Content uploaded by Seong Jong Park
Author content
All content in this area was uploaded by Seong Jong Park on Mar 03, 2018
Content may be subject to copyright.
Iran J Pediatr. In Press(In Press):e7212.
Published online 2017 June 12.
doi: 10.5812/ijp.7212.
Research Article
Platelet Indices as Predictive Markers of Prognosis in Pediatric Septic
Shock Patients
Seung Jun Choi,1Eun-Ju Ha,1Won Kyoung Jhang,1and Seong Jong Park1,*
1Division of Pediatric Critical Care Medicine, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Republic of
Korea
*Corresponding author: Dr. Seong Jong Park, Division of Pediatric Critical Care Medicine, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of
Ulsan College of Medicine, 388-1 Pungnap-2 dong, Songpa-gu, Seoul 138-736, Republic of Korea. Tel: +82-230103390, Fax: +82-230103725, E-mail: goodjobman79@naver.com
Received 2016 May 22; Revised 2017 February 09; Accepted 2017 March 19.
Abstract
Background: Platelet indices are used as predictive marker of mortality in adult critically ill patients.
Objectives: Tocompare platelet counts, mean platelet volumes (MPV), and platelet distribution widths (PDW) in surviving and non-
surviving pediatric septic shock patients and to assess whether platelet count and indices can be utilized as predictive markers of
mortality in these patients.
Methods: A retrospective study was performed based on collected data on pediatric patients admitted for septic shock to pediatric
intensive care unit. Complete blood cell count, platelet counts, MPV, and PDW on admission were compared in survivors and non-
survivors, as well as in patients with and without underlying hemato-oncologic disease.
Results: Of 83 children, 21 (25.3%) died within 28 days of hospital admission. Mean platelet count was significantly higher in the 62
survivors than in 21 non-survivors (146.6 ±133.7 ×103/mm3vs 46.1 ±44.1 ×103/mm3, P = 0.000). MPV and PDW were also higher in
survivors, though not statistically significant (P = 0.059, P = 0.077). The platelet counts were significantly higher in survivors than
in non-survivors with (P = 0.044) and without (P = 0.015) hemato-oncologic disease. Based on area under receiver operating charac-
teristic curves, platelet count was the strongest predictor of mortality in pediatric patients without underlying hemato-oncologic
disease (area under the curve = 0.857). The survival probability in this group was 96.77% when platelet count exceeded 106.5 ×
103/mm3.
Conclusions: Thrombocytopenia is a useful predictive marker of mortality in pediatric septic shock patients, both with and without
underlying hemato-oncologic disease.
Keywords: Septic Shock, Pediatrics, Platelet Indices, Pediatric Intensive Care Unit, Mortality
1. Introduction
Thrombocytopenia is frequently encountered in pa-
tients admitted to intensive care units (ICUs), and has been
shown to be predictive of mortality in adult patients (1-
4), as well as in pediatric patients admitted to pediatric
ICUs (PICUs) (5). Thrombocytopenia in sepsis patients is
caused by combinations of several mechanisms, including
decreased platelet synthesis, increased platelet destruc-
tion, and thrombus formation (6), with approximately 40%
of patients with severe sepsis having platelet counts below
80,000/mm3(7). During episodes of septic shock, platelets
aggregate around the site of inflammation, with subse-
quent multiorgan failure aggravating thrombocytopenia
(8).
Several studies have shown that platelet counts and
function are reduced in patients with severe sepsis and sep-
tic shock (9-11). Moreover, platelet indices, such as mean
platelet volume (MPV) and platelet distribution width
(PDW), have been associated with these conditions (12,13).
Increased MPV was observed in adults with septic shock
(14) and in neonatal sepsis patients (15). Less is known, how-
ever, about platelet counts and platelet indices in pediatric
sepsis patients.
This study was designed to evaluate the association of
platelet counts and platelet indices with mortality in pe-
diatric septic shock patients, as well as to assess whether
platelet parameters are predictive markers of survival
in these patients. Because the presence of underlying
hemato-oncologic disease may greatly influence baseline
platelet counts, the associations between platelet parame-
ters and mortality were separately analyzed in groups of
patients with and without underlying hemato-oncologic
disease.
2. Methods
The medical records of pediatric patients admitted to
the PICU of Asan medical center children’s hospital, Seoul,
Korea, from February 2012 through May 2015, with a diag-
nosis of septic shock, were retrospectively reviewed. Septic
Copyright © 2017, Iranian Journal of Pediatrics. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0
International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the
original work is properly cited.
Uncorrected Proof
Choi SJ et al.
shock was defined according to the 2005 international pe-
diatric sepsis consensus conference (IPSCC) criteria (16).
The demographic characteristics, underlying diseases,
sources of infection, and laboratory results of all included
patients were obtained from their medical records. The
severity of illness and organ dysfunction were assessed by
measuring Pediatric Risk of Mortality III (PRISM III) scores,
sequential organ failure assessment (SOFA) scores, and Va-
soactive Inotropic Scores (VIS) within 24 hrs of PICU admis-
sion.
Complete blood cell (CBC) count and blood chemistry
were measured within 1 hour of admission to the PICU.
Platelet count, MPV, and PDW were obtained from routine
CBC results. All statistical analyses were performed using
Windows SPSS software, version 18. Continuous variables
in survivors and non-survivors were compared using in-
dependent t-tests. Receiver operating characteristic (ROC)
curve analyses were performed to evaluate the usefulness
of platelet parameters as prognostic markers. For each
variable, 95% confidential intervals (CIs) and optimal cut-
off points were determined. A P value less than 0.05 was
considered statistically significant.
The study protocol was approved by the institutional
review board of the Asan Medical Center.
3. Results
A total of 90 pediatric patients were admitted to the
PICU for septic shock from February 2012 to May 2015.
Seven patients were excluded owing to a lack of relevant
data at admission, including MPV and PDW; thus, 83 pa-
tients were enrolled. The 28 day in-hospital mortality rate
was 25.3% (21/83). Of the 83 patients, 78 (94.0%) had un-
derlying diseases, with 38 having hemato-oncologic dis-
eases. Pathogenic microorganisms were documented in
47 patients. The most common Gram-positive and Gram-
negative bacteria were Staphylococcus aureus and Kleb-
siella pneumoniae, respectively, and all cases of fungal sep-
sis were attributed to Candida albicans (Table 1).
Age, sex, and length of PICU stay did not differ signif-
icantly in survivors and non-survivors. PRISM III, SOFA,
and VIS scores, all of which reflect disease severity, were
significantly greater in the non-survivors than in sur-
vivors. Documentation of pathogen was not associated
with survival, but underlying disease was. Of the 21 non-
survivors, 14 (66.7%) had underlying hemato-oncologic dis-
ease. C-reactive protein (CRP) and lactate concentrations
were significantly higher in non-survivors than in sur-
vivors. Platelet count was 3-fold higher in survivors than
in non-survivors (146.6 ±133.7 ×103/mm3vs 46.1 ±44.1 ×
103/mm3, P = 0.000). Mean MPV (P = 0.059) and PDW (P =
Table1. Patient Characteristicsa
Variables No. of Patients
N83
Age, months 128.0 ±159.6
Gender,male/female 52/31
Mortality 21 (25.3)
Underlying disease 78 (94.0)
Hemato-oncologic disease 38 (48.7)
Neurologic disease 13 (16.7)
Cardiac disease 8 (10.3)
Pulmonary disease 6 (7.7)
Chronic renal disease 5 (6.4)
Gastrointestinal disease 3 (3.8)
Endocrinologic disease 3 (3.8)
Other 2 (2.6)
Proven microorganism 47 (56.6)
Gram-positive bacteria 19 (40.4)
Staphylococcus aureus 5
Streptococcus mitis 3
Streptococcus agalactiae 2
Staphylococcus hominis 2
Enterococcus faecalis 2
Other 5
Gram-negative bacteria 22 (46.8)
Klebsiella pneumonia 9
Escherichia coli 5
Pseudomonas aeruginosa 4
Enterobacter cloacae 2
Other 2
Fungus 6 (12.8)
Candida albicans 6
aValues are expressed as mean ±SD or No. (%).
0.077) were higher in survivors, but the differences were
not statistically significant (Table 2).
The associations between platelet count and mortal-
ity according to underlying disease were analyzed sepa-
rately in the 38 patients with and the 45 without hemato-
oncologic disease. Mean platelet counts in both sub-
groups were significantly higher in survivors than in non-
survivors (Table 3). ROC analysis showed that the areas un-
der the curve (AUCs) were 0.796 for all patients, 0.722 for
patients with hemato-oncologic diseases, and 0.857 for pa-
2Iran J Pediatr. In Press(In Press):e7212.
Uncorrected Proof
Choi SJ et al.
Table2. Clinical Characteristics of Survivors and Non-Survivorsa
Variables All Patients (n = 83) Survivors (n = 62) Non-Survivors (n = 21) P Value
Age, mo 128.0 ±159.6 114.4 ±85.0 168.3 ±282.9 0.182
Male 52 (62.7) 38 (61.3) 14 (66.7) 0.796
Length of PICU stay 14.84 ±15.30 14.77±15.82 15.05 ±14.00 0.944
PRISM III score 15.67 ±8.17 13.55 ±5.67 21.95 ±10.95 0.003
SOFA score 9.71 ±3.17 8.87 ±2.72 12.19 ±3.16 0.000
VIS 35.00 ±38.46 27.66 ±25.19 56.68 ±58.88 0.039
Hemato-oncologic disease 38 (45.8) 24 (38.7) 14 (66.7) 0.042
Proven microorganism 47(56.6) 35 (56.5) 12 (57.1) 0.956
Laboratory findings
WBC, mm36,567 ±7,468 7,223 ±7,487 4,633 ±7,243 0.171
Platelet, ×103/mm3121.1 ±125.3 146.6 ±133.7 46.1 ±44.1 0.000
Mean platelet volume, fl 10.50 ±1.12 10.63 ±1.18 10.10 ±0.80 0.059
Platelet distribution width, fl 12.17 ±2.81 12.48 ±2.98 11.23 ±2.05 0.077
CRP,mg/dL 15.03 ±9.41 13.85±8.85 18.52 ±10.33 0.049
Lactate, mmol/L 3.88 ±4.06 2.45±2.21 8.10 ±5.25 0.000
Abbreviations: CRP, C-reactive protein; PICU,pediatric intensive care unit; PRISM III, pediatric risk of mortality III; SOFA, sequential organ failure assessment; VIS, vasoac-
tive inotropic scores; WBC, white blood cell.
aValues are expressed as mean ±SD or No. (%).
tients without hemato-oncologic diseases (Figure 1). Us-
ing Youden’s J-statistics, we calculated that the platelet
count cutoffs for predicting mortality were 52.0 ×103/mm3
for all patients, 30.5 ×103/mm3for patients with hemato-
oncologic diseases, and 106.5 ×103/mm3for patients with-
out hemato-oncologic diseases, with sensitivities of 71.4%,
78.6%, and 85.7%, respectively, and specificities of 71.0%,
66.7%, and 78.9%, respectively. The accuracies, positive pre-
dictive values, and negative predictive values for these cut-
offs are shown in Table 4. The risk ratios for mortality in
these three groups of patients with platelet counts under
the cutoff values were 6.111, 7.333, and 22.5, respectively (Ta-
ble 4). With the significant variable from the univariate
analysis, a multivariate logistic regression analysis was ex-
ecuted, and the platelet count was statistically significant
(OR = 0.988, P = 0.04, Table 5).
4. Discussion
Thrombocytopenia is frequently encountered in se-
vere sepsis patients (9) and has been associated with prog-
nosis (17,18). However the association between platelet
indices and mortality in septic shock patients is unclear.
For example, increased MPV has been associated with
mortality in adult septic shock patients (19,20), but has
shown contradictory results in neonatal patients with sep-
Table3. Mean Platelet Counts in Survivors and Non-Survivors
Platelet, ×
103/mm3
Survivors (n = 62) Non-Survivors (n
= 21)
P Value
All patients 146.6 ±133.7 46.1 ±44.1 0.000
With hemato-
oncologic
diseases
43.1 ±22.4 28.6 ±16.9 0.044
Without hemato-
oncologic
diseases
211.9 ±133.6 81.0 ±61.0 0.015
sis (21). Our study, involving pediatric septic shock pa-
tients, showed that platelet count on PICU admission was
significantly associated with mortality, but that platelet in-
dices such as MPV and PDW were not associated with mor-
tality in these patients.
This study had two major findings. First, platelet count
was predictive of mortality in pediatric septic shock pa-
tients, regardless of the underlying disease. Whether or
not these patients had an underlying hemato-oncologic
disease did not affect the association between platelet
count and mortality. Low platelet counts are not un-
common in patients with hemato-oncologic diseases, even
during disease-free periods, due both to the underly-
ing disease itself and to treatment methods such as
Iran J Pediatr. In Press(In Press):e7212. 3
Uncorrected Proof
Choi SJ et al.
000.0 697.0
With hemato-oncologic diseases 0.722 0.024 0.546–0.898
Without hemato-oncologic diseases 0.857 0.003 0.700–1.000
Abbreviations: H-O, hema to-oncologic diseases
All patient
Platelet AUC P - value 95% CI
Sensitivity
Total
H-O
Non-H-H
1 - Specificity
0.0 0.2 0.4 0.6 0.8 1.0
1.0
0.8
0.6
0.4
0.2
0.0
0.692–0.900
Figure 1. Receiver Operating Characteristic (ROC) Curve Analysis of the Associations Between Platelet Counts and Mortality
chemotherapy and irradiation. We found, however, that
the mean platelet count in surviving patients with hemato-
oncologic diseases was 43.1 ×103/mm3, which, although
lower than the normal reference range, and even lower
than minimum criteria(50.0 ×103/mm3) of the pediatric
risk of mortality (PRISM) III score, was significantly higher
than that of non-survivors with hemato-oncologic dis-
eases. Even among patients without hemato-oncologic dis-
eases, who had baseline platelet counts in the normal refer-
ence range, platelet count was predictive of mortality, with
an AUC of 0.857, a sensitivity of 85.7%, and a specificity of
78.9%.
The second major finding of this study was the deter-
mination of cutoff values for platelet count predictive of
mortality, suggesting specific reference ranges that can
be utilized in clinical settings. Platelet counts showed ex-
cellent negative predictive values in all patients (88.0%)
and in patients with (84.2%) and without (96.8%) hemato-
oncologic diseases. Patients with platelet count higher
than the cutoff values would therefore be at decreased risk
of 28 day mortality. For example, the predicted surviv-
ability rate in pediatric septic shock patients without un-
derlying hemato-oncologic diseases and an initial platelet
count of 106.5 ×103/mm3is 96.8%.
Additional studies are needed to determine whether
platelet transfusions that maintain adequate platelet
count can reduce mortality rates in pediatric septic shock
patients. Platelet transfusion guidelines recommend dif-
ferent criteria based on the underlying disease or clinical
status of the patients (22-24). We observed that a cutoff
value of 30.5 ×103/mm3had optimal sensitivity and speci-
ficity in patients with hemato-oncologic diseases. Thus,
future studies may address whether platelet transfusions
that maintain platelet counts above this cutoff in pediatric
septic shock patients with underlying hemato-oncologic
diseases can potentially enhance survival rate.
This study had several limitations. It was a retrospec-
tive observational study with a small sample size con-
ducted in a single medical center. Further, we did assess the
effects of microorganisms on platelet counts. Microorgan-
isms have been shown to alter platelet responses in both
very low birth weight infants (25,26) and adults (14). How-
4Iran J Pediatr. In Press(In Press):e7212.
Uncorrected Proof
Choi SJ et al.
Table 4. Cutoff Values for Platelet Count in Patients With and Without Hemato-
Oncologic Diseasesa
Validation
Values
All Patients With hemato-
Oncologic
Diseases
Without
Hemato-
Oncologic
Diseases
Platelet, ×
103/mm3
52.0 30.5 106.5
Sensitivity 71.4 78.6 85.7
Specificity 71.0 66.7 78.9
Accuracy 71.1 71.0 80.0
Positive
predictive value
45.5 57.9 42.9
Negative
predictive value
88.0 84.2 96.8
Risk ratio 6.111 7.333 22.500
95% CI 2.046 - 18.251 1.583 - 33.967 2.357 - 214.778
P Value 0.001 0.017 0.002
Abbreviation: CI, confidence interval.
aValues are expressed as %.
Table5. Multivariate Logistic Regression Analysis for Mortality
Variables Coefficient P Value Odds Ratio (95%
Confidence Interval)
PRISM III 0.092 0.145 1.096 (0.969 - 1.240)
SOFA 0.230 0.062 1.258 (0.988 - 1.601)
VIS -0.002 0.813 0.998 (0.981 - 1.015)
Platelet counts -0.012 0.040 0.988 (0.977 - 0.999)
MPV -0.694 0.230 0.500 (0.161 - 1.551)
PDW -0.008 0.974 0.992 (0.630 - 1.563)
Abbreviation: MPV, mean platelet volume; PDW, platelet distribution width;
PRISM III, pediatric risk of mortality III; SOFA, sequential organ failure assess-
ment; VIS, Vasoactive Inotropic Scores.
ever, microorganism growth was documented in few of
these patients. Large-scale, prospective, multicenter stud-
ies that include data on microorganisms are needed to val-
idate our findings.
In conclusion, platelet count is a useful predictor of
mortality in pediatric septic shock patients, regardless of
the presence of underlying hemato-oncologic disease. In
contrast, MPV and PDW were not significant predictors of
patient mortality.
References
1. Baughman RP, Lower EE, Flessa HC, Tollerud DJ. Thrombocytopenia in
the intensive care unit. Chest. 1993;104(4):1243–7. [PubMed: 8404200].
2. Stephan F, Hollande J, Richard O, Cheffi A, Maier-Redelsperger M, Fla-
hault A. Thrombocytopenia in a surgical ICU. Chest. 1999;115(5):1363–
70. [PubMed: 10334154].
3. Strauss R, Wehler M, Mehler K, Kreutzer D, Koebnick C, Hahn EG.
Thrombocytopenia in patients in the medical intensive care unit:
bleeding prevalence, transfusion requirements, and outcome. Crit
Care Med. 2002;30(8):1765–71. [PubMed: 12163790].
4. Vanderschueren S, De Weerdt A, Malbrain M, Vankersschaever D,
Frans E, Wilmer A, et al. Thrombocytopenia and prognosis in inten-
sive care. Crit Care Med. 2000;28(6):1871–6. [PubMed: 10890635].
5. Krishnan J, Morrison W, Simone S, Ackerman A. Implications of
thrombocytopenia and platelet course on pediatric intensive
care unit outcomes. Pediatr Crit Care Med. 2008;9(5):502–5. doi:
10.1097/PCC.0b013e3181849af1. [PubMed: 18679144].
6. Wittels EG, Siegel RD, Mazur EM. Thrombocytopenia in the Inten-
sive Care Unit Setting. J Intens Care Med. 1990;5(5):224–40. doi:
10.1177/088506669000500507.
7. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-
Rodriguez A, et al. Efficacy and safety of recombinant human acti-
vated protein C for severe sepsis. N Engl J Med. 2001;344(10):699–709.
doi: 10.1056/NEJM200103083441001. [PubMed: 11236773].
8. Gawaz M, Fateh-Moghadam S, Pilz G, Gurland HJ, Werdan K. Platelet
activation and interaction with leucocytes in patients with sepsis or
multiple organ failure. Eur J Clin Invest. 1995;25(11):843–51. [PubMed:
8582450].
9. Gawaz M, Dickfeld T, Bogner C, Fateh-Moghadam S, Neumann FJ.
Platelet function in septic multiple organ dysfunction syndrome. In-
tensive Care Med. 1997;23(4):379–85. [PubMed: 9142575].
10. Vincent JL, Yagushi A, Pradier O. Platelet function in sepsis. Crit Care
Med. 2002;30(5 Suppl):S313–7. [PubMed: 12004253].
11. Akca S, Haji-Michael P, de Mendonca A, Suter P, Levi M, Vincent JL.
Time course of platelet counts in critically ill patients. Crit Care Med.
2002;30(4):753–6. [PubMed: 11940740].
12. Vander Lelie J, Von dem Borne AK. Increased mean platelet volume in
septicaemia. J Clin Pathol. 1983;36(6):693–6. [PubMed: 6343437].
13. Dastugue N, Picheloup F, Sie P, Genestal M, Cathala B, Boneu B. [In-
crease in mean platelet volume in shock-related thrombocytopenia].
Nouv Presse Med. 1982;11(39):2899–901. [PubMed: 7145676].
14. Aydemir H, Piskin N, Akduman D, Kokturk F, Aktas E. Platelet
and mean platelet volume kinetics in adult patients with sep-
sis. Platelets. 2015;26(4):331–5. doi: 10.3109/09537104.2012.701027.
[PubMed: 22731700].
15. Oncel MY, Ozdemir R, Yurttutan S, Canpolat FE, Erdeve O, Oguz
SS, et al. Mean platelet volume in neonatal sepsis. J Clin Lab Anal.
2012;26(6):493–6. doi: 10.1002/jcla.21552. [PubMed: 23143634].
16. Goldstein B, Giroir B, Randolph A, International Consensus
Conference on Pediatric S. International pediatric sepsis con-
sensus conference: definitions for sepsis and organ dysfunc-
tion in pediatrics. Pediatr Crit Care Med. 2005;6(1):2–8. doi:
10.1097/01.PCC.0000149131.72248.E6. [PubMed: 15636651].
17. Boechat Tde O, Silveira MF, Faviere W, Macedo GL. Thrombocitope-
nia in sepsis: an important prognosis factor. Rev Bras Ter Intensiva.
2012;24(1):35–42. [PubMed: 23917711].
18. Zakynthinos SG, Papanikolaou S, Theodoridis T, Zakynthinos EG,
Christopoulou-Kokkinou V, Katsaris G, et al. Sepsis severity is the ma-
jor determinant of circulating thrombopoietin levels in septic pa-
tients. Crit Care Med. 2004;32(4):1004–10. [PubMed: 15071393].
19. Kim CH, Kim SJ, Lee MJ, Kwon YE, Kim YL, Park KS, et al. An in-
crease in mean platelet volume from baseline is associated with
mortality in patients with severe sepsis or septic shock. PLoS
One. 2015;10(3):e0119437. doi: 10.1371/journal.pone.0119437. [PubMed:
25742300].
20. Gao Y, Li Y, Yu X, Guo S, Ji X, Sun T, et al. The impact of vari-
ous platelet indices as prognostic markers of septic shock. PLoS
One. 2014;9(8):e103761. doi: 10.1371/journal.pone.0103761. [PubMed:
25118886].
Iran J Pediatr. In Press(In Press):e7212. 5
Uncorrected Proof
Choi SJ et al.
21. Ahmad MS, Waheed A. Platelet counts, MPV and PDW in culture
proven and probable neonatal sepsis and association of platelet
counts with mortality rate. J Coll Physicians Surg Pak. 2014;24(5):340–4.
[PubMed: 24848393].
22. British Committee for Standards in Haematology BTTF. Guidelines
for the use of platelet transfusions. Br J Haematol. 2003;122(1):10–23.
[PubMed: 12823341].
23. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal
SM, et al. Surviving sepsis campaign: international guidelines
for management of severe sepsis and septic shock: 2012. Crit
Care Med. 2013;41(2):580–637. doi: 10.1097/CCM.0b013e31827e83af.
[PubMed: 23353941].
24. Vander Linden T, Souweine B, Dupic L, Soufir L, Meyer P. Management
of thrombocytopenia in the ICU (pregnancy excluded). Ann Intensive
Care. 2012;2(1):42. doi: 10.1186/2110-5820-2-42. [PubMed: 22929300].
25. Guida JD, Kunig AM, Leef KH, McKenzie SE, Paul DA. Platelet
count and sepsis in very low birth weight neonates: is there
an organism-specific response?. Pediatrics. 2003;111(6 Pt 1):1411–5.
[PubMed: 12777561].
26. Bhat MA, Bhat JI, Kawoosa MS, Ahmad SM, Ali SW. Organism-specific
platelet response and factors affecting survival in thrombocytopenic
very low birth weight babies with sepsis. J Perinatol. 2009;29(10):702–
8. doi: 10.1038/jp.2009.72. [PubMed: 19554015].
6Iran J Pediatr. In Press(In Press):e7212.
Uncorrected Proof