Discriminative Accuracy of Novel and Traditional Biomarkers in Children With Suspected Appendicitis Adjusted For Duration of Abdominal Pain

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Acad Emerg Med. 2011 June ; 18(6): 567574. doi:10.1111/j.1553-2712.2011.01095.x.
Discriminative Accuracy of Novel and Traditional Biomarkers in

Children with Suspected Appendicitis Adjusted for Duration of
Abdominal Pain
Anupam B. Kharbanda, MD, MS, Yohaimi Cosme, MD, Khin Liu, Steven L. Spitalnik, MD,
and Peter S. Dayan, MD, MS
Division of Pediatric Emergency Medicine (ABK, YC, PSD), Department of Pathology and Cell
Biology (KL, SLS), Columbia University College of Physicians and Surgeons, New York, NY
Abstract
ObjectivesTo assess the accuracy of novel and traditional biomarkers in patients with
suspected appendicitis as a function of duration of symptoms.
MethodsThis was a prospective cohort study, conducted in a tertiary care emergency
department (ED). The authors enrolled children 3 to 18 years old with acute abdominal pain of
less than 96 hours, and measured serum levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), C reactive protein (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC).
Final diagnosis was determined by histopathology or telephone follow-up. Trends in biomarker
levels were examined based on duration of abdominal pain. The accuracy of biomarkers was
assessed with receiver operating characteristic (ROC) curves. Optimal cut-points and test
performance characteristics were calculated for each biomarker.
ResultsOf 280 patients enrolled, the median age was 11.3 years (IQR 8.6 to 14.8), 57% were
male, and 33% had appendicitis. Median IL-6, median CRP, mean WBC, and mean ANC differed
significantly (p < 0.001) between patients with non-perforated appendicitis and those without
appendicitis; median IL-8 levels did not differ between groups. In non-perforated appendicitis,
median IL-6, WBC, and ANC levels were maximal at less than 24 hrs of pain, while CRP peaked
between 24 and 48 hours. In perforated appendicitis, median IL-8 levels were highest by 24 hours,
WBC and IL-6 by 24 to 48 hours, and CRP after 48 hours of pain. The WBC appeared to be the
most useful marker to predict appendicitis in those with fewer than 24 or more than 48 hours of
pain, while CRP was the most useful in those with 24 to 48 hours of pain.
ConclusionsIn this population, the serum levels and accuracy of novel and traditional
biomarkers varies in relation to duration of abdominal pain. IL-6 shows promise as a novel
biomarker to identify children with appendicitis.
Introduction
Appendicitis remains a challenging diagnosis in the pediatric population.1 Clinicians
increasingly rely on diagnostic imaging, such as computed tomography (CT), to identify
patients with appendicitis.2 Although CT is highly accurate, substantial concerns have been
Corresponding Author and Reprints: Anupam Kharbanda, MD, MS, Division of Pediatric Emergency Medicine, University of
Minnesota, Amplatz Children's Hospital, 420 Delaware Street SE, MMC 814, Minneapolis, MN 55455, Office: 612-625-6678, Fax:
612-626-1144, abk@umn.edu.
New affiliation for ABK: Division of Pediatric Emergency Medicine, University of Minnesota, Minneapolis, MN
Presented in part at the annual meeting of Pediatric Academic Societies, Toronto, Canada, May 2010
Disclosure: The authors have no conflicts of interest to report.
Kharbanda et al.
Page 2
raised regarding the overuse of CT, particularly the adverse health effects resulting from
exposure to ionizing radiation.3,4
Biomarkers may serve as alternative diagnostic tools to identify patients at high or low risk
for appendicitis.5-7 To date, there is no optimal biomarker, or combination of biomarkers,
for diagnosing appendicitis. Two recent studies have suggested the prominent role of
cytokines (e.g. interleukins [IL-6 and IL-8]) in the inflammatory response of patients with
appendicitis.6, 8 Previous authors have demonstrated that serum IL-6, a potent inducer of the
systemic immune response to a bacterial infection, is up-regulated in appendicitis.9 IL-8, a
chemo-attractant for neutrophils, is also up-regulated in proportion to the degree of
neutrophil invasion in the affected appendix.10,11
Prior studies have revealed conflicting and variable performance of traditional biomarkers
such as the white blood cell count (WBC) to diagnose appendicitis, emphasizing the need to
explore and study novel biomarkers.1,9,12-14 The limited utility of traditional biomarkers
should not be surprising, as appendicitis is a dynamic, evolving process, for which
fluctuations in levels might be expected. This theory has been explored by researchers who
have demonstrated the diagnostic benefit of repeat laboratory measures (WBC, C-reactive
protein [CRP]) in hospitalized, adult patients with acute abdominal pain.15-17
We hypothesized that novel and standard biomarkers would have improved test performance
if correlated with a patient's evolving, inflammatory response to appendicitis. Therefore, we
aimed to describe the trends and accuracy in serum levels of novel (IL-6, IL-8) and
traditional (WBC, absolute neutrophil count [ANC], and CRP) biomarkers in relation to the
duration of abdominal pain in children with suspected appendicitis. By using duration of
pain as a surrogate for the degree of inflammation, we sought to identify which biomarkers
might be most useful for distinguishing appendicitis from other causes of acute abdominal
pain over the course of illness.
Methods
Study Design
We conducted a prospective, observational pilot study. We obtained written informed
consent from all parents, and assent from children seven years of age and older. The study
was approved by the local institutional review board.
Study Setting and Population
The study site was an urban, tertiary care, pediatric emergency department (ED), with
approximately 50,000 visits annually.
From August 2008 to November 2009, children three to eighteen years of age who presented
to the ED with acute abdominal pain of less than 96 hours duration and who were being
evaluated for possible appendicitis were enrolled. We defined possible appendicitis as
when the treating physician obtained blood tests, radiological studies (CT and/or
ultrasound), or a surgical consultation for the purpose of diagnosing appendicitis. In our ED,
it is standard practice to obtain a WBC with differential for all patients with suspected
appendicitis. Radiological studies or surgical consults are obtained at the discretion of the
treating physician. We excluded patients with any of the following conditions: pregnancy,
prior abdominal surgery (e.g. gastrostomy tube, abdominal hernia repair), chronic illness
that potentially affected the gastrointestinal system (e.g. cystic fibrosis, inflammatory bowel
disease, sickle cell anemia, chronic pancreatitis, diabetes, immunosuppression), or a medical
condition affecting the provider's ability to obtain an accurate history (e.g. substantial
language or developmental delay). We also excluded patients who had radiologic studies
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(CT or ultrasound) of the abdomen performed prior to ED arrival, or a history abdominal

trauma within seven days of the ED evaluation.
Study Protocol
Pediatric emergency physicians completed standardized histories and physical examinations
prior to knowledge of any radiological studies, if obtained. As part of the patient history,
clinicians categorized the duration of pain in 12 hour intervals. To assess the inter-observer
reliability of the duration of pain, a second physician assessor was asked to complete an
additional data collection tool on a subset of patients within 30 minutes of the first assessor.
The patient's medical record was abstracted to obtain data from laboratory, radiology,
pathology, and operative reports. A single research assistant (YC) abstracted the medical
record and entered it into Microsoft Access (Microsoft Corporation, Redmond, WA); all
data were double-checked for accuracy by one author (ABK), including a review of data
interpretation and data entry. We reviewed the daily ED admission log and electronic
tracking system to identify potentially eligible patients who were not enrolled (i.e. missed).
Serum Collection and Analysis
We obtained serum WBC and automated differentials per standard hospital procedure. We
obtained an additional aliquot of patient serum (3-5 cc) and placed it into a serum separator
tube to measure IL-6, IL-8, and CRP levels. These additional samples were sent to the
hospital clinical laboratory within one hour of collection where they were spun at a speed of
1300 relative centrifugal force for 10 minutes. During the hours of 0900 to 1600, trained
laboratory technicians immediately divided the sample into two aliquots and froze the blood
at -80C. After 1600 on weekdays and at all times on weekends, spun samples were stored at
4C. The following business day, the laboratory technicians divided the samples into two
aliquots and froze the blood at -80 C. We recorded the time the serum was drawn, delivered
to the laboratory, and frozen.
The study laboratory technicians analyzed the serum for IL-6 and IL-8 (R&D Systems,
Minneapolis MN) levels by enzyme-linked immunosorbent assay (ELISA). CRP (Siemens
Healthcare Diagnostics, Deerfield, IL) was measured by particle enhanced
immunonephelometry. If the initial IL-6 level was at the lower detection limit of 3.12 pg/ml
on the primary ELISA assay, an additional hypersensitive IL-6 assay (R&D Systems) was
performed to assess the full spectrum of IL-6 levels in patients with acute abdominal pain.
The technicians were blinded to the patient's final diagnosis.
Measures
The primary outcome was the presence or absence of appendicitis, determined by reviewing
the written attending pathologist histopathology report for patients who had an
appendectomy. A perforated appendix was determined by the attending surgeon's written
post-operative diagnosis. For patients who did not have surgery, we determined the outcome
by a follow-up telephone call 14 to 21 days following the index ED visit. If the family could
not be reached, a review of the hospital electronic record system was conducted to assess for
operations (i.e. appendectomy), hospitalizations, or ED visits during the follow-up period.
Those assessing the outcome were blinded to the biomarker levels.
Data Analysis
For each biomarker, we conducted descriptive analyses, exploring ranges, means with
standard deviations (SD), medians with inter-quartile ranges (IQR), and the respective 95%
confidence intervals (CI). We assessed the association between each biomarker and the
presence or absence of appendicitis with the unpaired t-test or Mann-Whitney U test for
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normally and asymmetrically distributed data, respectively. To assess biomarker trends and
accuracy among groups with similar illness severity, we then stratified our analyses by
appendicitis status (e.g. perforated appendicitis, non-perforated appendicitis, or no
appendicitis). Finally, we constructed receiver operating characteristic (ROC) curves to
determine the area under the curve (AUC) for the various serum biomarkers based on the
duration of abdominal pain in three clinically relevant time intervals: < 24, 24 to 48, and >
48 hours of pain. Within each time category, we calculated the cut-point from the ROC
curve that maximized sensitivity and specificity (based on the Youden index).18 The test
performance characteristics (including likelihood ratio [LR]) for this cut-point were then
calculated. We determined the inter-observer reliability between physicians for their
assessment of duration of abdominal pain using Cohen's unweighted kappa statistic.19-21 All
statistical analyses were performed using SPSS (SPSS Inc., Version 18.0, Chicago, Ill).
Results
Study Population
Over the 15-month study period, 380 patients 3 to 18 years of age presented to the ED with
acute abdominal pain and were considered for appendicitis. Two hundred ninety-one were
potentially eligible for participation, 280 were enrolled (96%), and 259 had complete
biomarker data available for analysis of trends and discriminative characteristics (Figure 1).
Patient Characteristics
Of the 280 enrolled patients, the median age was 11.3 years (IQR 8.6 to 14.8), and 160
(57%) were male. Comparisons between patients with appendicitis and those without
revealed no statistical difference by sex, age, duration of abdominal pain, history of right
lower quadrant pain, mean temperature in the ED, tenderness on exam, or percent who
underwent imaging (p > 0.05 for all comparisons). Pairs of physicians (n = 41) showed good
inter-observer agreement on their assessments of the duration of abdominal pain (kappa =
0.63).
Ninety-four patients were diagnosed with appendicitis (33%), of whom 22 (23%) had a
perforated appendix. We completed telephone follow-up on 177 (99%) of the 179 patients
who did not undergo an operation; none had an appendectomy during the follow-up period.
Medical records for the two patients lost to telephone follow-up revealed no further ED
visits, operations, or hospitalizations within two months of enrollment. Compared to
enrolled patients, eligible patients who were not enrolled were slightly older (median age
13.1) and more likely to be female (60%), but had similar likelihoods of undergoing CT or
ultrasound (73%), and having appendicitis (36%).
Levels of Biomarkers in Patients with and without Appendicitis

The biomarker levels in patients without appendicitis, with non-perforated appendicitis, and
with perforated appendicitis are shown in Table 1. Each serum biomarker level except IL-8
was statistically higher for patients with non-perforated appendicitis as compared to those
without appendicitis (p < 0.001). The serum levels of all biomarkers differed significantly
for children with perforated appendicitis as compared to those with non-perforated
appendicitis (p < 0.001).
Relationship of Duration of Abdominal Pain to Biomarker Levels
In Figures 2a-d, the biomarker levels for IL-6, IL-8, WBC (ANC results closely approximate
the WBC and are not shown), and CRP are shown for each time interval as stratified by
appendicitis status. As seen in each figure, biomarker levels in patients without appendicitis
remain low, and steadily decline across the time intervals. In comparison, in cases of either
Kharbanda et al.
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non-perforated or perforated appendicitis, biomarker levels rise and reach maximum values
at different rates. In non-perforated appendicitis, median IL-6 and WBC levels are maximal
by 24 hrs hours of pain, CRP by 24 to 48 hours, and median IL-8 levels were similar across
time categories. In perforated appendicitis, median IL-8 level is highest by 24 hours, WBC
and IL-6 by 24 to 48 hours, and CRP after 48 hours of pain.
Time Dependant Accuracy of Biomarkers
Table 2 displays the discriminative ability of the biomarkers studied to distinguish patients
with appendicitis (perforated and non-perforated) from those without appendicitis, stratified
by duration of abdominal pain. The WBC, ANC, and IL-6 had relatively similar AUCs for
children with less than 24 hours of pain, whereas CRP had a trend towards greater
discriminative accuracy (by AUC) in the 24 to 48 hour time period, and the WBC appeared
to be more accurate than other biomarkers in those with longer than 48 hours of abdominal
pain. Despite these trends, the 95% CIs for the AUCs of these biomarkers did overlap.
Within each time category, we also provide cut-points and test performance characteristics
for each biomarker, as calculated from their respective ROC curves. Each biomarker
exhibited fluctuations in test performance as a function of duration of pain. For example, the
test performance of the WBC count was maximal (LR+ of 3.8) in the > 48 hour time period,
while for IL-6 and CRP, optimal performance was seen in the 24 to 48 time period (LR+ of
3.3 and 6.6, respectively). Based on the LR+, the WBC appeared to be the most useful
marker to predict appendicitis in those with < 24 or > 48 hours of pain, while CRP was the
most useful in those with 24 to 48 hours of pain.
Discussion
In this pilot study, we have demonstrated the fluctuations in serum levels and accuracy of
novel and traditional biomarkers for pediatric appendicitis as a function of duration of pain.
In patients with non-perforated appendicitis, median serum IL-6, the WBC, and ANC levels
were highest in the 24 hours after symptoms of pain began, while median CRP levels
trended higher in those with 24 to 48 hours of pain. Furthermore, we found that the novel
biomarker IL-6 had substantial discriminative ability, whereas IL-8 was seemingly less
useful for diagnosing non-perforated appendicitis.
We believe that an understanding of the fluctuations in biomarker levels in relation to the

duration of abdominal pain may be clinically useful. IL-6 increased early in relation to
symptoms of pain, consistent with its role in stimulating the immune system to contain
infection; whereas CRP, which is stimulated by IL-6, required 24 to 36 hours for upregulation. In comparison, the WBC and ANC showed little fluctuations in patients with
non-perforated appendicitis. We found it interesting that the biomarkers studied in this pilot
did not necessarily exhibit their best test performance during time periods when their levels
would be expected to peak. For example, although overall CRP levels peaked in those with
> 48 hours of pain, CRP exhibited its best test performance in those with 24 to 48 hours of
pain. Similarly, the WBC revealed improving test performance as duration of pain increased.
If further research confirms our findings, clinicians could tailor which laboratory test(s) they
obtained in relation to a patient's history of symptoms. In addition, the thresholds (as
described in Table 2) that would trigger further action would also change based on an
understanding of these fluctuations. Based on our results, the WBC appears to be the most
useful biomarker in those patients with < 24 or > 48 hours of pain, while the CRP may be
the most useful in those with 24 to 48 hours of pain. In addition, if IL-6 is to be utilized in
the diagnosis of appendicitis, it may be most useful in those with symptoms for 24 to 48
hours or it may be used to distinguish which patients with appendicitis have a perforated
appendix.
Kharbanda et al.
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For each of the biomarkers analyzed in this study, serum levels remained low or declined in
patients without appendicitis, even as duration of symptoms increased. We believe that the
improved overall test performance of the WBC, as duration of pain increased, can be
attributed to the steady decline in the WBC in patients without appendicitis (who likely have
conditions that do not illicit as aggressive of an immune response). These findings add to
prior literature, in which low levels of the WBC and ANC have provided reassurance for the
absence of appendicitis.1,22,23 Furthermore, two recent studies have provided results that
would indicate that a normal WBC combined with a normal CRP value would make the
probability of appendicitis low.24,25 Further research is needed to determine whether a
combination of the biomarkers analyzed in this study provide marginal benefit over
individual biomarkers for the purpose of diagnosing appendicitis when correlated to a
patients symptoms of abdominal pain.
Similar to our findings, several prior publications have described improved test performance
characteristics of CRP in those with several days of symptoms.24,26 In addition, prior
researchers have noted the utility of serial CRP measurements with acute abdominal pain,
describing that an increasing CRP level over time was concerning for appendicitis.15,17
Although previous authors have noted that the dynamic nature of CRP levels may make
serial measurement useful, it may be clinically more feasible to associate a biomarker with
duration of symptoms, as serial blood draws can be problematic in the ED setting and in
children.17,26 We agree with previous authors that an elevation in CRP (either serial
measurements or as correlated to durations of symptoms) in children with acute abdominal
pain may aid in the diagnosis of appendicitis.
Our IL-6 findings differ from prior studies in which serum IL-6 levels were only elevated in
children with perforated appendicitis.9-11,13 Paajanen et al. measured cytokine levels in 80
patients (27 of them younger than 20 years) undergoing surgery for appendectomy, and
found that IL-6 levels correlated with increasing severity of inflammation seen on
histopathology, but that no significant differences were noted in IL-6 levels between patients
with non-perforated appendicitis and those without appendicitis.10 Similarly, Sack et al.
recently reported on 211 children with suspected appendicitis (189 underwent
appendectomies) and found that IL-6 levels in patients without appendicitis and with focal,
non-perforated appendicitis by histopathology were both low (median IL-6 levels 2.5 pg/ml
and 5.9 pg/ml, respectively).9 Our results may have differed due to the inclusion of a
population of patients who mostly did not have appendicitis (as opposed to higher rates of
appendicitis in previous studies), which provided us a more accurate estimate of IL-6 levels
in those without appendicitis. Additionally, we were unable to determine the timing of the
biomarker assessments in the previous IL-6 studies. IL-6 is up-regulated by mRNA
transcription (which takes 4 to 6 hours), and protein levels peak by 24 hours following the
development of a localized inflammatory process.10-11,13 Therefore, diagnostic performance
may depend on when in the disease course serum is collected.
Although IL-8 levels were elevated in children with perforated appendicitis, serum levels do
not distinguish patients with non-perforated appendicitis from those without appendicitis.
We studied IL-8 as recent research demonstrated that IL-8 gene expression was highly
elevated in appendicitis and that expression correlated with the degree of inflammation on
pathology.6 Although our results were consistent with this finding for those with perforation,
it is not clear why serum IL-8 levels were not elevated in patients with non-perforated
appendicitis. Similar to our findings, Yoon et al. found that serum IL-8 levels were
significantly elevated only in patients with perforated appendicitis.11
Kharbanda et al.
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Limitations
The current study has several limitations. First, although a relatively large number of
patients were prospectively enrolled, there were a limited number of patients with a longer
duration of abdominal pain and non-perforated appendicitis; this resulted in wide 95% CIs
for estimates of diagnostic accuracy. Second, the estimates of biomarker accuracy were
based on the premise that physicians could reliably determine, and parents and children
could reliably report, duration of pain. Although this is a potential source of variability, there
was good inter-observer reliability between physicians. Additionally, sequential serum
samples were not collected from patients; this mimics the routine emergency department
setting where only a single sample would typically be obtained. It should be noted that
although we had a very high follow-up rate, two patients were lost to telephone follow-up.
We cannot exclude that these patients sought care at an alternative medical facility. Finally,
the human IL-6 and IL-8 assay kits are presently intended for laboratory investigation, take
many hours to complete, and are not FDA-approved for clinical use. Further work must be
done to confirm biomarker utility and to develop assays to provide biomarker results in a
clinically useful timeframe. Nevertheless, this study provides important baseline information
to guide future research on novel biomarkers.
Conclusions
Although Interleuken-6, the white blood cell count, absolute neutrophil count, and C
reactive protein are all increased in patients with appendicitis, levels of these markers
fluctuate over the course of illness. Serum Interleuken-6 is a potentially useful novel
biomarker for patients with suspected appendicitis. Duration of symptoms may be an
important variable to consider when interpreting laboratory values in patients with acute
abdominal pain.
Acknowledgments
Funding: Supported by Grant Number UL1 RR024156 from the National Center for Research Resources (NICRR),
a component of the National Institute of Health (NIH) and NIH Roadmap for Medical Research.
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Figure 1. Study Patient Flow

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Figure 2.
2a. White Blood Cell Count Levels Based on Duration of Pain and Appendicitis Status
2b. Interleukin-6 Levels Based on Duration of Pain and Appendicitis Status
2c. Interleukin-8 Levels Based on Duration of Pain and Appendicitis Status
2d. C Reactive Protein Levels Based on Duration of Pain and Appendicitis Status

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Table 1
Biomarker Levels Stratified by Appendicitis Status

Biomarker
No Appendicitis
(n=186)
Non-Perforated Appendicitis
(n = 72)
Perforated Appendicitis
(n=22)
WBC ( 103/L)
10.4 ( 4.8)#
15.8 ( 4.5)
17.3 ( 4.4)
(n = 276)
[9.7-11.1]
[14.8-16.9]
[15.3-19.2]
ANC ( 103/L)
7.5 ( 4.7) #
12.7 ( 4.6)
14.7 ( 4.5)
(n = 262)
[6.8-8.2]
[11.6-13.8]
[12.6-16.7]
IL-6 (pg/ml)*
4.4 (1.3-16.1)#
21.0 (9.8-37.0)
122.3 (42.2-388.6)
(n = 259)
[2.4-5.7]
[15.7-25.1]
[43.8-250.6]
IL-8 (pg/ml)*
16.3 (11.0-24.2)
13.5 (10.6-21.2)
25.2 (19.0-55.6)
(n = 259)
[13.9-17.5]
[11.9-16.2]
[19.1-38.2]
CRP (mg/l)*
5.3 (0.49-17.8) #
14.1 (4.9-34.4)
115.1 (38.3-179.0)
(n = 260)
[2.7-7.4]
[7.3-22.9]
[38.5-155]
Median (IQR); Data for IL-6, IL-8, and CRP levels were skewed and thus not normally distributed
Mean ( SD); Data for WBC, ANC, and neutrophil count were normally distributed
values in square brackets [95% confidence intervals]
P value < 0.001 for comparisons between No Appendicitis and Non-Perforated Appendicitis groups
P value < 0.001 for comparisons between Non-Perforated Appendicitis and Perforated Appendicitis groups
IL-6: Interleukin-6, IL-8: Interleukin-8, WBC: White blood cell count, ANC: Absolute neutrophil count, CRP: C-Reactive Protein


0.64 [0.55-0.73]
0.89 [0.81-0.97]
0.85 [0.73-0.96]
24-48
> 48
0.57 [0.36-0.78]
> 48
<24
0.59 [0.44-0.74]
24-48
0.76 [0.60-0.93]
> 48
0.49 [0.40-0.59]
0.87 [0.79-0.95]
<24
0.78 [0.71-0.86]
24-48
0.89 [0.80-0.98]
> 48
<24
0.85 [0.76-0.95]
24-48
7.0
20.8
0.6
24.1
15.9
64.8
2.5
5.7
11.31
6.0
8.4
11.0
10.0
10.0
14.6
Cut-point maximizing overall

accuracy
100 [70-99]
87.0 [65-97]
92.9 [82-98]
41.2 [17-71]
65.2 [43-83]
5.3 [1.8-14.6]
91.7 [60-100]
95.6 [76-100]
82.1 [69-91]
91.7 [60-100]
90.5 [68-98]
69.1 [55-81]
100 [70-100]
95.6 [76-100]
67.8 [54-79]
56.1 [40-71]
86.8 [71-95]
28.1 [19-39]
86.8 [71-95]
63.2 [46-78]
81.8 [73-88]
58.5 [42-73]
71.1 [54-84]
68.5 [58-78]
66.7 [50-80]
80.0 [64-90]
74.7 [64-83]
73.3 [58-85]
71.4 [55-84]
80.0 [70-87]
Specificity at cut-point, % (95% CI)
2.3
6.6
1.3
3.2
1.8
0.3
1.3
3.3
2.6
2.8
4.5
2.7
3.8
3.3
3.4
LR+
AUC = area under the receiver operating characteristic curve; LR+ = likelihood ratio positive; IL-6 = Interleukin-6; IL-8 = Interleukin-8; WBC = white blood cell count; ANC = absolute neutrophil count;
CRP = C-reactive protein
CRP (mg/l)
IL-8 (pg/ml)
IL-6 (pg/ml)
ANC (
0.78 [0.70-0.85]
0.92 [0.84-0.99]
> 48
<24
0.87 [0.78-0.95]
24-48
103/L)
0.78 [0.70-0.85]
<24
WBC ( 103/L)
AUC (95% CI)
Duration of pain, hours
Biomarker
Sensitivity at cut-point, % (95% CI)

Table 2
Biomarker Performance Based on Duration of Abdominal Pain

Kharbanda et al.
Page 13

Discriminative Accuracy of Novel and Traditional Biomarkers in Children With Suspected Appendicitis Adjusted For Duration of Abdominal Pain

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Discriminative Accuracy of Novel and Traditional Biomarkers in Children With Suspected Appendicitis Adjusted For Duration of Abdominal Pain

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