UC). However, to date,this conclusion remains controversial. The aim of this meta-analysis is to investigate the prognostic significance of preoperative serum albumin in UC. A literature search was performed in PubMed, Web of Science, Embase and Cochrane Library up to July 04, 2017. Herein, a total of 15,506 patients from 23 studies were enrolled in our meta-analysis. Decreased preoperative serum albumin level predicted poor overall survival (HR = 1.88, 95% CI 1.44-2.45, P<0.0001), cancer specific survival (HR = 2.03, 95% CI 1.42-2.90, P=0.0001), recurrence free survival (HR = 1.85, 95% CI 1.15-2.97, P=0.01), 30-day complications after surgery (OR = 1.93, 95% CI 1.16-3.20, P=0.01), and 90-day mortality after surgery (OR= 4.24, 95% CI 2.20-8.16, P<0.001). The subgroup analyses indicated that low preoperative serum albumin level is still positively associated with a worse prognosis of UC based on ethnicity, cut-off value, tumor type,analysestype and sample size. Our meta-analysis indicated that reduced preoperative serum albumin level was a predictor of poor prognosis of UC. ©2018 The Author(s).

Long Non-Coding RNA CASC2 Improves Diabetic Nephropathy by Inhibiting JNK Pathway.

PubMed

Yang, Huihui; Kan, Quan E; Su, Yong; Man, Hua

2018-06-11

It's known that long non-coding RNA CASC2 overexpression inhibit the JNK pathway in some disease models, while JNK pathway activation exacerbates diabetic nephropathy. Therefore we speculate that long non-coding RNA CASC2 can improve diabetic nephropathy by inhibiting JNK pathway. Thus, our study was carried out to investigate the involvement of CASC2 in diabetic nephropathy. We found that serum level of CASC2 was significantly lower in diabetic nephropathy patients than in normal people, and serum level of CASC2 showed no significant correlations with age, gender, alcohol consumption and smoking habits, but was correlated with course of disease. ROC curve analysis showed that serum level of CASC2 could be used to accurately predict diabetic nephropathy. Diabetes mellitus has many complications. This study also included a series of complications of diabetes, such as diabetic retinopathy, diabetic ketoacidosis, diabetic foot infections and diabetic cardiopathy, while serum level of CASC2 was specifically reduced in diabetic nephropathy. CASC2 expression level decreased, while JNK1 phosphorylation level increased in mouse podocyte cells treated with high glucose. CASC2 overexpression inhibited apoptosis of podocyte cells and reduced phosphorylation level of JNK1. We conclude that long non-coding RNA CASC2 may improve diabetic nephropathy by inhibiting JNK pathway. © Georg Thieme Verlag KG Stuttgart · New York.

The Effects of Altered Membrane Cholesterol Levels on Sodium Pump Activity in Subclinical Hypothyroidism.

PubMed

Roy, Suparna; Dasgupta, Anindya

2017-03-01

Metabolic dysfunctions characteristic of overt hypothyroidism (OH) start at the early stage of subclinical hypothyroidism (SCH). Na⁺/K⁺-ATPase (the sodium pump) is a transmembrane enzyme that plays a vital role in cellular activities in combination with membrane lipids. We evaluated the effects of early changes in thyroid hormone and membrane cholesterol on sodium pump activity in SCH and OH patients. In 32 SCH patients, 35 OH patients, and 34 euthyroid patients, sodium pump activity and cholesterol levels in red blood cell membranes were measured. Serum thyroxine (T₄) and thyroid stimulating hormone (TSH) levels were measured using enzyme-linked immunosorbent assays. Differences in their mean values were analysed using post hoc analysis of variance. We assessed the dependence of the sodium pump on other metabolites by multiple regression analysis. Sodium pump activity and membrane cholesterol were lower in both hypothyroid groups than in control group, OH group exhibiting lower values than SCH group. In SCH group, sodium pump activity showed a significant direct dependence on membrane cholesterol with an inverse relationship with serum TSH levels. In OH group, sodium pump activity depended directly on membrane cholesterol and serum T₄ levels. No dependence on serum cholesterol was observed in either case. Despite the presence of elevated serum cholesterol in hypothyroidism, membrane cholesterol contributed significantly to maintain sodium pump activity in the cells. A critical reduction in membrane cholesterol levels heralds compromised enzyme activity, even in the early stage of hypothyroidism, and this can be predicted by elevated TSH levels alone, without any evident clinical manifestations. Copyright © 2017 Korean Endocrine Society

Association between PSA Levels and Biomarkers of Subclinical Systemic Inflammation in Middle-Aged Healthy Men from the General Population.

PubMed

Elzanaty, Saad; Rezanezhad, Babak; Borgquist, Rasmus

2016-10-01

This study was aimed to determine the association between PSA levels and biomarkers of subclinical systemic inflammation based on data from 119 middle-aged healthy men from the general population. Serum levels of PSA and biomarkers of systemic inflammation (CRP and fibrinogen) were measured. Demographic data were also collected. Subjects were divided into two groups according to PSA levels; < 2 ng/ml and ≥ 2 ng/ml. The mean (SD) age of men was 55 ± 4.0 years. We found a positive significant correlation between PSA and fibrinogen levels (r = 0.20, p = 0.04), and between CRP and fibrinogen levels (r = 0.60, p = 0.01). On the other hand, no significant correlation between PSA and CRP levels was found. Men with PSA values ≥ 2 ng/ml had significantly higher levels of fibrinogen as compared to those with PSA < 2 ng/ml (2.9 ng/ml vs. 2.4 ng/ml, p = 0.01). In a multivariate regression analysis model adjusted for the age of subjects, BMI, marital status, smoking, snuff, and alcohol intake with serum levels of PSA as a dependent variable, serum level of fibrinogen predicted higher PSA-values (odds ratio = 3.30, 95% CI = 1.05-10.20, p = 0.042). The present results indicate that serum fibrinogen is a biomarker of subclinical systemic inflammation associated with PSA elevation among middle-aged healthy men from the general population.

Clinical Investigation Program Report Control Symbol MED 300.

DTIC Science & Technology

1982-10-01

Preeclampsia as an Aid to Further Management. (C) (PR) 41 1961 Use of C-Reactive Protein in Prediction of ARD Prog- nosiS, (C) (PR) 42 1981 The Assessment...37 Status: Completed * Title: Routine Use of Serum Uric Acid Levels at 36 Weeks Gestation as Screening Test for Preeclampsia as an Aid to Further...nvestigators: .amily Pr-&ctiU. CPT Ellis M. Knight, MC Key Words: Serum Uric Acid Preeclampsia Accumulative MZDCASI Eat Accumulative Periodic Mar 82 Cost: ]A

The associations between serum VEGF, bFGF and endoglin levels with microvessel density and expression of proangiogenic factors in malignant and benign ovarian tumors.

PubMed

Szubert, Sebastian; Moszynski, Rafal; Michalak, Slawomir; Nowicki, Michal; Sajdak, Stefan; Szpurek, Dariusz

2016-09-01

To investigate whether serum levels of VEGF, bFGF and endoglin correlate with tumor VEGF and bFGF expression or microvessel density (MVD) in ovarian cancer. Forty five patients with epithelial ovarian cancers (EOCs) and 38 patients with benign ovarian tumors (BOTs) were included into the study. Serum levels of VEGF, bFGF and endoglin were assessed using ELISA. The expression of VEGF and bFGF in tumor samples were evaluated using ELISA of supernatants obtained from tumor homogenization. MVD was analyzed using immunohistochemistry with antibodies against CD31, CD34 and CD105. Serum VEGF levels were significantly higher in EOCs than in BOTs (436.6pg/ml [19.67-2860] vs 295.5pg/ml [123-539], P=0.025). Serum endoglin levels were lowered in the group EOCs when compared to BOTs (33,720g/ml [12,220-73,940] vs 42,390pg/ml [19,380-56,910], P=0.015). There were no differences in bFGF levels between studied groups. EOCs have significantly higher CD105 MVD (25 vessels/mm2 [0-57] vs 6 vessels/mm2 [0-70], P<0.001) and tumor VEGF (405.9pg/mg protein [0-3000] vs 2.225 [0-634.7], P<0.001) expression than BOTs, while, bFGF expression was higher in BOTs than in EOCs (2076pg/mg protein [668.1-8718] vs 847.3pg/mg protein [188.9-8333], P=0.003). In patients with EOCs we have observed negative correlation between serum VEGF concentration and its tissue expression (r Spearman=-0.571, P=0.0261), and serum VEGF concentration correlated positively with CD34-MVD (r Spearman=0.545, P=0.0289). In a multiple regression analysis we have observed only the negative correlation between serum VEGF and CD105-MVD (r=-0.5288, P=0.0427). Serum VEGF is a useful marker for prediction of ovarian cancer MVD and tumor VEGF expression. Copyright © 2016 Elsevier Inc. All rights reserved.

The Predictive Prognostic Values of Serum TNF-α in Comparison to SOFA Score Monitoring in Critically Ill Patients

PubMed Central

Yousef, Ayman Abd Al-Maksoud; Suliman, Ghada Abdulmomen

2013-01-01

Background. The use of inflammatory markers to follow up critically ill patients is controversial. The short time frame, the need for frequent and serial measurement of biomarkers, the presence of soluble receptor and their relatively high cost are the major drawbacks. Our study's objective is to compare the prognostic values of serum TNF-α and SOFA score monitoring in critically ill patients. Patients and Methods. A total of ninety patients were included in the study. Forty-five patients developed septic complication (sepsis group). Forty-five patients were critically ill without evidence of infectious organism (SIRS group). Patients' data include clinical status, central venous pressure, and laboratory analysis were measured. A serum level of TNF-α and SOFA score were monitored. Results. Monitoring of TNF-α revealed significant elevation of TNF-α at 3rd and 5th days of ICU admission in both groups. Monitoring of SOFA score revealed significant elevation of SOFA scores in both groups throughout their ICU stay, particularly in nonsurvivors. Positive predictive ability of SOFA score was demonstrated in critically ill patients. Conclusion. Transient significant increase in serum levels of TNF-α were detected in septic patients. Persistent elevation of SOFA score was detected in nonsurvivor septic patients. SOFA score is an independent prognostic value in critically ill patients. PMID:24175285

Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

Kumagai, Erina; Mano, Yohei; Yoshio, Sachiyo; Shoji, Hirotaka; Sugiyama, Masaya; Korenaga, Masaaki; Ishida, Tsuyoshi; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Kawaguchi, Takumi; Torimura, Takuji; Nozaki, Yuichi; Watanabe, Sumio; Mizokami, Masashi; Kanto, Tatsuya

2016-10-14

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. YKL-40, chitinase-like protein expressed in multiple tissues including liver, is involved in cell proliferation, inflammation and remodeling of the extracellular matrix. The aim of this study was to assess whether serum YKL-40 levels are associated with liver fibrosis in NAFLD patients. Serum YKL-40 levels were quantified in 111 NAFLD patients and 23 HCC patients with NAFLD. To identify the source of YKL-40, immunofluorescence staining of liver specimens from NAFLD patients was performed. Serum YKL-40 levels in NAFLD patients increased in accordance with the progression of liver fibrosis. Multivariate analysis revealed that YKL-40 was one of the independent factors significantly associated with severe fibrosis (F3-4). We established a new predictive model for fibrosis of NAFLD, using logistic regression analysis: YKL-40 based fibrosis score = -0.0545 + type IV collagen 7s * 0.3456 + YKL-40 * 0.0024. Serum YKL-40 levels of HCC patients with non-cirrhotic NAFLD were significantly higher than those without HCC. Immunofluorescence staining showed that YKL-40 was expressed by macrophages in liver tissue of NAFLD patients. In conclusion, macrophage-derived YKL-40 is a feasible biomarker of liver fibrosis in NAFLD patients.

Differential Serum Cytokine Levels and Risk of Lung Cancer between African and European Americans

PubMed Central

Pine, Sharon R.; Mechanic, Leah E.; Enewold, Lindsey; Bowman, Elise D.; Ryan, Bríd M.; Cote, Michele L.; Wenzlaff, Angela S.; Loffredo, Christopher A.; Olivo-Marston, Susan; Chaturvedi, Anil; Caporaso, Neil E.; Schwartz, Ann G.; Harris, Curtis C.

2015-01-01

Background African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races. Methods Differences in ten serum cytokine levels, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor (GMCSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the Wayne State University (WSU) Karmanos Cancer Institute case-control study. Results Six cytokines: IL-4, IL-5, IL-8, IL-10, IFNγ, and TNFα, were significantly higher among European-American as compared to African-American controls. Elevated IL-6 and IL-8 levels were associated with lung cancer among both races in all three studies. Elevated IL-1β, IL-10 and TNFα levels were associated with lung cancer only among African Americans. The association between elevated TNFα levels and lung cancer among European Americans was significant after adjustment for additional factors. Conclusions Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans. Impact Future work examining risk prediction models of lung cancer can measure circulating cytokines to accurately characterize risk within racial groups. PMID:26711330

Predictors of serum 25(Oh)D increase following bimonthly supplementation with 100,000IU vitamin D in healthy, men aged 25-65 years.

PubMed

Tepper, Sigal; Shahar, Danit R; Geva, Diklah; Ish-Shalom, Sofia

2014-10-01

Vitamin D replenishment therapy typically entails standard dosages, but related increases in serum 25(OH)D levels vary between individuals. This study was aimed to identify factors that affect the efficacy of vitamin D supplementation. 79 healthy men aged 25-65 with 25(OH)D<20ng/ml participated in a vitamin D supplementation study. All participants received 100,000IU vitamin D bimonthly, e.g., 1666IU/day. Personal and demographic information, physical activity and sun-exposure questionnaires were completed by the participants. Weight, height, and waist circumference were recorded. Serum calcium, creatinine, 25(OH)D, PTH, lipid profile, and liver-enzyme levels were assessed. All measurements were repeated after 6 and 12 months. The difference between baseline serum 25(OH)D and 12-month measurements was calculated (delta). Linear regression was performed to identify predictors for increases in 25(OH)D levels. Mean serum 25(OH)D level increases according to BMI were 12.6±5.29ng/ml for BMI≤25, 10.12±4.95ng/ml for 2530, which differed significantly from the other BMI categories (p=0.003). In a regression model to predict 25(OH)D increase, BMI was the main predictor (p<0.001), explaining 21.6% of the variance in serum 25(OH)D (inverse association). Age, sun-exposure, serum cholesterol, physical-activity, baseline 25(OH)D levels and seasonality were insignificant. The full model explained 27.9% of the variance in serum 25(OH)D. This study's main findings are that BMI affect vitamin D response in healthy men. Quantitative supplementation adjustments may be warranted in obese men, for whom the dose may need to be doubled. This article is part of a special issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Interrelationship between milk constituents, serum oestradiol and vaginal mucus indicators of oestrus in Egyptian buffaloes.

PubMed

Kandiel, M M M; El-Naggar, R A M; Abdel-Ghaffar, A E; Sosa, G A M; Abou El-Roos, N A

2014-02-01

The intensity of heat signs in buffaloes is generally low and the incidence of suboestrus varied from 15 to 73% (Buffalopedia). The objective of this study was to investigate the feasibility of monitoring the changes in some milk constituents, oestradiol levels and electrical conductivity of vaginal mucus during peri-oestrous period in prediction of the timing of oestrus in buffaloes. Twenty-one Egyptian buffaloes aged 3-9 year, 1st-6th lactations, were examined by oestrous detector and ultrasonographically for monitoring the ovarian and uterine activity for 7 days around the time of standing oestrus. Sodium, potassium, chloride and lactose were assayed in aqueous phase of milk; besides, oestradiol was estimated in serum. Current results declared highly significant acute changes in milk constituents at the time of oestrus characterized by peaking of chloride and sodium levels and lowering of potassium and lactose values. The alternation in milk composition when arranged in decreasing order of magnitude, sodium was the highest (77.78 ± 0.69%), followed by chloride (61.60 ± 1.52%) and potassium (-58.14 ± 10.89%). Concomitantly, milk lactose decreased by 26.07 ± 7.97% compared to baseline levels. Synchronously, vaginal electrical resistance (VER) showed a significant (p < 0.01) decrease, but serum oestradiol 17β levels surged (59.93 ± 7.29 pg/ml) on day of oestrus. Serum oestradiol level was negatively correlated with VER (r = -0.577), potassium (r = -0.661), positively correlated with chloride (r = 0.707) and sodium (r = 0.579) and not correlated with lactose levels. These results for the first time suggested that the changes in constituents of milk during peri-oestrous period may be used as a practical non-invasive indicator for oestrous detection and prediction of ovulation in Egyptian buffaloes. © 2013 Blackwell Verlag GmbH.

Serum sCD30: A promising biomarker for predicting the risk of bacterial infection after kidney transplantation.

PubMed

Fernández-Ruiz, Mario; Parra, Patricia; López-Medrano, Francisco; Ruiz-Merlo, Tamara; González, Esther; Polanco, Natalia; Origüen, Julia; San Juan, Rafael; Andrés, Amado; Aguado, José María

2017-04-01

The transmembrane glycoprotein CD30 contributes to regulate the balance between Th 1 and Th 2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post-transplant infection. Serum sCD30 was measured by a commercial ELISA assay at baseline and post-transplant months 1, 3, and 6 in 100 kidney transplant (KT) recipients (279 monitoring points). The impact of sCD30 levels on the incidence of overall, bacterial and opportunistic infection during the first 12 months after transplantation was assessed by Cox regression. There were no differences in serum sCD30 according to the occurrence of overall or opportunistic infection. However, sCD30 levels were higher in patients with bacterial infection compared to those without at baseline (P=.038) and months 1 (P<.0001), 3 (P=.043), and 6 after transplantation (P=.006). Patients with baseline sCD30 levels ≥13.5 ng/mL had lower 12-month bacterial infection-free survival (35.0% vs 80.0%; P<.0001). After adjusting for potential confounders, baseline sCD30 levels ≥13.5 ng/mL remained as an independent risk factor for bacterial infection (adjusted hazard ratio [aHR]: 4.65; 95% confidence interval [CI]: 2.05-10.53; <.001). Analogously, sCD30 levels ≥6.0 ng/mL at month 1 acted as a risk factor for subsequent bacterial infection (aHR: 5.29; 95% CI: 1.11-25.14; P=.036). Higher serum sCD30 levels were associated with an increased risk of bacterial infection after KT. We hypothesize that this biomarker reflects a Th 2 -polarized T-cell response, which exerts a detrimental effect on the immunity against bacterial pathogens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Decreased oxidative stress may contribute to the disease process in placenta accreta

PubMed

Öztaş, Efser; Özler, Sibel; Ergin, Merve; Erel, Özcan; Gümüş Güler, Başak; Çağlar, Ali Turhan; Yücel, Aykan; Uygur, Dilek; Danışman, Nuri

2017-08-23

Background/aim: The main aim of this study was to investigate serum total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and arylesterase levels in pregnant women with placenta accreta and to compare those with age-matched healthy pregnant women. Materials and methods: A total of 27 pregnant women who had clinically and pathologically proven placenta accreta and 30 age- and BMI- matched healthy pregnant women were enrolled in this case control study. Maternal serum TOS, TAS, OSI, and arylesterase levels were evaluated using logistic regression analysis to determine if there was an association with abnormal placental invasion or not. Results: Decreased OSI (OR= 0.999, 95%CI: 0.998-1.000, P = 0.035) and increased arylesterase levels (OR= 0.981, 95%CI: 0.970-0.993, P = 0.001) were significantly associated with the presence of placenta accreta. Maternal serum TOS, TAS, OSI, and arylesterase levels were not predictive for adverse perinatal outcomes (P > 0.05). Conclusions: Decreased OSI and increased arylesterase levels are significantly associated with placenta accreta and may contribute to the abnormal invasion process.

Fetal hemoglobin, α1-microglobulin and hemopexin are potential predictive first trimester biomarkers for preeclampsia.

PubMed

Anderson, Ulrik Dolberg; Gram, Magnus; Ranstam, Jonas; Thilaganathan, Basky; Kerström, Bo; Hansson, Stefan R

2016-04-01

Overproduction of cell-free fetal hemoglobin (HbF) in the preeclamptic placenta has been recently implicated as a new etiological factor of preeclampsia. In this study, maternal serum levels of HbF and the endogenous hemoglobin/heme scavenging systems were evaluated as predictive biomarkers for preeclampsia in combination with uterine artery Doppler ultrasound. Case-control study including 433 women in early pregnancy (mean 13.7weeks of gestation) of which 86 subsequently developed preeclampsia. The serum concentrations of HbF, total cell-free hemoglobin, hemopexin, haptoglobin and α1-microglobulin were measured in maternal serum. All patients were examined with uterine artery Doppler ultrasound. Logistic regression models were developed, which included the biomarkers, ultrasound indices, and maternal risk factors. There were significantly higher serum concentrations of HbF and α1-microglobulin and significantly lower serum concentrations of hemopexin in patients who later developed preeclampsia. The uterine artery Doppler ultrasound results showed significantly higher pulsatility index values in the preeclampsia group. The optimal prediction model was obtained by combining HbF, α1-microglobulin and hemopexin in combination with the maternal characteristics parity, diabetes and pre-pregnancy hypertension. The optimal sensitivity for all preeclampsia was 60% at 95% specificity. Overproduction of placentally derived HbF and depletion of hemoglobin/heme scavenging mechanisms are involved in the pathogenesis of preeclampsia. The combination of HbF and α1-microglobulin and/or hemopexin may serve as a prediction model for preeclampsia in combination with maternal risk factors and/or uterine artery Doppler ultrasound. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Body mass index for predicting hyperglycemia and serum lipid changes in Brazilian adolescents.

PubMed

Vieira, Ana Carolina R; Alvarez, Marlene M; Kanaan, Salim; Sichieri, Rosely; Veiga, Gloria V

2009-02-01

To determine the best cut-offs of body mass index for identifying alterations of blood lipids and glucose in adolescents. A probabilistic sample including 577 adolescent students aged 12-19 years in 2003 (210 males and 367 females) from state public schools in the city of Niterói, Southeastern Brazil, was studied. The Receiver Operating Characteristic curve was used to identify the best age-adjusted BMI cut-off for predicting high levels of serum total cholesterol (> or =150 mg/dL), LDL-C (> or =100 mg/dL), serum triglycerides (> or =100 mg/dL), plasma glucose (> 100 mg/dL) and low levels of HDL-C (< 45 mg/dL). Four references were used to calculate sensitivity and specificity of BMI cut-offs: one Brazilian, one international and two American. The most prevalent metabolic alterations (>50%) were: high total cholesterol and low HDL-C. BMI predicted high levels of triglycerides in males, high LDL-C in females, and high total cholesterol and the occurrence of three or more metabolic alterations in both males and females (areas under the curve range: 0.59 to 0.67), with low sensitivity (57%-66%) and low specificity (58%-66%). The best BMI cut-offs for this sample (20.3 kg/m(2) to 21.0 kg/m(2)) were lower than those proposed in the references studied. Although BMI values lower than the International cut-offs were better predictor of some metabolic abnormalities in Brazilian adolescents, overall BMI is not a good predictor of these abnormalities in this population.

Elevated Serum Pesticide Levels and Risk of Parkinson Disease

PubMed Central

Richardson, Jason R.; Shalat, Stuart L.; Buckley, Brian; Winnik, Bozena; O’Suilleabhain, Padraig; Diaz-Arrastia, Ramon; Reisch, Joan; German, Dwight C.

2012-01-01

Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD. PMID:19597089

Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism.

PubMed

Hamada, Noboru; Momotani, Naoko; Ishikawa, Naofumi; Yoshimura Noh, Jaeduk; Okamoto, Yasuyuki; Konishi, Toshiaki; Ito, Koichi; Ito, Kunihiko

2011-01-01

Serum levels of TSH receptor antibody (TRAb) often increase after radioiodine treatment for Graves' disease, and high-serum levels of maternal TRAb in late pregnancy indicate a risk of neonatal hyperthyroidism. The aim of this retrospective study is to investigate the characteristics of Graves' women who had a history of radioiodine treatment for intractable Graves' disease, and whose neonates suffered from hyperthyroidism. The subjects of this study were 45 patients with Graves' disease who became pregnant during the period from 1988 to 1998 after receiving radioiodine treatment at Ito Hospital. 25 of the 45 subjects had had a relapse of hyperthyroidism after surgical treatment for Graves' disease. 19 pregnancies were excluded because of artificial or spontaneous abortion. In the remaining 44 pregnancies of 35 patients, neonatal hyperthyroidism developed in 5 (11.3%) pregnancies of 4 patients. Serum levels of TRAb at delivery were higher in patients whose neonates suffered from hyperthyroidism (NH mother) than those of patients who delivered normal infants (N mother). Furthermore, serum levels of TRAb in NH mother did not change during pregnancy, although those of 4 patients of N mother, in which serum levels of TRAb before radioiodine treatment were as high as in NH mother, decreased significantly during pregnancy. In conclusion, women who delivered neonates with hyperthyroidism following radioiodine treatment seem to have very severe and intractable Graves' disease. Persistent high TRAb values during pregnancy observed in those patients may be a cause of neonatal hyperthyroidism.

Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: Comparison with Child-Pugh score and serum bile acid levels

PubMed Central

Festi, D.; Capodicasa, S.; Sandri, L.; Colaiocco-Ferrante, L.; Staniscia, T.; Vitacolonna, E.; Vestito, A.; Simoni, P.; Mazzella, G.; Portincasa, P.; Roda, E.; Colecchia, A.

2005-01-01

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV- related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients. PMID:15609414

Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical prognosis in inflammatory bowel disease.

PubMed

Tran, Diana Hoang-Ngoc; Wang, Jiani; Ha, Christina; Ho, Wendy; Mattai, S Anjani; Oikonomopoulos, Angelos; Weiss, Guy; Lacey, Precious; Cheng, Michelle; Shieh, Christine; Mussatto, Caroline C; Ho, Samantha; Hommes, Daniel; Koon, Hon Wai

2017-05-12

Cathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients. Serum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development. Serum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 6-18 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients. Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients.

Soluble CD30 levels in recipients undergoing heart transplantation do not predict post-transplant outcome.

PubMed

Ypsilantis, Efthymios; Key, Timothy; Bradley, J Andrew; Morgan, C Helen; Tsui, Stephen; Parameshwar, Jayan; Taylor, Craig J

2009-11-01

The pre-transplant serum level of soluble CD30 (sCD30), a proteolytic derivative of the lymphocyte surface receptor CD30, has been suggested as a biomarker for immunologic risk after organ transplantation. Pre-transplant serum sCD30 levels were determined in 200 consecutive adult heart transplant recipients undertaken at a single center. Transplant outcome (acute rejection in the first 12 months and patient survival up to 5 years post-transplant) was determined. Patients treated with a left ventricular assist device (LVAD) prior to transplantation (n = 28) had higher levels of sCD30 (median 64 U/ml, range 12 to 112 U/ml) than those (n = 172) with no LVAD (median 36 U/ml, range 1 to 158 U/ml, p < 0.0001). Recipients were categorized according to whether sCD30 levels were "low" (lower quartile, <24 U/ml, n = 50), "intermediate" (24 to 58 U/ml, n = 100) or "high" (upper quartile, >58 U/ml, n = 50). Neither acute rejection nor recipient survival differed according to sCD30 level, with values (mean +/- SEM) of 0.30 +/- 0.04, 0.23 +/- 0.03 and 0.30 +/- 0.05 acute rejection episodes per 100 days in the low, intermediate and high groups, respectively, with recipient survival rates at 1 year of 77.7%, 84.9% and 86% and at 5 years of 73.6%, 67.9% and 75.8%, respectively. Pre-transplant serum sCD30 level does not predict acute allograft rejection or recipient survival after heart transplantation, although sCD30 levels are increased by LVAD, possibly as a result of biomaterial-host immune interaction.

Configuration and validation of a novel prostate disease nomogram predicting prostate biopsy outcome: A prospective study correlating clinical indicators among Filipino adult males with elevated PSA level.

PubMed

Chua, Michael E; Tanseco, Patrick P; Mendoza, Jonathan S; Castillo, Josefino C; Morales, Marcelino L; Luna, Saturnino L

2015-04-01

To configure and validate a novel prostate disease nomogram providing prostate biopsy outcome probabilities from a prospective study correlating clinical indicators and diagnostic parameters among Filipino adult male with elevated serum total prostate specific antigen (PSA) level. All men with an elevated serum total PSA underwent initial prostate biopsy at our institution from January 2011 to August 2014 were included. Clinical indicators, diagnostic parameters, which include PSA level and PSA-derivatives, were collected as predictive factors for biopsy outcome. Multiple logistic-regression analysis involving a backward elimination selection procedure was used to select independent predictors. A nomogram was developed to calculate the probability of the biopsy outcomes. External validation of the nomogram was performed using separate data set from another center for determination of sensitivity and specificity. A receiver-operating characteristic (ROC) curve was used to assess the accuracy in predicting differential biopsy outcome. Total of 552 patients was included. One hundred and ninety-one (34.6%) patients had benign prostatic hyperplasia, and 165 (29.9%) had chronic prostatitis. The remaining 196 (35.5%) patients had prostate adenocarcinoma. The significant independent variables used to predict biopsy outcome were age, family history of prostate cancer, prior antibiotic intake, PSA level, PSA-density, PSA-velocity, echogenic findings on ultrasound, and DRE status. The areas under the receiver-operating characteristic curve for prostate cancer using PSA alone and the nomogram were 0.688 and 0.804, respectively. The nomogram configured based on routinely available clinical parameters, provides high predictive accuracy with good performance characteristics in predicting the prostate biopsy outcome such as presence of prostate cancer, high Gleason prostate cancer, benign prostatic hyperplasia, and chronic prostatitis.

Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea.

PubMed

Norman, Daniel; Bardwell, Wayne A; Arosemena, Farah; Nelesen, Richard; Mills, Paul J; Loredo, Jose S; Lavine, Joel E; Dimsdale, Joel E

2008-01-01

Nonalcoholic fatty liver disease (NAFLD) is a disorder that often presents with elevated serum aminotransferase levels. Although it has classically been linked with the metabolic syndrome, recent studies suggest NAFLD may also be associated with obstructive sleep apnea (OSA). This study evaluates the association between serum aminotransferase levels and factors connected with: either the metabolic syndrome (elevated body mass index [BMI], lipid profile, blood pressure, fasting glucose), or with OSA severity (apnea hypopnea index, lowest oxygen saturation level, oxygen desaturation index, percent of time below 90% saturation [%T<90]). Retrospective case series. 109 adult patients with OSA at a university hospital general clinical research center. Markers of hypoxia (lowest oxygen saturation level and %T<90), correlated significantly with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (Pearson's r = -0.31 to -0.38, P <0.003), while apnea hypopnea index, body mass index, blood pressure, fasting glucose, triglyceride, and cholesterol levels did not. Hierarchical linear regression was then done to determine the best predictors of aminotransferase levels. Markers of metabolic syndrome were entered as one block and markers of sleep apnea as another. Regression analyses explained 16.3% of the variance in AST and 18.9% of the variance in ALT, with %T<90 playing the largest role. In patients with obstructive sleep apnea, serum aminotransferase levels are better predicted by markers of oxygen desaturation than by factors traditionally associated with the metabolic syndrome.

Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: a pilot study.

PubMed

Rojas, Paulina Soledad; Fritsch, Rosemarie; Rojas, Romina Andrea; Jara, Pablo; Fiedler, Jenny Lucy

2011-09-30

Depressive patients often have altered cortisol secretion, an effect that likely derives from impaired activity of the glucocorticoid receptor (GR), the main regulator of the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoids reduce the levels of brain-derived neurotrophic factor (BDNF), a downstream target of antidepressants. Antidepressants promote the transcriptional activity of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), a regulator of BDNF expression. To identify potential biomarkers for the onset of antidepressant action in depressive patients, GR and phospho-CREB (pCREB) levels in lymphocytes and serum BDNF levels were repeatedly measured during the course of antidepressant treatment. Thirty-four depressed outpatients (10 male and 24 female) were treated with venlafaxine (75mg/day), and individuals exhibiting a 50% reduction in their baseline 17-Item Hamilton Depression Rating Scale score by the 6th week of treatment were considered responders. Responders showed an early improvement in parallel with a rise in BDNF levels during the first two weeks of treatment. Non-responders showed increased GR levels by the third week and reduced serum BDNF by the sixth week of treatment. In contrast, venlafaxine did not affect levels of pCREB. We conclude that levels of BDNF in serum and GR levels in lymphocytes may represent biomarkers that could be used to predict responses to venlafaxine treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Is low serum albumin associated with postoperative complications in patients undergoing oesophagectomy for oesophageal malignancies?

PubMed

Goh, Sean L; De Silva, Ramesh P; Dhital, Kumud; Gett, Rohan M

2015-01-01

A best evidence topic was written according to a structured protocol. The question addressed was: in patients undergoing oesophagectomy for oesophageal malignancy, is low serum albumin associated with postoperative complications? Altogether, 87 papers were found using the reported search, of which 16 demonstrated the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This paper includes 2 level 2 papers, 12 level 3 papers and 2 level 4 papers. All the papers compared either all or some of the following postoperative complications: mortality, morbidity, anastomotic leak, respiratory and non-respiratory complications, and length of hospital stay. Eleven of the 16 papers found an association between low serum albumin and postoperative complications. Of these, one study showed that low serum albumin combined with low fibrinogen levels (FA score) was predictive of postoperative recurrence of oesophageal cancer. Another study showed that when combined with white cell count and C-reactive protein (CRP, NUn score), serum albumin had a high diagnostic accuracy for major complications after postoperative day 3. The largest study compared the in-hospital mortality in 7227 patients who underwent oesophageal surgery for malignancy. The percentage of in-hospital mortality was associated with low serum albumin (<15.0 vs >35.0 g/l, 21.0 vs 11.3%, P <0.001). Five of the 16 papers found no significant association between low serum albumin and postoperative complications. Of these papers, one showed that low serum albumin was not an independent risk factor, while four others found no association between low serum albumin with respiratory complications, anastomotic leak and postoperative mortality. Instead, these studies found other factors responsible for postoperative complications such as: CRP, smoking, disease duration, malnutrition and low T-cell levels. Taken together, while low serum albumin is associated with postoperative complications, opinion regarding the prognostic value of low serum albumin and nutritional support remains conflicted. Because of the confounding factors encountered in these studies, the clinician should consider the finding of low serum albumin in patients, together with disease and surgical factors to provide optimal care for these patients. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

A Prospective Observational Study on the Predictive Value of Serum Cystatin C for Successful Weaning from Continuous Renal Replacement Therapy.

PubMed

Kim, Chang Seong; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2018-05-30

There is a paucity of literature that investigates a biomarker associated with successful renal recovery following continuous renal replacement therapy (CRRT). Our study aimed to identify potential renal biomarkers or clinical indicators that could predict the successful weaning from CRRT. We conducted a prospective, observational study of 110 patients who had received CRRT and were weaned after renal recovery. Patients were considered to have successfully weaned from CRRT once there was no need for renal replacement therapy (RRT) for at least 14 days. For patients who had to restart dialysis within 14 days were considered unsuccessful. Of the 110 patients evaluated, 89 (80.9%) were successfully weaned from CRRT. These patients had lower serum cystatin C (CysC) levels and higher urine output than the group that restarted RRT at the time of CRRT cessation. However, the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were not significantly lower in the successful group compared to the restart-RRT group. A multivariable logistic regression showed that serum CysC was an independent predictor for the successful weaning from CRRT. Furthermore, in a multivariable Cox proportional hazards analysis, the group that was successfully weaned from CRRT had a lower in-hospital mortality compared to the restarted RRT group. Serum CysC, at the time of CRRT cessation, is an independent predictor of the successful weaning from CRRT in critically ill patients with acute kidney injury. © 2018 The Author(s). Published by S. Karger AG, Basel.

Metallic ureteral stents in malignant ureteral obstruction: clinical factors predicting stent failure.

PubMed

Chow, Po-Ming; Hsu, Jui-Shan; Huang, Chao-Yuan; Wang, Shuo-Meng; Lee, Yuan-Ju; Huang, Kuo-How; Yu, Hong-Jheng; Pu, Yeong-Shiau; Liang, Po-Chin

2014-06-01

To provide clinical outcomes of the Resonance metallic ureteral stent in patients with malignant ureteral obstruction, as well as clinical factors predicting stent failure. Cancer patients who have received Resonance stents from July 2009 to March 2012 for ureteral obstruction were included for chart review. Stent failure was detected by clinical symptoms, image studies, and renal function tests. Survival analysis for stent duration was used to estimate patency rate and factors predicting stent failure. A total of 117 stents were inserted successfully into 94 ureteral units in 79 patients. There were no major complications. These stents underwent survival analysis and proportional hazard regression. The median duration for the stents was 5.77 months. In multivariate analysis, age (P=0.043), preoperative serum creatinine level (P=0.0174), and cancer type (P=0.0494) were significant factors associated with stent failure. Cancer treatment before and after stent insertion had no effect on stent duration. Resonance stents are effective and safe in relieving malignant ureteral obstructions. Old age and high serum creatinine level are predictors for stent failure. Stents in patients with lower gastrointestinal cancers have longer functional duration.

The relationship between maternal serum iron and zinc levels and their nutritional intakes in early pregnancy with gestational diabetes.

PubMed

Behboudi-Gandevani, Samira; Safary, Kolsum; Moghaddam-Banaem, Lida; Lamyian, Minoor; Goshtasebi, Azita; Goshtasbi, Azita; Alian-Moghaddam, Narges

2013-07-01

The aim of this study was to investigate the association between maternal iron/zinc serum levels and their nutritional intake in early pregnancy with gestational diabetes. The maternal serum zinc/iron levels were measured in 1,033 healthy singleton pregnant women aged 20-35 between 14 and 20 weeks of gestation, within two groups: namely, normal and gestational diabetes, and participants were followed up to 24-28 weeks of gestation. Food frequency questionnaire was used to assess nutritional intakes of iron/zinc. The main outcome was gestational diabetes screened with the 50-g glucose challenge test and diagnosed with oral glucose tolerance test at 24-28 weeks of gestation. Gestational diabetes occurred in 72 (6.96 %) of 1,033 women in study. There was a statistical relationship between early pregnancy maternal serum iron and gestational diabetes, mean (SD), 143.8 (48.7) vs. 112.5 (83.5) μg/dl, P value of <0.0001. There was no statistical significant difference in zinc levels and iron/zinc nutritional intake between groups. The results remained unchanged after using regression model for adjustment of potential risk factors with an adjusted OR of 1.006 (95 % CI 1.002 to 1.009; P = 0.001) for early pregnancy maternal serum iron to cause gestational diabetes. The receiver-operator characteristic curve identified that a maternal serum iron above 100 μg/dl in early pregnancy is the optimum cutoff value for predicting gestational diabetes, which showed a sensitivity and specificity of 80.6 and 50.7 %, respectively. In conclusion, high maternal serum iron in early pregnancy could increase the risk of gestational diabetes. Also, it could be used as a sensitive and specific predictor for gestational diabetes.

Serum bilirubin levels are negatively associated with diabetic retinopathy in patients with type 1 diabetes and normal renal function.

PubMed

Bulum, Tomislav; Tomić, Martina; Duvnjak, Lea

2018-06-01

Previous studies suggested that total serum bilirubin levels are negatively associated with diabetic retinopathy (DR) and nephropathy in patients with diabetes mellitus. The objective of this study was to explore the relationship between serum total bilirubin levels and prevalence of DR in patients with type 1 diabetes (T1DM) and normal renal function. Study included 163 T1DM with normal renal function (urinary albumin excretion rate <30 mg/24 h, estimated glomerular filtration rate (eGFR) >60 ml min -1 1.73 m -2 ). Photo-documented retinopathy status was made according to the EURODIAB protocol. Patients with DR were older (49 vs 42 years, p = 0.001), had higher systolic blood pressure (130 vs 120 mmHg, p = 0.001), triglycerides (0.89 vs 0.77 mmol/L, p = 0.01), and lower serum total bilirubin (12 vs 15 U/L, p = 0.02) and eGFR (100 vs 106 ml min -1 1.73 m -2 , p = 0.03). In multivariate logistic regression analysis, only total serum bilirubin was significantly associated with risk of DR in our subjects (OR 0.88, CI 0.81-0.96, p = 0.006). These data suggest that serum total bilirubin levels are independently negatively associated with DR in T1DM with normal renal function. Prospective studies are needed to confirm whether lower serum total bilirubin has predictive value for the development of DR in T1DM with normal renal function.

Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke.

PubMed

Zhong, Chongke; Yang, Jingyuan; Xu, Tan; Xu, Tian; Peng, Yanbo; Wang, Aili; Wang, Jinchao; Peng, Hao; Li, Qunwei; Ju, Zhong; Geng, Deqin; Zhang, Yonghong; He, Jiang

2017-08-22

To examine the association between serum matrix metalloproteinases-9 (MMP-9) levels and prognosis of acute ischemic stroke. We measured serum MMP-9 levels in 3,186 participants (2,008 men and 1,178 women) from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Study outcome data on death, major disability (modified Rankin Scale score ≥3), and vascular disease were collected at 3 months after stroke onset. During 3 months of follow-up, 767 participants (24.6%) experienced major disability or died. Serum MMP-9 was significantly associated with an increased risk of death and major disability after adjustment for age, sex, time from onset to randomization, current smoking, alcohol drinking, admission NIH Stroke Scale score, diastolic blood pressure, plasma glucose, white blood cell counts, use of antihypertensive medications, and history of hypertension, coronary heart disease, and diabetes mellitus. For example, 1-SD (0.32 ng/mL) higher log-MMP-9 was associated with an odds ratio (95% confidence interval) of 1.16 (1.06-1.28) for the combined outcome of death and major disability, 1.12 (1.01-1.23) for major disability, and 1.29 (1.01-1.66) for death. The addition of serum MMP-9 to conventional risk factors improved risk prediction of the combined outcome of death or major disability (net reclassification index 9.1%, p = 0.033; integrated discrimination improvement 0.4%, p = 0.004). Higher serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of mortality and major disability, suggesting that serum MMP-9 could be an important prognostic factor for ischemic stroke. © 2017 American Academy of Neurology.

Prognostic utility of serum CRP levels in combination with CURB-65 in patients with clinically suspected sepsis: a decision curve analysis.

PubMed

Yamamoto, Shungo; Yamazaki, Shin; Shimizu, Tsunehiro; Takeshima, Taro; Fukuma, Shingo; Yamamoto, Yosuke; Tochitani, Kentaro; Tsuchido, Yasuhiro; Shinohara, Koh; Fukuhara, Shunichi

2015-04-28

The prognostic utility of serum C reactive protein (CRP) alone in sepsis is controversial. We used decision curve analysis (DCA) to evaluate the clinical usefulness of combining serum CRP levels with the CUBR-65 score in patients with suspected sepsis. Retrospective cohort study. Emergency department (ED) of an urban teaching hospital in Japan. Consecutive ED patients over 15 years of age who were admitted to the hospital after having a blood culture taken in the ED between 1 January 2010 and 31 December 2012. 30-day in-hospital mortality. Data from 1262 patients were analysed for score evaluation. The 30-day in-hospital mortality was 8.4%. Multivariable analysis showed that serum CRP ≥150 mg/L was an independent predictor of death (adjusted OR 2.0; 95% CI 1.3 to 3.1). We compared the predictive performance of CURB-65 with the performance of a modified CURB-65 with that included CRP (≥150 mg/L) to quantify the clinical usefulness of combining serum CRP with CURB-65. The areas under the receiver operating characteristics curves of CURB-65 and a modified CURB-65 were 0.76 (95% CI 0.72 to 0.80) and 0.77 (95% CI 0.72 to 0.81), respectively. Both models had good calibration for mortality and were useful among threshold probabilities from 0% to 30%. However, while incorporating CRP into CURB-65 yielded a significant category-free net reclassification improvement of 0.387 (95% CI 0.193 to 0.582) and integrated discrimination improvement of 0.015 (95% CI 0.004 to 0.027), DCA showed that CURB-65 and the modified CURB-65 score had comparable net benefits for prediction of mortality. Measurement of serum CRP added limited clinical usefulness to CURB-65 in predicting mortality in patients with clinically suspected sepsis, regardless of the source. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Effect of vitamin D deficiency on hypocalcaemia after total thyroidectomy due to benign goitre].

PubMed

Díez, Manuel; Vera, Cristina; Ratia, Tomás; Diego, Lucía; Mendoza, Fernando; Guillamot, Paloma; San Román, Rosario; Mugüerza, José M; Rodríguez, Angel; Medina, Carlos; Gómez, Beatriz; Granell, Javier

2013-04-01

The purpose of this study was to analyse the relationship between preoperative serum levels of vitamin D and postoperative hypocalcaemia after total thyroidectomy. A prospective observational study was conducted on 113 patients treated by total thyroidectomy due to benign disease. Preoperative vitamin D serum levels and postoperative albumin-corrected calcium and parathormone (PTH) levels were determined. Sensitivity, specificity, positive predictive value and negative predictive value of vitamin D and PTH levels, respectively, in the diagnosis of postoperative hypocalcaemia were calculated. Hypocalcaemia was diagnosed in 44 (38.9%) patients. Vitamin D levels were significantly higher in the group of patients with normal postoperative calcium (median: 25.4pg/mL; range: 4-60), compared to those who developed hypocalcaemia (median: 16.4pg/mL; range: 6.3-46.9) (P=.001). Postoperative hypocalcaemia was more frequent in patients with vitamin D < 30ng/mL (39/78) (50%), than among those with normal levels (5/35) (14.2%) (P=.001). Sensitivity, specificity, positive predictive value and negative predictive value were 88% and 68%, 43% and 82%, 50% and 71%, and 85% and 80% for vitamin D and PTH, respectively. Vitamin D and PTH showed independent prognostic values on the risk of hypocalcaemia. The OR associated with vitamin D < 30ng/mL was 4.25 (95% CI: 1.31-13.78) (P=.016), and the OR of PTH<13pg/mL was 15.4 (95% CI: 4.83-49.1) (P<.001). Vitamin D deficiency is a risk factor of hypocalcaemia after total thyroidectomy for benign goitre. The vitamin D level provides independent prognostic information, which is complementary to that given by PTH. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Significance of day-1 viral response of hepatitis C virus in patients with chronic hepatitis C receiving direct-acting antiviral therapy.

PubMed

Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Yama, Tsuyoki; Mizuno, Kazuyuki

2018-06-01

On-treatment response of serum hepatitis C virus (HCV) is reportedly less useful to predict the outcome of anti-HCV therapy with interferon (IFN)-free regimen with direct-acting antivirals than with IFN-based regimens in clinical trials. We evaluated the significance of very early viral response after the start of therapy, which indicates direct HCV response to the drugs, on therapeutic outcome. Reductions in serum HCV-RNA levels were measured at 1 day after the start of therapy in 544 patients who underwent IFN-free direct-acting antiviral regimens. The association between these reductions and the achievement or failure of sustained virologic response (SVR) was evaluated. Patient characteristics did not influence 1-day reduction in serum HCV-RNA except for liver fibrosis. There was no difference in 1-day HCV reduction between SVR and non-SVR patients treated with a 24-week regimen. In contrast, in patients treated with a 12-week regimen, 1-day reduction was significantly greater in SVR than in non-SVR patients (P = 0.0013) and was predictive of SVR versus non-SVR (area under the receiver-operating characteristics curve: 0.80). Whereas the reduction in serum HCV-RNA levels at 1 day after the start of therapy was not associated with treatment outcomes in patients who underwent a 24-week regimen of IFN-free therapy, there was an association in patients receiving a 12-week regimen, and this reduction was predictive of SVR, thus potentially serving as a factor to identify patients at risk of treatment failure. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Reevaluation of the thyroidal radioactive iodine uptake test, with special reference to reversible primary hypothyroidism with elevated thyroid radioiodine uptake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okamura, K.; Sato, K.; Ikenoue, H.

The clinical significance of the thyroidal radioactive iodine uptake (RAIU) test was reevaluated in patients with various thyroid disorders. Compared with 262 normal subjects or 194 patients with euthyroid diffuse goiter with normal serum TSH levels, RAIU values were significantly higher in 100 patients with latent primary hypothyroidism (serum TSH, 5-40 mU/L). In 126 patients with overt primary hypothyroidism (serum TSH, greater than 40 mU/L), RAIU values were either extremely high (49 patients with reversible hypothyroidism and 10 patients with postpartum hypothyroidism) or low (67 patients with irreversible hypothyroidism). The increase in RAIU values in latent, or reversible overt hypothyroidismmore » was TSH dependent, and there was a good correlation between RAIU values and serum TSH levels (r = 0.6203; P less than 0.001). In overt primary hypothyroidism, spontaneous recovery of thyroid function during iodide restriction alone occurred in 52 of 53 patients with RAIU values above 35%, in only 7 of 23 patients with RAIU values between 10-35%, and in none of 50 patients with RAIU below 10%. Thus, recovery was predicted by high RAIU values (P less than 0.001; prediction rate, 91.4%). Goiter was found in about 80% of the patients with reversible hypothyroidism, compared with only 34% of the patients with irreversible hypothyroidism. Recovery of thyroid function during iodide restriction also occurred in 71% of the patients with latent hypothyroidism. However, RAIU measurements did not predict the prognosis of patients with latent hypothyroidism. We conclude that iodine-induced reversible hypothyroidism is common in our patient population, and RAIU measurements may be helpful in determining the prognosis of patients with overt primary hypothyroidism.« less

Development of an algorithm to predict serum vitamin D levels using a simple questionnaire based on sunlight exposure.

PubMed

Vignali, Edda; Macchia, Enrico; Cetani, Filomena; Reggiardo, Giorgio; Cianferotti, Luisella; Saponaro, Federica; Marcocci, Claudio

2017-01-01

Sun exposure is the main determinant of vitamin D production. The aim of this study was to develop an algorithm to assess individual vitamin D status, independently of serum 25(OHD) measurement, using a simple questionnaire, mostly relying upon sunlight exposure, which might help select subjects requiring serum 25(OHD) measurement. Six hundred and twenty adult subjects living in a mountain village in Southern Italy, located at 954 m above the sea level and at a latitude of 40°50'11″76N, were asked to fill the questionnaire in two different periods of the year: August 2010 and March 2011. Seven predictors were considered: month of investigation, age, sex, BMI, average daily sunlight exposure, beach holidays in the past 12 months, and frequency of going outdoors. The statistical model assumes four classes of serum 25(OHD) concentrations: ≤10, 10-19.9, 20-29.9, and ≥30 ng/ml. The algorithm was developed using a two-step procedure. In Step 1, the linear regression equation was defined in 385 randomly selected subjects. In Step 2, the predictive ability of the regression model was tested in the remaining 235 subjects. Seasonality, daily sunlight exposure and beach holidays in the past 12 months accounted for 27.9, 13.5, and 6.4 % of the explained variance in predicting vitamin D status, respectively. The algorithm performed extremely well: 212 of 235 (90.2 %) subjects were assigned to the correct vitamin D status. In conclusion, our pilot study demonstrates that an algorithm to estimate the vitamin D status can be developed using a simple questionnaire based on sunlight exposure.

High Vitamin D-Binding Protein Concentration, Low Albumin, and Mode of Remission Predict Relapse in Crohn's Disease.

PubMed

Ghaly, Simon; Murray, Kevin; Baird, Angela; Martin, Katherine; Prosser, Ruth; Mill, Justine; Simms, Lisa A; Hart, Prue H; Radford-Smith, Graham; Bampton, Peter A; Lawrance, Ian C

2016-10-01

Vitamin D (25(OH)D) deficiency occurs in active Crohn's disease (CD) and may be secondary to reduced sunlight exposure and oral intake. Vitamin D-binding protein (VDBP) levels, however, fluctuate less with season and sunlight. The aim, therefore, was to examine patients with CD in remission and determine any associations between VDBP, serum 25(OH)D, and the calculated free 25(OH)D concentrations with the risk of disease flare. Subjects were identified from prospectively maintained inflammatory bowel disease databases at 3 teaching hospitals in Australia. Patients were in steroid-free clinical remission at the time of blood draw and were followed for at least 12 months. Total and epimer-25(OH)D3, VDBP concentrations, and genotypes were determined. A total of 309 patients with CD (46% men) met the inclusion criteria. A disease flare occurred in 100 (32.4%). Serum 25(OH)D3 was deficient (<50 nmol/L) in 36 (12%) and insufficient (50-75 nmol/L) in 107 (35%) patients. Total, free, and epimer-25(OH)D3 serum levels did not predict disease flare. Higher VDBP concentrations, however, significantly correlated with increased risk of disease flare (hazard ratio 1.2, 95% CI, 1.0-1.5). On multivariate analysis, VDBP concentration, low albumin, and medication-induced remission were significantly more associated with disease flare. VDBP genotypes were significantly associated with 25(OH)D and VDBP concentrations but not disease flare. Vitamin D deficiency was uncommon in our patients with CD in remission, and serum 25(OH)D3 did not predict disease flare, whereas higher VDBP concentrations were significantly associated with disease flare. Further investigations to explore the possible mechanisms for this association are warranted.

Validation of serum progesterone <35nmol/L as a predictor of miscarriage among women with threatened miscarriage.

PubMed

Lek, Sze Min; Ku, Chee Wai; Allen, John C; Malhotra, Rahul; Tan, Nguan Soon; Østbye, Truls; Tan, Thiam Chye

2017-03-06

Our recent paper, based on a pilot cohort of 119 women, showed that serum progesterone <35 nmol/L was prognostic of spontaneous miscarriage by 16 weeks in women with threatened miscarriage in early pregnancy. Using a larger cohort of women from the same setting (validation cohort), we aim to assess the validity of serum progesterone <35 nmol/L with the outcome of spontaneous miscarriage by 16 weeks. In a prospective cohort study, 360 pregnant women presenting with threatened miscarriage between gestation weeks 6-10 at a tertiary hospital emergency unit for women in Singapore were recruited for this study. The main outcome measure measured is spontaneous miscarriage prior to week 16 of gestation. Area under the ROC curve (AUC) and test characteristics (sensitivity, specificity, positive and negative predictive value) at a serum progesterone cutpoint of <35 nmol/L for predicting high and low risk of spontaneous miscarriage by 16 weeks were compared between the Pilot and Validation cohorts. Test characteristics and AUC values using serum progesterone <35 nmol/L in the validation cohort were not significantly different from those in the Pilot cohort, demonstrating excellent accuracy and reproducibility of the proposed serum progesterone cut-off level. The cut-off value for serum progesterone (35 nmol/L) demonstrated clinical relevance and allow clinicians to stratify patients into high and low risk groups for spontaneous miscarriage.

Circulating complexes between tumour necrosis factor-alpha and etanercept predict long-term efficacy of etanercept in juvenile idiopathic arthritis.

PubMed

Kahn, Robin; Berthold, Elisabet; Gullstrand, Birgitta; Schmidt, Tobias; Kahn, Fredrik; Geborek, Pierre; Saxne, Tore; Bengtsson, Anders A; Månsson, Bengt

2016-04-01

The relationship between tumour necrosis factor-alpha (TNF-α) and drug survival had not been studied in juvenile idiopathic arthritis (JIA), and there were no laboratory tests to predict the long-term efficacy of biological drugs for JIA. We studied whether serum levels of TNF-α, free or bound to etanercept, could predict long-term efficacy of etanercept in children with JIA. We included 41 biologic-naïve patients with JIA who started treatment with etanercept at Skåne University Hospital between 1999 and 2010. Serum taken at the start of treatment and at the six-week follow-up were analysed for TNF-α and the long-term efficacy of etanercept was assessed using the drug survival time. Levels of TNF-α increased significantly at the six-week follow-up, and this was almost exclusively comprised of TNF-α in complex with etanercept. The increase in TNF-α showed a dose-dependent correlation to long-term drug survival (p < 0.01). Increasing levels of circulating TNF-α at treatment initiation predicted long-term efficacy of etanercept in children with JIA, which may have been due to different pathophysiological mechanisms of inflammation. Our result may provide a helpful clinical tool, as high levels of circulating TNF-α/etanercept complexes could be used as a marker for the long-term efficacy of etanercept. ©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

PubMed

Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

2017-03-16

We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

Soluble B7-H4 blood serum levels are elevated in women at high risk for preeclampsia in the first trimester, as well as in patients with confirmed preeclampsia.

PubMed

Mach, Pawel; Nolte-Boenigk, Luisa; Droste, Leonie; Fox, Laura; Frank, Mirjam; Schmidt, Boerge; Herse, Florian; Verlohren, Stefan; Wicherek, Lukasz; Iannaccone, Antonella; Birdir, Cahit; Andrikos, Dimitrios; Kimmig, Rainer; Gellhaus, Alexandra; Köninger, Angela

2018-05-24

B7-H4 negatively regulates T-cell-mediated immunity and might play an important role in preeclampsia (PE). Here, we have investigated the association between PE and maternal soluble B7-H4 (sB7-H4) serum levels and B7-H4 mRNA expression in the placenta. Maternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in women between 11 and 13 weeks' gestation with elevated risk for PE (n = 48) and women without elevated risk for PE (n = 47). In the third trimester, sB7-H4 serum levels (n = 166) and B7-H4 mRNA expression in the placenta (n = 54) were determined in women with early-onset PE, late-onset PE, fetal growth restriction (FGR), and in healthy controls. In the first trimester, significant higher levels of sB7-H4 were detected in women at elevated risk for PE compared to women without risk for PE (P < .0001). sB7-H4 has some predictive ability to identify cases with an elevated risk of developing PE with area under the curve (AUC) value of 0.88 (95% CI 0.8-0.94). Using a specificity of 90.0% led to a sensitivity of 47.9% and a threshold of 3.63 ng/mL. In the third trimester, the highest serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in early-onset PE. Significant higher serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in women with early-onset PE (P = .01 and P = .006, respectively) and late-onset PE (P = .03 and P = .004, respectively) compared to healthy controls, but not compared to FGR. sB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester of pregnancy, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

PubMed

Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

2017-12-18

Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P < .001) and at months 1 (8.0 ± 1.7 vs 11.8 ± 2.4; P < .001), 3 (7.7 ± 1.6 vs 9.6 ± 1.7; P = .002), and 6 (7.4 ± 1.6 vs 8.9 ± 0.9; P = .005). Our preliminary findings suggest that tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

Relationship between serum anti-Mullerian hormone and intrafollicular AMH levels in PCOS women.

PubMed

Stracquadanio, M; Ciotta, L; Palumbo, M A

2018-03-01

Polycystic ovary syndrome is a complex disease characterized by various endocrine disorders that are the potential cause of anovulation and hyperandrogenism. Anti-Müllerian hormone expression is suspected to be overexpressed in PCOS granulosa cells. AMH acts as a regulator of folliculogenesis: it is produced by the granulosa cells of follicles from the stage of the primary follicle to the initial formation of the antrum. Serum and intrafollicular AMH levels are elevated in patients with PCOS due to increased number of small follicles and an increased secretion within each of these small follicles. This excess of AMH is strongly suspected to play a role in the characteristic follicular arrest of PCOS, through a negative action on aromatase expression and on FSH action. Value above 5 ng/ml or 35 pmol/l might be considered as a diagnostic criterion for PCOS. The aim of our study is to demonstrate the presence of higher AMH serum levels and higher AMH intrafollicular fluid level of PCOS patients, undergone to IVF cycles, compared to normovulatory patients. The results clearly indicate that blood and intrafollicular AMH levels are significantly higher in PCOS women comparing to the normovulatory population. Serum AMH level appears to be a good predictive marker for the risk ovarian hyperstimulation syndrome: thus, its evaluation should be recommended before starting a controlled ovarian stimulation for IVF.

The effect of preoperative serum triglycerides and high-density lipoprotein-cholesterol levels on the prognosis of breast cancer.

PubMed

Li, Xing; Tang, Hailin; Wang, Jin; Xie, Xinhua; Liu, Peng; Kong, Yanan; Ye, Feng; Shuang, Zeyu; Xie, Zeming; Xie, Xiaoming

2017-04-01

Although dyslipidemia has been documented to be associated with several types of cancer including breast cancer, it remains uncertainty the prognostic value of serum lipid in breast cancer. The purpose of this study is to evaluate the association between the preoperative plasma lipid profile and the prognostic of breast cancer patients. The levels of preoperative serum lipid profile (including cholesterol [CHO], Triglycerides [TG], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoAI], and apolipoprotein B [ApoB]) and the clinical data were retrospectively collected and reviewed in 1044 breast cancer patients undergoing operation. Kaplan-Meier method and the Cox proportional hazards regression model were used in analyzing the overall survival [OS] and disease-free survival [DFS]. Combining the receiver-operating characteristic and Kaplan-Meier analysis, we found that preoperative lower TG and HDL-C level were risk factors of breast cancer patients. In multivariate analyses, a decreased HDL-C level showed significant association with worse OS (HR: 0.528; 95% CI: 0.302-0.923; P = 0.025), whereas a decreased TG level showed significant association with worse DFS (HR: 0.569; 95% CI: 0.370-0.873; P = 0.010). Preoperative serum levels of TG and HDL-C may be independent factor to predict outcome in breast cancer patient. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients.

PubMed

Deng, Qiu-Kui; Lei, Yong-Gang; Lin, Ying-Li; Ma, Jian-Guo; Li, Wen-Ping

2016-02-16

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

Follistatin-like 1 in Chronic Systolic Heart Failure: A Marker of Left Ventricular Remodeling

PubMed Central

El-Armouche, Ali; Ouchi, Noriyuki; Tanaka, Komei; Doros, Gheorghe; Wittköpper, Katrin; Schulze, Thomas; Eschenhagen, Thomas; Walsh, Kenneth; Sam, Flora

2011-01-01

Background Follistatin-like 1 (FSTL1) is an extracellular glycoprotein that is found in human serum. Recent work suggests that FSTL1 is secreted in response to ischemic injuries and that its overexpression is protective in the heart and vasculature. Methods and Results Here, we examined serum FSTL1 levels in patients with chronic heart failure with left ventricular (LV) ejection fraction <40% (n=86). The distribution of the sample, from these chronic heart failure patients, was separated into three tertiles of low, medium and high FSTL1 levels. Serum FSTL1 levels were increased 56% above age- and gender-matched, healthy controls. Diabetes mellitus, brain natriuretic peptide level, left atrial size, LV posterior wall thickness, LV end-diastolic diameter and LV mass were significant determinants of FSTL1 serum levels by bivariate analysis. After controlling for significant covariates, FSTL1 levels predicted LV hypertrophy (as measured by LV mass index) by multivariate linear regression analysis (P<0.001). Unadjusted survival analysis demonstrated increased mortality in patients with increasing FSTL1 levels (P=0.09). After adjusting for significant parameters, patients with increased FSTL1 remained at the highest risk of death [hazard ratio (95% confidence limits) 1.028, (0.98 and 1.78)]; (P=0.26). To determine whether elevated FSTL1 may be derived from the myocardium, FSTL1 protein expression was measured in samples from explanted, failing (n=18) and non-failing human hearts (n=7). LV failing hearts showed 2.5-fold higher FSTL1 protein levels than non-failing control hearts (P<0.05). Conclusions Elevated serum FSTL1 in human heart failure patients was associated with LV hypertrophy. Further studies on the role of FSTL1 as a biomarker in chronic systolic heart failure are warranted. PMID:21622850

Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs.

PubMed

Marsella, Rosanna; Ahrens, Kim; Sanford, Rachel

2018-02-01

IL-31 is a cytokine that is believed to play an important role in atopic dermatitis (AD). IL-31 levels positively correlate with disease severity in children with AD. Currently, there is no study that has investigated such a correlation in atopic dogs. The purpose of this study was to evaluate the correlation between IL-31 serum levels and severity of dermatitis. It was hypothesized that a positive correlation exists between severity of AD and circulating levels of IL-31. Sixteen atopic beagles experimentally sensitized to house dust mites. Atopic beagles were exposed to dust mites epicutaneously twice weekly for four weeks. Severity of dermatitis was scored by the Canine Atopic Dermatitis and Extent Severity Index, 3 rd iteration (CADESI-03) on days 0 and 28. Blood samples were taken on days 0 and 28 to measure serum IL-31 using a commercially available ELISA. Correlation between CADESI-03 scores and serum IL-31 levels was not detected on day 0 (Pearson, r = -0.2609, P = 0.3291). After flare-up of dermatitis was induced with allergen exposure, a significant positive correlation was detected between serum IL-31 and CADESI-03 on Day 28 (r = 0.6738, P = 0.004). Positive correlation was detected in active disease between severity of dermatitis and circulating levels of IL-31. Additional studies are needed to investigate this correlation in other breeds of dogs and to test whether circulating levels of IL-31 may predict clinical response to biological agents aimed at IL-31. © 2017 ESVD and ACVD.

Polybrominated Diphenyl Ethers in Human Milk and Serum from the U.S. EPA MAMA Study: Modeled Predictions of Infant Exposure and Considerations for Risk Assessment

PubMed Central

Marchitti, Satori A.; Fenton, Suzanne E.; Mendola, Pauline; Kenneke, John F.; Hines, Erin P.

2016-01-01

Background: Serum concentrations of polybrominated diphenyl ethers (PBDEs) in U.S. women are believed to be among the world’s highest; however, little information exists on the partitioning of PBDEs between serum and breast milk and how this may affect infant exposure. Objectives: Paired milk and serum samples were measured for PBDE concentrations in 34 women who participated in the U.S. EPA MAMA Study. Computational models for predicting milk PBDE concentrations from serum were evaluated. Methods: Samples were analyzed using gas chromatography isotope-dilution high-resolution mass spectrometry. Observed milk PBDE concentrations were compared with model predictions, and models were applied to NHANES serum data to predict milk PBDE concentrations and infant intakes for the U.S. population. Results: Serum and milk samples had detectable concentrations of most PBDEs. BDE-47 was found in the highest concentrations (median serum: 18.6; milk: 31.5 ng/g lipid) and BDE-28 had the highest milk:serum partitioning ratio (2.1 ± 0.2). No evidence of depuration was found. Models demonstrated high reliability and, as of 2007–2008, predicted U.S. milk concentrations of BDE-47, BDE-99, and BDE-100 appear to be declining but BDE-153 may be rising. Predicted infant intakes (ng/kg/day) were below threshold reference doses (RfDs) for BDE-99 and BDE-153 but above the suggested RfD for BDE-47. Conclusions: Concentrations and partitioning ratios of PBDEs in milk and serum from women in the U.S. EPA MAMA Study are presented for the first time; modeled predictions of milk PBDE concentrations using serum concentrations appear to be a valid method for estimating PBDE exposure in U.S. infants. Citation: Marchitti SA, Fenton SE, Mendola P, Kenneke JF, Hines EP. 2017. Polybrominated diphenyl ethers in human milk and serum from the U.S. EPA MAMA Study: modeled predictions of infant exposure and considerations for risk assessment. Environ Health Perspect 125:706–713; http://dx.doi.org/10.1289/EHP332 PMID:27405099

Untangling the complex relationships between incident gout risk, serum urate, and its comorbidities.

PubMed

Sun, Mengying; Vazquez, Ana I; Reynolds, Richard J; Singh, Jasvinder A; Reeves, Mathew; Merriman, Tony R; Gaffo, Angelo L; Los Campos, Gustavo de

2018-05-03

Many gout comorbidities (e.g., hypertension) are correlated with serum urate. In this investigation, we identified risk factors (e.g., systolic blood pressure [SBP]), that (1) are associated with incident gout, (2) have effects on gout risk that cannot be fully explained by correlated differences in serum urate, and (3) may modulate the relationship between gout and serum urate. Using data from the Atherosclerosis Risk in Communities (ARIC) study, we estimated the unadjusted associations between gout and risk factors by calculating ORs and using chi-square tests. The adjusted associations were analyzed using logistic regression by sequentially adding (1) one risk factor at a time or (2) all risk factors, to a baseline model that includes serum urate only. Stepwise selection was used to select main effects. Two-way interactions of variables from the main effects model were also analyzed. Average gout incidence was 2.7 per 1000 people per year. Serum urate was highly associated with incident gout, with odd ratios of 3.16 [95% CI 2.11, 4.76] and 25.9 [95% CI 17.2, 38.4] for moderately high (6-8 mg/dl) and high serum urate (> 8 mg/dl), relative to normal serum urate (< 6 mg/dl), respectively. Ethnicity and SBP were independently and additively associated with gout after accounting for serum urate levels. No significant interactions were found between serum urate and ethnicity or SBP. Ethnicity and hypertension are predictive of gout risk, and the associations cannot be fully explained by serum urate. For serum urate levels near the crystallization threshold (6-8 mg/dl) African Americans and people with hypertension are at two to three times greater risk for developing gout. The gout risk for this group appears to increase before the onset of severe hyperuricemia.

Model to predict hyperbilirubinemia in healthy term and near-term newborns with exclusive breast feeding.

PubMed

Huang, Hsin-Chung; Yang, Hwai-I; Chang, Yu-Hsun; Chang, Rui-Jane; Chen, Mei-Huei; Chen, Chien-Yi; Chou, Hung-Chieh; Hsieh, Wu-Shiun; Tsao, Po-Nien

2012-12-01

The aim of this study was to identify high-risk newborns who will subsequently develop significant hyperbilirubinemia Days 4 to 10 of life by using the clinical data from the first three days of life. We retrospectively collected exclusively breastfeeding healthy term and near-term newborns born in our nursery between May 1, 2002, to June 30, 2005. Clinical data, including serum bilirubin were collected and the significant predictors were identified. Bilirubin level ≥15mg/dL during Days 4 to 10 of life was defined as significant hyperbilirubinemia. A prediction model to predict subsequent hyperbilirubinemia was established. This model was externally validated in another group of newborns who were enrolled by the same criteria to test its discrimination capability. Totally, 1979 neonates were collected and 1208 cases were excluded by our exclusion criteria. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during Days 4 to 10 of life. In the logistic regression analysis, gestational age, maximal body weight loss percentage, and peak bilirubin level during the first 72 hours of life were significantly associated with subsequent hyperbilirubinemia. A prediction model was derived with the area under receiver operating characteristic (AUROC) curve of 0.788. Model validation in the separate study (N = 209) showed similar discrimination capability (AUROC = 0.8340). Gestational age, maximal body weight loss percentage, and peak serum bilirubin level during the first 3 days of life have highest predictive value of subsequent significant hyperbilirubinemia. We provide a good model to predict the risk of subsequent significant hyperbilirubinemia. Copyright © 2012. Published by Elsevier B.V.

Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification (Part II): Psychiatric complaints and their relation to delta-9-tetrahydrocannabinol and its metabolites in serum.

PubMed

Bonnet, Udo; Borda, Thorsten; Scherbaum, Norbert; Specka, Michael

2015-10-01

To investigate the impact of inpatient detoxification treatment on psychiatric symptoms of chronic cannabis addicts and to analyze the influence of serum cannabinoid levels on the severity of these symptoms. Thirty five treatment-seeking, not active co-morbid chronic cannabis dependents (ICD-10) were studied on admission and on abstinence days 8 and 16, using several observational and self-report scales, such as Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Young Mania Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS), and the Symptom Checklist-90-Revised (SCL-90-R). Simultaneously obtained serum was analyzed with regard to levels of delta-9-tetrahydrocannabinol (THC) and its main metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). At admission, nearly 90% of the patients were not, or only mildly, affected by depression, anxiety or manic symptoms. In contrast, patients' self-description indicated a strong psychiatric burden in approximately 60% of the cases. All patients improved significantly within 16 days of the treatment. Effect sizes ranged from 0.7 to 1.4. (Cohen's d) for the respective scales. Serum THC-levels were positively associated with impairment of cognition in HAMA and motor retardation in BPRS. All other test results were not significantly related to the serum levels of the measured cannabinoids. Effects of the cannabis withdrawal syndrome and executive dysfunctions might explain the discrepancy between the observer ratings and self-reported psychiatric burden. Inpatient cannabis detoxification treatment significantly improved psychiatric symptoms. Serum THC-levels were not associated with affective symptoms and anxiety but predicted cognitive impairment and motor retardation. Copyright © 2015. Published by Elsevier Ireland Ltd.

Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies.

PubMed

Sharapova, T; Devanarayan, V; LeRoy, B; Liguori, M J; Blomme, E; Buck, W; Maher, J

2016-01-01

MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases. © The Author(s) 2015.

Method for identifying type I diabetes mellitus in humans

DOEpatents

Metz, Thomas O [Kennewick, WA; Qian, Weijun [Richland, WA; Jacobs, Jon M [Pasco, WA; Smith, Richard D [Richland, WA

2011-04-12

A method and system for classifying subject populations utilizing predictive and diagnostic biomarkers for type I diabetes mellitus. The method including determining the levels of a variety of markers within the serum or plasma of a target organism and correlating this level to general populations as a screen for predisposition or progressive monitoring of disease presence or predisposition.

[Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction].

PubMed

Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Cumsille, Miguel Angel

2012-05-01

Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselected pregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.

New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

PubMed

Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

2017-05-01

The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

Serum Trimethylamine N-oxide, Carnitine, Choline and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol and Beta Carotene Study

PubMed Central

Guertin, Kristin A.; Li, Xinmin S.; Graubard, Barry I.; Albanes, Demetrius; Weinstein, Stephanie J.; Goedert, James J.; Wang, Zeneng; Hazen, Stanley L.; Sinha, Rashmi

2017-01-01

Background TMAO, a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk. Methods We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC-MS/MS. Logistic regression models estimated the odds ratio (OR) and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine and betaine concentrations. Results Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ±10 years (in fully adjusted models, Q4 vs. Q1 OR, 3.22; 95% CI, 2.24–4.61; P trend<0.0001). The prognostic value of serum choline for prediction of incident colorectal cancer development was similarly robust for proximal, distal and rectal colon cancers (all P<0.0001). The association between serum TMAO, carnitine, or betaine and colorectal cancer risk was not statistically significant (P=0.25, P=0.71 and P=0.61, respectively). Conclusions Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer. Impact Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risks across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis. PMID:28077427

Serum Trimethylamine N-oxide, Carnitine, Choline, and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study.

PubMed

Guertin, Kristin A; Li, Xinmin S; Graubard, Barry I; Albanes, Demetrius; Weinstein, Stephanie J; Goedert, James J; Wang, Zeneng; Hazen, Stanley L; Sinha, Rashmi

2017-06-01

Background: Trimethylamine N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk. Methods: We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine, and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC/MS-MS. Logistic regression models estimated the ORs and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine, and betaine concentrations. Results: Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ± 10 years (in fully adjusted models, Q4 vs. Q1, OR, 3.22; 95% CI, 2.24-4.61; P trend < 0.0001). The prognostic value of serum choline for prediction of incident colorectal cancer was similarly robust for proximal, distal, and rectal colon cancers (all P < 0.0001). The association between serum TMAO, carnitine, or betaine and colorectal cancer risk was not statistically significant ( P = 0.25, 0.71, and 0.61, respectively). Conclusions: Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer. Impact: Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risk across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis. Cancer Epidemiol Biomarkers Prev; 26(6); 945-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure?

PubMed

Lala, Radu Ioan; Darabantiu, Dan; Pilat, Luminita; Puschita, Maria

2016-02-01

Heart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression. The aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients. A total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed. Elevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young's modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions. This study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.

[The Role of Urinary Lipocalin in Prognostication of Hospital Complications in Patients With Ischemic Heart Disease After Coronary Artery Bypass Grafting].

PubMed

Shafranskaya, K S; Kuzmina, O K; Sumin, D A; Krivoshapova, K Ye; Uchasova, Ye G; Ivanov, S V; Zykov, M V; Kashtalap, V V; Barbarash, O L

2016-10-01

To assess significance of urinary neutrophil gelatinase-associated lipocalin (NGAL) for predicting hospital complications in subjects with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG). The study included 720 subjects who underwent CABG between 03/2011 and 04/2012. Blood serum creatinine level, glomerular filtration rate (GFR) (MDRD formula) and NGAL concentration were measured before and on day 7 after CABG. The following unfavorable outcomes of operative intervention: myocardial infarction (MI), stroke or transient ischemic attack, acute or progression of chronic renal disease, remediastinotomy were registered during in-hospital period. Additive EuroSCORE was calculated for all patients. There were no significant differences in serum creatinine level and GFR both before and on day 7 after CABG between groups of patients with different risk assessed by EuroSCORE, and with complicated and uncomplicated postoperative course. Urine NGAL level before and on day 7 after CABG was significantly higher in high and medium compared with low EuroSCORE risk groups. Preoperative NGAL urine level was significantly higher in patients with than in those without MI or stroke after CABG. NGAL urine level was also higher in patients with development of acute renal failure (ARF) compared with those without ARF. Both pre- and postoperative NGAL urine levels were higher in patients with unfavorable outcome while there were no significant differences in serum creatinine levels and CRF between patients with favorable and unfavorable outcomes. Preoperative measurement of urinary NGAL - a preclinical marker of acute kidney injury - allowed to predict more accurately the hospital risk of development of adverse cardiovascular and renal complications of CABG.

Levels of serum uric acid at admission for hypoglycaemia predict 1-year mortality.

PubMed

Bonaventura, Aldo; Gallo, Fiorenza; Carbone, Federico; Liberale, Luca; Maggi, Davide; Sacchi, Giovanni; Dallegri, Franco; Montecucco, Fabrizio; Cordera, Renzo

2018-04-01

Hypoglycaemia represents a critical burden with clinical and social consequences in the management of diabetes. Serum uric acid (SUA) has been associated with cardiovascular diseases (CVD), but no conclusive findings are available nowadays in patients suffering from hypoglycaemia. We investigated whether SUA levels at the time of hypoglycaemia could predict all-cause mortality after 1-year follow-up. In total, 219 patients admitted to the Emergency Department (ED) of Ospedale Policlinico S. Martino of Genoa (Italy) have been enrolled between January 2011 and December 2014. The primary endpoint of the study consisted in determining whether SUA levels at the time of ED admission could predict the occurrence of death after 1 year. The majority of patients were diabetic, especially type 2. CVD and chronic kidney disease were prevalent comorbidities. By a cut-off value obtained by the receiver operating characteristic curve analysis, a Kaplan-Meier analysis demonstrated that patients with SUA levels > 5.43 mg/dL were more prone to death after 1 year compared to those with lower SUA levels. The risk of death increased with high SUA levels both in the univariate and the multivariate models including estimated glomerular filtration rate, C-reactive protein, type of diabetes, and age-adjusted Charlson comorbidity index. SUA could be useful as a predictor of 1-year mortality in hypoglycaemic patients, irrespective of severe comorbidities notably increasing the risk of death in these frail patients.

High serum testosterone levels during postpartum period are associated with postpartum depression.

PubMed

Aswathi, A; Rajendiren, Soundravally; Nimesh, Archana; Philip, R Ravi; Kattimani, Shivanand; Jayalakshmi, D; Ananthanarayanan, P H; Dhiman, Pooja

2015-10-01

In view of the reported cases of mood disorders that occur in mothers following childbirth and believing that sex steroid hormones contribute to mood and behavioral changes, this study has been aimed to explore the role of sex steroid hormones as an etiological factor for postpartum depression (PPD). This study was conducted at JIPMER, Puducherry, India between January 2010 and 2011. 103 women were recruited in the study after childbirth, out of which 62 women who were believed to be suffering from PPD were categorized as cases and the remaining 41 with no mood changes as controls, using Edinburgh Postpartum Depression Scale (EPDS) (cases had EPDS score ≥10 at 24-28h, controls had score <10 at 24-48h postpartum). The hormones estimated in these two groups included estradiol, progesterone and testosterone, and their levels were compared between these two groups. A significantly high testosterone levels were observed in cases with PPD at 24-28h when compared to controls. Estradiol and progesterone levels did not show significant difference between cases and controls. ROC analysis done at 24-28h showed that testosterone levels beyond 42.71ng/mL predict the development of PPD with 79% sensitivity, 63% specificity, 68% positive predictive value, 74% negative predictive value with AUC being 0.708. This study shows that there is an association between persistent high serum testosterone level in women following childbirth and PPD. Copyright © 2015 Elsevier B.V. All rights reserved.

Serum levels of prostate-specific antigen and vitamin D in peritoneal dialysis patients.

PubMed

Passadakis, Ploumis; Ersoy, Fevzi; Tam, Paul; Memmos, Dimitrios; Siamopoulos, Konstantinos; Ozener, Cetin; Akçiçek, Fehmi; Camsari, Taner; Ates, Kenan; Ataman, Rezzan; Vlachojannis, John; Dombros, Nicholas; Utas, Cengiz; Akpolat, Tekin; Bozfakioglu, Semra; Wu, George G; Karayaylali, Ibrahim; Arinsoy, Tekin; Stathakis, Charalampos; Yavuz, Mahmut; Tsakiris, Dimitrios; Dimitriades, Athanasios; Yilmaz, Mehmet E; Gültekin, Meral; Karayalçin, Binnur; Challa, Anna; Polat, Nese; Oreopoulos, Dimitrios G

2004-01-01

Measuring the free:total ratio of prostate-specific antigen (f/t-PSA) can improve the specificity of single-serum PSA values, distinguishing between benign prostatic hyperplasia (BPH) and prostatic carcinoma (PCa) in men over the age of 50. Additionally, clinical trials have shown that dihydroxyvitamin D3 can slow the rate of PSA rise in PCa patients. However, little is known regarding the applicability of those findings in men undergoing chronic peritoneal dialysis (CPD). In the present study, we investigated the prevalence of increased serum PSA levels among CPD patients and correlated those values with serum levels of vitamin D [25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3]. We undertook a cross-sectional study of 71 male CPD patients without a known history of prostate cancer from 24 centers in Canada, Greece, and Turkey. All of the patients were more than 50 years of age. In these patients, we measured serum concentrations of PSA, free PSA (f-PSA), total PSA (t-PSA), prostate alkaline phosphatase (PAP), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone (iPTH). We recorded serum PSA levels < 4 ng/mL in 62 patients (87.3%, group A) and levels > 4 ng/mL in 9 patients (12.7%, group B). The f/t-PSA ratio was < 0.25 in 16 patients (22.5%). Group B patients were older than those in group A (median: 73 years vs. 65 years, p < 0.01) and had a lower body weight (median: 66.5 kg vs. 76.7 kg, p < 0.05). We observed no statistically significant difference between the two groups for serum 1,25-dihydroxyvitamin D3 (median: 9.8 ng/mL vs. 10.1 ng/mL) or 25-hydroxyvitamin D3 (8 ng/mL vs. 8.2 ng/mL) levels. Also, we observed no correlation between vitamin D levels and f/t-PSA, but iPTH levels were significantly higher in group A (200.5 pg/mL vs. 61.2 pg/mL, p < 0.04). Also, serum PAP levels correlated significantly with PSA (r = 0.49, p = 0.01) and with f-PSA (r = 0.56, p = 0.000). Our results showed no clear relationship between vitamin D and serum levels of PSA or-of f/t-PSA in PD patients. However, further studies are needed to better define the uses of these PSA markers in PD patients because, in such patients, other relevant factors might be implicated in their predictive value.

Calprotectin and TNF trough serum levels identify power Doppler ultrasound synovitis in rheumatoid arthritis and psoriatic arthritis patients in remission or with low disease activity.

PubMed

Inciarte-Mundo, José; Ramirez, Julio; Hernández, Maria Victoria; Ruiz-Esquide, Virginia; Cuervo, Andrea; Cabrera-Villalba, Sonia Raquel; Pascal, Mariona; Yagüe, Jordi; Cañete, Juan D; Sanmarti, Raimon

2016-07-08

Serum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi. We conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate <3.2). Associations of calprotectin, TNFi trough serum levels and acute phase reactants with PDUS synovitis were assessed using correlation and linear regression analyses. The accuracy and discriminatory capacity in detecting PDUS synovitis was assessed using ROC curves. PDUS synovitis was found in 62.4 % of RA patients and 32 % of PsA patients. Both RA and PsA patients with PDUS synovitis had higher calprotectin levels and lower TNFi trough serum levels. Calprotectin positively correlated with ultrasound scores (all r coefficients >0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was ≥1.66 μg/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52-0.85, p < 0.001) but their accuracy (AUC <0.5) was less than that of calprotectin. TNFi trough serum levels were inversely correlated with calprotectin and PDUS synovitis in RA and PsA patients receiving ADA and ETN. Calprotectin and TNFi trough serum levels may help identify PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity.

Elevated Cystatin C Levels Are Associated with Cognitive Impairment and Progression of Parkinson Disease.

PubMed

Hu, Wei-Dong; Chen, Jing; Mao, Cheng-Jie; Feng, Ping; Yang, Ya-Ping; Luo, Wei-Feng; Liu, Chun-Feng

2016-09-01

We investigated the relationship between serum cystatin C (CysC) levels and cognitive dysfunction and disease progression in patients with Parkinson disease. Previous studies have reported altered CysC levels in neurodegenerative disorders, but only a few studies have explored the role of CysC and its relationship to cognitive dysfunction in Parkinson disease. We measured serum levels of CysC, creatinine, urea, and uric acid in 142 patients with Parkinson disease and 146 healthy controls. We assessed disease progression using the Hoehn and Yahr scale, and cognitive function using the Montreal Cognitive Assessment (Beijing version). The patients with Parkinson disease had significantly higher CysC levels than the controls (P<0.001). CysC level correlated significantly with age (r=0.494, P<0.001), sex (r=0.150, P=0.011), and serum creatinine level (r=0.377, P<0.001), but not with levels of urea or uric acid (P>0.05). CysC level was a significant independent predictor of Parkinson disease (odds ratio=23.143, 95% confidence interval: 5.485-97.648, P<0.001) in multivariate logistic regression analysis. In the Parkinson disease group, a higher CysC level was associated with a more advanced Hoehn and Yahr stage (r=0.098, P<0.05) and a lower Montreal Cognitive Assessment score (r=-0.381, P=0.003). Serum CysC levels can predict disease severity and cognitive dysfunction in patients with Parkinson disease. The exact role of CysC remains to be determined.

Serum biomarkers as predictors of long-term outcome in severe traumatic brain injury: analysis from a randomized placebo-controlled Phase II clinical trial.

PubMed

Raheja, Amol; Sinha, Sumit; Samson, Neha; Bhoi, Sanjeev; Subramanian, Arulselvi; Sharma, Pushpa; Sharma, Bhawani Shankar

2016-09-01

OBJECTIVE There has been increased interest in the potential importance of biochemical parameters as predictors of outcome in severe traumatic brain injury (sTBI). METHODS Of 107 patients with sTBI (age 18-65 years with a Glasgow Coma Scale score of 4-8 presenting within 8 hours after injury) who were randomized for a placebo-controlled Phase II trial of progesterone with or without hypothermia, the authors serially analyzed serum biomarkers (S100-B, glial fibrillary acidic protein [GFAP], neuron-specific enolase [NSE], tumor necrosis factor-α, interleukin-6 [IL-6], estrogen [Eg], and progesterone [Pg]). This analysis was performed using the sandwich enzyme-linked immunosorbent assay technique at admission and 7 days later for 86 patients, irrespective of assigned group. The long-term predictive values of serum biomarkers for dichotomized Glasgow Outcome Scale (GOS) score, functional independence measure, and survival status at 6 and 12 months were analyzed using an adjusted binary logistic regression model and receiver operating characteristic curve. RESULTS A favorable GOS score (4-5) at 1 year was predicted by higher admission IL-6 (above 108.36 pg/ml; area under the curve [AUC] 0.69, sensitivity 52%, and specificity 78.6%) and Day 7 Pg levels (above 3.15 ng/ml; AUC 0.79, sensitivity 70%, and specificity 92.9%). An unfavorable GOS score (1-3) at 1 year was predicted by higher Day 7 GFAP levels (above 9.50 ng/ml; AUC 0.82, sensitivity 78.6%, and specificity 82.4%). Survivors at 1 year had significantly higher Day 7 Pg levels (above 3.15 ng/ml; AUC 0.78, sensitivity 66.7%, and specificity 90.9%). Nonsurvivors at 1 year had significantly higher Day 7 GFAP serum levels (above 11.14 ng/ml; AUC 0.81, sensitivity 81.8%, and specificity 88.9%) and Day 7 IL-6 serum levels (above 71.26 pg/ml; AUC 0.87, sensitivity 81.8%, and specificity 87%). In multivariate logistic regression analysis, independent predictors of outcome at 1 year were serum levels of Day 7 Pg (favorable GOS-OR 3.24, CI 1.5-7, p = 0.003; and favorable survival-OR 2, CI 1.2-3.5, p = 0.01); admission IL-6 (favorable GOS-OR 1.04, CI 1.00-1.08, p = 0.04); and Day 7 GFAP (unfavorable GOS-OR 0.79, CI 0.65-0.95, p = 0.01; and unfavorable survival-OR 0.80, CI 0.66-0.96, p = 0.01). CONCLUSIONS Serial Pg, GFAP, and IL-6 monitoring could aid in prognosticating outcomes in patients with acute sTBI. A cause and effect relationship or a mere association of these biomarkers to outcome needs to be further studied for better understanding of the pathophysiology of sTBI and for choosing potential therapeutic targets. Clinical trial registration no.: CTRI/2009/091/000893 ( http://www.ctri.nic.in ).

Predictive impact of polymorphism of PNPLA3 on HCC development after interferon therapy in Japanese patients with chronic hepatitis C.

PubMed

Moritou, Yuki; Ikeda, Fusao; Iwasaki, Yoshiaki; Baba, Nobuyuki; Takaguchi, Kouichi; Senoh, Tomonori; Nagano, Takuya; Takeuchi, Yasuto; Yasunaka, Tetsuya; Ohnishi, Hideki; Miyake, Yasuhiro; Takaki, Akinobu; Nouso, Kazuhiro; Yamamoto, Kazuhide

2013-12-01

The impact of single-nucleotide polymorphisms (SNP) of patatin-like phospholipase domain-containing protein 3 (PNPLA3) on development of hepatocellular carcinoma (HCC) is not clarified for Japanese patients with chronic hepatitis C. The present study investigated the associations of rs738409 PNPLA3 with HCC development after the antiviral therapy with peg-interferon and ribavirin for Japanese patients with hepatitis C virus serotype 1 and high viral load. Of the 271 patients enrolled in the study, 20 patients developed HCC, during a median follow-up period of 4.6 years. Multivariate analysis in the proportional hazards models revealed that sex, body mass index, platelet counts, and alpha feroprotein (AFP) had significant associations with HCC development (p = 0.011, 0.029, 0.0002, and 0.046, respectively). Multivariate regression analysis revealed that PNPLA3 148 M was significantly associated with serum AFP level (p = 0.032), other than body mass index, platelet count, and alanine aminotransferase (p = 0.0006, 0.0002, and 0.037, respectively), and that serum AFP level was significantly associated with PNPLA3 148 M (p = 0.017). Serum AFP level is an important factor in predicting HCC development after the antiviral therapy for Japanese patients with chronic hepatitis C, the mechanism of which might involve its significant associations with the SNP genotype of PNPLA3.

Overexpression of stathmin plays a pivotal role in the metastasis of esophageal squamous cell carcinoma

PubMed Central

Han, Gaijing; Wu, Zongyong; Zhao, Nan; Zhou, Lanping; Liu, Fang; Niu, Fangfei; Xu, Yang; Zhao, Xiaohang

2017-01-01

Purpose Esophageal squamous cell carcinoma (ESCC) is a serious malignant tumor that affects human health. We analyzed the correlation between serum stathmin level and ESCC and elucidated the molecular mechanisms of stathmin's promotion of ESCC cell invasion and metastasis. Methods Stathmin level in ESCC and healthy control serum were detected by enzyme-linked immunosorbent assay (ELISA), and the clinical parameters were analyzed. We established ESCC cells with stathmin overexpression or knockdown and then evaluated the effects of stathmin on invasion and metastasis in ESCC. Differentially expressed genes were analyzed by Human Transcriptome Array and confirmed by RT-PCR. The expression levels of the integrin family, focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) were detected by immunoblotting. Results Serum levels of stathmin were significantly higher in ESCC than in control serum and associated with lymph node metastasis, tumor stage and size. Furthermore, we found that stathmin promoted migration and invasion of ESCC cells in vitro and in vivo. In addition, we confirmed that the activation of the integrinα5β1/FAK/ERK pathway is increased in stathmin-overexpression cells and accelerates cell motility by enhancing cell adhesion ability. Conclusion Stathmin may predict a potential metastasis biomarker for ESCC. PMID:28977901

Serum Levels of Toxic AGEs (TAGE) May Be a Promising Novel Biomarker for the Onset/Progression of Lifestyle-Related Diseases.

PubMed

Takeuchi, Masayoshi

2016-06-07

Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE)), were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer's disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD.

Serum Levels of Toxic AGEs (TAGE) May Be a Promising Novel Biomarker for the Onset/Progression of Lifestyle-Related Diseases

PubMed Central

Takeuchi, Masayoshi

2016-01-01

Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE)), were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer’s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD. PMID:27338481

Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus.

PubMed

Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Park, Ji Hyun; Park, Sung Kwang; Yi, Ho Keun; Lee, Dae-Yeol

2006-03-01

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

Accuracy of prediction equations for serum osmolarity in frail older people with and without diabetes1234

PubMed Central

Siervo, Mario; Bunn, Diane; Prado, Carla M; Hooper, Lee

2014-01-01

Background: Serum osmolality is an accurate indicator of hydration status in older adults. Glucose, urea, and electrolyte concentrations are used to calculate serum osmolarity, which is an indirect estimate of serum osmolality, but which serum osmolarity equations best predict serum osmolality in the elderly is unclear. Objective: We assessed the agreement of measured serum osmolality with calculated serum osmolarity equations in older people. Design: Serum osmolality was measured by using freezing point depression in a cross-sectional study. Plasma glucose, urea, and electrolytes were analyzed and entered into 38 serum osmolarity-prediction equations. The Bland-Altman method was used to evaluate the agreement and differential bias between measured osmolality and calculated osmolarity. The sensitivity and specificity of the most-promising equations were examined against serum osmolality (reference standard). Results: A total of 186 people living in UK residential care took part in the Dehydration Recognition In our Elders study (66% women; mean ± SD age: 85.8 ± 7.9 y; with a range of cognitive and physical impairments) and were included in analyses. Forty-six percent of participants had impending or current dehydration (serum osmolality ≥295 mmol/kg). Participants with diabetes (n = 33; 18%) had higher glucose (P < 0.001) and serum osmolality (P < 0.01). Of 38 predictive equations used to calculate osmolarity, 4 equations showed reasonable agreement with measured osmolality. One [calculated osmolarity = 1.86 × (Na+ + K+) + 1.15 × glucose + urea +14; all in mmol/L] was characterized by narrower limits of agreement and the capacity to predict serum osmolality within 2% in >80% of participants, regardless of diabetes or hydration status. The equation's sensitivity (79%) and specificity (89%) for impending dehydration (≥295 mmol/kg) and current dehydration (>300 mmol/kg) (69% and 93%, respectively) were reasonable. Conclusions: The assessment of a panel of equations for the prediction of serum osmolarity led to identification of one formula with a greater diagnostic performance. This equation may be used to predict hydration status in frail older people (as a first-stage screening) or to estimate hydration status in population studies. This trial was registered at the Research Register for Social Care (http://www.researchregister.org.uk) as 122273. PMID:25030781

Apolipoprotein E polymorphism and lipoprotein levels in a Gulf Arab population in Kuwait: a pilot study.

PubMed

Al-Shammari, S; Fatania, H; Al-Radwan, R; Akanji, A O

2004-01-01

APOE polymorphism is believed to confer susceptibility to coronary heart disease (CHD) and Alzheimer's disease. It is well known that patterns of APOE polymorphisms differ between populations and ethnic groups, although most of the data available so far have been in whites. We evaluated the frequencies of APOE genotypes and their relationships with serum levels of lipids, lipoproteins and apolipoproteins in two groups of Gulf Arab citizens: a control population of healthy voluntary blood donors (n=106), and a group of patients presenting to the lipid clinic for the first time with combined hyperlipidaemia (CH) (n=41). In both groups, fasting serum total cholesterol (TC), triglycerides (TG), HDL, LDL and apolipoprotein A1 and B levels were measured by routine autoanalyzer methods, and APOE genotyping was performed by validated PCR methods. The lipid and lipoprotein levels were related to the specific APOE allele frequencies. Allele frequencies were 5.7% for *E2, 85.4% for *E3, and 9.0% for *E4 in the healthy blood donor group. An essentially similar pattern was seen in the patients with CH. This APOE allelic distribution conforms to patterns described in Chinese, whites and South Asians. In both the blood donor and CH groups there were no consistent links between specific APOE pattern and serum lipoproteins, as would have been predicted from APO *E2 and APO *E4 frequencies. We conclude that APOE allelic patterns in healthy Kuwaiti blood donors and a smaller group of patients with CH do not satisfactorily predict circulating blood levels of lipids and lipoproteins.

Role of serum immunoglobulins for predicting sarcoidosis outcome: A cohort study.

PubMed

Belhomme, Nicolas; Jouneau, Stéphane; Bouzillé, Guillaume; Decaux, Olivier; Lederlin, Mathieu; Guillot, Stéphanie; Perlat, Antoinette; Jégo, Patrick

2018-01-01

Sarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis. We conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients. Eighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01-1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4-24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years. There was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.

Serum iron parameters in liver cirrhosis

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Maail, W.

2018-03-01

The liver plays a fundamental role in iron homeostasis. Iron parameters change, especially ferritin, need to be evaluated in patients with liver cirrhosis. Serum ferritin could predict the prognosis of patients with decompensated cirrhosis since it reflects immunemediated and infectious stimuli. Ferritin could express the severity of liver disease and possible subsequent complications. Finally, it might reflect an iron overload condition resulting in significant morbidity and early mortality. 70 patients with decompensated liver cirrhosis divided into three Child-Pugh subgroups. Serum iron parameters include serum iron (SI), total iron binding capacity (TIBC) and ferritin was measured in these groups. From these 70 patients, 30 (42.9%) with HbsAg positive, 26 (37.1%) with anti-HCV positive and 14 (20%) with both HbsAg and anti-HCV positive. Of the 70 patients, 14 (20%) had CTP Class A cirrhosis, 17 (24.3%) had CTP Class B cirrhosis, and 39 (55.7%) had CTP C cirrhosis. The median (range) value of serum iron was 36 (10-345) μg/dl, TIBC was 160 (59-520) μg/dl, Ferritin was 253.5 (8-6078) ng/ml and the transferrin saturation was 22.9 (3.65-216.98) %.We found a significant difference in serum ferritin level with CTP score. Ferritin levels increased as Child-Pugh class progressed (p<0.001).

Evaluation of Serum Vascular Adhesion Protein-1 as a Potential Biomarker in Thyroid Cancer

PubMed Central

Zhao, Pengxin; Zhang, Kaili

2016-01-01

Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules) and subgroup 2 (57 cases with thyroid cancer). Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC) curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg) levels in thyroid cancer patients (r = −0.81; p < 0.001). The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer. PMID:27446209

Mid-regional proadrenomedullin: An early marker of response in critically ill patients with severe community-acquired pneumonia?

PubMed

Pereira, J M; Azevedo, A; Basílio, C; Sousa-Dias, C; Mergulhão, P; Paiva, J A

Mid-regional proadrenomedullin (MR-proADM) is a novel biomarker with potential prognostic utility in patients with community-acquired pneumonia (CAP). To evaluate the value of MR-proADM levels at ICU admission for further severity stratification and outcome prediction, and its kinetics as an early predictor of response in severe CAP (SCAP). Prospective, single-center, cohort study of 19 SCAP patients admitted to the ICU within 12h after the first antibiotic dose. At ICU admission median MR-proADM was 3.58nmol/l (IQR: 2.83-10.00). No significant association was found between its serum levels at admission and severity assessed by SAPS II (Spearman's correlation=0.24, p=0.31) or SOFA score (SOFA<10: <3.45nmol/l vs. SOFA≥10: 3.90nmol/l, p=0.74). Hospital and one-year mortality were 26% and 32%, respectively. No significant difference in median MR-proADM serum levels was found between survivors and non-survivors and its accuracy to predict hospital mortality was bad (aROC 0.53). After 48h of antibiotic therapy, MR-proADM decreased in all but 5 patients (median -20%; IQR -56% to +0.1%). Its kinetics measured by the percent change from baseline was a good predictor of clinical response (aROC 0.80). The best discrimination was achieved by classifying patients according to whether MR-proADM decreased or not within 48h. No decrease in MR-proADM serum levels significantly increased the chances of dying independently of general severity (SAPS II-adjusted OR 174; 95% CI 2-15,422; p=0.024). In SCAP patients, a decrease in MR-proADM serum levels in the first 48h after ICU admission was a good predictor of clinical response and better outcome. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Serum levels of interleukin-9 correlate with negative prognostic factors in extranodal NK/T-cell lymphoma.

PubMed

Zhang, Jing; Wang, Wei-da; Geng, Qi-Rong; Wang, Liang; Chen, Xiao-Qin; Liu, Cheng-Cheng; Lv, Yue

2014-01-01

Interleukin-9 (IL-9) is more functionally diverse than previously expected, especially with regards to lymphomagenesis. However, the relationship between IL-9 and the clinicopathological features of extranodal NK/T-cell lymphoma is less well established. Patients with this lymphoma in Sun Yat-Sen University Cancer Center between January 2003 and March 2013 were systematically reviewed in an intention-to-treat analysis. Baseline serum IL-9 levels were determined using sandwich enzyme-linked immunosorbent assays. A total of seventy-four patients were enrolled in this study. The mean concentration of serum IL-9 for all patients was 6.48 pg/mL (range: 1.38-51.87 pg/mL). Age, B symptoms and local lymph node involvement were found to be related to high serum IL-9 levels. Patients with low IL-9 levels tended to have higher rates of complete remission. Notably, the median progression-free survival (PFS) and overall survival (OS) were longer in the low IL-9 level group than in the high IL-9 level group (PFS: 68.7 months vs. 28.3 months, P<0.001; OS: 86 months vs. 42.8 months, P = 0.001). Multivariate analysis revealed independent prognostic factors for PFS. Similarly, high IL-9 levels (P = 0.003) and old age (P = 0.007) were independently predictive of shorter OS. Serum IL-9 is closely related to several clinical features, such as age, B symptoms and local lymph node involvement. It can also be a significant independent prognostic factor for extranodal NK/T-cell lymphoma, which suggests a role for IL-9 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.

Serum and Plasma Metabolomic Biomarkers for Lung Cancer.

PubMed

Kumar, Nishith; Shahjaman, Md; Mollah, Md Nurul Haque; Islam, S M Shahinul; Hoque, Md Aminul

2017-01-01

In drug invention and early disease prediction of lung cancer, metabolomic biomarker detection is very important. Mortality rate can be decreased, if cancer is predicted at the earlier stage. Recent diagnostic techniques for lung cancer are not prognosis diagnostic techniques. However, if we know the name of the metabolites, whose intensity levels are considerably changing between cancer subject and control subject, then it will be easy to early diagnosis the disease as well as to discover the drug. Therefore, in this paper we have identified the influential plasma and serum blood sample metabolites for lung cancer and also identified the biomarkers that will be helpful for early disease prediction as well as for drug invention. To identify the influential metabolites, we considered a parametric and a nonparametric test namely student׳s t-test as parametric and Kruskal-Wallis test as non-parametric test. We also categorized the up-regulated and down-regulated metabolites by the heatmap plot and identified the biomarkers by support vector machine (SVM) classifier and pathway analysis. From our analysis, we got 27 influential (p-value<0.05) metabolites from plasma sample and 13 influential (p-value<0.05) metabolites from serum sample. According to the importance plot through SVM classifier, pathway analysis and correlation network analysis, we declared 4 metabolites (taurine, aspertic acid, glutamine and pyruvic acid) as plasma biomarker and 3 metabolites (aspartic acid, taurine and inosine) as serum biomarker.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors.

PubMed

Bernhard, Felix P; Heinzel, Sebastian; Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

PubMed Central

Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders. PMID:26967642

Hyaluronic acid concentration in liver diseases.

PubMed

Gudowska, Monika; Gruszewska, Ewa; Panasiuk, Anatol; Cylwik, Bogdan; Flisiak, Robert; Świderska, Magdalena; Szmitkowski, Maciej; Chrostek, Lech

2016-11-01

The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn's index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC)-57 patients, non-alcoholic cirrhosis (NAC)-30 and toxic hepatitis (HT)-22. Cirrhotic patients were classified according to Child-Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child-Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful.

Serum cytokine/chemokine profiles in patients with dengue fever (DF) and dengue hemorrhagic fever (FHD) by using protein array.

PubMed

Oliveira, Renato Antonio Dos Santos; Cordeiro, Marli Tenório; Moura, Patrícia Muniz Mendes Freire de; Baptista Filho, Paulo Neves Bapti; Braga-Neto, Ulisses de Mendonça; Marques, Ernesto Torres de Azevedo; Gil, Laura Helena Vega Gonzales

2017-04-01

DENV infection can induce different clinical manifestations varying from mild forms to dengue fever (DF) or the severe hemorrhagic fever (DHF). Several factors are involved in the progression from DF to DHF. No marker is available to predict this progression. Such biomarker could allow a suitable medical care at the beginning of the infection, improving patient prognosis. The aim of this study was to compare the serum expression levels of acute phase proteins in a well-established cohort of dengue fever (DF) and dengue hemorrhagic fever (DHF) patients, in order to individuate a prognostic marker of diseases severity. The serum levels of 36 cytokines, chemokines and acute phase proteins were determined in DF and DHF patients and compared to healthy volunteers using a multiplex protein array and near-infrared (NIR) fluorescence detection. Serum levels of IL-1ra, IL-23, MIF, sCD40 ligand, IP-10 and GRO-α were also determined by ELISA. At the early stages of infection, GRO-α and IP-10 expression levels were different in DF compared to DHF patients. Besides, GRO-α was positively correlated with platelet counts and IP-10 was negatively correlated with total protein levels. These findings suggest that high levels of GRO-α during acute DENV infection may be associated with a good prognosis, while high levels of IP-10 may be a warning sign of infection severity. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum Iron Protects from Renal Postischemic Injury.

PubMed

Vaugier, Céline; Amano, Mariane T; Chemouny, Jonathan M; Dussiot, Michael; Berrou, Claire; Matignon, Marie; Ben Mkaddem, Sanae; Wang, Pamella H M; Fricot, Aurélie; Maciel, Thiago T; Grapton, Damien; Mathieu, Jacques R R; Beaumont, Carole; Peraldi, Marie-Noëlle; Peyssonnaux, Carole; Mesnard, Laurent; Daugas, Eric; Vrtovsnik, François; Monteiro, Renato C; Hermine, Olivier; Ginzburg, Yelena Z; Benhamou, Marc; Camara, Niels O S; Flamant, Martin; Moura, Ivan C

2017-12-01

Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients ( n =169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF- κ B and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants. Copyright © 2017 by the American Society of Nephrology.

Serum copper concentration as an index of clinical lung injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molteni, A.; Ward, W.F.; Kim, Y.T.

1989-01-01

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer, and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smokemore » inhalation. Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients.« less

Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males

PubMed Central

Shoji, Tatsuya; Shinzawa, Maki; Hasuike, Yukiko; Nagatoya, Katsuyuki; Yamauchi, Atsushi; Hayashi, Terumasa; Kuragano, Takayuki; Moriyama, Toshiki; Isaka, Yoshitaka; Nakanishi, Takeshi

2016-01-01

Background Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. Study Design Multicenter retrospective cohort study. Setting & Participants 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. Predictor Uric acid levels at renal biopsy. Outcomes The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". Measurements The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. Results An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. Limitations A cohort analyzed retorospectively. Conclusions This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients. PMID:27560997

Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab.

PubMed

Suzukawa, Maho; Matsumoto, Hisako; Ohshima, Nobuharu; Tashimo, Hiroyuki; Asari, Isao; Tajiri, Tomoko; Niimi, Akio; Nagase, Hiroyuki; Matsui, Hirotoshi; Kobayashi, Nobuyuki; Shoji, Shunsuke; Ohta, Ken

2018-01-01

Omalizumab, a humanized anti-IgE monoclonal antibody, is the first molecularly targeted drug for severe asthmatics. However, responses to omalizumab vary widely among patients. This study aimed to assess the potential of baseline serum cytokine levels as predictors of responsiveness to omalizumab. Thirty-one patients with severe, persistent asthma were enrolled in this study and administered omalizumab for at least 1 year. Response to omalizumab was assessed based on the physician's global evaluation of treatment effectiveness (GETE) at 48 weeks of treatment. Blood samples were collected at baseline and 16 and 32 weeks after starting omalizumab and measured for 30 cytokines by Luminex 200 and ELISA. Exhaled nitric oxide (FeNO) levels, peripheral blood eosinophil counts, pre-bronchodilator pulmonary functions and Asthma Quality of Life Questionnaire scores were determined at baseline and 16, 32 and 48 weeks after starting omalizumab. The numbers of clinically significant asthma exacerbations in the previous year and during 48 weeks of treatment with omalizumab were assessed. GETE assessment showed 19 responders (61.3%) and 12 non-responders (38.7%). Responders showed significantly higher levels of CXCL10 and IL-12 at baseline compared to non-responders (CXCL10: responders, 1530.0 ± 315.2 pg/ml vs. non-responders, 1066.0 ± 396.8 pg/ml, P = 0.001; IL-12: responders, 60.2 ± 39.2 pg/ml vs. non-responders, 32.2 ± 26.3 pg/ml, P = 0.04). ROC curves to distinguish responders from non-responders using the baseline serum CXCL10 level showed a good AUC of 0.83. At 32 weeks of omalizumab therapy, serum CXCL10 tended to be increased (1350 ± 412.3 pg/ml at baseline vs. 1529 ± 637.6 pg/ml at 32 weeks, P = 0.16) and serum IL-12 tended to be decreased (49.4 ± 37.0 pg/ml at baseline vs. 43.9 ± 30.9 pg/ml at 32 weeks, P = 0.05). On the other hand, serum IL-5 and PDGF were significantly decreased (IL-5: 54.2 ± 13.8 pg/ml at baseline vs. 49.1 ± 12.5 pg/ml at 32 weeks, P = 0.008; PDGF: 4821 ± 2458 pg/ml at baseline vs. 4219 ± 1951 pg/ml at 32 weeks, P = 0.048). High baseline serum CXCL10 and IL-12 levels may be useful in predicting a good omalizumab response in severe asthmatics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low serum immunglobulin G (IgG) during nephrosis is a predictor of urinary tract infection (UTI) in children with nephrotic syndrome.

PubMed

Afroz, S; Roy, D K; Khan, A H

2013-04-01

Low serum level of IgG, complement C3 and C4 in nephrotic syndrome children may cause increased susceptibility to infection. Serum level of IgG and complements in nephrotic children (NS) with UTI has been analyzed in this cross sectional study. It was carried out in the department of Pediatric nephrology, National Institute of Kidney Diseases & Urology (NIKDU), Dhaka, Bangladesh. The study subjects were followed up prospectively for one year to see and compare the frequency of relapse of NS and UTI. Patients were selected in a nonrandom purposive technique. Nephrotic syndrome children with initial attack between 1-12 year of age were included over a period of one year. The patients were grouped into Group I - UTI positive and Group II - UTI negative depending on urine culture positivity and colony count >10⁵ CFU/ml. Serum IgG and complements C3, C4 levels were done in both groups during nephrosis and were compared. A total of 101 children M: F 1.7:1, mean age 5.96±3.2 years were included in this study. Group I, n=45 vs. Group II, n=56. The mean serum level of IgG was low in Group I (549.91±210.71 vs. 728.64±235.81mg/dl, p<0.001). Serum IgG level less than 700mg/dl was found in 37 vs. 23 children {x² (¹) 17.52 p<0.001, OR=6.63}. Mean serum complement C3 level was also low in Group I (123.09±40.52 vs. 143.38±37.06mg/dl, p<0.05). But complement C3 and C4 level do not carry any risk of developing UTI in nephrotic children. Higher number of children in Group II were at remission (n=24) during follow up, while frequent relapsers were high in Group I (n=22). Increased frequency of UTI attack (88 episodes) was found in Group I children compared to none in Group II during follow up. So low serum level of IgG in children with NS during nephrosis can predict UTI with an odds ratio of 6.63 as well as relapse. Serum level of C3, C4 do not associated with any risk of development of UTI in NS children.

Semen cryopreservation in pubertal boys before gonadotoxic treatment and the role of endocrinologic evaluation in predicting sperm yield.

PubMed

van Casteren, Niels J; Dohle, Gert R; Romijn, Johanens C; de Muinck Keizer-Schrama, Sabine M P F; Weber, Robertus F A; van den Heuvel-Eibrink, Marry M

2008-10-01

To evaluate the feasibility of semen cryopreservation in pubertal boys before they receive gonadotoxic therapy and to identify which pretreatment parameters might predict successful cryopreservation. Retrospective data analysis. Tertiary fertility center, academic children's hospital. Between 1995 and 2005, 80 boys (median age 16.6 years, range 13.7-18.9 years) consulted the outpatient clinic of andrology for semen cryopreservation before a potentially gonadotoxic treatment. We assessed the pretreatment semen parameters, hormone levels, and patients' characteristics. Measurement of the number of adolescents able to cryopreserve semen. Thirteen boys were unable to produce semen by masturbation. In 53 boys semen quality was adequate for cryopreservation. In 14 patients semen analysis did not show motile spermatozoa, and therefore semen cryopreservation could not be performed. Although inhibin B showed a strong correlation with sperm count, no significant difference was found in serum T, inhibin B, LH, and FSH levels in the patients with or without successful sperm yield. Moreover, median age was not different between patients with and without a successful sperm yield. Semen cryopreservation in boys is a feasible method to preserve spermatozoa before gonadotoxic therapy is started and should be offered to all pubertal boys despite their young age. Serum hormone levels do not predict sperm yield.

Estimating glomerular filtration rate in diabetes: a comparison of cystatin-C- and creatinine-based methods.

PubMed

Macisaac, R J; Tsalamandris, C; Thomas, M C; Premaratne, E; Panagiotopoulos, S; Smith, T J; Poon, A; Jenkins, M A; Ratnaike, S I; Power, D A; Jerums, G

2006-07-01

We compared the predictive performance of a GFR based on serum cystatin C levels with commonly used creatinine-based methods in subjects with diabetes. In a cross-sectional study of 251 consecutive clinic patients, the mean reference (plasma clearance of (99m)Tc-diethylene-triamine-penta-acetic acid) GFR (iGFR) was 88+/-2 ml min(-1) 1.73 m(-2). A regression equation describing the relationship between iGFR and 1/cystatin C levels was derived from a test population (n=125) to allow for the estimation of GFR by cystatin C (eGFR-cystatin C). The predictive performance of eGFR-cystatin C, the Modification of Diet in Renal Disease 4 variable formula (MDRD-4) and Cockcroft-Gault (C-G) formulas were then compared in a validation population (n=126). There was no difference in renal function (ml min(-1) 1.73 m(-2)) as measured by iGFR (89.2+/-3.0), eGFR-cystatin C (86.8+/-2.5), MDRD-4 (87.0+/-2.8) or C-G (92.3+/-3.5). All three estimates of renal function had similar precision and accuracy. Estimates of GFR based solely on serum cystatin C levels had the same predictive potential when compared with the MDRD-4 and C-G formulas.

Performance of serum α-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass

PubMed Central

Chan, Stephen L; Mo, Frankie; Johnson, Philip J; Siu, Deyond Y W; Chan, Michael H M; Lau, Wan Y; Lai, Paul B S; Lam, Christopher W K; Yeo, Winnie; Yu, Simon C H

2014-01-01

Objectives The role of serum α-fetoprotein (AFP) measurements in the diagnosis of hepatocellular carcinoma (HCC) remains controversial. Some guidelines have advised against the use of AFP in the diagnosis of HCC. This study was conducted to evaluate the performance of AFP in the diagnosis of HCC, and to identify the optimal cut-off value of serum AFP in the diagnosis of HCC in patients with a hepatic mass. Methods Patients who presented during the period from May 1997 to March 2003 with hepatic lesions, for whom paired data on serum AFP values at baseline and lesion histology were available, were reviewed. The performance of AFP in the diagnosis of HCC was determined using receiver operating characteristic curve analysis. Results Data for a total of 805 patients were evaluated. The mean AFP value was 26 900 ng/ml (range: 0–1 965 461 ng/ml). The histological diagnosis was HCC in 557 patients. The optimal AFP cut-off value was 10 ng/ml (for sensitivity of 82.6% and specificity of 70.4%). At a cut-off level of 200 ng/ml, sensitivity, specificity, and positive and negative predictive values were 47.7%, 97.1%, 97.5% and 44.4%, respectively. The diagnostic performance of AFP remains similar in patients with chronic hepatitis B virus infection, despite a lower negative predictive value. Common aetiologies of liver lesions associated with elevated AFP include cholangiocarcinoma and neuroendocrine tumours. Conclusions In Asian patients with suspicious liver lesions, the cut-off AFP level of 200 ng/ml is useful to achieve a diagnosis of HCC with high specificity and reasonable sensitivity. The measurement of serum AFP should not be excluded from guidelines for the diagnosis of HCC. PMID:23980880

The usefulness of rapid point-of-care creatinine testing for the prevention of contrast-induced nephropathy in the emergency department.

PubMed

You, Je Sung; Chung, Yong Eun; Park, Jong Woo; Lee, Woonhyoung; Lee, Hye-Jeong; Chung, Tae Nyoung; Chung, Sung Phil; Park, Incheol; Kim, Seungho

2013-07-01

Renal dysfunction is the most important factor to consider when predicting a patient's risk of developing contrast-induced nephropathy (CIN). Measurement of creatinine (Cr) via rapid point-of-care blood urea nitrogen/creatinine testing (POCT-BUN/Cr) to determine CIN risk could potentially reduce the time required to achieve an accurate diagnosis and to initiate and complete treatment in the emergency department (ED). The aim of our study was to compare the results of POCT-BUN/Cr and reference laboratory tests for BUN and serum Cr. A retrospective analysis of suspected stroke patients who presented between November 2009 and November 2010, and had BUN and Cr levels measured by POCT-BUN/Cr, and the reference laboratory tests performed with the blood sample which was transferred to the central laboratory by an air-shoot system. Two assays were conducted on the whole blood (POCT) and serum (reference) by trained technicians. The time interval from arrival at the ED to reporting of the results was assessed for both assays via a computerised physician order entry system. The mean standard deviation (SD) interval from arrival at the ED to reporting of the results was 11.4 (4.9) min for POCT-BUN/Cr and 46.8 (38.5) min for the serum reference laboratory tests (p<0.001). Intra-class correlation coefficient (ICC) analysis demonstrated a high level of agreement (the consistency agreement) between POCT and the serum reference tests for both BUN (ICC=0.914) and Cr (ICC=0.980). This study suggests that POCT-BUN/Cr results correlate well with those of serum reference tests in terms of BUN and Cr levels and, in turn, predicting CIN. POCT-BUN/Cr is easily performed with a rapid turnaround time, suggesting its use in the ED may have substantial clinical benefit.

Effects on health, performance, and tissue residues of the ionophore antibiotic salinomycin in finishing broilers (21 to 38 d).

PubMed

Diaz, Gonzalo J; Aguillón, Yandy; Cortés, Amparo

2018-06-01

A study was conducted to evaluate the effects of feeding salinomycin at the recommended prophylactic level, and at 2 and 3 times this level, to finishing male broilers (d 21 to 38). Four treatment groups were given the experimental diets containing 0, 60, 120, or 180 parts per million (ppm) salinomycin from d 21 to 38. Performance, relative organ weights, selected serum enzymes, and salinomycin residues in liver, muscle, and serum were determined. Salinomycin supplementation had no effect on body weight, feed intake, or feed conversion, and caused no overt signs of toxicity. After a week of being fed the salinomycin diets, the serum activity of aspartate aminotransferase was significantly increased in chickens fed 180 ppm compared with controls. These birds also showed microscopic lesions in breast and thigh muscles, but not in cardiac muscle. Salinomycin residues were not detected by high-performance liquid chromatography coupled to tandem mass spectrometry in liver or muscle samples from the birds fed 0, 60, or 120 ppm salinomycin. However, chickens fed 180 ppm salinomycin had detectable levels in liver and muscle above the maximum residue level of 5 μg/kg established by the European Union. All birds fed salinomycin had salinomycin in their sera with levels ranging from N.D. (not detected) in the controls to 24.4 ± 7.9, 61.4 ± 18.9, and 94.5 ± 9.1 μg/L for salinomycin dietary levels of 60, 120, and 180 ppm, respectively. Serum salinomycin concentration was linearly related with salinomycin content in feed (y = 0.584x - 10, r2 = 0.999). The results showed that even at 3 times the prophylactic level, salinomycin does not induce clinical toxicosis or mortality. No salinomycin residues were found in edible tissues at the recommended dietary level or at 2 times this level. However, salinomycin was detected in serum regardless of the dietary level. A simple method for salinomycin determination in serum is described which can be used as a marker of exposure and/or to predict levels in the diet.

Geographic Model and Biomarker-Derived Measures of Pesticide Exposure and Parkinson’s Disease

PubMed Central

RITZ, BEATE; COSTELLO, SADIE

2013-01-01

For more than two decades, reports have suggested that pesticides and herbicides may be an etiologic factor in idiopathic Parkinson’s disease (PD). To date, no clear associations with any specific pesticide have been demonstrated from epidemiological studies perhaps, in part, because methods of reliably estimating exposures are lacking. We tested the validity of a Geographic Information Systems (GIS)-based exposure assessment model that estimates potential environmental exposures at residences from pesticide applications to agricultural crops based on California Pesticide Use Reports (PUR). Using lipid-adjusted dichlorodiphenyldichloroethylene (DDE) serum levels as the “gold standard” for pesticide exposure, we conducted a validation study in a sample taken from an ongoing, population-based case–control study of PD in Central California. Residential, occupational, and other risk factor data were collected for 22 cases and 24 controls from Kern county, California. Environmental GIS–PUR-based organochlorine (OC) estimates were derived for each subject and compared to lipid-adjusted DDE serum levels. Relying on a linear regression model, we predicted log-transformed lipid-adjusted DDE serum levels. GIS–PUR-derived OC measure, body mass index, age, gender, mixing and loading pesticides by hand, and using pesticides in the home, together explained 47% of the DDE serum level variance (adjusted r2 = 0.47). The specificity of using our environmental GIS–PUR-derived OC measures to identify those with high-serum DDE levels was reasonably good (87%). Our environmental GIS–PUR-based approach appears to provide a valid model for assessing residential exposures to agricultural pesticides. PMID:17119217

Prostate Cancer: Serum and Tissue Markers

PubMed Central

Miller, Gary J; Brawer, Michael K; Sakr, Wael A; Thrasher, J Brantley; Townsend, Ronald

2001-01-01

The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the “gold standard,” has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging. PMID:16985995

Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis.

PubMed

Deswal, Ritu; Yadav, Arun; Dang, Amita Suneja

2018-02-01

Sex hormone-binding globulin (SHBG) is a glycoprotein which regulates bioavailability of sex steroid hormones. Interest in SHBG has escalated in recent years because of its inverse association with polycystic ovary syndrome (PCOS), obesity, insulin resistance, metabolic syndrome, and diabetes type II. This meta-analysis was performed to examine the associations of SHBG with PCOS and to correlate serum SHBG levels with various PCOS associated endocrine and metabolic dysregulation as well as to determine the effects of various therapeutic agents on serum SHBG levels in PCOS patients in order to assess the true accuracy of SHBG in the prediction of PCOS. A literature search was performed using Pub-Med, Science direct, google scholar, EMBASE, and Cochrane library. A total of 675 relevant records were identified, of which 62 articles were included. Meta-analysis using a random-effects model was performed using STATA version 13 to calculate standardized mean difference (SMD) with 95% confidence intervals (95 % CIs). SHBG levels in controls were significantly higher than that of PCOS patients (SMD= -0.83, 95%CI = -1.01, -0.64), with significant heterogeneity across studies (I 2 = 93.9% and p=0.000). Our results suggest that the lower serum SHBG levels are associated with the risk of PCOS. SHBG may also play an important role in various metabolic disturbances in PCOS patients. Therapeutic interventions improved SHBG levels in PCOS women which further reduced PCOS associated complications. Therefore, SHBG levels may prove to be a useful biomarker for the diagnosis and treatment of PCOS. Systematic review registration: PROSPERO CRD42017057972 Abbreviations: PCOS: polycystic ovary syndrome; SHBG: sex hormone-binding globulin.

Correlation of Free and Total Phenytoin Serum Concentrations in Critically Ill Patients.

PubMed

Buckley, Mitchell S; Reeves, Brittany A; Barletta, Jeffrey F; Bikin, Dale S

2016-04-01

Phenytoin is a common medication for seizure treatment and prophylaxis in the intensive care unit (ICU). The clinical utility of the Sheiner-Tozer equation for adjusting total phenytoin levels for hypoalbuminemia remains controversial. The purpose of this study was to evaluate the correlation of this formula in predicting phenytoin serum concentrations. A retrospective cohort study was conducted in the adult ICU between January 1, 2010, and June 21, 2013. Patients meeting the following study criteria were included: age ≥18 years, admission to the ICU, simultaneously drawn total and free serum phenytoin concentrations with albumin ≤48 hours of phenytoin draws. Study end points were the correlation as well as the level of agreement in the interpretation of the free and adjusted phenytoin concentrations using the Sheiner-Tozer formula in critically ill patients with hypoalbuminemia. A total of 238 patients were analyzed. Mean adjusted total phenytoin and free levels were 16.1 ± 8.1 and 1.5 ± 0.8 µg/mL, respectively (r = 0.817; P < 0.001). Absolute agreement with level interpretation between adjusted total phenytoin and free levels was 77% (κ = 0.633; P < 0.001). Adjusted phenytoin serum concentrations more frequently overestimated the free level. There is a significant correlation between free and adjusted total phenytoin levels using the Sheiner-Tozer equation in critically ill patients. However, disagreement was noted with interpretation, primarily because of the adjusted concentration overestimating the free level. This imprecision may lead to inaccurate decision making regarding the management of phenytoin in this patient population. Thus, free phenytoin levels should be utilized. © The Author(s) 2016.

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.

PubMed

Yamashita, Taro; Kitao, Azusa; Matsui, Osamu; Hayashi, Takehiro; Nio, Kouki; Kondo, Mitsumasa; Ohno, Naoki; Miyati, Tosiaki; Okada, Hikari; Yamashita, Tatsuya; Mizukoshi, Eishiro; Honda, Masao; Nakanuma, Yasuni; Takamura, Hiroyuki; Ohta, Tetsuo; Nakamoto, Yasunari; Yamamoto, Masakazu; Takayama, Tadatoshi; Arii, Shigeki; Wang, XinWei; Kaneko, Shuichi

2014-11-01

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in ∼15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n=70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n=109). This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease. © 2014 by the American Association for the Study of Liver Diseases.

Gd-EOB-DTPA-enhanced Magnetic Resonance Imaging and Alpha-fetoprotein Predict Prognosis of Early-Stage Hepatocellular Carcinoma

PubMed Central

Yamashita, Taro; Kitao, Azusa; Matsui, Osamu; Hayashi, Takehiro; Nio, Kouki; Kondo, Mitsumasa; Ohno, Naoki; Miyati, Tosiaki; Okada, Hikari; Yamashita, Tatsuya; Mizukoshi, Eishiro; Honda, Masao; Nakanuma, Yasuni; Takamura, Hiroyuki; Ohta, Tetsuo; Nakamoto, Yasunari; Yamamoto, Masakazu; Takayama, Tadatoshi; Arii, Shigeki; Wang, Xin Wei; Kaneko, Shuichi

2014-01-01

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here, we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in approximately 15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n = 70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n = 109). Conclusion: This non-invasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease. PMID:24700365

Serum metalloproteinases 1 and 7 in the diagnosis of idiopathic pulmonary fibrosis and other interstitial pneumonias.

PubMed

Morais, António; Beltrão, Marília; Sokhatska, Oksana; Costa, Diogo; Melo, Natalia; Mota, Patricia; Marques, Agostinho; Delgado, Luís

2015-08-01

Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) has important therapeutic and prognostic implications and would be greatly aided by reliable diagnostic biomarkers as IPF has sometimes overlapping features with other interstitial lung diseases (ILD). To explore the value of serum metalloproteinases (MMP) 1 and 7 levels in the differential diagnosis of IPF with other ILD. MMP-1/7 serum levels were measured using Luminex xMAP technology in 139 patients- 47 IPF, 36 non-IPF Usual Interstitial Pneumonia (UIP), 14 idiopathic Nonspecific Interstitial Pneumonia (iNSIP), 29 secondary NSIP (secNSIP), 13 stage IV sarcoidosis- and 20 healthy controls, and compared using the Mann-Whitney U test. MMP-1 was significantly higher in IPF than non-IPF UIP (P = .042) and sarcoidosis (P = .027). MMP-7 was significantly higher in IPF than controls (P < .001), non-IPF UIP (P = .003), secNSIP (P < .001), and sarcoidosis (P < .001). The Area Under the Curve for IPF versus other ILD was 0.63 (95%CI, 0.53-0.73) for MMP-1, 0.73 (95%CI, 0.65-0.81) for MMP-7, and 0.74 (95%CI, 0.66-0.82) for MMP-1/MMP-7 combined. Sensitivity and specificity for MMP-7 cutoff = 3.91 ng/mL was 72.3% and 66.3%, respectively, Positive Predictive Values = 52.3% and Negative Predictive Values = 82.4%. MMP-1 and particularly MMP-7 serum levels were significantly higher in IPF than in non-IPF UIP, the main entity in differential diagnosis. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF diagnosis needs to be considered and further explored. Copyright © 2015 Elsevier Ltd. All rights reserved.

Luteinizing hormone-follicle stimulating hormone ratio as biological predictor of post-partum depression.

PubMed

Ramachandran Pillai, R; Sharon, Leena; Premkumar, Nancy R; Kattimani, Shivanand; Sagili, Haritha; Rajendiran, Soundravally

2017-01-01

Post-partum depression (PPD) is the common adverse outcome of child bearing which affects the wellbeing of both mother and newborn and has long-term effects. Hence, reliable potential biological tests for early detection of PPD are essential. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were associated with depressive disorders and the present study estimated the levels of serum FSH, LH in postpartum depression and explored them as predictive biomarkers in the development of PPD. In this nested case control study done at a tertiary care hospital in South India, 450 postpartum women were screened at 6th week post-delivery for PPD. Socio-demographic and clinical data were recorded and depressive symptoms were assessed using Edinburgh Postnatal Depression Scale (EPDS). Out of 450 subjects screened, 100 women with depressive symptoms were categorized as cases and 100 controls were selected from the remaining subjects matching for age and BMI with cases. Serum levels of FSH and LH were measured using direct competitive immunoassay by chemiluminescene technology. Serum LH/FSH ratio was found to be significantly (p=0.02) low in PPD women when compared to normal postpartum subjects. We also found a significant negative correlation between LH/FSH ratio and EPDS scores. Based on the receiver operating characteristic curve, the optimal cut-off value for serum of LH/FSH levels in predicting postpartum depression was estimated to be 0.22mlU/mL with an AUC of 0.598 (95%CI, 0.291-0.859). Our study demonstrated that low LH/FSH ratio after delivery was associated with increased risk for the development of PPD. Low LH/FSH ratio at six-week post delivery can be used as a robust biochemical predictor of post-partum depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harima, Yoko, E-mail: harima@takii.kmu.ac.jp; Ikeda, Koshi; Utsunomiya, Keita

Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in themore » validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.« less

Exploring the Link between Serum Phosphate Levels and Low Muscle Strength, Dynapenia, and Sarcopenia.

PubMed

Chen, Yuan-Yuei; Kao, Tung-Wei; Chou, Cheng-Wai; Wu, Chen-Jung; Yang, Hui-Fang; Lai, Ching-Huang; Wu, Li-Wei; Chen, Wei-Liang

2018-02-23

Emerging evidences addressed an association between phosphate and muscle function. Because little attention was focused on this issue, the objective of our study was to explore the relationship of phosphate with muscle strength, dynapenia, and sarcopenia. From the National Health and Nutrition Examination Survey, a total of 7421 participants aged 20 years or older were included in our study with comprehensive examinations included anthropometric parameters, strength of the quadriceps muscle, and appendicular lean masses. Within the normal range of serum phosphate, we used quartile-based analyses to determine the potential relationships of serum phosphate with dynapenia, and sarcopenia through multivariate regression models. After adjusting for the pertinent variables, an inverse association between the serum phosphate quartiles and muscle strength was observed and the linear association was stronger than other anthropometric parameters. Notably, the significant association between phosphate and muscle strength was existed in >65 years old age group, not in 20-65 years old. The higher quartiles of phosphate had higher likelihood for predicting the presence of dynapenia rather than sarcopenia in entire population. Our study highlighted that higher quartiles of phosphate had significant association with lower muscle strength and higher risks for predicting the presence of dynapenia.

Elevated cystatin C: is it a reflection for kidney or liver impairment in hepatic children?

PubMed

El-Sayed, Behairy; El-Araby, Hanaa; Adawy, Nermin; Hassona, Mona; El-Nady, Naglaa; Zakaria, Haidy; Khedr, Mohammed

2017-09-01

To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment ( p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) ( p < 0.0001). Cyst-C at cutoff levels of 1.65 mg/l showed 100% accuracy in discrimination between those with and those without renal impairment. Cyst-C > 2.34 mg/l predicting GFR < 40 ml/min with accuracy of 90%. Cyst-C > 2.73 mg/l predicting GFR < 20 ml/min with accuracy of 81.5%. Serum Cyst-C is a promising marker to estimate renal impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children.

PubMed

Watanabe, Kae; Karimpour-Fard, Anis; Michael, Alix; Miyamoto, Shelley D; Nakano, Stephanie J

2018-04-30

Cardiac allograft vasculopathy (CAV) is a leading cause of retransplantation and death in pediatric heart transplant recipients. Our aim was to evaluate the association between serum vascular endothelial growth factor-A (VEGF) and CAV development in the pediatric heart transplant population. In this retrospective study performed at a university hospital, VEGF concentrations were measured by enzyme-linked immunosorbent assay in banked serum from pediatric heart transplant recipients undergoing routine cardiac catheterization. In subjects with CAV (n = 29), samples were obtained at 2 time-points: before CAV diagnosis (pre-CAV) and at the time of initial CAV diagnosis (CAV). In subjects without CAV (no-CAV, n = 16), only 1 time-point was used. VEGF concentrations (n = 74) were assayed in duplicate. Serum VEGF is elevated in pediatric heart transplant recipients before catheter-based diagnosis of CAV (no-CAV mean: 144.0 ± 89.05 pg/ml; pre-CAV mean: 316.2 ± 118.3 pg/ml; p = 0.0002). Receiver-operating characteristic curve analysis of pre-CAV VEGF levels demonstrated an area under the curve of 87.7% (p = 0.0002), with a VEGF level of 226.3 pg/ml predicting CAV development with 77.8% sensitivity and 91.7% specificity. VEGF is similarly elevated in subjects with angiographically diagnosed CAV and in those with normal angiography but intravascular ultrasound (IVUS) evidence of CAV. The increase in serum VEGF before onset of detectable CAV is fundamental to its utility as a predictive biomarker and suggests further investigations of VEGF in the pathogenesis of CAV are warranted in the pediatric heart transplant population. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Early Elevation of Serum MMP-3 and MMP-12 Predicts Protection from World Trade Center-Lung Injury in New York City Firefighters: A Nested Case-Control Study

PubMed Central

Echevarria, Ghislaine C.; Comfort, Ashley L.; Naveed, Bushra; Prezant, David J.; Rom, William N.; Nolan, Anna

2013-01-01

Objective After 9/11/2001, some Fire Department of New York (FDNY) workers had excessive lung function decline. We hypothesized that early serum matrix metalloproteinases (MMP) expression predicts World Trade Center-Lung Injury (WTC-LI) years later. Methods This is a nested case-control analysis of never-smoking male firefighters with normal pre-exposure Forced Expiratory Volume in one second (FEV1) who had serum drawn up to 155 days post 9/11/2001. Serum MMP-1, 2,3,7,8, 9, 12 and 13 were measured. Cases of WTC-LI (N = 70) were defined as having an FEV1 one standard deviation below the mean (FEV1≤77%) at subspecialty pulmonary evaluation (SPE) which was performed 32 months (IQR 21–53) post-9/11. Controls (N = 123) were randomly selected. We modeled MMP's ability as a predictor of cases status with logistic regression adjusted for time to blood draw, exposure intensity, weight gain and pre-9/11 FEV1. Results Each log-increase in MMP-3 and MMP-12 showed reduced odds of developing WTC-LI by 73% and 54% respectively. MMP-3 and MMP-12 consistently clustered together in cases, controls, and the cohort. Increasing time to blood draw significantly and independently increased the risk of WTC-LI. Conclusions Elevated serum levels of MMP-3 and MMP-12 reduce the risk of developing WTC-LI. At any level of MMP-3 or 12, increased time to blood draw is associated with a diminished protective effect. PMID:24146820

Prediction of non-biochemical recurrence rate after radical prostatectomy in a Japanese cohort: development of a postoperative nomogram.

PubMed

Okubo, Hidenori; Ohori, Makoto; Ohno, Yoshio; Nakashima, Jun; Inoue, Rie; Nagao, Toshitaka; Tachibana, Masaaki

2014-05-01

To develop a nomogram based on postoperative factors and prostate-specific antigen levels to predict the non-biochemical recurrence rate after radical prostatectomy ina Japanese cohort. A total of 606 Japanese patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to 2010 were studied. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum prostate-specific antigen and pathological factors in the radical prostatectomy specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot. With a mean follow up of 60.0 months, a total of 187 patients (30.9%) experienced biochemical recurrence, with a 5-year non-biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a nomogram was constructed to predict non-biochemical recurrence using serum prostate-specific antigen level and pathological features in radical prostatectomy specimens. The concordance index was 0.77, and the calibration plots appeared to be accurate. The postoperative nomogram described here can provide valuable information regarding the need for adjuvant/salvage radiation or hormonal therapy in patients after radical prostatectomy.

Investigating the clinical potential for 14-3-3 zeta protein to serve as a biomarker for epithelial ovarian cancer

PubMed Central

2013-01-01

Objective Recently, 14-3-3 zeta protein was identified as a potential serum biomarker of epithelial ovarian cancer (EOC). The goal of this study was to investigate the clinical potential of 14-3-3 zeta protein for monitoring EOC progression compared with CA-125 and HE4. Design Prospective follow-up study. Setting University of Pecs Medical Center Department of Obstetrics and Gynecology/Oncology (Pecs, Hungary). Population Thirteen EOC patients with advanced stage (FIGO IIb-IIIc) epithelial ovarian cancer that underwent radical surgery and received six consecutive cycles of first line chemotherapy (paclitaxel, carboplatin) in 21-day intervals. Methods Pre- and post-chemotherapy computed tomography (CT) scans were performed. Serum levels of CA-125, HE4, and 14-3-3 zeta protein were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative electrochemiluminescence assay (ECLIA). Main outcome measures Serum levels of CA-125, HE4, and 14-3-3 zeta protein, as well as lesion size according to pre- and post-chemotherapy CT scans. Results Serum levels of CA-125 and HE4 were found to significantly decrease following chemotherapy, and this was consistent with the decrease in lesion size detected post-chemotherapy. In contrast, 14-3-3 zeta protein levels did not significantly differ in healthy postmenopausal patients versus EOC patients. Conclusions Determination of CA-125 and HE4 serum levels for the determination of the risk of ovarian malignancy algorithm (ROMA) represents a useful tool for the prediction of chemotherapy efficacy for EOC patients. However, levels of 14-3-3 zeta protein were not found to vary significantly as a consequence of treatment. Therefore we question if 14-3-3 zeta protein is a reliable biomarker, which correlates with the clinical behavior of EOC. PMID:24238270

Brain-Derived Neurotrophic Factor in TBI-related mortality: Interrelationships between Genetics and Acute Systemic and CNS BDNF Profiles

PubMed Central

Failla, Michelle D.; Conley, Yvette P.; Wagner, Amy K.

2015-01-01

Background Older adults have higher mortality rates after severe traumatic brain injury (TBI) compared to younger adults. Brain derived neurotrophic factor (BDNF) signaling is altered in aging and is important to TBI given its role in neuronal survival/plasticity and autonomic function. Following experimental TBI, acute BDNF administration has not been efficacious. Clinically, genetic variation in BDNF (reduced signaling alleles: rs6265, Met-carriers; rs7124442, C-carriers) were protective in acute mortality. Post-acutely, these genotypes carried lower mortality risk in older adults, and greater mortality risk among younger adults. Objective Investigate BDNF levels in mortality/outcome following severe TBI in the context of age and genetic risk. Methods CSF and serum BDNF were assessed prospectively during the first week following severe TBI (n=203), and in controls (n=10). Age, BDNF genotype, and BDNF levels were assessed as mortality/outcome predictors. Results CSF BDNF levels tended to be higher post-TBI (p=0.061) versus controls and were associated with time until death (p=0.042). In contrast, serum BDNF levels were reduced post-TBI versus controls (p<0.0001). Both gene*BDNF serum and gene*age interactions were mortality predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to be negatively correlated post-TBI (p=0.07). Conclusions BDNF levels predicted mortality, in addition to gene*age interactions, suggesting levels capture additional mortality risk. Higher CSF BDNF post-TBI may be detrimental due to injury and age-related increases in pro-apoptotic BDNF target receptors. Negative CSF and serum BDNF correlations post-TBI suggest blood-brain barrier transit alterations. Understanding BDNF signaling in neuronal survival, plasticity, and autonomic function may inform treatment. PMID:25979196

Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related Mortality: Interrelationships Between Genetics and Acute Systemic and Central Nervous System BDNF Profiles.

PubMed

Failla, Michelle D; Conley, Yvette P; Wagner, Amy K

2016-01-01

Older adults have higher mortality rates after severe traumatic brain injury (TBI) compared to younger adults. Brain-derived neurotrophic factor (BDNF) signaling is altered in aging and is important to TBI given its role in neuronal survival/plasticity and autonomic function. Following experimental TBI, acute BDNF administration has not been efficacious. Clinically, genetic variation in BDNF (reduced signaling alleles: rs6265, Met-carriers; rs7124442, C-carriers) can be protective against acute mortality. Postacutely, these genotypes carry lower mortality risk in older adults and greater mortality risk among younger adults. Investigate BDNF levels in mortality/outcome following severe TBI in the context of age and genetic risk. Cerebrospinal fluid (CSF) and serum BDNF were assessed prospectively during the first week following severe TBI (n = 203) and in controls (n = 10). Age, BDNF genotype, and BDNF levels were assessed as mortality/outcome predictors. CSF BDNF levels tended to be higher post-TBI (P = .061) versus controls and were associated with time until death (P = .042). In contrast, serum BDNF levels were reduced post-TBI versus controls (P < .0001). Both gene * BDNF serum and gene * age interactions were mortality predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to be negatively correlated post-TBI (P = .07). BDNF levels predicted mortality, in addition to gene * age interactions, suggesting levels capture additional mortality risk. Higher CSF BDNF post-TBI may be detrimental due to injury and age-related increases in pro-apoptotic BDNF target receptors. Negative CSF and serum BDNF correlations post-TBI suggest blood-brain barrier transit alterations. Understanding BDNF signaling in neuronal survival, plasticity, and autonomic function may inform treatment. © The Author(s) 2015.

Serum Level of Heart-Type Fatty Acid Binding Protein (H-FABP) Before and After Treatment of Congestive Heart Failure in Children.

PubMed

Zoair, Amr; Mawlana, Wegdan; Abo-Elenin, Amany; Korrat, Mostafa

2015-12-01

Remodeling of the heart following injury affects the morbidity and mortality in children presented with heart failure (HF). Heart-type fatty acid binding protein (H-FABP) is a novel biomarker that could be of help to predict the prognosis and risk stratification in those children. We aimed to evaluate the diagnostic and prognostic value of H-FABP in children with heart failure before and after treatment. The study was conducted as a prospective cohort study. It included 30 children with HF as a patient group and 20 healthy children matched for age and sex as a control group. Echocardiographic assessment of the heart was done using conventional Doppler echocardiography. Serum levels of (H-FABP) were measured using enzyme-linked immunosorbent assay before and after treatment of HF. All patients were observed during follow-up period of 3 months. There was a significant difference in the serum level of H-FABP in our patients before treatment (5.278 ± 3.253 ng/ml) compared with after treatment (2.089 ± 0.160 ng/ml) with significant difference compared with the control group. There was a significant increase in the serum level of H-FABP with increase in the severity of heart failure according to Ross classification. Significant increase in the H-FABP was associated with adverse outcome. Serum levels of H-FABP strongly correlated with clinical and echocardiographic assessment of LV performance of children with HF, and its levels significantly increased in children with adverse outcome suggesting its value as a useful diagnostic and prognostic predictor (with high sensitivity and specificity).

Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer.

PubMed

Marmorino, Federica; Salvatore, Lisa; Barbara, Cecilia; Allegrini, Giacomo; Antonuzzo, Lorenzo; Masi, Gianluca; Loupakis, Fotios; Borelli, Beatrice; Chiara, Silvana; Banzi, Maria Chiara; Miraglio, Emanuela; Amoroso, Domenico; Dargenio, Francesco; Bonetti, Andrea; Martignetti, Angelo; Paris, Myriam; Tomcikova, Daniela; Boni, Luca; Falcone, Alfredo; Cremolini, Chiara

2017-01-01

Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out. A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23-0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74-1.64)). Consistent results were reported in overall survival (OS; P=0.075). As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted.

Low Serum Levels of Uric Acid are Associated With Development of Poststroke Depression.

PubMed

Gu, Yingying; Han, Bin; Wang, Liping; Chang, Yaling; Zhu, Lin; Ren, Wenwei; Yan, Mengjiao; Zhang, Xiangyang; He, Jincai

2015-11-01

Poststroke depression (PSD) is a frequent complication of stroke that has been associated with poorer outcome of stroke patients. This study sought to examine the possible association between serum uric acid levels and the development of PSD.We recruited 196 patients with acute ischemic stroke and 100 healthy volunteers. Serum uric acid levels were tested by uricase-PAP method within 24 hr after admission. Neuropsychological evaluations were conducted at 3-month poststroke. The 17-item Hamilton Depression Scale was used to assess depressive symptoms. Diagnosis of PSD was made in accordance with DSM-IV criteria for depression. Multivariate analyses were conducted using logistic regression models.Fifty-six patients (28.6%) were diagnosed as having PSD at 3 months. PSD patients showed significantly lower levels of uric acid at baseline as compared to non-PSD patients (237.02 ± 43.43 vs 309.10 ± 67.44 μmol/L, t = -8.86, P < 0.001). In multivariate analyses, uric acid levels (≤239.0 and ≥328.1 μmol/L) were independently associated with the development of PSD (OR, 7.76; 95% confidence interval [CI], 2.56-23.47, P < 0.001 and OR, 0.05; 95% CI, 0.01-0.43, P = 0.01, respectively) after adjustment for possible variables.Serum uric acid levels at admission are found to be correlated with PSD and may predict its development at 3 months after stroke.

Mineral Metabolism in European Children Living with a Renal Transplant: A European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry Study

PubMed Central

Bonthuis, Marjolein; Busutti, Marco; Jager, Kitty J.; Baiko, Sergey; Bakkaloğlu, Sevcan; Battelino, Nina; Gaydarova, Maria; Gianoglio, Bruno; Parvex, Paloma; Gomes, Clara; Heaf, James G.; Podracka, Ludmila; Kuzmanovska, Dafina; Molchanova, Maria S.; Pankratenko, Tatiana E.; Papachristou, Fotios; Reusz, György; Sanahuja, Maria José; Shroff, Rukshana; Groothoff, Jaap W.; Schaefer, Franz; Verrina, Enrico

2015-01-01

Background and objectives Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients. Design, setting, participants, & measurements This study included 1237 children (0–17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure. Results Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR. Conclusions Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction. PMID:25710805