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      Assessment of a bedside test for N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac causes of pleural effusion in cats

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          Abstract

          Background

          Cats with pleural effusion represent common emergencies in small animal practice. The aim of this prospective study was to investigate the diagnostic ability of a point-of-care ELISA (POC-ELISA) for the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac disease in cats with pleural effusion. The sample material for use of this rapid test was either plasma or diluted pleural effusion.

          Twenty cats with moderate to severe pleural effusion were prospectively recruited. The cats were grouped into two groups, with or without congestive heart failure (CHF; N-CHF), after complete work-up. Blood and effusion were collected in EDTA tubes. Plasma and pleural effusion supernatants were transferred into stabilizer tubes and frozen. POC-ELISA for NT-proBNP was performed with plasma and diluted effusion (1:1). Quantitative NT-proBNP measurement was performed in plasma and diluted and undiluted effusions.

          Results

          Six cats were assigned to the CHF group. Of the 14 cats in the N-CHF group, 6 had concurrent cardiac abnormalities that were not responsible for the effusion. For the detection of CHF, the test displayed respective sensitivities and specificities of 100% and 79% in plasma and 100% and 86% in diluted pleural fluid. Receiver operating characteristic (ROC) analysis for quantitative NT-proBNP measurement of plasma and diluted and undiluted pleural effusions displayed areas under the curve of 0.98, sensitivities of 100% and specificities of 86%. The optimum cut-off was calculated at 399 pmol/l in plasma and 229 pmol/l in the diluted effusion and 467 pmol/l in the undiluted effusion.

          Conclusions

          POC-ELISA for NT-proBNP in both plasma and diluted pleural effusion was suitable to differentiate cardiac from non-cardiac causes of feline pleural effusion. According to our results, use of pleural effusion is feasible, but dilution of the effusion before measurement seems to improve specificity.

          Electronic supplementary material

          The online version of this article (10.1186/s12917-017-1319-6) contains supplementary material, which is available to authorized users.

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          Most cited references28

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          Echocardiographic assessment of spontaneously occurring feline hypertrophic cardiomyopathy. An animal model of human disease.

          Necropsy studies in domestic cats have suggested the occurrence of a primary cardiac disease resembling hypertrophic cardiomyopathy (HCM) in humans. We used two-dimensional echocardiography to define morphological and functional features of HCM during life in 46 domestic cats evaluated in a subspecialty veterinary clinic. Cats were 8 months to 14 years old (mean, 6 years). During the follow-up period of as long as 49 months, 18 cats died (or were euthanatized) due to congestive heart failure, peripheral embolization, or both, and 3 other cats experienced out-of-hospital sudden, unexpected death. Echocardiography showed a small left ventricular cavity, associated with a variety of patterns of hypertrophy. Wall thickening was most often diffuse (involving ventricular septum and free wall) in 31 cats (67%) and segmental in 15 (33%), including 12 with thickening confined to anterior septum; wall thickening was judged to be asymmetrical in 42 and symmetrical (concentric) in 4. In 30 cats (65%), marked mitral valve systolic anterior motion produced dynamic obstruction to left ventricular outflow (Doppler estimated gradients, 25 to 110 mm Hg). Compared with survivors, cats with HCM that died with heart failure had greater left ventricular thickness (8.1 +/- 1.5 versus 7.3 +/- 0.9 mm; P < .05) and larger left atria (20.1 +/- 4.6 versus 16.8 +/- 3.4 mm; P = .01) and more often had the nonobstructive form (89% versus 48%; P < .01). A spontaneously occurring disease of domestic cats was identified by echocardiography and was similar in its phenotypic expression to HCM in humans; it was characterized by unexplained left ventricular hypertrophy in a variety of patterns with or without evidence of outflow obstruction. Unfavorable prognosis was associated with greater magnitude of hypertrophy and absence of outflow obstruction. Feline HCM may prove to be a valuable animal model of the human disease.
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            A comparison of several methods for analyzing censored data.

            The purpose of this study was to compare the performance of several methods for statistically analyzing censored datasets [i.e. datasets that contain measurements that are less than the field limit-of-detection (LOD)] when estimating the 95th percentile and the mean of right-skewed occupational exposure data. The methods examined were several variations on the maximum likelihood estimation (MLE) and log-probit regression (LPR) methods, the common substitution methods, several non-parametric (NP) quantile methods for the 95th percentile and the NP Kaplan-Meier (KM) method. Each method was challenged with computer-generated censored datasets for a variety of plausible scenarios where the following factors were allowed to vary randomly within fairly wide ranges: the true geometric standard deviation, the censoring point or LOD and the sample size. This was repeated for both a single-laboratory scenario (i.e. single LOD) and a multiple-laboratory scenario (i.e. three LODs) as well as a single lognormal distribution scenario and a contaminated lognormal distribution scenario. Each method was used to estimate the 95th percentile and mean for the censored datasets (the NP quantile methods estimated only the 95th percentile). For each scenario, the method bias and overall imprecision (as indicated by the root mean square error or rMSE) were calculated for the 95th percentile and mean. No single method was unequivocally superior across all scenarios, although nearly all of the methods excelled in one or more scenarios. Overall, only the MLE- and LPR-based methods performed well across all scenarios, with the robust versions generally showing less bias than the standard versions when challenged with a contaminated lognormal distribution and multiple LODs. All of the MLE- and LPR-based methods were remarkably robust to departures from the lognormal assumption, nearly always having lower rMSE values than the NP methods for the exposure scenarios postulated. In general, the MLE methods tended to have smaller rMSE values than the LPR methods, particularly for the small sample size scenarios. The substitution methods tended to be strongly biased, but in some scenarios had the smaller rMSE values, especially for sample sizes <20. Surprisingly, the various NP methods were not as robust as expected, performing poorly in the contaminated distribution scenarios for both the 95th percentile and the mean. In conclusion, when using the rMSE rather than bias as the preferred comparison metric, the standard MLE method consistently outperformed the so-called robust variations of the MLE-based and LPR-based methods, as well as the various NP methods, for both the 95th percentile and the mean. When estimating the mean, the standard LPR method tended to outperform the robust LPR-based methods. Whenever bias is the main consideration, the robust MLE-based methods should be considered. The KM method, currently hailed by some as the preferred method for estimating the mean when the lognormal distribution assumption is questioned, did not perform well for either the 95th percentile or mean and is not recommended.
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              Multicenter evaluation of plasma N-terminal probrain natriuretic peptide (NT-pro BNP) as a biochemical screening test for asymptomatic (occult) cardiomyopathy in cats.

              B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved.
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                Author and article information

                Contributors
                Gabriel.Wurtinger@vetmed.uni-giessen.de
                Estelle.Henrich@vetmed.uni-giessen.de
                Nicolai.B.Hildebrandt@vetmed.uni-giessen.de
                Nicola.Wiedemann@vetmed.uni-giessen.de
                Matthias.A.Schneider@vetmed.uni-giessen.de
                Esther.Hassdenteufel@vetmed.uni-giessen.de
                Journal
                BMC Vet Res
                BMC Vet. Res
                BMC Veterinary Research
                BioMed Central (London )
                1746-6148
                20 December 2017
                20 December 2017
                2017
                : 13
                : 394
                Affiliations
                ISNI 0000 0001 2165 8627, GRID grid.8664.c, Small Animal Clinic (Internal Medicine), , Justus-Liebig-University Giessen, ; Frankfurter Strasse 126, 35392 Giessen, Köln, Germany
                Author information
                http://orcid.org/0000-0002-6378-1241
                Article
                1319
                10.1186/s12917-017-1319-6
                5738779
                29262821
                67ee56bc-57e3-4d93-8a3b-3cf1c6e1abf3
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 April 2017
                : 12 December 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Veterinary medicine
                feline,pleural effusion,biomarker,point-of-care test
                Veterinary medicine
                feline, pleural effusion, biomarker, point-of-care test

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