Diagnostic Value of Laboratory Parameters for Complicated Appendicitis: A Two-center Study

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BACKGROUND The present study aimed to examine the efficacy of the laboratory parameters with respect to complicated appendicitis. METHODS A total of 1514 cases with acute appendicitis at the Beijing Tsinghua Changgung Hospital and Aerospace Center Hospital from January 2016 to September 2021 were reviewed in this retrospective study. All cases were divided into uncomplicated and complicated appendicitis groups according to the appendix pathology. The efficacy of the laboratory parameters was evaluated in recognition of complicated appendicitis. Independent variables were analyzed by univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis was used to identify the significant parameters in multivariate analysis. Cutoff values, sensitivity, specificity, and accuracy with the area under the curve (AUC) > 0.600 were considered significant parameters.” RESULTS Significant difference were detected in age (p < 0.001), temperature (p < 0.001), white blood cell count (WBC, p < 0.001), C-reactive protein (CRP, p < 0.001), neutrophil (p < 0.001), neutrophil-to-lymphocyte ratio (NLR, p = 0.019), platelet-to-lymphocyte ratio (PLR, p < 0.001), platelet count (p < 0.001), coefficient of variation of erythrocyte distribution width (RDW-CV, p < 0.001), standard deviation of erythrocyte distribution width (RDW-SD, p < 0.001), mean platelet volume (MPV, p < 0.001), T-bilirubin (p < 0.001), and direct bilirubin (p < 0.001) between the two groups. CRP, neutrophil, NLR, PLR, platelet count, RDW-CV, RDW-SD, MPV, and direct bilirubin were independent variables for diagnosing complicated appendicitis. CONCLUSIONS In patients with acute appendicitis, CRP > 22.95 mg/L, NLR > 5.7, serum D-bilirubin > 6.1 mmol/L, or RDW-SD > 17.7 fl are significantly associated with the presence of complicated appendicitis.
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METHODS A total of 1514 cases with acute appendicitis at the Beijing Tsinghua Changgung Hospital and Aerospace Center Hospital from January 2016 to September 2021 were reviewed in this retrospective study. All cases were divided into uncomplicated and complicated appendicitis groups according to the appendix pathology. The efficacy of the laboratory parameters was evaluated in recognition of complicated appendicitis. Independent variables were analyzed by univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis was used to identify the significant parameters in multivariate analysis. Cutoff values, sensitivity, specificity, and accuracy with the area under the curve (AUC) > 0.600 were considered significant parameters.” RESULTS Significant difference were detected in age (p < 0.001), temperature (p < 0.001), white blood cell count (WBC, p < 0.001), C-reactive protein (CRP, p < 0.001), neutrophil (p < 0.001), neutrophil-to-lymphocyte ratio (NLR, p = 0.019), platelet-to-lymphocyte ratio (PLR, p < 0.001), platelet count (p < 0.001), coefficient of variation of erythrocyte distribution width (RDW-CV, p < 0.001), standard deviation of erythrocyte distribution width (RDW-SD, p < 0.001), mean platelet volume (MPV, p < 0.001), T-bilirubin (p < 0.001), and direct bilirubin (p < 0.001) between the two groups. CRP, neutrophil, NLR, PLR, platelet count, RDW-CV, RDW-SD, MPV, and direct bilirubin were independent variables for diagnosing complicated appendicitis. CONCLUSIONS In patients with acute appendicitis, CRP > 22.95 mg/L, NLR > 5.7, serum D-bilirubin > 6.1 mmol/L, or RDW-SD > 17.7 fl are significantly associated with the presence of complicated appendicitis. General Surgery complicated appendicitis bilirubin mean platelet volume neutrophil-to-lymphocyte ratio platelet count Figures Figure 1 Introduction Acute appendicitis is a common acute abdominal issue. The morbidity is 1.5–1.9/10 million, and that in males is 1.4-fold higher than in females [ 1 , 2 ]. Reportedly, the risk of acute appendicitis is 7–8% in a lifetime. About 17–30% of patients present appendiceal perforation, and this proportion is much higher in the elderly [ 1 – 3 ]. Appendicitis can be divided into uncomplicated and complicated appendicitis according to its pathology. Uncomplicated appendicitis has a mild infection and fewer complications and can be treated with antibiotics. On the other hand, surgery is the primary treatment for complicated appendicitis. Also, early diagnosis and management are crucial to decrease the incidence of complications and the duration of hospitalization. The diagnosis of acute appendicitis depends on the clinical features, laboratory parameters, and imaging results. Only 60% of patients present typical symptoms, including shifting right lower abdominal pain, fever, nausea, and vomiting [ 1 , 4 , 5 ]. The frequently measured laboratory parameters are C-reactive protein (CRP), white blood cell (WBC) count, and neutrophil percentage. However, these tests can only evaluate the presence of abdominal infection and the specificity of the severity [ 1 , 3 , 6 , 7 ]. Abdominal ultrasound and computed tomography (CT) scan are used in the diagnosis of appendicitis. According to the literature, the sensitivity and specificity of ultrasound were 86% and 81% due to the influence of the intestinal gas [ 8 , 9 ]. Although CT has better sensitivity and specificity than ultrasound [ 1 , 10 , 11 ], the high cost and the risk of radiation limits its application. Therefore, evaluation of the type of acute appendicitis based on laboratory tests is essential. Since the last decade, studies have proved that neutrophil count, neutrophil percentage, neutrophil-to-lymphocyte ratio (NLR), platelet (PLT), mean platelet volume (MPV) and direct bilirubin are valuable parameters in the diagnosis of appendicitis and predicting the complications [ 1 , 12 – 17 ]. However, the case numbers were small and the results varied. This study aimed to evaluate the diagnostic value of CRP, WBC, NLR, PLT, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratios (LMR), erythrocyte distribution width (RDW), MPV, and serum bilirubin levels in the type of acute appendicitis. We also established a standard to guide the management of acute appendicitis. Materials And Methods Materials A total of 1514 cases with acute appendicitis at the Beijing Tsinghua Changgung Hospital Gastrointestinal Department (978, 64.6%) and Aerospace Center Hospital General Surgery Department (536, 35.4%) from January 2016 to September 2021 were reviewed in this retrospective study. All cases underwent laparoscopic appendectomy. The inclusion criteria were as follows: 1)age ≥ 14years-old; 2) the pathology proved the diagnosis. The exclusion criteria were as follows: 1) combined with autoimmune diseases; 2) combined with diseases affecting the bilirubin level. The blood tests were carried out within 12 h before the operation. The complete blood count and blood chemistry (Flow cytometry, Sison Meikang) were performed by the clinical laboratory department. All the cases underwent laparoscopic appendectomy. The appendix pathology was evaluated by the experienced pathologist from the two hospitals. The four categories of pathology results were simple appendicitis, phlegmonous appendicitis, gangrenous appendicitis, and perforated appendicitis. All the cases were divided into uncomplicated appendicitis (simple appendicitis and phlegmonous appendicitis) and complicated appendicitis (gangrenous appendicitis and perforated appendicitis) groups. Data collection Age, gender, temperature, WCC, CRP, MPV, neutrophil count, neutrophil percentage, lymphocyte count, coefficient of variation of erythrocyte distribution width (RDW-CV), standard deviation of erythrocyte distribution width (RDW-SD), total bilirubin, direct bilirubin, NLR, LMR and PLR were estimated and recorded. Statistical analysis All parameters were analyzed by SPSS 25.0 (SPSS, Chicago, IL, USA). Continuous variables of normal distribution were expressed as mean ± standard deviation (mean ± SD) and compared using the t-test. Continuous variables with abnormal distribution were expressed as median and compared using the Kruskal–Wallis H test. The enumeration data were expressed as case numbers and percentages and compared using the chi-square test. Logistic regression analysis was performed as multivariate analysis on parameters with significant differences observed in univariate analysis. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. The appropriate cutoff values were identified, and sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated for parameters with an area under the curve (AUC) > 0.600. All the tests were two-sided. p < 0.05 was considered statistically significant. Results The cohort comprised 780 (51.5%) males and 734 (48.5%) females, aged 36±15.135 (range: 14–88)-years-old. Moreover, 1172 (77.4%) cases constituted the uncomplicated appendicitis group, while the other 342 (22.6%) cases were in the complicated appendicitis group. Age (p0.001), temperature (p<0.001), WCC (p<0.001), CRP (p<0.001), neutrophil percentage (p<0.001), neutrophil (p<0.001), NLR (p<0.001), PLR (p<0.001), PLT (p<0.001), RDW-CV (p<0.001), RDW-SD (p<0.001), MPV (p<0.001), total bilirubin (p<0.001), and direct bilirubin (p<0.001) showed significant difference between groups after univariate analysis (Table 1). Table 1 Univariate analysis between groups Group A Group B p Number of cases 1172 342 Age (years) † 35 (14–81) 41 (16–88) 0.000 Gender (n) 0.868 Male 606 (51.7%) 174 (50.9%) Female 566 (48.3%) 168 (49.1%) Temperature ( ℃) ‡ 37.0±0.7 37.5±0.93 0.000 WCC (×10 9 /L) ‡ 13.0±3.92 14.24±3.98 0.000 CRP (mg/L) ‡ 10.18±50.8 43.29±74.41 0.000 Neutrophil granulocyte (%) ‡ 84.4±9.4 86.2±7.73 0.000 Neutrophil (×10 9 /L) ‡ 10.79±3.93 12.17±3.67 0.000 NLR ‡ 8.21±8.36 9.95±11.88 0.000 LMR ‡ 2.43±3.12 1.87±3.43 0.919 PLR ‡ 167.53±200.27 191.43±374.31 0.000 PLT (×10 9 /L) ‡ 222.5±57.46 225.5±58.21 0.000 RDW-CV (%) ‡ 11.9±1.55 12.1±1.36 0.000 RDW-SD (fl) ‡ 37.4±12.6 38.5±10.56 0.000 MPV (fl) ‡ 10.3±14.28 10.1±11.8 0.000 Bilirubin ( m mol/l) ‡ 14.6±8.78 17.95±10.78 0.000 Direct Bilirubin ( m mol/l) ‡ 4.24±2.6 5.8±3.8 0.000 †Median (range); ‡Mean (±standard deviation). WCC: white cell count; CRP: C-reactive protein; NLR: neutrophil-to-lymphocyte ratios; LMR: lymphocyte-to-monocyte ratios; PLR: platelet-to-lymphocyte ratios; PLT: platelet count; RDW: red cell volume distribution width; MPV: mean platelet volume. Logistic regression suggested CRP (p<0.001), neutrophil (p<0.001), NLR (p=0.019), PLR (p<0.001), platelet (p<0.001), RDW-CV (p=0.045), RDW-SD (p<0.001), MPV (p=0.007), and direct bilirubin (p0.600 after ROC curve analysis were CRP (p<0.001), NLR (p<0.001), RDW-SD (p<0.001), and direct bilirubin (p<0.001) (Figure 1, Table 2). The cutoff value of CRP, NLR, RDW-SD, and direct bilirubin is shown in Table 3. Table 2 Logistic regression and ROC curve in factors associated with complicated appendicitis Multivariate analysis ROC curve Analysis OR 95% CI p AUC 95% CI p CRP (mg/L) 1.008 1.005–1.010 <0.001 0.679 0.642–0.714 <0.001 Neutrophil (×10 9 /L) 1.120 1.055–1.189 <0.001 0.589 0.556–0.621 <0.001 NLR 0.944 0.900–0.991 0.019 0.603 0.556–0.621 <0.001 PLR 1.005 1.003–1.008 <0.001 0.573 0.537–0.607 <0.001 PLT (×10 9 /L) 0.996 0.993–1.000 0.039 0.502 0.466–0.535 <0.001 RDW-CV (%) 0.809 0.657–0.996 0.045 0.579 0.544–0.610 <0.001 RDW-SD (fl) 1.147 1.079–1.219 <0.001 0.605 0.571–0.637 <0.001 MPV (fl) 1.067 1.018–1.118 0.007 0.567 0.535–0.601 <0.001 Direct bilirubin ( m mol/L) 1.128 1.075–1.184 <0.001 0.657 0.622–0.690 <0.001 OR: odds ratio; AUC: area under the curve; CRP: C-reactive protein; NLR: neutrophil-to-lymphocyte ratios; PLR: platelet-to-lymphocyte ratios; PLT: platelet count; RDW: red cell volume distribution width; MPV: mean platelet volume. Table 3 Proposed cut-off values for significant parameters in prediction of acute complicated appendicitis Cutoff value Sensitivity (%) Specificity (%) PPV NPV pLLR nLLR AUC CRP (mg/L) 22.95 64.24 66.09 38.10 85.00 1.89 0.54 0.679 NLR 5.7 82.46 32.51 26.30 86.40 1.22 0.54 0.603 RDW-SD (fl) 17.7 82.16 33.45 26.50 86.50 1.23 0.53 0.605 Direct Bilirubin ( m mol/L) 6.1 47.66 78.16 38.90 83.70 2.18 0.67 0.657 PPV: positive predictive value; NPV: negative predictive value; OR: odds ratio; pLLR: positive likelihood ratio; nLLR: negative likelihood ratio; AUC: area under the curve; CRP: C-reactive protein; NLR: neutrophil-to-lymphocyte ratios; RDW: red cell volume distribution width. Discussion Acute appendicitis is one of the common acute abdominal issues. The reported morbidity is up to 2% [1, 18]. The diagnosis of appendicitis depends on symptoms, signs, laboratory tests, and imaging results [1, 4, 5]. The primary management for acute appendicitis is surgery, especially for complicated appendicitis [19-22]. Reportedly, the ratio of complicated appendicitis accounts for 18–34% of acute appendicitis [2]. Recent studies suggested that conservative treatment is the first choice for uncomplicated appendicitis. Therefore, easy access and effective standards should be established to distinguish complicated from uncomplicated appendicitis in order to guide the management selection. Parameters, such as temperature, CRP, WBC, NLR, PLR, MPV, RDW-CV, RDW-SD, and bilirubin, might help diagnose complicated appendicitis; however, the efficacy is varied [7, 14-18, 23-25]. The present study analyzed 1514 cases who underwent a laparoscopic appendectomy at two surgery centers. The results suggested that CRP, neutrophil, NLR, PLR, PLT, RDW-CV, RDW-SD, MPV, and direct bilirubin are the independent risk factors associated with complicated appendicitis. Furthermore, CRP is a serum inflammatory marker and a critical factor associated with complicated appendicitis [2, 14, 17, 26]. It increases rapidly to several-fold of the normal value in the early stage of inflammation (6–12 h) [27]. Interestingly, WBC count is a sensitive indicator during the first 24 h of acute appendicitis, while CRP was sensitive after the first 24 h [27]. Ahmed et al. [28] reported that the probability of appendix perforation increased significantly when CRP>48 mg/dL. A study including 42 acute appendicitis cases found that the sensitivity and specificity of perforated appendicitis were 71% and 100%, respectively, when CRP was >40.1 mg/dL [29]. Choudhary et al. [30] reported that the sensitivity and specificity of perforated appendicitis were 100% and 54%, respectively, when CRP was >6.15 mg/L. Hence, the appropriate cutoff of CRP is crucial for distinguishing complicated appendicitis. After the analysis of 1514 cases, the present study found that the sensitivity and specificity of complicated appendicitis were 64.24% and 66.09%, respectively, when CRP was >22.95 mg/L. This cutoff was lower than that reported in previous studies. NLR can be obtained from complete blood count. It is a routine and cost-effective blood test during the diagnosis of appendicitis. NLR can effectively elucidate the severity of acute appendicitis [16, 23, 24, 31, 32], but the cutoff is yet controversial. Ishizuka et al. [12] reported that an NLR 8.0 is significantly associated with gangrenous appendicitis based on the analysis of 314 cases that underwent appendectomy. Kahramanca et al. [13] analyzed 897 cases and reported an NLR of 5.74 associated with complicated appendicitis. The sensitivity and specificity of the clinical features were 70.8% and 48.5%, respectively. The current study reported an NLR of 5.7 associated with complicated appendicitis, and the sensitivity and specificity were 82.46% and 32.51%. This finding was similar to that of Shimizu et al. and lower than that of Ishizuka et al. The study[12]proposed that the lower the cutoff value of NLR, the higher the sensitivity of NLR. When the cutoff value was 3.5, it reached the highest sensitivity [33], and the specificity increased when NLR was >5.0 [18]. Further investigation of a large number of cases is needed to find a reasonable cutoff of NLR. The serum bilirubin level increases due to liver dysfunction during infection, especially sepsis. Hence, bilirubin was included in the evaluation of patients with complicated appendicitis [33-35]. The sensitivity and specificity of total bilirubin and direct bilirubin in recognizing complicated appendicitis were 48% and 61%, respectively [36]. Sand et al. reported that hyperbilirubinemia had a specificity of 86% for appendiceal perforation or gangrene, while CRP had a specificity of only 35% [37]. Estrada et al. also found that bilirubin levels >1 mg/dL have a three-fold risk of perforated appendicitis [38]. On the contrary, some studies reported no diagnostic value for bilirubin in the prediction of perforated appendicitis [39, 40]. Bilirubin alone is sufficient in identifying patients with acute appendicitis and predicting perforated appendicitis. The significance of bilirubin as a marker is increased when combined with clinical symptoms and other blood markers [39, 41]. In this study, total bilirubin and direct bilirubin levels were significantly elevated in the complicated appendicitis group. Direct bilirubin was found to be the independent risk factor associated with complicated appendicitis with a sensitivity of 47.66% and a specificity of 78.16% when the cutoff was 6.1 mmol/L. Although total bilirubin is available, few studies have reported the efficiency of direct bilirubin. However, this result needs to be substantiated with further studies. RDW reflects the volume heterogeneity of red blood cells. At present, it is mainly used for the differential diagnosis of anemia. Recent studies reported that the RDW level is altered in some inflammatory and infectious diseases, such as inflammatory bowel disease, celiac disease, acute pancreatitis, rheumatoid arthritis, bacteremia, sepsis, and septic shock [42-45]. Previous studies reported a strong correlation between RDW and inflammatory markers, such as CRP, erythrocyte sedimentation rate, and interleukin 6 [42, 46]. The inflammatory mediators affect the survival of red blood cells in the circulation by suppressing erythrocyte maturation. Thus, newer, larger reticulocytes enter the peripheral circulation and increase the RDW [46]. Narci et al. [47] reported that RDW decreases significantly among patients with acute appendicitis compared to healthy individuals. Conversely, Aktimur et al. [48] and Tanrikulu et al. [49] did not identify any diagnostic value of RDW in acute appendicitis. Jung et al. [50] showed that the RDW level was significantly higher in the complicated appendicitis group compared to the uncomplicated appendicitis group. On the other hand, the parameter did not differ significantly between the appendicitis patients and healthy individuals. Thus, our results indicated that RDW-CV and RDW-SD levels are the independent risk factors associated with complicated appendicitis. RDW-SD had a sensitivity of 82.16% and a specificity of 33.45% for complicated appendicitis when the cutoff was 17.7fl. Therefore, RDW could be used as a parameter to identify complicated appendicitis. Limitations Although this was a multicenter study including a large number of cases, it was a retrospective analysis and could not avoid bias. Thus, a randomized controlled trial should be performed for further investigation. Conclusion In conclusion, no simple or perfect test is yet available for recognizing complicated appendicitis. According to the current results, CRP > 22.95mg/L, NLR > 5.7, RDW-SD > 17.7fl, and direct bilirubin > 6.1 mmol/L are valuable indicators for the recognition of acute complicated appendicitis, and surgery should be recommended as the primary treatment. Declarations Acknowledgments The authors acknowledge no competing interests and are solely responsible for the content of the present article. Ethics approval was not required due to the retrospective nature of the study. Conflict of interest: None declared. References 1. Baird DLH, Simillis C, Kontovounisios C, Rasheed S, Tekkis PP. Acute appendicitis. BMJ. 2017;357:j1703. Epub 2017/04/21. doi: 10.1136/bmj.j1703. PubMed PMID: 28424152. 2. Rafiq MS, Khan MM, Khan A, Ahmad B. 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Evaluation of the predictive power of laboratory markers in the diagnosis of acute appendicitis in the elderly. North Clin Istanb. 2019;6(3):293-301. Epub 2019/10/28. doi: 10.14744/nci.2019.93457. PubMed PMID: 31650118; PubMed Central PMCID: PMCPMC6790928. 27. Cetinkaya E, Erdogan A, Akgul O, Celik C, Tez M. High serum cancer antigen 125 level indicates perforation in acute appendicitis. Am J Emerg Med. 2015;33(10):1465-7. Epub 2015/08/04. doi: 10.1016/j.ajem.2015.07.001. PubMed PMID: 26233617. 28. Ahmed N. C-Reactive Protein: An Aid For Diagnosis Of Acute Appendicitis. J Ayub Med Coll Abbottabad. 2017;29(2):250-3. Epub 2017/07/19. PubMed PMID: 28718241. 29. Cy L, Yk L, Ca G. Could C-reactive protein be a potential biomarker of complicated acute appendicitis? Hong Kong Journal of Emergency Medicine. 2014;21(6):354-60. 30. Choudhary SK, Yadav BL, Gupta S, Kumar N, Verma PK. Diagnostic value of C-reactive protein as a predictor of complicated appendicitis like perforated/gangrenous appendicitis. International Surgery Journal. 2019;6(5):1761. 31. Yazar FM, Urfalioglu A, Bakacak M, Boran OF, Bulbuloglu E. Efficacy of the Evaluation of Inflammatory Markers for the Reduction of Negative Appendectomy Rates. Indian J Surg. 2018;80(1):61-7. Epub 2018/03/28. doi: 10.1007/s12262-016-1558-y. PubMed PMID: 29581687; PubMed Central PMCID: PMCPMC5866802. 32. Celik B, Nalcacioglu H, Ozcatal M, Altuner Torun Y. Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department. Ulus Travma Acil Cerrahi Derg. 2019;25(3):222-8. Epub 2019/05/29. doi: 10.5505/tjtes.2018.06709. PubMed PMID: 31135939. 33. Brienza N, Dalfino L, Cinnella G, Diele C, Bruno F, Fiore T. Jaundice in critical illness: promoting factors of a concealed reality. Intensive Care Med. 2006;32(2):267-74. Epub 2006/02/02. doi: 10.1007/s00134-005-0023-3. PubMed PMID: 16450099. 34. Emmanuel A, Murchan P, Wilson I, Balfe P. The value of hyperbilirubinaemia in the diagnosis of acute appendicitis. Ann R Coll Surg Engl. 2011;93(3):213-7. Epub 2011/04/12. doi: 10.1308/147870811X566402. PubMed PMID: 21477433; PubMed Central PMCID: PMCPMC3291137. 35. Hong YR, Chung CW, Kim JW, Kwon CI, Ahn DH, Kwon SW, et al. Hyperbilirubinemia is a significant indicator for the severity of acute appendicitis. J Korean Soc Coloproctol. 2012;28(5):247-52. Epub 2012/11/28. doi: 10.3393/jksc.2012.28.5.247. PubMed PMID: 23185704; PubMed Central PMCID: PMCPMC3499425. 36. Motie MR, Nik MM, Gharaee M. Evaluation of the diagnostic value of serum level of total bilirubin in patients with suspected acute appendicitis. Electron Physician. 2017;9(4):4048-54. Epub 2017/06/14. doi: 10.19082/4048. PubMed PMID: 28607634; PubMed Central PMCID: PMCPMC5459271. 37. Sand M, Bechara FG, Holland-Letz T, Sand D, Mehnert G, Mann B. Diagnostic value of hyperbilirubinemia as a predictive factor for appendiceal perforation in acute appendicitis. Am J Surg. 2009;198(2):193-8. Epub 2009/03/25. doi: 10.1016/j.amjsurg.2008.08.026. PubMed PMID: 19306980. 38. Estrada JJ, Petrosyan M, Barnhart J, Tao M, Sohn H, Towfigh S, et al. Hyperbilirubinemia in appendicitis: a new predictor of perforation. J Gastrointest Surg. 2007;11(6):714-8. Epub 2007/04/17. doi: 10.1007/s11605-007-0156-5. PubMed PMID: 17436050. 39. Panagiotopoulou IG, Parashar D, Lin R, Antonowicz S, Wells AD, Bajwa FM, et al. The diagnostic value of white cell count, C-reactive protein and bilirubin in acute appendicitis and its complications. Ann R Coll Surg Engl. 2013;95(3):215-21. Epub 2013/07/06. doi: 10.1308/003588413X13511609957371. PubMed PMID: 23827295; PubMed Central PMCID: PMCPMC4165248. 40. Beltran MA, Mendez PE, Barrera RE, Contreras MA, Wilson CS, Cortes VJ, et al. Is hyperbilirubinaemia in appendicitis a better predictor of perforation than C-reactive protein? - a prospective study. Indian J Surg. 2009;71(5):265-72. Epub 2009/10/01. doi: 10.1007/s12262-009-0074-8. PubMed PMID: 23133170; PubMed Central PMCID: PMCPMC3452791. 41. Giordano S, Paakkonen M, Salminen P, Gronroos JM. Elevated serum bilirubin in assessing the likelihood of perforation in acute appendicitis: a diagnostic meta-analysis. Int J Surg. 2013;11(9):795-800. Epub 2013/06/05. doi: 10.1016/j.ijsu.2013.05.029. PubMed PMID: 23732757. 42. Senol K, Saylam B, Kocaay F, Tez M. Red cell distribution width as a predictor of mortality in acute pancreatitis. Am J Emerg Med. 2013;31(4):687-9. Epub 2013/02/13. doi: 10.1016/j.ajem.2012.12.015. PubMed PMID: 23399348. 43. Sadaka F, O'Brien J, Prakash S. Red cell distribution width and outcome in patients with septic shock. J Intensive Care Med. 2013;28(5):307-13. Epub 2012/07/20. doi: 10.1177/0885066612452838. PubMed PMID: 22809690. 44. Ku NS, Kim HW, Oh HJ, Kim YC, Kim MH, Song JE, et al. Red blood cell distribution width is an independent predictor of mortality in patients with gram-negative bacteremia. Shock. 2012;38(2):123-7. Epub 2012/06/12. doi: 10.1097/SHK.0b013e31825e2a85. PubMed PMID: 22683729. 45. Harmanci O, Kav T, Sivri B. Red cell distribution width can predict intestinal atrophy in selected patients with celiac disease. J Clin Lab Anal. 2012;26(6):497-502. Epub 2012/11/13. doi: 10.1002/jcla.21553. PubMed PMID: 23143635; PubMed Central PMCID: PMCPMC6807621. 46. Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med. 2009;133(4):628-32. Epub 2009/04/28. doi: 10.1043/1543-2165-133.4.628 10.5858/133.4.628. PubMed PMID: 19391664. 47. Narci H, Turk E, Karagulle E, Togan T, Karabulut K. The role of red cell distribution width in the diagnosis of acute appendicitis: a retrospective case-controlled study. World J Emerg Surg. 2013;8(1):46. Epub 2013/11/13. doi: 10.1186/1749-7922-8-46. PubMed PMID: 24216220; PubMed Central PMCID: PMCPMC3826504. 48. Aktimur R, Cetinkunar S, Yildirim K, Ozdas S, Aktimur SH, Gokakin AK. Mean Platelet Volume is a Significant Biomarker in the Differential Diagnosis of Acute Appendicitis. European Journal of Preventive Cardiology. 2015;19(3):484-9. 49. Tanrikulu CS, Tanrikulu Y, Sabuncuoglu MZ, Karamercan MA, Akkapulu N, Coskun F. Mean platelet volume and red cell distribution width as a diagnostic marker in acute appendicitis. Iran Red Crescent Med J. 2014;16(5):e10211. Epub 2014/07/18. doi: 10.5812/ircmj.10211. PubMed PMID: 25031841; PubMed Central PMCID: PMCPMC4082501. 50. Jung SK, Rhee DY, Lee WJ, Woo SH, Seol SH, Kim DH, et al. Neutrophil-to-lymphocyte count ratio is associated with perforated appendicitis in elderly patients of emergency department. Aging Clin Exp Res. 2017;29(3):529-36. Epub 2016/05/25. doi: 10.1007/s40520-016-0584-8. PubMed PMID: 27216860. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1523689","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":96130412,"identity":"301236b4-aa99-446a-856a-f9fa04550641","order_by":0,"name":"Qian Zhang","email":"","orcid":"","institution":"Beijing Tsinghua Changgung Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Zhang","suffix":""},{"id":96130908,"identity":"3fa69ad0-67ec-4f2e-8e35-9245592e8f92","order_by":1,"name":"Hongwei Zhao","email":"","orcid":"","institution":"Beijing Tsinghua Changgung Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hongwei","middleName":"","lastName":"Zhao","suffix":""},{"id":96131230,"identity":"89a02532-1864-4ec6-9532-764f7a85a4ef","order_by":2,"name":"Fangli Wang","email":"","orcid":"","institution":"Aerospace Center Hospital, School of Clinical Medicine, Peking University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fangli","middleName":"","lastName":"Wang","suffix":""},{"id":96131231,"identity":"0faef212-f49c-4d64-aac9-00d20c0a4c7b","order_by":3,"name":"Wenqiang Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqUlEQVRIiWNgGAWjYDCCA2DShoefvYF4LYxAtWkykj0HSNNy2MbghgOROviONz9/+KPsPA/DDQbGDx9ziNAieeaYYYPEuds8jLMbmCVnbiNCi8GNHMYGw7bbPMwyB9iYeYnWkth2jodNIoEULQfbDvDwEK0F5JeZDeeSeSR4DjYT5xdgiD34+KPMzt7+ePPBDx+J0QIBbCACFD/EAzZSFI+CUTAKRsGIAwBxDjios+uivQAAAABJRU5ErkJggg==","orcid":"","institution":"Aerospace Center Hospital, School of Clinical Medicine, Peking University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Wenqiang","middleName":"","lastName":"Li","suffix":""},{"id":96131291,"identity":"8e7f28fe-8b2e-4237-872f-72d21f98c6d0","order_by":4,"name":"Peng Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIie3PsWoCQRCA4ZGVrRa33WvOVxgQjoDX5UXmMJxNFCEg1ykceEU08VGsrPcYsLqQ1vJ8BLvrjKkV99Kl2K+en5kB8Lx/SOrcWsJ4oYUoa2pid9Izh8TWWUpBIUd4WqfuJITXQVlXTPitoqCW3OIwqNAmKzFFVlFGikEX7/Q4EavZNZFvAcv5kZ7GYKqvnWML766J6nyw2B9JDQHNxJXQ72Gms2SIZiRFm+QFLVWYbLkbAcnnFok5kKWMBkEuRyZZp8r5S/8z53ODl1BrLs9NE4e62DxObqi/jXue53l3/QBg105nL+nN2AAAAABJRU5ErkJggg==","orcid":"","institution":"Beijing Tsinghua Changgung Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2022-04-05 01:09:46","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-1523689/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1523689/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":20085567,"identity":"e7d1feef-5b52-4b22-b7dc-fdc9d97da0d6","added_by":"auto","created_at":"2022-04-07 20:03:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63772,"visible":true,"origin":"","legend":"\u003cp\u003eSee figure for legend.\u003c/p\u003e","description":"","filename":"fig.png","url":"https://assets-eu.researchsquare.com/files/rs-1523689/v1/e10f78defcfc8656ead45a07.png"},{"id":20085568,"identity":"66ca9f53-6d46-45b2-b09a-483c98f9fb6c","added_by":"auto","created_at":"2022-04-07 20:03:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":256505,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1523689/v1/f78cc0e8-5ad2-4254-8310-a0e829d99470.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eDiagnostic Value of Laboratory Parameters for Complicated Appendicitis: A Two-center Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute appendicitis is a common acute abdominal issue. The morbidity is 1.5\u0026ndash;1.9/10\u0026nbsp;million, and that in males is 1.4-fold higher than in females [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Reportedly, the risk of acute appendicitis is 7\u0026ndash;8% in a lifetime. About 17\u0026ndash;30% of patients present appendiceal perforation, and this proportion is much higher in the elderly [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Appendicitis can be divided into uncomplicated and complicated appendicitis according to its pathology. Uncomplicated appendicitis has a mild infection and fewer complications and can be treated with antibiotics. On the other hand, surgery is the primary treatment for complicated appendicitis. Also, early diagnosis and management are crucial to decrease the incidence of complications and the duration of hospitalization.\u003c/p\u003e \u003cp\u003eThe diagnosis of acute appendicitis depends on the clinical features, laboratory parameters, and imaging results. Only 60% of patients present typical symptoms, including shifting right lower abdominal pain, fever, nausea, and vomiting [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The frequently measured laboratory parameters are C-reactive protein (CRP), white blood cell (WBC) count, and neutrophil percentage. However, these tests can only evaluate the presence of abdominal infection and the specificity of the severity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Abdominal ultrasound and computed tomography (CT) scan are used in the diagnosis of appendicitis. According to the literature, the sensitivity and specificity of ultrasound were 86% and 81% due to the influence of the intestinal gas [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although CT has better sensitivity and specificity than ultrasound [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], the high cost and the risk of radiation limits its application. Therefore, evaluation of the type of acute appendicitis based on laboratory tests is essential.\u003c/p\u003e \u003cp\u003eSince the last decade, studies have proved that neutrophil count, neutrophil percentage, neutrophil-to-lymphocyte ratio (NLR), platelet (PLT), mean platelet volume (MPV) and direct bilirubin are valuable parameters in the diagnosis of appendicitis and predicting the complications [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, the case numbers were small and the results varied. This study aimed to evaluate the diagnostic value of CRP, WBC, NLR, PLT, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratios (LMR), erythrocyte distribution width (RDW), MPV, and serum bilirubin levels in the type of acute appendicitis. We also established a standard to guide the management of acute appendicitis.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eMaterials\u003c/p\u003e \u003cp\u003e A total of 1514 cases with acute appendicitis at the Beijing Tsinghua Changgung Hospital Gastrointestinal Department (978, 64.6%) and Aerospace Center Hospital General Surgery Department (536, 35.4%) from January 2016 to September 2021 were reviewed in this retrospective study. All cases underwent laparoscopic appendectomy. The inclusion criteria were as follows: 1)age\u0026thinsp;\u0026ge;\u0026thinsp;14years-old; 2) the pathology proved the diagnosis. The exclusion criteria were as follows: 1) combined with autoimmune diseases; 2) combined with diseases affecting the bilirubin level.\u003c/p\u003e \u003cp\u003eThe blood tests were carried out within 12 h before the operation. The complete blood count and blood chemistry (Flow cytometry, Sison Meikang) were performed by the clinical laboratory department. All the cases underwent laparoscopic appendectomy.\u003c/p\u003e \u003cp\u003eThe appendix pathology was evaluated by the experienced pathologist from the two hospitals. The four categories of pathology results were simple appendicitis, phlegmonous appendicitis, gangrenous appendicitis, and perforated appendicitis. All the cases were divided into uncomplicated appendicitis (simple appendicitis and phlegmonous appendicitis) and complicated appendicitis (gangrenous appendicitis and perforated appendicitis) groups.\u003c/p\u003e \u003cp\u003eData collection\u003c/p\u003e \u003cp\u003eAge, gender, temperature, WCC, CRP, MPV, neutrophil count, neutrophil percentage, lymphocyte count, coefficient of variation of erythrocyte distribution width (RDW-CV), standard deviation of erythrocyte distribution width (RDW-SD), total bilirubin, direct bilirubin, NLR, LMR and PLR were estimated and recorded.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll parameters were analyzed by SPSS 25.0 (SPSS, Chicago, IL, USA). Continuous variables of normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) and compared using the t-test. Continuous variables with abnormal distribution were expressed as median and compared using the Kruskal\u0026ndash;Wallis H test. The enumeration data were expressed as case numbers and percentages and compared using the chi-square test. Logistic regression analysis was performed as multivariate analysis on parameters with significant differences observed in univariate analysis. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. The appropriate cutoff values were identified, and sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated for parameters with an area under the curve (AUC)\u0026thinsp;\u0026gt;\u0026thinsp;0.600. All the tests were two-sided. p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe cohort comprised 780 (51.5%) males and 734 (48.5%) females, aged 36\u0026plusmn;15.135 (range: 14\u0026ndash;88)-years-old.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMoreover, 1172 (77.4%) cases constituted the uncomplicated appendicitis group, while the other 342 (22.6%) cases were in the complicated appendicitis group. Age (p0.001), temperature (p\u0026lt;0.001), WCC (p\u0026lt;0.001), CRP (p\u0026lt;0.001), neutrophil percentage (p\u0026lt;0.001), neutrophil (p\u0026lt;0.001), NLR (p\u0026lt;0.001), PLR (p\u0026lt;0.001), PLT (p\u0026lt;0.001), RDW-CV (p\u0026lt;0.001), RDW-SD (p\u0026lt;0.001), MPV (p\u0026lt;0.001), total bilirubin (p\u0026lt;0.001), and direct bilirubin (p\u0026lt;0.001) showed significant difference between groups after univariate analysis (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eTable 1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Univariate analysis between groups\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 4.5e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border-color: windowtext currentcolor;border-style: solid none;border-width: 2.25pt medium;padding: 0in 5.4pt;height: 0.2in;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style=\"line-height:107%;font-family:SimSun;color:black;\"\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border-color: windowtext currentcolor;border-style: solid none;border-width: 2.25pt medium;padding: 0in 5.4pt;height: 0.2in;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003eGroup A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-color: windowtext currentcolor;border-style: solid none;border-width: 2.25pt medium;padding: 0in 5.4pt;height: 0.2in;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003eGroup B\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-color: windowtext currentcolor;border-style: solid none;border-width: 2.25pt medium;padding: 0in 5.4pt;height: 0.2in;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003ep\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 0.2in;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003eNumber of cases\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 0.2in;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e1172\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 0.2in;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e342\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 0.2in;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003eAge (years)\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u0026dagger;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e35 (14\u0026ndash;81)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e41 (16\u0026ndash;88)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003eGender (n)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.868\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e606 (51.7%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e174 (50.9%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e566 (48.3%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e168 (49.1%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTemperature (\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e℃)\u003c/span\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026Dagger;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e37.0\u0026plusmn;0.7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e37.5\u0026plusmn;0.93\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003eWCC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='line-height:107%;font-family: \"Times New Roman\",serif;color:#333333;'\u003e\u0026Dagger;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e13.0\u0026plusmn;3.92\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e14.24\u0026plusmn;3.98\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003eCRP (mg/L)\u0026nbsp;\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026Dagger;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e10.18\u0026plusmn;50.8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e43.29\u0026plusmn;74.41\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003eNeutrophil granulocyte (%) \u0026Dagger;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e84.4\u0026plusmn;9.4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp 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style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003eMPV (fl)\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026Dagger;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e10.3\u0026plusmn;14.28\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e10.1\u0026plusmn;11.8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003eBilirubin (\u003c/span\u003e\u003cspan style=\"line-height:107%;font-family:Symbol;color:#333333;\"\u003em\u003c/span\u003e\u003cspan style='line-height: 107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003emol/l)\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003e\u0026Dagger;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e14.6\u0026plusmn;8.78\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e17.95\u0026plusmn;10.78\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: medium none;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170.1pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003eDirect Bilirubin (\u003c/span\u003e\u003cspan style=\"line-height:107%;font-family:Symbol;color:#333333;\"\u003em\u003c/span\u003e\u003cspan style='line-height: 107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003emol/l)\u003c/span\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003e\u0026Dagger;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106.3pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e4.24\u0026plusmn;2.6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 15.6pt;vertical-align: bottom;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003e5.8\u0026plusmn;3.8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 15.6pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;text-indent:21.0pt;\"\u003e\u003cspan style='line-height:107%;font-family:\"Times New Roman\",serif;color:#010205;'\u003e0.000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:left;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:11px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026dagger;Median (range); \u0026Dagger;Mean (\u0026plusmn;standard deviation). WCC: white cell count;\u003c/span\u003e\u003cspan style='font-size:11px;line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;'\u003e\u0026nbsp;CRP: C-reactive protein;\u003c/span\u003e\u003cspan style='font-size:11px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:11px;line-height:107%;font-family:\"Times New Roman\",serif;color:black;'\u003eNLR: neutrophil-to-lymphocyte ratios;\u0026nbsp;LMR:\u003c/span\u003e\u003cspan style='font-size:11px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;lymphocyte-to-monocyte ratios; PLR: platelet-to-lymphocyte ratios;\u0026nbsp;PLT: platelet count;\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:11px;line-height:107%;font-family:\"Times New Roman\",serif;color:#333333;background:white;'\u003eRDW: red cell volume distribution width;\u003c/span\u003e\u003cspan style='font-size:11px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;MPV: mean platelet volume.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eLogistic regression suggested CRP (p\u0026lt;0.001), neutrophil (p\u0026lt;0.001), NLR (p=0.019), PLR (p\u0026lt;0.001), platelet (p\u0026lt;0.001), RDW-CV (p=0.045), RDW-SD (p\u0026lt;0.001), MPV (p=0.007), and direct bilirubin (p\u0026lt;0.001) were the independent risk factors associated with complicated appendicitis. Factors with AUC\u0026gt;0.600 after ROC curve analysis were CRP (p\u0026lt;0.001), NLR (p\u0026lt;0.001), RDW-SD (p\u0026lt;0.001), and direct bilirubin (p\u0026lt;0.001) (Figure 1, Table 2). The cutoff value of CRP, NLR, RDW-SD, and direct bilirubin is shown in Table 3.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eTable 2 Logistic regression and ROC curve in factors associated with complicated appendicitis\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 4.3e+2pt;margin-left:-14.2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:120.55pt;border:none;border-top:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:156.05pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eMultivariate analysis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:155.95pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eROC curve Analysis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:120.55pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.5pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eOR\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e95% CI\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:49.75pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ep\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:42.55pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eAUC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.75pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e95% CI\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:49.65pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ep\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120.55pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eCRP (mg/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1.008\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1.005\u0026ndash;1.010\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.75pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.679\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.642\u0026ndash;0.714\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120.55pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eNeutrophil (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp 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style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eMPV (fl)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1.067\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1.018\u0026ndash;1.118\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.75pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.007\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.567\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.535\u0026ndash;0.601\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120.55pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eDirect bilirubin (\u003c/span\u003e\u003cspan style=\"font-size:13px;line-height:200%;font-family: Symbol;\"\u003em\u003c/span\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003emol/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1.128\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1.075\u0026ndash;1.184\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.75pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.657\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.622\u0026ndash;0.690\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-color: currentcolor currentcolor windowtext;border-style: none none solid;border-width: medium medium 2.25pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:200%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:11px;line-height:107%;font-family:\"Times New Roman\",serif;'\u003eOR: odds ratio; AUC: area under the curve; CRP: C-reactive protein; NLR: neutrophil-to-lymphocyte ratios; PLR: platelet-to-lymphocyte ratios; PLT: platelet count; RDW: red cell volume distribution width; MPV: mean platelet volume.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eTable 3 Proposed cut-off values for significant parameters in prediction of acute complicated appendicitis\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 5.0e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:141.75pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style=\"font-size:16px;line-height:150%;\"\u003e \u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.45pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eCutoff value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:62.15pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eSensitivity\u003c/span\u003e\u003c/p\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e(%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:62.8pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eSpecificity\u003c/span\u003e\u003c/p\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e(%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:37.8pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003ePPV\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:37.8pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eNPV\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:39.5pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003epLLR\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:39.5pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003enLLR\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:37.8pt;border-top:solid windowtext 2.25pt;border-left:none;border-bottom:solid windowtext 2.25pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eAUC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:141.75pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eCRP (mg/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp 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style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e0.603\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:141.75pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eRDW-SD (fl)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp 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style=\"width:39.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e1.23\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:39.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e0.53\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:37.8pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:.2in;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e0.605\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:141.75pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eDirect Bilirubin\u0026nbsp;(\u003c/span\u003e\u003cspan style=\"font-size:16px;line-height:150%;font-family:Symbol;\"\u003em\u003c/span\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003emol/L)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.45pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e6.1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:62.15pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e47.66\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:62.8pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e78.16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:37.8pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e38.90\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:37.8pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e83.70\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:39.5pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e2.18\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:39.5pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e0.67\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:37.8pt;border:none;border-bottom:solid windowtext 2.25pt;padding:0in 5.4pt 0in 5.4pt;height:13.8pt;\"\u003e\n \u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:150%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e0.657\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;text-align:justify;line-height:107%;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size: 11px; line-height: 107%; font-family: \"Times New Roman\", serif; color: rgb(0, 0, 0);'\u003ePPV: positive predictive value; NPV: negative predictive value; OR: odds ratio; pLLR: positive likelihood ratio; nLLR: negative likelihood ratio; AUC: area under the curve; CRP: C-reactive protein; NLR: neutrophil-to-lymphocyte ratios; RDW: red cell volume distribution width.\u003c/span\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAcute appendicitis is one of the common acute abdominal issues. The reported morbidity is up to 2%\u0026nbsp;[1, 18]. The diagnosis of appendicitis depends on symptoms, signs, laboratory tests, and imaging results\u0026nbsp;[1, 4, 5]. The primary management for acute appendicitis is surgery, especially for complicated appendicitis\u0026nbsp;[19-22]. Reportedly, the ratio of complicated appendicitis accounts for 18\u0026ndash;34% of acute appendicitis\u0026nbsp;[2]. Recent studies suggested that conservative treatment is the first choice for uncomplicated appendicitis. Therefore, easy access and effective standards should be established to distinguish complicated from uncomplicated appendicitis in order to guide the management selection. Parameters, such as temperature, CRP, WBC, NLR, PLR, MPV, RDW-CV, RDW-SD, and bilirubin, might help diagnose complicated appendicitis; however, the efficacy is varied\u0026nbsp;[7, 14-18, 23-25]. The present study analyzed 1514 cases who underwent a laparoscopic appendectomy at two surgery centers. The results suggested that CRP, neutrophil, NLR, PLR, PLT, RDW-CV, RDW-SD, MPV, and direct bilirubin are the independent risk factors associated with complicated appendicitis.\u003c/p\u003e\n\u003cp\u003eFurthermore, CRP is a serum inflammatory marker and a critical factor associated with complicated appendicitis\u0026nbsp;[2, 14, 17, 26]. It increases rapidly to several-fold of the normal value in the early stage of inflammation (6\u0026ndash;12 h)\u0026nbsp;[27]. Interestingly, WBC count is a sensitive indicator during the first 24 h of acute appendicitis, while CRP was sensitive after the first 24 h\u0026nbsp;[27]. Ahmed et al.\u0026nbsp;[28]\u0026nbsp;reported that the probability of appendix perforation increased significantly when CRP\u0026gt;48 mg/dL.\u0026nbsp;A study including 42 acute appendicitis cases found that the sensitivity and specificity of perforated appendicitis were 71% and 100%, respectively, when CRP was \u0026gt;40.1 mg/dL\u0026nbsp;[29]. Choudhary\u0026nbsp;et al.\u0026nbsp;[30]\u0026nbsp;reported that the sensitivity and specificity of perforated appendicitis were 100% and 54%, respectively, when CRP was \u0026gt;6.15 mg/L. Hence, the appropriate cutoff of CRP is crucial for distinguishing complicated appendicitis. After the analysis of 1514 cases, the present study found that the sensitivity and specificity of complicated appendicitis were 64.24% and 66.09%, respectively, when CRP was \u0026gt;22.95 mg/L. This cutoff was lower than that reported in previous studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNLR can be obtained from complete blood count. It is a routine and cost-effective blood test during the diagnosis of appendicitis. NLR can effectively elucidate the severity of acute appendicitis\u0026nbsp;[16, 23, 24, 31, 32], but the cutoff is yet controversial. Ishizuka et al.\u0026nbsp;[12]\u0026nbsp;reported that an NLR 8.0 is significantly associated with gangrenous appendicitis based on the analysis of 314 cases that underwent appendectomy. Kahramanca et al.\u0026nbsp;[13]\u0026nbsp;analyzed 897 cases and reported an NLR of 5.74 associated with complicated appendicitis. The sensitivity and specificity of the clinical features were 70.8% and 48.5%, respectively. The current study reported an NLR of 5.7 associated with complicated appendicitis, and the sensitivity and specificity were 82.46% and 32.51%. This finding was similar to that of Shimizu et al. and lower than that of Ishizuka et al. The study[12]proposed that the lower the cutoff value of NLR, the higher the sensitivity of NLR. When the cutoff value was 3.5, it reached the highest sensitivity [33], and the specificity increased when NLR was \u0026gt;5.0\u0026nbsp;[18]. Further investigation of a large number of cases is needed to find a reasonable cutoff of NLR.\u003c/p\u003e\n\u003cp\u003eThe serum bilirubin level increases due to liver dysfunction during infection, especially sepsis. Hence, bilirubin was included in the evaluation of patients with complicated appendicitis\u0026nbsp;[33-35]. The sensitivity and specificity of total bilirubin and direct bilirubin in recognizing complicated appendicitis were 48% and 61%, respectively\u0026nbsp;[36]. Sand et al. reported that hyperbilirubinemia had a specificity of 86% for appendiceal perforation or gangrene, while CRP had a specificity of only 35%\u0026nbsp;[37]. Estrada et al. also found that bilirubin levels \u0026gt;1 mg/dL have a three-fold risk of perforated appendicitis\u0026nbsp;[38]. On the contrary, some studies reported no diagnostic value for bilirubin in the prediction of perforated appendicitis\u0026nbsp;[39, 40]. Bilirubin alone is sufficient in identifying patients with acute appendicitis and predicting perforated appendicitis. The significance of bilirubin as a marker is increased when combined with clinical symptoms and other blood markers\u0026nbsp;[39, 41]. In this study, total bilirubin and direct bilirubin levels were significantly elevated in the complicated appendicitis group. Direct bilirubin was found to be the independent risk factor associated with complicated appendicitis with a sensitivity of 47.66% and a specificity of 78.16% when the cutoff was 6.1\u0026nbsp;mmol/L. Although total bilirubin is available, few studies have reported the efficiency of direct bilirubin. However, this result needs to be substantiated with further studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRDW reflects the volume heterogeneity of red blood cells. At present, it is mainly used for the differential diagnosis of anemia. Recent studies reported that the RDW level is altered in some inflammatory and infectious diseases, such as inflammatory bowel disease, celiac disease, acute pancreatitis, rheumatoid arthritis, bacteremia, sepsis, and septic shock\u0026nbsp;[42-45]. Previous studies reported a strong correlation between RDW and inflammatory markers, such as CRP, erythrocyte sedimentation rate, and interleukin 6\u0026nbsp;[42, 46]. The inflammatory mediators affect the survival of red blood cells in the circulation by suppressing erythrocyte maturation. Thus, newer, larger reticulocytes enter the peripheral circulation and increase the RDW\u0026nbsp;[46]. Narci et al.\u0026nbsp;[47]\u0026nbsp;reported that RDW decreases significantly among patients with acute appendicitis compared to healthy individuals. Conversely, Aktimur et al.\u0026nbsp;[48]\u0026nbsp;and Tanrikulu\u0026nbsp;et al.\u0026nbsp;[49]\u0026nbsp;did not identify any diagnostic value of RDW in acute appendicitis. Jung\u0026nbsp;et al.\u0026nbsp;[50]\u0026nbsp;showed that the RDW level was significantly higher in the complicated appendicitis group compared to the uncomplicated appendicitis group. On the other hand, the parameter did not differ significantly between the appendicitis patients and healthy individuals. Thus, our results indicated that RDW-CV and RDW-SD levels are the independent risk factors associated with complicated appendicitis. RDW-SD had a sensitivity of 82.16% and a specificity of 33.45% for complicated appendicitis when the cutoff was 17.7fl. Therefore, RDW could be used as a parameter to identify complicated appendicitis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough this was a multicenter study including a large number of cases, it was a retrospective analysis and could not avoid bias. Thus, a randomized controlled trial should be performed for further investigation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, no simple or perfect test is yet available for recognizing complicated appendicitis. According to the current results, CRP\u0026thinsp;\u0026gt;\u0026thinsp;22.95mg/L, NLR\u0026thinsp;\u0026gt;\u0026thinsp;5.7, RDW-SD\u0026thinsp;\u0026gt;\u0026thinsp;17.7fl, and direct bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;6.1 mmol/L are valuable indicators for the recognition of acute complicated appendicitis, and surgery should be recommended as the primary treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge no competing interests and are solely responsible for the content of the present article. Ethics approval was not required due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003eConflict of interest: None declared.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Baird DLH, Simillis C, Kontovounisios C, Rasheed S, Tekkis PP. Acute appendicitis. BMJ. 2017;357:j1703. Epub 2017/04/21. doi: 10.1136/bmj.j1703. PubMed PMID: 28424152.\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Rafiq MS, Khan MM, Khan A, Ahmad B. Total leukocyte and neutrophil count as preventive tools in reducing negative appendectomies. Ulus Travma Acil Cerrahi Derg. 2015;21(2):102-6. Epub 2015/04/24. doi: 10.5505/tjtes.2015.29626. PubMed PMID: 25904270.\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Unal Y. A new and early marker in the diagnosis of acute complicated appendicitis: immature granulocytes. 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PubMed PMID: 27216860.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Beijing Tsinghua Changgung Hospital","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"complicated appendicitis, bilirubin, mean platelet volume, neutrophil-to-lymphocyte ratio, platelet count","lastPublishedDoi":"10.21203/rs.3.rs-1523689/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1523689/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003eThe present study aimed to examine the efficacy of the laboratory parameters with respect to complicated appendicitis.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003e A total of 1514 cases with acute appendicitis at the Beijing Tsinghua Changgung Hospital and Aerospace Center Hospital from January 2016 to September 2021 were reviewed in this retrospective study. All cases were divided into uncomplicated and complicated appendicitis groups according to the appendix pathology. The efficacy of the laboratory parameters was evaluated in recognition of complicated appendicitis. Independent variables were analyzed by univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis was used to identify the significant parameters in multivariate analysis. Cutoff values, sensitivity, specificity, and accuracy with the area under the curve (AUC)\u0026thinsp;\u0026gt;\u0026thinsp;0.600 were considered significant parameters.\u0026rdquo;\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eSignificant difference were detected in age (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), temperature (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), white blood cell count (WBC, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), C-reactive protein (CRP, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), neutrophil (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), neutrophil-to-lymphocyte ratio (NLR, p\u0026thinsp;=\u0026thinsp;0.019), platelet-to-lymphocyte ratio (PLR, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), platelet count (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), coefficient of variation of erythrocyte distribution width (RDW-CV, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), standard deviation of erythrocyte distribution width (RDW-SD, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), mean platelet volume (MPV, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), T-bilirubin (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and direct bilirubin (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) between the two groups. CRP, neutrophil, NLR, PLR, platelet count, RDW-CV, RDW-SD, MPV, and direct bilirubin were independent variables for diagnosing complicated appendicitis.\u003c/p\u003e\u003ch2\u003eCONCLUSIONS\u003c/h2\u003e \u003cp\u003eIn patients with acute appendicitis, CRP\u0026thinsp;\u0026gt;\u0026thinsp;22.95 mg/L, NLR\u0026thinsp;\u0026gt;\u0026thinsp;5.7, serum D-bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;6.1 mmol/L, or RDW-SD\u0026thinsp;\u0026gt;\u0026thinsp;17.7 fl are significantly associated with the presence of complicated appendicitis.\u003c/p\u003e","manuscriptTitle":"Diagnostic Value of Laboratory Parameters for Complicated Appendicitis: A Two-center Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-07 20:03:10","doi":"10.21203/rs.3.rs-1523689/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"11de36bc-5d3a-4ec4-8a75-440be59d26a8","owner":[],"postedDate":"April 7th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":11609288,"name":"General Surgery"}],"tags":[],"updatedAt":"2022-04-07T20:03:10+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-07 20:03:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1523689","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1523689","identity":"rs-1523689","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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