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American Journal of Emergency Medicine xxx (2013) xxx–xxx

YAJEM-53572; No of Pages 7

Contents lists available at SciVerse ScienceDirect

American Journal of Emergency Medicine

.e lsev ie r .com/ locate /a jem

Original Contribution

j ourna l homepage: www

Role of procalcitonin in the diagnosis of infective endocarditis: a meta-analysis☆,☆☆

Chin-Wei Yu MD a, Ling-I Juan MD b, Shou-Chien Hsu MD a, Chun-Kuei Chen MD c, Chun-Wei Wu MD c,Chien-Chang Lee MD MSc d,e,⁎, Jiunn-Yih Wu MD a,⁎a Department of Emergency Medicine, Chang Gung Memorial Hospital, keelung and Chang Gung University College of Medicine, Taoyuan, Taiwanb Buddhist Tzu Chi General Hospital Taipei Branch, Department of Radiology, Taiwanc Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan and Chang Gung University College of Medicine, Taoyuan, Taiwand Department of Emergency Medicine, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwane Department of Epidemiology, Harvard School of Public Health, Boston, USA

☆ Conflict of interest: None declared.☆☆ Funding: None declared.⁎ Corresponding authors. C.-C. Lee is to be contacted

Taiwan. Tel.: +886 5532391x2326; fax: +886 5534145Taiwan. Tel.: +886 33281200x2505; fax: +886 332877

E-mail addresses: cclee100@gmail.com (C-C. Lee), a(J-Y. Wu).

0735-6757/$ – see front matter © 2013 Elsevier Inc. Alhttp://dx.doi.org/10.1016/j.ajem.2013.03.008

Please cite this article as: Yu C-W, et al, Ro(2013), http://dx.doi.org/10.1016/j.ajem.20

a b s t r a c t

a r t i c l e i n f o

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Article history:

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Received 19 February 2013Accepted 4 March 2013Available online xxxx

Background: Infective endocarditis (IE) is a diagnostic challenge. We aimed to systemically summarize thecurrent evidence on the diagnostic value of procalcitonin (PCT) in identifying IE.Methods: We searched EMBASE, MEDLINE, Cochrane database, and reference lists of relevant articles with nolanguage restrictions through September 2012 and selected studies that reported the diagnostic performanceof PCT alone or compare with other biomarkers to diagnose IE. We summarized test performance

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characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves, andbivariate random effects models.Results: We found 6 qualifying studies that included 1006 episodes of suspected infection with 216 (21.5%)confirmed IE episodes from 5 countries. Bivariate pooled sensitivity, specificity, positive likelihood ratios, andnegative likelihood ratios were 64% (95% confidence interval [CI], 52%-74%), 73% (95% CI 58%-84%), 2.35 (95% CI1.40-3.95), and 0.50 (95% CI 0.35-0.70), respectively. Of the 5 studies examining C-reactive protein (CRP), thepooledsensitivity, specificity, positive likelihood ratios, andnegative likelihood ratioswere75%(95%CI62%-85%),73% (95% CI 61%-82%), 2.81 (95% CI 1.70-4.65), and 0.34 (95% CI 0.19-0.60), respectively. The global measures ofaccuracy, area under the receiver operating characteristic curve (AUC) and diagnostic odds ratio (dOR), showedCRP (AUC 0.80, dOR 8.55) may have higher accuracy than PCT (AUC 0.71, dOR 4.67) in diagnosing IE.Conclusions: Current evidence does not support the routine use of serum PCT or CRP to rule in or rule out IE inpatients suspected to have IE.

© 2013 Elsevier Inc. All rights reserved.

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1. Introduction

Infective endocarditis (IE) is a life-threatening disease with anincidence varying between 30 and 100 cases per million persons, anda mortality rate of up to 40% [1–4]. By definition, IE is an infection ofthe endocardial surface of the heart, usually the heart valves, muralendocardium, or a septal defect [3]. IE may cause intracardiac effectssuch as severe valvular insufficiency, or congestive heart failure, andextracardiac effects such as disseminated infected emboli and variousimmunological phenomena [3–5]. Since the first systematic analysisby SirWilliam Osler in 1885, the clinical features of IE have undergonegreat changes in developed countries, from a disease commonly

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at Douliou, Yunlin County 640,2. J.-Y. Wu, Taipei City 11267,15.sepsis.wu@msa.hinet.net

l rights reserved.

le of procalcitonin in the dia13.03.008

affecting patients with rheumatic valvular heart disease to a diseaseaffecting injection drug users, elderly persons with valvular sclerosis,patients with cardiovascular prostheses, hospitalized patients withindwelling catheters, and hemodialysis patients [1,2,6]. Mortality andmorbidity continue to remain high, despite advances in medical andsurgical treatment [3,4].

In clinical practice, IE still poses a diagnostic challenge forclinicians because of the various clinical presentations. Currentdiagnosis is largely based on the modified Duke’s criteria thatintegrates clinical findings, microbiological study results, and imagingfindings. However, the typical clinical manifestations may be maskedby the indiscriminate use of antimicrobial agents, or by underlyingconditions in elderly individuals or immunosuppressed persons.Therefore, these criteria have been reported to over- or underdiag-nose IE in patients with subacute disease or atypical presentations[3,5]. Given that the mortality for IE is as high as 12 to 30% within thefirst year of diagnosis, and that patients may benefit from the earlyadministration of appropriate antibiotics, early diagnosis is manda-tory [4]. A biomarker with high sensitivity and specificity will greatlyimprove the diagnostic rate, and thereby influence outcomes.

gnosis of infective endocarditis: a meta-analysis, Am J Emerg Med

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Fig. 1. Flow chart of study identification and inclusion.

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2 C-W. Yu et al. / American Journal of Emergency Medicine xxx (2013) xxx–xxx

Procalcitonin (PCT) is a precursor of calcitonin that is constitu-tively secreted by C cells of the thyroid gland and K cells of the lung[7]. In healthy individuals, PCT is normally undetectable (b0.01 ng/mL). When stimulated by endotoxin, PCT is rapidly produced byparenchymal tissue throughout the body [8,9]. Unlike CRP, PCT doesnot respond to sterile inflammation or viral infection [10]. Thisdistinctive characteristicmakes PCT a valuable diagnostic markerwithbroadening range of clinical indications, including the early diagnosisof IE. Despite the early encouraging report from Mueller et al [11],subsequent reports have shown mixed results [12–16].

The aim of this study is to systematically and quantitativelyevaluate the role of PCT in the early diagnosis of IE by performing ameta-analysis of published reports.

Table 1Characteristics of the 6 included studies that used biomarkers to assess

Author, year, country Prevalence(N)

Meanage

Biomarker PCTtestingsystems

Cutoff(PCT, ng/mL;CRP, mg/L)

Oude

Kocazeybek B 2003,Turkey [12]

0.2 (50) 42 PCT,CRP LUMItest PCT = 0.19CRP = 10.6

Du

Mueller C 2004,Switzerland [11]

0.31(67) 49 PCT,CRP Kryptor PCT= 2.3CRP=NA

DuanDu

Watkin RW 2007,UK [13]

0.47(134) 49.4 PCT,CRP, IL-6,LPSBP, TNF-α

PCT-Q PCT= 0.5CRP=NA

Du

Cuculi F 2008,Switzerland [14]

0.19(77) 60.2 PCT,CRP Kryptor PCT= 0.64,CRP =NA

M

Jereb M 2009,Slovenia [15]

0.43(53) 55.3 PCT,CRP LUMItest PCT= 0.5CRP=NA

Du

Knudsen JB 2010,Denmark [16]

0.19(759) 54.4 PCT Kryptor PCT= 0.12 Du

IL-6, interleukin-6; LPSBP, lipopolysaccharide binding protein; CNS: coagulase negative stap

Please cite this article as: Yu C-W, et al, Role of procalcitonin in the dia(2013), http://dx.doi.org/10.1016/j.ajem.2013.03.008

2. Methods

2.1. Systemic meta-analysis guideline adherence

We adhered to the standard methods and procedures forsystematic reviews and meta-analyses of diagnostic tests [17,18].

2.2. Literature search strategy

We performed a search on PubMed without language restrictionsusing the keyword 'procalcitonin' crossed with ‘endocarditis,’ ‘infectiveendocarditis,’ ‘infectious endocarditis,’ ‘endocarditis lenta,’ and ‘sub-acute bacterial endocarditis.’ Our search was limited to human studiespublished from inception toMarch2012. The last updatewasperformedon September 2012. A similar search strategy and similar search termswere used to search in EMBASE. PubMed and EMBASE searches wereconducted independently by 2 authors. To ensure a comprehensiveacquisition of literature, independent supplemental manual searcheswere performed on the reference lists of relevant articles and theCochrane database. Medical Subject Heading (MeSH) and EMbase TREEtool (EMTREE) were used to guide the choice of appropriate searchterms. Any inconsistencies between the 2 investigators in articleinclusion and exclusion were resolved by consensus.

2.3. Study selection and data extraction

We included studies that met all of the following inclusion criteria:(1) evaluation of PCT alone or compared with other laboratorymarkers, such as CRP, to diagnose IE; and (2) sufficient data toreconstruct a 2 × 2 contingency table for meta-analysis. Two authorsindependently assessed all titles/abstracts to determine whetherinclusion criteria were satisfied. Full-text articles were retrieved if anyof the reviewers considered the abstracts suitable. The 2 reviewersthen independently assessed the full text of the retrieved studies fortheir suitability for inclusion. Discrepancies between the 2 reviewerswere resolved by having an additional reviewer assess the full articles.The decision about whether to include any article was made byconsensus. The 2 original reviewers independently extracted datafrom each included study. Among the predefined variables collectedwere year of publication, study design (prospective or retrospective,cross-sectional or case-control), number of enrolled patients, agegroup (adults or children), setting (emergency department or ward),study population (general, drug abuser, immunocompromised),reference diagnostic standard for IE, timing of the PCT measurement,

tcome(s)finition

Causative microorganisms PCTSensitivitySpecificity

CRPSensitivity,Specificity

ke Criteria S. sanguis, E. faecalis, Candidaalbicans, E. coli, A. baumannii

84.0 %88.0 %

100 %72.0 %

ke Criteriad the modifiedke Criteria

S. aureus, S. aureus plusstreptococci, Viridansstreptococci, S. pyogenes,S. pneumoniae

81.0 %85.0 %

62.5 %71.0 %

ke Criteria S. aureus, CNS, Viridansstreptococci , Enterococcus spp.

46.0 %84.0%

81.5 %74.0 %

odified Duke Criteria S. aureus, S. viridans, enterococcus,coagulase negative bacteraemia

52.0 %56.0 %

52.0 %54.0 %

ke Criteria S. aureus, S. coagulase negative,E. faecalis, V. streptococci

66.0%81.0%

67.0 %90.0%

ke Criteria S. viridans, S. aureus, coagulase-negative staphylococci, enterococci,S. pneumoniae

67.0 %47.0 %

NA

hylococci; TNF-α, tumor necrosis factor alpha.

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Fig. 2. QUADAS criteria for included studies.

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markers other than PCT, cutoff of the tested markers, and studyresults, including sensitivity and specificity. Grading of quality wasperformed according to the Quality Assessment of Diagnostic-Accuracy Studies (QUADAS) instrument [19], which is an established,evidence-based tool for systematic reviews of diagnostic studies.When multiple pairs of sensitivity or specificity were reported in 1study, we consistently used the data with the highest Youden index(sensitivity + specificity− 1) for meta-analysis. This tool uses a list of14 questions, which are answered as “yes,” “no,” or “unclear,” toexamine the potential for bias in a study.

2.4. Data preparation and statistical analysis

Because pooling sensitivity and specificity separately can producebiased estimates of test accuracy, we preferred to generate pooledestimates when both sensitivity and specificity were reported in astudy. We used the random effects bivariate random effectsregression model for diagnostic meta-analysis to obtain pooledestimates of the sensitivity and specificity of PCT [20]. Zero cellswere handled using a 0.5 continuity correction. The bivariateapproach assumes a bivariate distribution for the logit-transformedsensitivity and specificity. The bivariate model estimates and adjustsfor the negative correlation between the sensitivity and specificity ofthe index test due to the threshold effect [20]. The random effectmodel takes into consideration the between-study variation. We alsogenerated hierarchical summary receiver operating characteristic(HSROC) curves as a way to summarize the global test performancefrom different diagnostic studies [21]. HSROC curves differ fromtraditional ROC curves in allowing random effects by each individualstudy. The HSROC curves generated the curve restricted by theobserved range of sensitivity and specificity from the included studies.It does not extrapolate beyond the available data. Both bivariatemodel and HSROCmethods are supported by the Cochrane DiagnosticTest Accuracy Working Methods group.

Multiple sources of heterogeneity frequently exist in diagnosticstudies. In addition to visual assessment with use of the forest plots,we calculated the inconsistency index (I [2] statistics) to estimatebetween-study variation that cannot be explained by the within-study variation.We also performed a diagnostic odds ratio (OR)meta-analysis and plotted the forest plots for the diagnostic OR. To test for

Please cite this article as: Yu C-W, et al, Role of procalcitonin in the dia(2013), http://dx.doi.org/10.1016/j.ajem.2013.03.008

possible publication bias, we used a linear regression of log ORs on theinverse root of effective sample sizes to test funnel plot asymmetry[22]. We defined a priori the clinical and study design characteristicsas potential relevant covariates: cutoff value and the PCT testingsystems used. Statistical analyses were conducted using STATA 11.0(Stata Corp, College Station, TX), notably with the user-written“midas” and “metandi” programs for stata. All statistical tests were 2sided, and statistical significance was defined as a P b .05.

3. Results

In total, 171 studies (excluding duplicates) were identified usingthe search strategy outlined earlier (Fig. 1). After the first roundscreening of title and abstracts, 156 nonrelevant studies, case reports,or reviews were excluded. Fifteen potential relevant studies wereretrieved for full text evaluation, of which 6 further studies wereexcluded for varying reasons, leaving 6 that met the inclusion criteria.

These studies included 1006 episodes of suspected infection with216 (21.5%) confirmed IE episodes. Only 2 of the 6 studies reporteddata using the standard PCT cutoff value (0.5 ng/mL). Table 1 presentsa summary of the characteristics of the included studies and patients.The number of subjects with IE in each study was 15 to 147, and theirmean/median age was 42 to 60.2 years. Four studies used DukeCriteria, and the rest used modified Duke Criteria as the referencediagnostic standards. Common bacteria isolated were Staphylococcusaureus, Viridans streptococci, Enterococcus faecalis, coagulase-negativestreptococci, Acinetobacter baumannii, Streptococcus sanguis, Escher-ichia coli, and Streptococcus pneumoniae, and Candida albicans was acommonnonbacterial isolate.Measurements of serumPCT levelswereperformed by 3 different types of assays: semi-quantitative PCT-Q in 1study, immunoluminometric LUMI test in 2 studies, and TRACE (timeresolved amplified cryptate emission) technology Kryptor test in 3studies. Five studies also examined the value of CRP in diagnosing IE.

We used the QUADAS tool for study quality assessment. Fig. 2provides an overall impression of the methodological quality of thestudies. All blood draws were taken in close proximity to theconfirmation diagnosis. All patients were verified by the samereference standard in all studies. None of the included studiesexplained withdrawals or reported uninterpretable results, and inonly one study the physicians were blinded to the index test while

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Fig. 3. Receiver operating curve analysis summary receiver operating characteristic(SROC) curve (solid line) of PCT (A) and CRP (B) for patients with infective endocarditisand the bivariate summary estimate (solid square), together with the corresponding95%confidence ellipse (inner dashed line) and 95% prediction ellipse (outer dottedline). The symbol size for each study is proportional to the study size.

4 C-W. Yu et al. / American Journal of Emergency Medicine xxx (2013) xxx–xxx

verifying outcomes by reference standards. We could not exclude thepossibility of incorporation bias.

3.1. Diagnostic accuracy indices

Results of the meta-analysis indicated that PCT testing has a lowdegree of accuracy for diagnosing IE. We constructed summary ROCsfor both PCT and CRP (Fig. 3). PCT had an area under the ROC of 0.77(95% confidence interval [CI] 0.73-0.80). Pooled sensitivity andspecificity estimates of PCT were 0.64 (95% CI 0.52-0.74) and 0.73(95% CI 0.58-0.84), respectively (Fig. 4). The positive likelihood ratio(LR+, 2.35; 95% CI 1.40-3.95) of the PCT test was not sufficiently highto be used as a rule-in test, and the high negative likelihood ratio(LR−, 0.64; 95% CI 0.32-0.73) could not reduce the pretest probabilityto a level that would enable systemic infection to be safely ruled out.CRP had an AUC of 0.80 (95% CI 0.77-0.84). The pooled sensitivity andspecificity estimates of CRP were 0.75 (95% CI 0.62-0.85) and 0.73(95% CI 0.61-0.82), respectively (Fig. 5). The positive likelihood ratio(LR+, 2.81; 95% CI 1.70-4.65) of CRP testing was not sufficient tosupport CRP as a rule-in test, but the negative likelihood ratio (LR−,0.34; 95% CI 0.19-0.60) has moderate rule-out value. Overall, CRP hasa higher discriminative capability than PCT in differentiating IE fromother causes of systemic inflammatory response syndrome. Thediagnostic OR for CRP was 8.55 (95%CI 2.6-28.1), while the diagnosticOR for PCT was 4.67(95% CI 2.0-11.0). We observed a substantialdegree of heterogeneity for PCT (I2 = 79.2%; 95% CI 54.5-90.5) andCRP (I2 = 77.8%; 95% CI 45.8-90.7). No significant evidence ofpotential publication bias was noted by Egger’s test for funnel plotasymmetry (Table 2).

3.2. Subgroup analysis

We performed subgroup analysis by restricting analysis to the 3studies using the high sensitive measurement tool for PCT (KryptorPCT system, BRHAMS, Berlin, Germany). The specificity did increase,but the sensitivity deceased substantially. Overall, the accuracy wasnot enhanced (AUC 0.74, diagnostic OR 4.57). We used Galbraith plotsto explore sources of heterogeneity. The Galbraith plots showed thatstudies by Kocazeybek et al and Mueller et al in early years werepotential sources of heterogeneity. These 2 studies tend to showhigher accuracy for PCT to diagnose IE. Subgroup analysis removingthese 2 studies showed improved heterogeneity (I2 = 60.2%; 95% CI0.0-86.71) with further declined accuracy. Notably, the pooledsensitivity decreased from 0.64 to 0.55 (95% CI 0.44-0.66) and theAUC from 0.71 to 062 (95% CI 0.57-0.66).

4. Discussion

IE is generally thought to originate from bacterial seeding to theturbulence-damaged endothelial surface of the heart. The epidemiol-ogy of IE has changed over the past decade. Increased numbers ofelderly, chronically ill, and immunosuppressed patients has madeclinical diagnosis more challenging because these patients are oftenafebrile and unable tomount an adequate immune response to exhibitthe classic stigmata of IE caused by autoimmune reaction andperipheral embolization [1,5]. Thus, there is a need for a sensitivediagnostic aid before culture results are available. Advanced imagingmodalities such as transesophageal echocardiography or multi-slicecomputed tomography have developed into useful tools for meetingthis clinical challenge, but they are expensive, time consuming, andare not universally available in all levels of hospitals. Thus, a rapid,economical, and accessible biomarker assay may aid in establishingthe diagnosis of IE earlier such that appropriate antibiotic treatmentcan be provided.

PCT have been recently shown to have moderate to high accuracyin diagnosing various systemic bacterial infection, but several report

Please cite this article as: Yu C-W, et al, Role of procalcitonin in the dia(2013), http://dx.doi.org/10.1016/j.ajem.2013.03.008

have shown inconsistent results on the accuracy of PCT in thediagnosis of IE [12–16]. Our study was designed to evaluate thediagnostic performance of PCT for the diagnosis of IE. We found thatserum PCT assays, either high or low sensitive assays, have little valueas a screening tool in patients who are clinical suspected of having IE.The specificity or negative likelihood ratio of PCT is also unacceptablypoor to be used as a rule-out tool. Our data showed CRP has a superioraccuracy, notably in specificity, over PCT for diagnosis of IE.

Previous meta-analyses addressing the value of serum PCT havesuggested that PCT is of moderate value (AUC 0.84, 95% CI 0.75-0.9;sensitivity 0.76, 95% CI 0.66-0.84; specificity 0.70, 95% CI 0.60-0.79) indistinguishing sepsis from other noninfectious causes of systemic

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Fig. 4. Forest plots for (A) sensitivity and (B) specificity for studies using PCT to detect among patients with infective endocarditis.

5C-W. Yu et al. / American Journal of Emergency Medicine xxx (2013) xxx–xxx

inflammation syndrome [23]. Our meta-analysis showed PCT mayhave even lower accuracy in diagnosing IE than in diagnosing of othersources of sepsis. The overall positive likelihood ratio after excluding 2potential outlier studies was only 2.22 (95% CI 1.36-3.65), notsufficiently high to be used as a reliable rule-in tool [24]. In a virtualpopulationwith a 20% prevalence (pretest probability) of IE, a positivelikelihood ratio of 2.22 translates into a positive predictive value(posttest probability) of 36%. In other words, only 1 in 3 patients withpositive PCT test results can be expected to have confirmed IE.Similarly, a negative likelihood ratio of 0.60 translates into 13%posttest probability. In other words, only 1 in 8 patients with negativePCT results may turn out to have IE. Compared to PCT, the posttestprobability for patients with positive and negative CRP test result is41% and 8%, respectively, still not sufficiently accurate as a majordiagnostic tool for IE. IE is a disorder with a high mortality rate if nottreated promptly. Thus, the decision to exclude a patient with possibleIE from further imaging based on a negative serum PCT or CRP valuemight be hazardous. We do not, however, think that PCT and CRP areof no diagnostic value in the setting of IE. Instead, we recommend thatfurther studies are needed to examine whether PCT has additionaldiagnostic or prognostic value to conventional clinical variables.

Please cite this article as: Yu C-W, et al, Role of procalcitonin in the dia(2013), http://dx.doi.org/10.1016/j.ajem.2013.03.008

High heterogeneity was observed for the overall accuracyestimated for PCT. We tried to explore the potential source forheterogeneity and found studies byMueller et al and Kocazeybek et alwere potential outliers on Galbraith plot [25]. The 2 studies reportedsignificantly higher accuracy than other studies. Mueller et al reportedan optimum PCT cutoff value of 2.3 ng/mL, which is significantlyhigher than those in other studies (range 0.12-0.64 ng/mL) [11].Kocazeybek et al adopted a case–control design comparing IE to non-infected and non-IE infected controls [12]. It has been shown that thecase-control design tends to over-estimate the accuracy of adiagnostic test [17]. In addition, 3 different assay kits used in the 6included studies may also have contributed to the between-studyinconsistency. The 3 PCT assays used were Kryptor (BRHAMS, Berlin,Germany), LUMItest (BRHAMS), and the PCT-Q assay systems(BRHAMS). The PCT-Q assay system is a semi-quantitative bedsideassay and the LUMItest PCT test uses an immunoluminometricmethod with a reported functional sensitivity (20% CV) of 0.5 ng/mL. Values b0.5 ng/mL, which is still of clinical importance in patientswith IE, may lack precision. Only 3 studies used the Kryptor PCT assaywith higher precision (detection limit of 0.02 ng/mL; functionalsensitivity of 0.06 ng/mL) [26]. Subgroup analysis on studies using the

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Fig. 5. Forest plots for (A) sensitivity and (B) specificity for studies using CRP to detect among patients with infective endocarditis.

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6 C-W. Yu et al. / American Journal of Emergency Medicine xxx (2013) xxx–xxx

high sensitive kit, however, did not show significant improvementin the diagnostic accuracy. Further studies are still needed to verifythis result.

Our study has some potential limitations. First, although a singlethreshold of 0.5 ng/mL is usually used to define a positive serum PCTfinding, we do not have enough data to provide a pooled summaryaccuracy estimate on this cutoff value. Second, because of the limitednumber of included studies, we did not perform meta-regressionanalyses to further investigate the statistical heterogeneity.

Table 2Summary of subgroup analysis of the 6 included studies

Variable Studies(n)

Sensitivity(95% CI)

Specificity(95% CI)

Likelihoodratio+

Likerati

PCT [11–16] 6 0.64(0.52-0.74) 0.73(0.58-0.84) 2.35(1.40-3.95) 0.50PCT excludingpotential outlier

4 0.55(0.44-0.66) 0.75(0.60-0.86) 2.22(1.36-3.65) 0.60

Kryptor [11,14,16] 3 0.67 (0.60-0.74) 0.50(0.47-0.54) 1.89(0.90-3.98) 0.58CRP [11–15] 5 0.75(0.62-0.85) 0.73(0.61-0.82) 2.81(1.70-4.65) 0.34

Please cite this article as: Yu C-W, et al, Role of procalcitonin in the dia(2013), http://dx.doi.org/10.1016/j.ajem.2013.03.008

5. Conclusions

In conclusion, current evidence does not support the routine use ofserum PCT or CRP as a biochemical test to rule in or rule out IE inpatients who are suspected to have IE. The high sensitive PCT test doesnot appear to help clinicians to screen out more patients who needadvanced diagnostic imaging. Considering the small sample size andsuboptimal case-control design of the currently available studies, asufficiently powered cohort design prospective study is needed to

lihoodo−

AUROC (95% CI) Diagnostic OR(95% CI)

I2 (95% CI) Publication bias(Egger’s test p)

(0.35-0.70) 0.71(0.67-0.75) 4.67(2.0-11.0) 79.2 (54.5-90.5) 0.534(0.46-0.76) 062(0.57-0.66) 4.37(1.7-11.0) 60.2 (0.0-86.71) 0.534

(0.33-102) 0.74(0.47-0.91) 3.57(0.9-14.5) 85.1(35.3-94.6) 0.670(0.19-0.60) 0.80(0.77-0.84) 8.55(2.6-28.1) 77.8(45.8-90.7) 0.647

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conclusively address the usefulness of serum PCT as a diagnostic aidin IE.

Acknowledgments

We thank Pei-Shan Hsieh fromMedical Wisdom Inc for her help increating tables and graphics.

References

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gnosis of infective endocarditis: a meta-analysis, Am J Emerg Med

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