臺灣博碩士論文加值系統

敗血症死亡率相當高，及早治療可以有效降低死亡率，但是初期診斷十分困難，血液培養是細菌性敗血症診斷標準，然而血液血瓶培養包括鑑定與藥敏試驗至少要12-48小時以上，所以發展早期診斷是相當重要的。臨床上常用CRP或WBC的檢驗值當判斷的依據，但因為特異性較低，所以需要其他新的判斷指標，近十幾年來已使用Procalcitonin（PCT）當早期診斷的工具。本研究著重在討論急診的成人細菌性敗血病患者在PCT、Lactate與High-sensitivity C-reactive Protein （ hs-CRP）與細菌血液培養的預測表現差異並分別論述革蘭氏陽性菌與陰性菌的結果偵測能力，本研究得到的結果是在革蘭氏陰性菌的預測上，PCT的AUR(area under the ROC curve)為0.786，較Lactate與hs-CRP有較佳的預測能力，PCT也具有區分陽性細菌培養與污染菌的能力。hs-CRP在0.8 mg / dL用於預測陽性細菌培養，表現不佳，並且無辨識陽性菌與污染菌的能力。

Sepsis has a high mortality rate that can be effectively decreased with early treatment, but the initial diagnosis is difficult. Blood culture is the diagnostic standard for bacterial sepsis, however, blood culture, including identification and antibiotic sensitivity test, requires at least 12- 48 h; hence the development of early-stage diagnosis is critical. C-reactive protein (CRP) or white blood cell (WBC) values are commonly used as a basis for diagnosis, but since they have low specificity, other new markers are needed. In the past decade, procalcitonin (PCT) has been used as an early diagnostic tool. This study focuses on the prediction differences between PCT, lactate, and high-sensitivity C-reactive protein (hs-CRP) and bacterial blood culture of adults with bacterial sepsis in the emergency department. The detection capabilities for gram-positive and gram-negative bacteria are discussed separately. The results of this study show that procalcitonin has an acceptable discriminative ability for bacterial blood culture and a better discriminative ability for gram-negative bacteremia（AUR=0.786 area under the ROC curve）when compared with lactate and high-sensitivity C-reactive protein. It can also for distinguishing blood bacterial culture results of contamination and positivity. High-sensitivity C-reactive protein at a cutoff of 0.8 mg/dL provides poor prediction of positive bacterial culture and it is unable to distinguish for all positive pathogen from contaminants.

目次
中文摘要…………………………………………………………………………i
英文摘要…………………………………………………………………………ii
致謝………………………………………………………………………………iii
目次………………………………………………………………………………iv
圖目錄……………………………………………………………………………vi
表目錄……………………………………………………………………………viii
本研究使用術語中英對照表……………………………………………….…….x 　
第一章 導論………………………………………………………………………1
1.1背景………………………………………………………………………...1
1.2研究動機……………………………………………………………...……5
1.3研究目的……………………………………………………………….......7
1.4論文結構…………………………………………………………………...8
第二章 材料與方法………………………………………………………………11
2.1檢驗資料的來源……………………………………………………………11
2.2研究倫理和個人資料保護法………………………………………………12
2.3檢驗項目……………………………………………………………………13
2.4 Statistical Analysis…………………………………………………………..19
2.5 ROC Curve…………………………………………………………………..20
第三章 分析結果………………………………………………………………….21
3.1 血液血瓶培養結果………………………………………………...……….21
3.2 血液血瓶培養與生化檢驗結果………………………………..…………..21
3.3 陽性菌生化檢驗四分位分布……………………………….….…………..24
3.4 生化檢驗盒狀圖分布情形…………………………………..……………..25
3.5 血液血瓶培養與生化指標以ROC Curve比較………………….………..29
3.6 以ROC Curve觀察生物指標分辨污染菌與陽性菌效能………….……..33
3.7 以Optimal cut-off value觀察886筆資料結果…………………….……..35
第四章 討論.........................................................41
4.1 污染菌偵測能力-檢定…………………………………………………...…41
4.2 污染菌偵測能力-ROC Curve……………………………………………….41
4.3 長病原菌的3項指標四分位表現探討……………….……………………42
4.4 ROC optimal cut-off value與檢驗效能……………………..…………44
4.5 與其他人的研究比較……………………………………………………….45
4.6 導入Optimal cut-off value組合型的檢測效能…………………………...47
4.7 非細菌感染而PCT濃度上升的情況....................................49
4.8 資料驗證……………………………………………………………………49
第五章 結論與後續……………………………………………………………….51
參考文獻.......................................................53
圖目錄

圖 2.1 研究資料流程圖……………………………………………………………12

圖 3.1 Data are presented as box plots pct level with all positive bacterial culture
results Y axis scale is 0-210 (left)，0-45(right)………………………..……26
圖 3.2 Data are presented as box plots hs-CRP(left)，Lactate(right) level with all
positive bacterial culture results ………………………………….…………27
圖 3.3 Data are presented as box plots PCT(1)、 hs-CRP(2)，Lactate(3) level with
gram(-) positive bacterial culture results …………………………………….27
圖 3.4 Data are presented as box plots pct level with gram(+) positive bacterial
culture results Y axis scale is 0-210 (left)，0-45(right)……………………...28
圖 3. 5 Data are presented as box plots hs-CRP(left)，Lactate(right) level with
gram(+) positive bacterial culture results ………………………..…………...28
圖 3.6 Data are presented as box plots log pct level with( 1)- all 、(2)-gram(-)、
(3)-gram(+)positive bacterial culture results………………………..………...28
圖 3.7 Data are presented as box plots log pct level with gram(+)positive bacterial culture results………………………..……………………………………....29
圖 3.8 The receiver operating characteristic (ROC) curve for procalcitonin (PCT)、
hs-CRP(CRP) and lactate(LACT) test analysis results relative to the “gold
standard” of a blood culture results（positive for all pathogen） in 886
Emergency Department Adult Patients.Wilcoxon estimate of area under ROC
Curve…………………………………………………………………………..30
圖 3.9 The receiver operating characteristic (ROC) curve for procalcitonin (PCT)、
hs-CRP(CRP) and lactate(LACT) test analysis results relative to the “gold
standard” of a blood culture results（positive for Gram-Negative Bacilli
pathogen） in 886 Emergency Department Adult Patients. Wilcoxon estimate
of area under ROC curve…………..………………………………………...31
圖 3.10The receiver operating characteristic (ROC) curve for procalcitonin (PCT)、
hs-CRP(CRP) and lactate(LACT) test analysis results relative to the “gold
standard” of a blood culture results（positive for Gram Positive cocci pathogen）
in 886 Emergency Department Adult Patients.Wilcoxon estimate of area under
ROC curve…………………………………….………………………………..32


表目錄

表 1.1 二項分類檢驗測試結果與疾病狀態分類表……………………………..10
表 3.1. Procalcitonin and blood culture results in 886 adult patients admitted to the
Emergency Department undergoing workup for presumed bacteremia or
sepsis………………………………………………………………..………22
表3.2. Hs-CRP and blood culture results in 886 adult patients admitted to the
Emergency Department undergoing workup for presumed bacteremia or
sepsis …………………………………………………………………….…..22
表3.3. Lactate and blood culture results in 886 adult patients admitted to the
Emergency Department undergoing workup for presumed bacteremia
or sepsis ……………………………………………………………….…….23
表3.4 PCT、hs-CRP＆ LACTATE levels in Gram(+) and Gram(-) measured…....24
表3.5 The receiver operating characteristic (ROC) curve value for procalcitonin
(PCT)、hs-CRP(CRP) and lactate(LACT) test analysis results relative
to the “gold standard” of a blood culture results（positive for all pathogen
vs contamination ）in 886 Emergency Department Adult Patients…………33
表3.6 The receiver operating characteristic (ROC) curve value for procalcitonin
(PCT)、hs-CRP(CRP) and lactate(LACT) test analysis results relative to the
“gold standard” of a blood culture results（ positive for Gram-Negative
Bacilli pathogen vs contamination ） in 886 Emergency Department
Adult Patients………………………………………………..………………..34
表3.7 The receiver operating characteristic (ROC) curve value for procalcitonin
(PCT)、hs-CRP(CRP) and lactate(LACT) test analysis results relative to the
“gold standard” of a blood culture results（ positive for Gram-Positive
Bacilli pathogen vs contamination ） in 886 Emergency Department
Adult Patients…………………………………………………………………35
表3.8 Diagnostic variables associated with elevation of either procalcitonin (PCT ≥
3.9 ng/mL), blood lactate (≥17.9 mg/dL) or high sensitivity-C reactive protein
(hs-CRP ≥ 13 mg/dL), two variables, and all of them in predicting positive
blood cultures…………………………………………………………………..38
表3.9 Diagnostic variables associated with elevation of either procalcitonin (PCT ≥3.9
ng/mL), blood lactate (≥25.1mg/dL) or high sensitivity C-reactive protein
(hs-CRP ≥4.42mg/dL), two variables, and all of them in predicting blood
culture positive with Gram-Negative Bacilli pathogen………………….….39
表3.10. Diagnostic variables associated with elevation of either procalcitonin (PCT ≥
4.13 ng/mL), blood lactate (≥18.7 mg/dL) or high sensitivity C-reactive protein
(hs-CRP ≥13.18 mg/dL), two variables, and all of them in predicting blood
culture positive with Gram positive cocci pathogen…………………….……..40

1.中國醫藥大學附設醫院檢驗醫學部技術文件SIP-T22- CM005 High Sensitivity C-Reactive Protein
2.中國醫藥大學附設醫院檢驗醫學部技術文件SIP-T22-CM009 Lactate
3.中國醫藥大學附設醫院檢驗醫學部技術文件SIP-T22-HE005 Procalcitonin(PCT)
4. 林委正 ； 高雅慧 ； 柯文謙.2004- 血液培養污染之臨床衝擊及改善方法. 感染控制雜誌； 14卷6期(2004 / 12 / 01) ， P390 – 397
5. BD PhoenixTM 全自動微生物鑑定及藥敏性試驗分析儀中文操作手冊
6.Aalto H, Takala A, Kautiainen H, Repo H.（2004）. Laboratory markers of systemic
inflammation as predictors of bloodstream infection in acutely ill patients
admitted to hospital in medical emergency. European Journal of Clinical Microbiology and Infectious Diseases 23:699_704 DOI 10.1007/s10096-004-1191-8.
7.Alemayehu D, and Zou KH.（2012）. Applications of ROC analysis in medical research: recent developments and future directions. Acad Radiol 19:1457-1464. 10.1016/j.acra.2012.09.006
8.Arora R, Campbell JP, Simon G, and Sahni N.（2017）. Does serum procalcitonin aid in the diagnosis of bloodstream infection regardless of whether patients exhibit the systemic inflammatory response syndrome? Infection 45:291-298. 10.1007/s15010-016-0965-0
9. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C.
(1993). High serum procalcitonin concentrations in patients with
sepsis and infection. Lancet 341:515–518.
10..Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. (1996). Serial blood
lactate levels can predict the development of multiple organ failure
following septic shock. Am J Surg 171:221–226.
11.Carter, J.V., et al., 2016 ROC-ing along: Evaluation and interpretation of receiver operating characteristic curves. Surgery. 159(6): p. 1638-1645
12.Cesar Henriquez-Camacho and Juan Losa,（2014 ）“Biomarkers for Sepsis,” BioMed Research International, vol., Article ID 547818, 6 pages, 2014. doi:10.1155/2014/547818
13.Chan YL, Tseng CP, Tsay PK, Chang SS, Chiu TF, Chen JC. Procalcitonin as a marker of bacterial infection in the emergency department: an observational study. Crit Care Med. 2004;8:12–20.
14.Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber
PR, Tamm M, Muller B. (2004). Effect of procalcitonin-guided
treatment on antibiotic use and outcome in lower respiratory tract
infections: Cluster-randomised, single-blinded intervention trial.
Lancet 363:600–607.
15.Claessens YE, Schmidt J, Batard E, Grabar S, Jegou D, Hausfater P, Kierzek
G, Guerin S, Pourriat JL, Dhainaut JF, Ginsburg C; BIS Study Group.
(2010a). Can C-reactive protein, procalcitonin and mid-regional
pro-atrial natriuretic peptide measurements guide choice of
in-patient or out-patient care in acute pyelonephritis? Biomarkers
In Sepsis (BIS) multicentre study. Clin Microbiol Infect 16:753–760.
16.Claessens YE, Mathevon T, Kierzek G, Grabar S, Jegou D, Batard E,
Loyer C, Davido A, Hausfater P, Robert H, Lavagna-Perez L, Bernot
B, Plaisance P, Leroy C, Renaud B. (2010b). Accuracy of C-reactive
protein, procalcitonin, and mid-regional pro-atrial natriuretic
peptide to guide site of care of community-acquired pneumonia.
Intensive Care Med 36:799–809
17.Claeys R, Vinken S, Spapen H, ver Elst K, Decochez K, Huyghens L,Gorus FK. (2002). Plasma procalcitonin and C-reactive proteinin acute septic shock: Clinical and biological correlates. Crit Care Med 30:757–762.
18.Ferrer R, Martin-Loeches I, Phillips G.（2014）. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med.2014; 42: 1749-55.
19.Freund Y, Delerme S, Goulet H, Bernard M, Riou B, Hausfater P.（2012）.Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection. Biomarkers;17:590–596. doi: 10.3109/1354750X.2012.704645.
20.Glas AS, Lijmer JG, Prins MH, Bonsel GJ, and Bossuyt PMM.（2003）. The diagnostic odds ratio: a single indicator of test performance. Journal of Clinical Epidemiology 56:1129-1135. 10.1016/s0895-4356(03)00177-x
21.Guo, S. Y., Zhou, Y., Hu, Q. F., Yao, J., & Wang, H. (2015). Procalcitonin Is a Marker of Gram-Negative Bacteremia in Patients With Sepsis. The American Journal of the Medical Sciences, 349(6), 499–504. http://doi.org/10.1097/MAJ.0000000000000477
22,Hajian-Tilaki, K.（2013）. Receiver Operating Characteristic (ROC) Curve Analysis for Medical Diagnostic Test Evaluation . Caspian Journal of Internal Medicine, 4(2), 627–635.
23.Hausfater P, Garric S, Ayed SB, Rosenheim M, Bernard M, Riou B. (2002).
Usefulness of procalcitonin as a marker of systemic infection in
emergency department patients: A prospective study. Clin Infect
Dis 34:895–901.
24.Hausfater P, Juillien G, Madonna-Py B, Haroche J, Bernard M, Riou
B. (2007). Serum procalcitonin measurement as diagnostic and
prognostic marker in febrile adult patients presenting to the
emergency department. Crit Care 11:R60.
25.Hoenigl M, Raggam RB, Wagner J, Prueller F, Grisold AJ, Leitner E, Seeber K, Prattes J, Valentin T, Zollner-Schwetz I, Schilcher G, Krause R.（2014）. Procalcitonin fails to predict bacteremia in SIRS patients: a cohort study. International Journal of Clinical Practice 68:1278_1281 DOI 10.1111/ijcp.12474.
26.Howell MD, Donnino M, Clardy P, Talmor D, Shapiro NI. (2007). Occult
hypoperfusion and mortality in patients with suspected infection.
Intensive Care Med 33:1892–1899.
27.Julian-Jimenez A, Gutierrez-Martin P, Lizcano-Lizcano A, Lopez-Guerrero MA, Barroso-Manso A, and Heredero-Galvez E. 2015. Usefulness of procalcitonin and C-reactive protein for predicting bacteremia in urinary tract infections in the emergency department. Actas Urol Esp 39:502-510. 10.1016/j.acuro.2015.03.003
28.Kibe S, Adams K, Barlow G. 2011. Diagnostic and prognostic biomarkers of sepsis in critical care. Journal of Antimicrobial Chemotherapy 66(Suppl 2):ii33_ii40 DOI 10.1093/jac/dkq523.
29.Kim MH, Lim G, Kang SY, Lee WI, Suh JT, and Lee HJ. 2011. Utility of procalcitonin as an early diagnostic marker of bacteremia in patients with acute fever. Yonsei Med J 52:276-281. 10.3349/ymj.2011.52.2.276
30.Leli C, Cardaccia A, Ferranti M, Cesarini A, D'Alo F, Ferri C, Cenci E, and Mencacci A. 2014. Procalcitonin better than C-reactive protein, erythrocyte sedimentation rate, and white blood cell count in predicting DNAemia in patients with sepsis. Scand J Infect Dis 46:745-752. 10.3109/00365548.2014.936493
31.Lindvig KP, Nielsen SL, Henriksen DP, Jensen TG, Kolmos HJ, Pedersen C, Vinholt PJ, and Lassen AT. 2016. Mortality and prognostic factors of patients who have blood cultures performed in the emergency department: a cohort study. Eur J Emerg Med 23:166-172. 10.1097/mej.0000000000000250
32.Lin C, Lu J, Chen Y, Kok VC, Horng J.（2017）. Diagnostic value of serum procalcitonin, lactate, and high-sensitivity C-reactive protein for predicting bacteremia in adult patients in the emergency department. PeerJ 5:e4094 https://doi.org/10.7717/peerj.4094
33.Linscheid P, Seboek D, Nylen ES, Langer I, Schlatter M, Becker KL, Keller U, and Muller B.（2003）. In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Endocrinology 144:5578-5584. 10.1210/en.2003-0854
34.Ljungstrom L, Pernestig AK, Jacobsson G, Andersson R, Usener B, and Tilevik D. （2017）. Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis. PLoS One 12:e0181704. 10.1371/journal.pone.0181704
35.Jansen TC, van Bommel J, Woodward R, Mulder PG, Bakker J. (2009).
Association between blood lactate levels, Sequential Organ Failure
Assessment subscores, and 28-day mortality during early and late
intensive care unit stay: A retrospective observational study. Crit
Care Med 37:2369–2374.
36.Jayawant N. Mandrekar . 2010. Receiver Operating Characteristic Curve in Diagnostic Test Assessment, In Journal of Thoracic Oncology, Volume 5, Issue 9, Pages 1315-1316, ISSN 1556-0864, https://doi.org/10.1097/JTO.0b013e3181ec173d.
37.Meisner M., J Lab Med 1999;23:263-72
38.Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta. 2002;323:17–29.
39.Meisner, M. 2014. Update on Procalcitonin Measurements. Ann Lab Med, 34(4), 263-273. https://doi.org/10.3343/alm.2014.34.4.263
40.Milone MT, Kamath AF, and Israelite CL. 2014. Converting between high- and low-sensitivity C-reactive protein in the assessment of periprosthetic joint infection. J Arthroplasty 29:685-689. 10.1016/j.arth.2013.09.015
41.Michael L, Wilson MD: M47-a: .2007. Principles and procedures for blood cultures; approved guideline. CLSI M47-A.
42.Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV,
Bellamy SL, Christie JD. (2009). Serum lactate is associated with
mortality in severe sepsis independent of organ failure and shock.
Crit Care Med 37:1670–1677.
43.Ming Jin, Adil I. Khan; Procalcitonin: Uses in the Clinical Laboratory for the Diagnosis of Sepsis, Laboratory Medicine, Volume 41, Issue 3, 1 March 2010, Pages 173–177, https://doi.org/10.1309/LMQ2GRR4QLFKHCH9
44. Mohsen, A. H. A., & Kamel, B. A. (2015). Predictive values for procalcitonin in the diagnosis of neonatal sepsis. Electronic Physician, 7(4), 1190–1195. http://doi.org/10.14661/2015.1190-1195
45.Mokline, A., Garsallah, L., Rahmani, I., Jerbi, K., Oueslati, H., Tlaili, S., … Messadi, A. A. (2015). Procalcitonin: a diagnostic and prognostic biomarker of sepsis in burned patients. Annals of Burns and Fire Disasters, 28(2), 116–120.
46.Müller B, Becker KL, Schächinger H, Rickenbacher PR, Huber PR, Zimmerli W, et al.,2000. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med. 2000;28:977–83.
47.Nishikawa H, Shirano M, Kasamatsu Y, Morimura A, Iida K, Kishi T, Goto T, Okamoto S, and Ehara E. 2016. Comparative usefulness of inflammatory markers to indicate bacterial infection-analyzed according to blood culture results and related clinical factors. Diagn Microbiol Infect Dis 84:69-73. 10.1016/j.diagmicrobio.2015.09.015
48.Nishikawa H, Shirano M, Kasamatsu Y, Morimura A, Iida K, Kishi T, Goto T, Okamoto S, and Ehara E. 2017. Comparison between procalcitonin and C-reactive protein in predicting bacteremias and confounding factors: a case-control study. Clin Chem Lab Med 55:1043-1052. 10.1515/cclm-2016-0705
49.Nishikura T. 1999. Procalcitonin (PCT) production in a thyroidectomized patient. Intensive Care Med 25:1031.
50.Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA,
Tomlanovich MC. (2004). Early lactate clearance is associated with
improved outcome in severe sepsis and septic shock. Crit Care
Med 32:1637–1642.
51.Oussalah A, Ferrand J, Filhine-Tresarrieu P, Aissa N, Aimone-Gastin I, Namour F,
Garcia M, Lozniewski A, Gueant JL. 2015. Diagnostic accuracy of procalcitonin forpredicting blood culture results in patients with suspected bloodstream infection: an observational study of 35,343 consecutive patients (A STROBE-Compliant Article).Medicine 94:e1774 DOI 10.1097/md.0000000000001774.
52.Philip M. Gleason, Jeffrey Harris, Patricia M. Sheean, Carol J. Boushey, Barbara Bruemmer .2010. Publishing Nutrition Research: Validity, Reliability, and Diagnostic Test Assessment in Nutrition-Related Research, In Journal of the American Dietetic Association, Volume 110, Issue 3, Pages 409-419, ISSN 0002-8223, https://doi.org/10.1016/j.jada.2009.11.022.(http://www.sciencedirect.com/science/article/pii/S0002822309019567)
53.Pierrakos, C. and J.-L. Vincent, Sepsis biomarkers: a review. 2010. Critical Care, 14(1): p. R15
54.Prescott Hallie C, Osterholzer John J, Langa Kenneth M, Angus Derek C, Iwashyna Theodore J.（2016） Late mortality after sepsis: propensity matched cohort study BMJ 2016; 353 :i2375
55.Rajkumari, N., Mathur, P., Sharma, S., Gupta, B., Bhoi, S., & Misra, M. C. (2013). Procalcitonin as a Predictor of Sepsis and Outcome in Severe Trauma Patients: A Prospective Study. Journal of Laboratory Physicians, 5(2), 100–108. http://doi.org/10.4103/0974-2727.119852
56.Riedel S, Melendez JH, An AT, Rosenbaum JE, and Zenilman JM.（2011.） Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am J Clin Pathol 135:182-189. 10.1309/ajcp1mfyinqlecv2
57.Riedel S. 2012. Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis. Diagn Microbiol Infect Dis 73:221-227. 10.1016/j.diagmicrobio.2012.05.002
58.Rhodes, A., et al., Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Medicine, 2017. 43(3): p. 304-377
59.Schuetz P, Mueller B, and Trampuz A. 2007. Serum procalcitonin for discrimination of blood contamination from bloodstream infection due to coagulase-negative staphylococci. Infection 35:352-355. 10.1007/s15010-007-7065-0
60.Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe
RE, Weiss JW. (2005). Serum lactate as a predictor of mortality in
emergency department patients with infection. Ann Emerg Med
45:524–528.
61. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. (2004). Serum
procalcitonin and C-reactive protein levels as markers of bacterial
infection: A systematic review and meta-analysis. Clin Infect Dis
39:206–217.
62. Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., … Angus, D. C. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315(8), 801–810. http://doi.org/10.1001/jama.2016.0287
63.Stefan Riedel, Johan H. Melendez, Amanda T. An, Janet E. Rosenbaum, Jonathan M. Zenilman .2011. Procalcitonin as a Marker for the Detection of Bacteremia and Sepsis in the Emergency Department, American Journal of Clinical Pathology, Volume 135, Issue 2, 1 February, Pages 182–189, https://doi.org/10.1309/AJCP1MFYINQLECV2
64.Su YJ, Liao SC, Cheng BC, Hwang JC, Chen JB. 2013. Increasing high-sensitive
Creactive protein level predicts peritonitis risk in chronic peritoneal dialysis
patients. BMC Nephrology 14:185 DOI 10.1186/1471-2369-14-185.
65.Sudhir, U., Venkatachalaiah, R. K., Kumar, T. A., Rao, M. Y., & Kempegowda, P. (2011). Significance of serum procalcitonin in sepsis. Indian Journal of Critical Care Medicine : Peer-Reviewed, Official Publication of Indian Society of Critical Care Medicine, 15(1), 1–5. http://doi.org/10.4103/0972-5229.78214
66.Szumilas, M. (2010). Explaining Odds Ratios. Journal of the Canadian Academy of Child and Adolescent Psychiatry, 19(3), 227–229.
67.Trzeciak S, Dellinger RP, Chansky ME, et al . 2007. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med.;33:970-977.
68.Vincent JL, Dufaye P, Berre J, Leeman M, Degaute JP, Kahn RJ. (1983).
Serial lactate determinations during circulatory shock. Crit Care
Med 11:449–451.
69.Whang KT, Steinwald PM, White JC, Nylen ES, Snider RH, Simon GL, et al.,（1988）.Serum calcitonin precursors in sepsis and systemic inflammation. J Clin Endocrinol Metab. 1998;83:3296–301.
70.Wang T, Cui YL, Lin ZF, and Chen DC. 2016. Comparative Study of Plasma Endotoxin with Procalcitonin Levels in Diagnosis of Bacteremia in Intensive Care Unit Patients. Chin Med J (Engl) 129:417-423. 10.4103/0366-6999.176064
71.Windgassen EB, Funtowicz L, Lunsford TN, Harris LA, and Mulvagh SL. 2011. C-reactive protein and high-sensitivity C-reactive protein: an update for clinicians. Postgrad Med 123:114-119. 10.3810/pgm.2011.01.2252
72.Yildiz B, Poyraz H, Cetin N, Kural N, and Colak O. 2013. High sensitive C-reactive protein: a new marker for urinary tract infection, VUR and renal scar. Eur Rev Med Pharmacol Sci 17:2598-2604.