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- Evaluation of bilirubin displacement effect by acetaminophen in vitro. [JOURNAL ARTICLE]
- Ann Clin Biochem 2014 Dec 18.
- Analytical validation of a second-generation immunoassay for the quantification of N-terminal pro-B-type natriuretic peptide in canine blood. [Journal Article]
- J Vet Diagn Invest 2015 Jan; 27(1):61-7.
N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been shown to have clinical utility as a biomarker in dogs with heart disease. There were several limitations associated with early diagnostic assay formats including a limited dynamic range and the need for protease inhibitors to maintain sample stability. A second-generation Cardiopet® proBNP enzyme-linked immunosorbent assay (IDEXX Laboratories Inc., Westbrook, Maine) was developed to address these limitations, and the present study reports the results of the analytical method validation for the second-generation assay. Coefficients of variation for intra-assay, interassay, and total precision based on 8 samples ranged from 3.9% to 8.9%, 2.0% to 5.0%, and 5.5% to 10.6%, respectively. Analytical sensitivity was established at 102 pmol/l. Accuracy averaged 102.0% based on the serial dilutions of 5 high-dose canine samples. Bilirubin, lipids, and hemoglobin had no effect on results. Reproducibility across 3 unique assay lots was excellent with an average coefficient of determination (r (2)) of 0.99 and slope of 1.03. Both ethylenediamine tetra-acetic acid plasma and serum gave equivalent results at time of blood draw (slope = 1.02, r (2) = 0.89; n = 51) but NT-proBNP was more stable in plasma at 25°C with median half-life measured at 244 hr and 136 hr for plasma and serum, respectively. Plasma is the preferred sample type and is considered stable up to 48 hr at room temperature whereas serum should be frozen or refrigerated when submitted for testing. Results of this study validate the second-generation canine Cardiopet proBNP assay for accurate and precise measurement of NT-proBNP in routine sample types from canine patients.
- Prognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with non-metastatic breast cancer. [JOURNAL ARTICLE]
- Carcinogenesis 2014 Dec 18.
Liver function tests (LFTs) have been reported as independent predictors of non-liver disease-related morbidity and mortality in general population and cancer patients. In this study, we evaluated the relationship between pretreatment serum LFTs and overall survival (OS) in non-metastatic Caucasian breast cancer patients. Seven LFTs, including albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total bilirubin, and total protein, were measured in pretreatment serum from 2,425 female Caucasian patients with newly diagnosed, histologically confirmed non-metastatic invasive breast cancer. Multivariate Cox model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for the association of individual LFTs with 5-year OS while adjusting for age, smoking status, pathological characteristics and treatment regimen. We found that serum albumin, LDH, and total bilirubin were significantly associated with 5-year OS in multivariate Cox analyses. Patients with higher albumin level exhibited 45% reduced risk of death (HR=0.55, 95% CI, 0.40-0.75) compared to those with lower albumin level. Patients with higher total bilirubin level had a nearly 40% reduction in the risk of death (HR=0.62, 95% CI, 0.45-0.85) and patients with higher LDH levels had a 1.42-fold increased risk of death (HR=1.42, 95% CI, 1.08-1.88). Furthermore, cumulative analysis showed a significant dose-response trend of significantly increasing risk of death with increasing number of unfavorable LFT levels. Our result highlighted the potential of using pretreatment serum levels of albumin, LDH and total bilirubin as prognostic factors for overall survival in patients with non-metastatic breast cancer.
- Extracorporeal membrane oxygenation as a bridge to lung transplantation in the United States: An evolving strategy in the management of rapidly advancing pulmonary disease. [Journal Article]
- J Thorac Cardiovasc Surg 2015 Jan; 149(1):291-6.
Improvements in technology have led to a resurgence in the use of extracorporeal membrane oxygenation as a bridge to lung transplantation. By using a national registry, we sought to evaluate how short-term survival has evolved using this strategy.With the use of the United Network for Organ Sharing database, we analyzed data from 12,458 adults who underwent lung transplantation between 2000 and 2011. Patients were categorized into 2 cohorts: 119 patients who were bridged to transplantation using extracorporeal membrane oxygenation and 12,339 patients who were not. The study period was divided into four 3-year intervals: 2000 to 2002, 2003 to 2005, 2006 to 2008, and 2009 to 2011. With Kaplan-Meier analysis, 1-year survival was compared for the 2 cohorts of patients in each of the time periods. A propensity score-adjusted Cox regression model was used to estimate the risk of 1-year mortality.Of the total number of recipients, 4 (3.4%) were bridged between 2000 and 2002, 17 (14.3%) were bridged between 2003 and 2005, 31 (26.1%) were bridged between 2006 and 2008, and 67 were bridged (56.3%) between 2009 and 2011. Recipients bridged using extracorporeal membrane oxygenation were more likely to be younger and diabetic and to have higher serum creatinine and bilirubin levels. The 1-year survival for those bridged with extracorporeal membrane oxygenation was significantly lower in subsequent periods: 25.0% versus 81.0% (2000-2002), 47.1% versus 84.2% (2006-2008), and 74.4% versus 85.7% (2009-2011). However, this survival progressively increased with each period, as did the number of patients bridged using extracorporeal membrane oxygenation.Short-term survival with the use of extracorporeal membrane oxygenation as a bridge to lung transplantation has significantly improved over the past few years.
- Movement disorders due to bilirubin toxicity. [REVIEW]
- Semin Fetal Neonatal Med 2014 Dec 16.
Advances in the care of neonatal hyperbilirubinemia have led to a decreased incidence of kernicterus. However, neonatal exposure to high levels of bilirubin continues to cause severe motor symptoms and cerebral palsy (CP). Exposure to moderate levels of unconjugated bilirubin may also cause damage to the developing central nervous system, specifically the basal ganglia and cerebellum. Brain lesions identified using magnetic resonance imaging following extreme hyperbilirubinemia have been linked to dyskinetic CP. Newer imaging techniques, such as diffusion tensor imaging or single-photon emission computed tomography, allow quantification of more subtle white matter injury following presumed exposure to unbound bilirubin, and may explain more subtle movement disorders. New categories of bilirubin-induced neurologic dysfunction, characterized by subtle bilirubin encephalopathy following moderate hyperbilirubinemia, have been implicated in long-term motor function. Further research is needed to identify subtle impairments resulting from moderate-severe neonatal hyperbilirubinemia, to understand the influence of perinatal risk factors on bilirubin toxicity, and to develop neuroprotective treatment strategies to prevent movement disorders due to bilirubin toxicity.
- Hepatitis C infection is associated with hepatic toxicity but does not compromise the survival of patients with diffuse large B cell lymphoma treated with rituximab-based chemotherapy. [JOURNAL ARTICLE]
- Leuk Res 2014 Nov 29.
The influence of hepatitis C virus (HCV) infection on the outcome of patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab-based chemotherapy is controversial. We retrospectively analyzed the characteristics and clinical outcomes of 168 patients with DLBCL diagnosed between January 2005 and December 2011. Twenty-nine patients who were HCV-positive before lymphoma treatment were compared with 139 patients who did not have HCV infection. The median follow-up duration was 3.0 (0.07-8.02) years. HCV infection resulted in more hepatic toxicity in both univariate (p=0.001) and multivariate (p=0.003) analyses. In addition, HCV-positive DLBCL patients were more likely to have treatment delay (20.1% vs. 0.7%, p<0.001). For patients who developed hepatic toxicity during immunochemotherapy, HCV-positive patients had significantly higher folds of aspartate aminotransferase elevation (p=0.042) and total bilirubin elevation (p=0.012) compared with those who were HCV negative. However, HCV did not influence the 5-year progression-free survival rate (p=0.412) or 5-year overall survival rate (p=0.410). In conclusion, HCV infection is associated with increased hepatic toxicity and delayed chemotherapy without compromised survival in DLBCL patients treated with rituximab-based chemotherapy.
- Hepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis of randomized clinical trials. [REVIEW]
- Crit Rev Oncol Hematol 2014 Nov 27.
A meta-analysis of randomized controlled trials (RCT) was conducted to determine the relative risk (RR) of hepatotoxicity with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Citations from PubMed/Medline, abstracts from major conferences, clinicaltrials.gov and package inserts were reviewed to include RCTs comparing arms with or without a VEGFR TKI. The RRs of all-grade ALT, AST, ALP and bilirubin elevation in 18,282 patients from 52 trials were 1.57 (95% CI 1.38-1.79, p<0.001), 1.57 (95% CI 1.36-1.81, p<0.001), 1.20 (95% CI 1.09-1.83, p<0.001) and 1.55 (95% CI 1.21-1.97, p<0.001) respectively, and high-grade elevations were 1.66 (95% CI 1.25-2.20, p=0.001), 1.61 (95% CI 1.21-2.14, p=0.001), 1.02 (95% CI 0.70-1.47, p=0.932) and 1.34 (95% CI 1.0-1.81, p=0.054) respectively compared to those in the non-TKI group. The incidence of hepatic failure with VEGFR TKIs was 0.8%.
- The abnormal reaction data-detecting function of the automated biochemical analyzer was useful to prevent erroneous total-bilirubin measurement and to identify monocloncal proteins. [JOURNAL ARTICLE]
- Clin Chim Acta 2014 Dec 15.
Recently, to detect abnormal reactions and failures of the device in biological analysis, a reaction data monitoring system has been provided for automated biochemical analyzers. We investigated the usefulness of this function for Total-bilirubin (T-Bil) measurement in routine testing.Abnormal reactions of T-Bil were detected in the reaction data over time based on the following items: whether the absorbance variance after mixing of the first reagent and sample exceeds the cut-off value.In the cases in which the abnormal reaction was observed, the absorbance rapidly rose because of turbidity after mixing the sample with Reagent-1. The measured value was higher than the actual T-Bil level, for which the analyzer showed a warning mark with the output data. When this particular serum sample was subjected to immunofixation electrophoresis, the presence of a monoclonal protein was confirmed. We encountered seven similar cases out of 30,731 samples.The reaction data monitoring system of the automated biochemical analyzers was useful to prevent false reports (misdiagnosis) due to unpredictable problems during T-Bil measurement. It was also suggested that detection of false reaction with a reagent may be a clue to find a new pathology, such as monoclonal gammopathy.
- The Prevalence and Risk Factors for Gallstone Disease in Taiwanese Vegetarians. [JOURNAL ARTICLE]
- PLoS One 2014; 9(12):e115145.
Gallstone disease (GSD) and its complications are major public health issues globally. Although many community-based studies had addressed the risk factors for GSD, little is known about GSD prevalence and risk factors among Taiwanese vegetarians.This study included 1721 vegetarians who completed a questionnaire detailing their demographics, medical history, and life-styles. GSD was ascertained by ultrasonography or surgical history of cholecystectomy for GSD. The predictive probability of GSD for male and female vegetarians was estimated from the fitted model.The prevalence of GSD was 8.2% for both male and female vegetarians. The risk of GSD is similar in men and women across all age groups, and increases steadily with increasing age. For male vegetarians, age (OR: 1.04; 95% CI: 1.00-1.08) and serum total bilirubin level (OR: 2.35; 95% CI: 1.31-4.22) predict risk for GSD. For female vegetarians, age (OR: 1.03; 95% CI: 1.01-1.05), BMI (OR: 1.07; 95% CI: 1.01-1.13), and alcohol consumption (OR: 7.85; 95% CI: 1.83-33.73) are associated with GSD. GSD is not associated with type of vegetarian diet, duration of vegetarianism, low education level, physical inactivity, diabetes, coronary artery disease, cerebral vascular accident, chronic renal failure, hepatitis C virus infection, and lipid abnormalities. GSD is also not associated with age at menarche, postmenopausal status, and multiparity in female vegetarians.Risk factors useful for predicting GSD in vegetarians are (1) age and total bilirubin level in men, and (2) age, BMI, and alcohol consumption in women. Many previously identified risk factors for general population does not seem to apply to Taiwanese vegetarians.
- Third heart sound in hospitalised patients with acute heart failure: insights from the ATTEND study. [JOURNAL ARTICLE]
- Int J Clin Pract 2014 Dec 18.
Several previous studies have suggested that detection of a third heart sound (S3) in patients with chronic congestive heart failure is associated with adverse long-term outcomes. However, the short-term prognostic value of identifying an S3 on admission in patients with acute heart failure (AHF) is not well established. We therefore analysed the in-hospital prognostic value of detecting an S3 on admission in hospitalised patients with AHF.The Acute Decompensated Heart Failure Syndromes (ATTEND) study investigators enrolled 4107 patients hospitalised with AHF. Investigators evaluated the presence or absence of an S3 during routine physical examination.On admission to hospital, 1673 patients (41%) had an S3. Patients with an S3 had a higher heart rate, higher serum level of B-type natriuretic peptide and higher creatinine levels than patients without an S3. However, there were no significant differences of systolic blood pressure, serum sodium, haemoglobin, C-reactive protein and total bilirubin between the two groups. Multivariate analysis adjusted for various markers of disease severity revealed that only the presence of an S3 was independently associated with an increase of in-hospital all cause death [adjusted odds ratio (OR), 1.69; 95% confidence interval (CI), 1.19-2.41; p = 0.003] and cardiac death (adjusted OR, 1.66; 95% CI, 1.08-2.54; p = 0.020) among the congestive physical findings related to heart failure (S3, rales, jugular venous distension and peripheral oedema).Detecting an S3 on admission was independently associated with adverse in-hospital outcomes in patients with AHF. Our findings suggest that careful bedside assessment is clinically meaningful.