The use of the ratio of C-reactive protein to albumin for the diagnosis of complicated appendicitis in children

a b s t r a c t

Purpose: No reliably specific marker for complicated appendicitis has been identified. The ratio of serum C- reactive protein (CRP) to albumin (ALB) (CRP/ALB ratio) is a new inflammation-based prognostic score that is as- sociated with the severity of inflammation. The aim of this study was to evaluate the predictive value of CRP/ALB ratio for the diagnosis of complicated appendicitis in children.

Methods: A retrospective study of 296 children with acute appendicitis was conducted with assessments of de- mographic data, clinical symptoms, pre-operative laboratory results, abdominal ultrasound examinations and clinical outcomes. According to the postoperative pathological results, patients were divided into a simple appen- dicitis group (169 patients) and a complicated appendicitis group (127 patients). SPSS version 22.0 was used to analyse the data.

Results: Of the 296 patients, CRP/ALB ratio was higher in complicated appendicitis than in simple appendicitis (P < 0.05). Logistic regression analysis showed that higher levels of white blood cell count , CRP, CRP/ ALB ratio, and increased incidence in submucosal layer loss and appendicolith were independent risk factors for complicated appendicitis in children. receiver operating characteristic curve analysis showed that the area under the curve of the CRP/ALB ratio (0.883) was larger than that of WBC (0.702), CRP (0.802), ALB (0.835), sub- mucosal layer loss (0.633) and appendicolith (0.673). A CRP/ALB ratio >= 1.39 was found to be a significant marker in the prediction of complicated appendicitis, with 86.61% sensitivity and 84.62% specificity. Patients with a CRP/ ALB ratio >= 1.39 had a 31.263 times higher chance of having complicated appendicitis (95% CI: 16.449-59.418) than those with a CRP/ALB ratio < 1.39.

Conclusion: The admission CRP/ALB ratio was significantly higher in children with complicated appendicitis. The CRP/ALB ratio is a novel but promising haematological marker that aids in the differentiation of acute compli- cated and simple appendicitis.

(C) 2021

  1. Introduction

Acute appendicitis is the most common surgical disease in chil- dren, and its incidence is reported to be increasing [1]. The diagnosis of acute appendicitis has a classic clinical appearance in only one-third of all patients. Clinical appearance in Younger children is often atypical, and misdiagnosis in this age group is not rare, which can lead to an

Abbreviations: AA, Acute appendicitis; CRP, C-reactive protein; ALB, Albumin; WBC, White blood cell countW; SD, Symptom duration; AUC, rea under the curveA.

? CRP/ALB ratio diagnoses complicated appendicitis.

* Corresponding author at: 136 Zhongshan 2nd Road, Yuzhong District, Chongqing, China.

E-mail address: [email protected] (Y. Wang).

increased rate of perforation [2]. Clinical presentation, Pediatric Appen- dicitis Score (PAS), Alvarado score, computed tomography, ultra- sound and blood tests may be helpful in the diagnosis of AA, but it is difficult to confirm the type of appendicitis (simple or complicated ap- pendicitis) [3-5]. Being able to diagnose simple vs. complicated appen- dicitis allows the surgeon to choose the best surgical approach, ranging from antibiotics and delayed appendectomy to laparotomy [6]. Perforated appendicitis after surgery requires antibiotic monother- apy or Combination therapy [7]. The determination of the optimum al- gorithm for Diagnostic procedures in complicated AA may reduce not only the number of unnecessary operations but also the frequency of complications and may contribute significantly to reducing the cost of treating patients with acute abdominal conditions. There are tools to de- termine the severity of AA (abdominal magnetic resonance imaging and

0735-6757/(C) 2021

computed tomography) [8]; nevertheless, these tools may be limited in some centres, e.g., owing to technicians who cannot give a final report or a lack of personnel to carry them out. Furthermore, they were associ- ated with either radiation exposure or injection of a contrast medium. Consequently, simple and effective methods, including serological indi- cator and Sonographic findings, to estimate complicated appendicitis are currently of interest.

Serum C-reactive protein (CRP) is a positive acute phase reactant synthesized by the liver, and its level in the blood increases within hours in response to inflammation and infection [9]. Albumin (ALB) is a negative acute phase reactant synthesized by the liver, and its level in the blood decreases during inflammation, which is associated with inflammation severity, Disease prognosis and mortality [10]. The ratio of CRP to ALB (CRP/ALB ratio) is a new inflammation-based prognostic score that is correlated with inflammation severity [11]. In recent years, many studies have shown that the CRP/ALB ratio can indicate the degree of inflammation and prognosis in neonatal septicaemia, in- flammatory bowel disease and pancreatitis [9,12]. Moreover, the CRP/ ALB ratio is used as a prognostic factor for many malignancies, such as Hepatocellular carcinoma and nasopharyngeal carcinoma [13,14].

However, there is no study available that investigates the relation- ship of this marker with complicated appendicitis. The present study in- vestigated the predictive significance of the CRP/ALB ratio for the diagnosis of complicated appendicitis in children.

  1. Methods
    1. Study population

This is a single institution, retrospective study. All procedures per- formed in this study involving human participants were in accordance with the relevant guidelines and regulations approved by the Institu- tional Research Ethics Board of Children’s Hospital of Chongqing Medi- cal University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Additionally, the Institu- tional Research Ethics Board of Children’s Hospital of Chongqing Medi- cal University waived the requirement for informed consent.

We reviewed the files of AA patients in the General & Neonatal Sur- gery Department of Chongqing Children’s Hospital (a tertiary hospital and National Children’s Medical Center in China) from July 2018 to Sep- tember 2019. In the process of data collection, we found that the nega- tive appendicectomy rate in our hospital was 1.35% (4/296). The cases of a total of 338 patients were retrieved initially, all of which were con- firmed to be AA by intraoperative findings and postoperative patholog- ical results. Patients were excluded from this study who had received antibiotics or other anti-inflammatory drugs before admission, because these interventions can alter laboratory data and body temperature (BT), and can modify the pathological features of appendicitis. Patients with inflammatory diseases (such as pneumonia and cholecystitis), chronic wasting diseases (such as tuberculosis, malnutrition and tu- mours), treated nonoperatively with antibiotics and drainage proce- dures because of the formation of a well-defined abscess, and those who had acute onset of chronic appendicitis were excluded from the study. For cases with abscess and masses, the therapy we always chose was abscess drainage or (and) antibiotics, not immediate appen- dectomy. The reference value for guiding clinical treatment was limited (conservative treatment or appendectomy), so these patients were not included in this retrospective study. The definition of acute onset of chronic appendicitis has been controversial in decades past, we thought it could be defined as chronic Inflammatory changes or fibrosis of the appendix on Histologic findings that presents clinically as prolonged or intermittent abdominal pain longer than 3 weeks before emergency de- partment visit [15,16]. Thus, 42 patients were excluded, and 296 sub- jects were enrolled for the following study.

    1. Study design

The characteristics of subjects, including (1) demographic data: age, gender, body mass index (BMI); (2) clinical features: physical examina- tions (BT and right lower quadrant tenderness), symptom duration (SD), postoperative pathological results, operative technique (laparo- scopic or open appendectomy); (3) outcomes: duration of surgery, postoperative antibiotic duration, length of hospital stay , postop- erative Intra-abdominal abscess and Wound infection were extracted from inpatient medical records. Furthermore, Abdominal ultrasound ex- aminations were performed by experienced sonographers for patients to aid diagnosis, and the reports mainly included the following: loss of the normally echogenic submucosal layer, periappendiceal fat inflam- mation, free abdominal fluid and appendicolith.

The white blood cell count , Neutrophil count (NEUT), per- centage of neutrophils (PN), lymphocyte count (LYMPH), CRP, platelet count , procalcitonin , mononuclear cell count (MC) and ALB data tested on admission (within 1 h) in venous blood samples were collected. Serum ALB is associated with inflammation severity, nu- tritional status, and postoperative recovery, so children with AA in our unit undergo testing of ALB to understand the condition. Accepted stan- dard normal ranges for this study of serum ALB were like the following: 37.0-52.0 (g/L).

    1. Definitions

The children were divided into a complicated appendicitis group (127 patients) and a simple appendicitis group (169 patients) according to the pathological results. Histopathologically, catarrhal appendicitis was defined as the apparent enlargement of lymphoid follicles in the appendix mucosa, and cellulitis appendicitis was defined as neutrophil infiltration into all layers. Gangrenous appendicitis was defined as neu- trophil infiltration and muscle layer necrosis, and perforated appendici- tis was defined as necrosis and perforation in all layers. Of these patients, 76 had catarrhal appendicitis, 93 had cellulitis appendicitis, 82 had gangrenous appendicitis, and 45 had perforated appendicitis. The patients with pathology report of catarrhal appendicitis and celluli- tis appendicitis matched the simple appendicitis group. Complicated appendicitis was defined as a pathologically proven gangrenous or per- forated appendix [17].

    1. Statistical analysis

Excel software was used for data entry, and Statistical Package for Social Sciences (SPSS) software was used for statistical assessments. The normal distribution of the data was evaluated with the Shapiro- Wilk test. Values with normal distribution are presented as the mean +- the standard deviation (mean +- SD), and values without normal distri- bution are presented as medians and interquartile ranges. Categorical variables are presented as numbers and percentages. numerical values in the simple appendicitis group and the complicated appendicitis group were compared using Student’s t-test and the Mann-Whitney U test. The chi-squared test was used to compare categorical data.

Univariable analysis was utilized to determine the effects of poten- tial factors on complicated appendicitis. Significant factors were in- cluded in the stepwise multivariate logistic regression model, and independent predictors were identified. The diagnostic discrimination of independent predictors in complicated appendicitis was examined with ROC curve analysis and the area under the curve (AUC). The Youden index method was used to find the best cut-off point of the CRP/ALB ratio for the diagnosis of complicated appendicitis. In statistical analysis, a P < 0.05 with 95% confidence interval (95% CI) and 5% margin of error was considered statistically significant.

  1. Results
    1. Patient characteristics

We included 296 patients in our study (Fig. 1): 142 females (48.0%) and 154 males (52.0%). So, male:female ratio was 1.1: 1. Overall occur- rence of complicated appendicitis was 42.9% (127 out of them 68 were males and 59 females) and 68.2% (169 out of them 86 were males and 83 were females) subjects had simple appendicitis. The mean age of all 296 subjects was 8.10 +- 3.14 years (range 0.5-15.6 years). The mean age for males was 8.15 +- 3.21 years (range 0.6-15.6 years) and the mean age for females was 8.03 +- 3.07 years (range 0.5-14.2 years). Majority (58.8%) of the cases belongs to school age (6-12 years) (Fig. 2). The range of symptom duration before operation was 6 to 117 h, and Majority (45.9%) of the cases occured within 48 h.

    1. CRP/ALB ratio

Correlation analysis was conducted between CRP/ALB ratio and the continuous data collected in this study. It showed that the CRP/ALB ratio had a positive correlation with symptom duration (r = 0.162, P = 0.005), WBC (r = 0.265, P < 0.001), NEUT (r = 0.221, P < 0.001), CRP (r = 0.971, P < 0.001), MC (r = 0.168, P = 0.004) and PCT (r =

0.274, P < 0.001) and a negative correlation with age (r = -0.214,

P < 0.001) and ALB (r = -0.371, P < 0.001) levels.

    1. Independent risk factors

Significantly influenced factors were included in the backward step- wise regression analysis (Tables 1-2). In the univariate analysis, the fac- tors of age, SD, BT, ALB, WBC, NEUT, PN, MC, LYMPH, PCT, CRP, ALB and

CRP/ALB ratio were associated with the type of AA (all P < 0.05). For the results of abdominal ultrasound examinations, patients with compli- cated appendicitis were significantly associated with an increased inci- dence in submucosal layer loss (26.6% versus 53.2%, P < 0.001), periappendiceal fat inflammation (35.5% versus 58.3%, P < 0.001) and appendicolith (11.8% versus 46.5%, P < 0.001). However, they were comparable in terms of gender, BMI, LRQ tenderness, LYMPH, PLT and the presence free abdominal fluid of ultrasound results (Table 2).

Significant influenced factors mentioned above were included in the backward stepwise regression analysis. WBC, CRP, ALB, CRP/ALB ratio, submucosal layer loss and appendicolith were the independent

predictors for complicated appendicitis in children. Higher levels of WBC (OR:1.144, 95% CI:1.057-1.237), CRP (OR:1.048, 95% CI: 1.032-1.065) and CRP/ALB ratio (OR: 6.922, 95% CI: 3.206-14.943)

were independent risk factors for complicated appendicitis, while ALB (OR: 0.625, 95% CI: 0.526-0.742) was a protective factor. In addition, ab- dominal ultrasound findings of submucosal layer loss (OR: 3.603, 95% CI: 1.629-7.972) and appendicolith (OR: 9.626, 95% CI: 3.827-24.211)

were associated with the higher risk of complicated appendicitis. An in- crease in the CRP/ALB ratio of 1 unit resulted in an increase in the risk of complicated appendicitis by 6.922 times.

    1. ROC curve analysis of the CRP/ALB ratio

ROC curve analysis of the CRP/ALB ratio resulted in an AUC of 0.883. When the CRP/ALB ratio was 1.39, the Youden index was the largest (0.71). The AUCs of WBC, CRP, ALB, submucosal layer loss and appendicolith were 0.702, 0.802, 0.835, 0.633 and 0.673, respectively (Fig. 3). The predictive values of the CRP/ALB ratio were 86.61% sensitiv- ity, 84.62% specificity, 80.60% positive predictive value (PPV) and 88.27% negative predictive value (NPV). When the predictive values for complicated appendicitis were evaluated using different variables, sensitivity and specificity corresponding to the best cut-off values were shown in Table 3. The CRP/ALB ratio showed a clearly better pre- dictive performance for the diagnosis of complicated appendicitis than WBC, CRP, ALB, submucosal layer loss and appendicolith.

According to the best cut-off point of the CRP/ALB ratio of 1.39, pa- tients with the CRP/ALB ratio of 1.39 or greater were considered to be more likely to have complicated appendicitis. It was found in 85.04% of patients with complicated appendicitis and in 15.38% of those with simple appendicitis (P < 0.001). Compared with a CRP/ALB ratio < 1.39, patients with CRP/ALB ratio >= 1.39 had a 31.263 times higher chance of having complicated appendicitis (95% CI: 16.449-59.418).

    1. Outcomes based on the type of AA and CRP/ALB ratio

Bivariate analysis was done to compare some outcomes of patients in two groups. The medians duration of surgery and LOS were signifi- cantly higher (duration of surgery: 45 versus 52 [minutes]; LOS: 5 ver- sus 9 [days], P < 0.001 for both) in complicated appendicitis group than in simple appendicitis group. Similarly, there were significant dif- ferences in operative technique (open appendectomy), intraabdominal

Image of Fig. 1

Fig. 1. Flow chart of the study population.

Image of Fig. 2

Fig. 2. Showing age specific cumulative distribution of study population having AA and complicated appendicitis.

abscess and 30-day unplanned rehospitalization in the two groups (P = 0.021, P = 0.006, and P = 0.021, respectively) (Table 4).

Furthermore, according to the best cut-off levele of CRP/ALB ratio, groups comparison showed that CRP/ALB ratio >= 1.39 was significantly associated with an increased incidence in surgical reduction (0.6% ver- sus 5.2%, P = 0.025), intraabdominal abscess (0.6% versus 6.0%, P =

0.013), 30-day unplanned rehospitalization (0.6% versus 6.7%, P =

0.006), longer duration of surgery (45 versus 52 [minutes], P < 0.001) and LOS (6 versus 8 [days], P<0.001). However, there were no differ- ences in the operative technique between the CRP/ALB ratio >= 1.39 and < 1.39 groups.

  1. Discussion

In this retrospective study, we found that WBC, CRP, ALB, CRP/ALB ratio, submucosal layer loss and appendicolith on admission were inde- pendently associated with complicated appendicitis. Regarding predic- tion, the CRP/ALB ratio could identify children at high risk for complicated appendicitis, with a specificity of 84.62%, better than that of other haematological markers, and a high negative predictive value of 88.27%. In addition, the predictive value of the CRP/ALB ratio was bet- ter than that of CRP, which was the best haematological indicator re- ported by previous studies [17-19].

AA remains a clinical diagnosis with laboratory tests and ultrasonog- raphy as auxiliary diagnostic methods. Since AA has a complication rate of approximately 40%, different methods for the prediction of compli- cated appendicitis have been tested with inconsistent results. In this study, we noticed that the ration of complicated appendicitis was higher than reported in the literature. We thought that this difference may be caused by the regional factor, economic level, age composition and sea- sonality, those factors have been reported to affect the severity of ap- pendicitis [20,21]. The increased use of radiological tests and ultrasonography has been shown to aids in differentiating the type of appendicitis, but they had the disadvantages of ionizing radiation, Delay in diagnosis and surgery, and a false-negative rate of approxi- mately 20% (poor sensitivity) in the prediction of complicated appendi- citis [22,23]. Furthermore, pediatric surgeon thought that SD, vital signs (eg. Abdominal distention) and clinical associated symptoms such as di- arrhea and nausea/vomiting may guide probability of perforation and often predicts guidance of antibiotic treatment. Several studies have shown that longer DS of AA, the more likely it was to develop perforated [24,25]. Even though the above variables were discussed in previous

studies as well as in ours, we should notice that the factor is of subjective nature and its reproducibility is low. Additionally, objective variables obtained from blood sample usually better reproducible and therefore of higher value. Thus, we included only those factors available in clinical database that were simple and easy to obtain.

The use of common serum biomarkers, such as PCT, CRP, WBC, fi- brinogen and total bilirubin, is increasing [8]. The majority of studies have focused on the efficacy of the standard serum markers in the diag- nosis of acute appendicitis and concluded that an elevation of CRP, PCT and WBC can support the diagnosis of complicated appendicitis in chil- dren [18]. Caruso [26] et al. found that admission CRP is more accurate than PCT, WBC and PN to aid in the differentiation of acute complicated and simple appendicitis. In a meta-analysis evaluating the diagnostic value of serum markers in 1011 patients with perforated or non- perforated appendicitis, CRP was found to have the best discriminative capability [27]. Similarly, our study showed that CRP was found to have better discriminative capability than PCT and WBC in the diagnosis of appendicitis. However, the differences in CRP between simple and complicated appendicitis were noticeable in children between 5 and 17 years of age but not in those younger than 5 [18]. Cordemans [28] et al. found that in the inflammatory response, due to the role of inflam- matory mediators, increased capillary permeability leads to ALB leak- age. The CRP/ALB ratio has been used in several cohort studies as a surrogate for CRP in assessments of the severity of the inflammatory re- sponse [9,12,29]. In our current clinical practice, CRP increases and ALB decreases in children with AA. After multivariate regression analysis, in- teractions between variables can be balanced and comparable so that non-random grouping data can be used to study the relationship be- tween trial factors and outcomes, and obtain more reliable research re- sults. As an alternative novel indicator of inflammation, the CRP/ALB ratio showed a good correlation with CRP and could have better predic- tive value for complicated appendicitis. Of course, the clinical features should also be taken seriously by pediatric surgeons, personal experi- ence combined with the exam may be more effective in determining the condition.

Perforation in children group often leads to diffuse peritonitis, and

the most important thing in the management is to establish the accurate diagnosis and perform surgical treatment, assisted by broad-spectrum antimicrobial therapy. Recently, several trials have focused on the non-operative treatment of AA [26,30]. Studies have suggested that dif- ferent treatment strategies should be selected according to the type of AA: conservative antibiotic treatment should be the preferred

Table 1

Univariate analysis of each variable on AA type.

Variables Simple

appendicitis (N = 169)

General characteristics

Complicated appendicitis (N = 127)

P value

treatment for simple appendicitis, while complicated appendicitis re- quires appendectomy in most cases [6,17]. A child’s appendix is not a non-functional organ left in the body. The appendix is a “storage pool” for the gut microbiota to balance the steady state of the proinflamma- tory and anti-inflammatory activities of the intestine, and the high con- tent of lymphoid tissue (mainly lymphocyte CD8+ T cells) in the

Age (years, n/%)? <0.001


0 (0.0)

5 (3.9)


2 (1.2)

10 (7.9)


26 (15.4)

29 (22.8)


98 (58.0)

73 (57.5.9)


Gender (n/%)?

41 (24.3)

12 (9.4)


Male 86 (50.9) 68 (53.5)

Female 83 (49.1) 59 (46.5)

BMI (kg/m2)? 15.4 +- 4.2 17.8 +- 5.9 0.181

SD (hours, n/%)? <0.001


99 (58.6)

13 (10.2)


29 (17.2)

45 (35.4)


10 (5.9)

29 (22.8)


31 (18.3)

40 (31.5)

LRQ tenderness (n/%)? 150 (88.8) 117 (92.1) 0.335

BT (?C, n/%)? <0.001


32 (18.9)

16 (12.6)

Fever <38.5

83 (49.1)

39 (30.7)


54 (32.0)

72 (56.7)

17.84 +- 5.89 <0.001

Laboratory results WBC (x109/L)?

14.39 +- 4.23

NEUT (x109/L)#


PN (%)#

0.79 (0.72,0.83)

MC (x109/L)#

0.71 (0.48,0.80)

LYMPH (x109/L)#

1.31 (0.67-1.66)

PLT (x109/L)?

276.4 +- 66.7

PCT (ug/L)#

0.17 (0.09,0.33)

CRP (mg/L)#


ALB (g/L)#

47.4 (46.0,49.3)

CRP/ALB ratio#

1.07 (0.65-1.25)

Ultrasound examinations Submucosal layer loss (n/%)?

45 (26.6)

appendix plays an important role in the immune function of the body [31]. Conservative treatment for simple appendicitis can preserve the appendix, which not only helps maintain intestinal flora homeostasis and immune system development, but also reduces Medical costs. Therefore, antibiotic conservative treatment priority strategies can be adopted to avoid unnecessary appendectomy for patients with a CRP/ ALB ratio < 1.39. If the patient has a high possibility of complicated ap- pendicitis (CRP/ALB ratio >= 1.39), an immediate appendectomy and broad-spectrum antimicrobial therapy may be necessary.

Furthermore, discrimination between simple and complicated ap- pendicitis is important, as it may guide appropriate intravenous fluid re- suscitation and antibiotic administration prior to surgical intervention. The CRP/ALB ratio upon admission could guide preoperative (or postop- erative) antibiotic selection and predict prognosis, with the best cut-off point of the CRP/ALB ratio being 1.39. Although appendicitis protocols vary widely among centres, children with simple appendicitis typically receive a single antibiotic preoperatively, may not even receive postop- erative treatment and may be discharged home relatively soon [18].

Conversely, children with complicated appendicitis recognized on ad-













mission typically receive a combination of more antibiotics, undergo op- erative treatment, and continue antibiotic therapy postoperatively.

In this study, we also analyzed some outcomes between complicated appendicitis and simple appendicitis, and found that there were signif- icant difference in operative technique (open appendectomy), duration of surgery, LOS, wound infection, intraabdominal abscess and 30-day

279.2 +- 60.6 0.082

unplanned rehospitalization. Laparoscopic appendectomy was the pre-













ferred operative technique in our hospital, and open appendectomy would be chosen when the pediatric surgeon judged that laparoscopic surgery was difficult. It showed that the outcome of complicated appen- dicitis may be worse than simple appendicitis. Hence, the identification of predictive indicators for complicated appendicitis is essential. Fur- thermore, the impact of the CRP/ALB ratio on outcomes was investi- gated, CRP/ALB ratio >= 1.39 was significantly associated with an increased incidence in surgical reduction, intraabdominal abscess, 30-

Periappendiceal fat inflammation (n/%)?

67 (53.2) <0.001

60 (35.5) 74 (58.3) <0.001

day unplanned rehospitalization, longer duration of surgery and LOS. So, This haematological marker was valuable for the postoperative

Free abdominal fluid (n/%)? 71 (42.0) 65 (51.2) 0.117

Appendicolith (n/%)? 20 (11.8) 59 (46.5) <0.001

BMI: body Mass Index; SD: symptom duration; LRQ: right lower quadrant; BT: body tem- perature; ALB: albumin; WBC: white blood cell count; NEUT: neutrophile granulocyte count; PN: percentage of neutrophils; MC: mononuclear cell count; LYMPH: lymphocyte count; PLT: platelet count; PCT: procalcitonin; CRP: C-reactive protein.

Bold values indicate that difference between the two groups for this variable was statisti- cally significant (P < 0.05).

# Values are presented as medians (IQR) and used Mann-Whitney U test.

? Chi-square test.

* Values are presented as mean +- SD and used Student’s t-test.

Table 2

Multivariate Logistic regression analysis for the complicated appendicitis.





95% CI

P value

WBC (x109/L)






CRP (mg/L)






ALB (g/L)






CRP/ALB ratio






Submucosal layer loss












?: regression coefficient; SE:standard error; OR:odds ratio; 95% CI: 95% confidence inter- val. WBC: white blood cell count; CRP: C-reactive protein; ALB: albumin.

Bold values indicate that this variable was statistically significant in multivariate Logistic regression analysis (P < 0.05).

prognosis of AA.

It should be borne in mind that this analysis was retrospective and conducted in one hospital with relatively small cohort, further research with a larger prospective cohort study is necessary to validate the use- fulness of the CRP/ALB ratio. Furthermore, the definitions of simple and complicated appendicitis are based on the postoperative patholog- ical results, and nonoperatively were excluded. In addition, there was an inevitable limitation of this study that the assessment of the blood pa- rameters may be influenced by the significant difference of symptom duration.

  1. Conclusion

In conclusion, our study shows that on admission, WBC, CRP, ALB, CRP/ALB ratio, submucosal layer loss and appendicolith may help clini- cians predict the occurrence of complicated appendicitis in children, and the CRP/ALB ratio had better predictive value for complicated ap- pendicitis than other haematological markers. Specifically, patients with a CRP/ALB ratio >= 1.39 had a 31.263 times higher chance of compli- cated appendicitis than patients with a CRP/ALB ratio < 1.39. The CRP/ ALB ratio, as a routine haematological marker, has better universality and simplicity and can be a novel but promising predictor for compli- cated appendicitis in children.

Image of Fig. 3

Fig. 3. Diagnostic assessment of independent predictors of complicated appendicitis with ROC curve analysis. AUC; area under curve; WBC: white blood cell count; CRP: C-reactive protein; ALB: albumin.

Table 3

Predictive values of independent predictors for complicated appendicitis in children.


The best cut-off level

Youden index (largest)

Sensitivity (%)

Specifificity (%)

PPV (%)

NPV (%)

WBC (x109/L)







CRP (mg/L)







ALB (g/L)







CRP/ALB ratio







Submucosal layer loss










PPV: positive predictive value; NPV: negative predictive value; PPV and NPV were calculated for the best cut-off levels. PCT: procalcitonin; CRP: C-reactive protein; MC: mononuclear cell count.

Table 4

Bivariate analysis for outcomes in two groups.


Simple appendicitis

Complicate appendicitis

P value

CRP/ALB ratio >= 1.39

CRP/ALB ratio < 1.39

P value

(N = 169)

(N = 127)

(N = 134)

(N = 162)

Operative technique (open appendectomy, n/%)?

2 (1.2)

8 (6.3)


3 (1.9)

7 (5.2)


Duration of surgery (minutes)#

45 (40,50)

52 (46,59)


45 (45,50)

54 (48,59)


LOS (days)#

5 (5,6)

9 (7,9)


6 (5,6)

8 (7,9)


Wound infection (n/%)?

2 (1.2)

6 (4.7)


1 (0.6)

7 (5.2)


Intraabdominal abscess (n/%)?

1 (0.6)

8 (6.3)


1 (0.6)

8 (6.0)


30-day unplanned rehospitalization (n/%)?

2 (1.2)

8 (6.3)


1 (0.6)

9 (6.7)


LOS: length of hospital stay.

Bold values indicate that difference between the two groups for this variable was statistically significant (P < 0.05).

# Values are presented as medians (IQR) and used Mann-Whitney U test.

? Chi-square test.


This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

Financial support

No funding was secured for this study.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influ- ence the work reported in this paper.


Not applicable.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2021.12.007.


  1. Buckius MT, McGrath B, Monk J, Grim R, Bell T, Ahuja V. Changing epidemiology of acute appendicitis in the United States: study period 1993-2008. J Surg Res. 2012; 175(2):185-90.
  2. Pogorelic Z, Domjanovic J, Jukic M, Pericic TP. Acute appendicitis in children younger than five years of age: diagnostic challenge for pediatric surgeons. published online ahead of print, 2019 Oct 16Surg Infect (Larchmt). 2019. 2019.175.
  3. Salo M, Roth B, Stenstrom P, Arnbjornsson E, Ohlsson B. Urinary biomarkers in pedi- atric appendicitis. Pediatr Surg Int. 2016;32(8):795-804. s00383-016-3918-x.
  4. Pogorelic Z, Buljubasic M, Susnjar T, Jukic M, Pericic TP, Juric I. Comparison of open and laparoscopic appendectomy in children: a 5-year single center experience. Indian Pediatr. 2019;56(4):299-303.
  5. Pogorelic Z, Rak S, Mrklic I, Juric I. Prospective validation of Alvarado score and pe- diatric appendicitis score for the diagnosis of acute appendicitis in children. Pediatr Emerg Care. 2015;31(3):164-8.
  6. Rogers MB, Brower-Sinning R, Firek B, Zhong D, Morowitz MJ. Acute appendicitis in children is associated with a local expansion of Fusobacteria. Clin Infect Dis. 2016;63


  1. Pogorelic Z, Silov N, Jukic M, Elezovic Baloevic S, Poklepovic Pericic T, Jeroncic A. Ertapenem monotherapy versus gentamicin plus metronidazole for perforated ap- pendicitis in pediatric patients. Surg Infect (Larchmt). 2019;20(8):625-30. https://
  2. Alvarez-Alvarez FA, Maciel-Gutierrez VM, Rocha-Munoz AD, Lujan JH, Ploneda- Valencia CF. Diagnostic value of serum fibrinogen as a predictive factor for compli- cated appendicitis (perforated). A cross-sectional study. Int J Surg. 2016;25: 109-13.
  3. Kaplan M, Ates I, Akpinar MY, et al. Predictive value of C-reactive protein/albumin ratio in acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2017;16(4):424-30.
  4. Goh SL, De Silva RP, Dhital K, Gett RM. Is low serum albumin associated with post- operative complications in patients undergoing oesophagectomy for oesophageal malignancies? Interact Cardiovasc Thorac Surg. 2015;20(1):107-13. https://doi. org/10.1093/icvts/ivu324.
  5. Ni XF, Wu J, Ji M, et al. Effect of C-reactive protein/albumin ratio on prognosis in ad- vanced non-small-cell Lung cancer. Asia Pac J Clin Oncol. 2018;14(6):402-9. https://
  6. Qin G, Tu J, Liu L, et al. Serum albumin and C-reactive protein/albumin ratio are use- ful biomarkers of Crohn’s disease activity. Med Sci Monit. 2016;22:4393-400.
  7. Shen Y, Wang H, Li W, Chen J. Prognostic significance of the CRP/Alb and Neutrophil to lymphocyte ratios in hepatocellular carcinoma patients undergoing TACE and RFA. J Clin Lab Anal. 2019.;33(9):e22999.
  8. Yang S, Zhao K, Ding X, Jiang H, Lu H. Prognostic significance of hematological markers for patients with nasopharyngeal carcinoma: a Meta-analysis. J Cancer. 2019;10(11):2568-77.
  9. Kim D, Butterworth SA, Goldman RD. Chronic appendicitis in children. Can Fam Phy- sician. 2016;62(6):e304-5.
  10. Rao PM, Rhea JT, Novelline RA, McCabe CJ. The computed tomography appearance of recurrent and chronic appendicitis. Am J Emerg Med. 1998;16(1):26-33. https://doi. org/10.1016/s0735-6757(98)90060-2.
  11. Gorter RR, Wassenaar ECE, de Boer OJ, et al. Composition of the cellular infiltrate in patients with simple and complex appendicitis. J Surg Res. 2017;214:190-6. https://
  12. Zani A, Teague WJ, Clarke SA, et al. Can common serum biomarkers predict compli- cated appendicitis in children? Pediatr Surg Int. 2017;33(7):799-805. https://doi. org/10.1007/s00383-017-4088-1.
  13. Aydin OU, Soylu L, Dandin O, Uysal Aydin E, Karademir S. Laboratory in complicated appendicitis prediction and predictive value of monitoring. Bratisl Lek Listy. 2016; 117(12):697-701.
  14. Tom CM, Friedlander S, Sakai-Bizmark R, Shekherdimian S, Jen H, DeUgarte DA, et al. Outcomes and costs of pediatric appendectomies at Rural hospitals. J Pediatr Surg. 2019;54(1):103-7.
  15. Ozkurt E. Factors affecting patient outcomes in acute appendicitis in rural areas: an observational cohort study. World J Surg. 2021;45(8):2337-46. 1007/s00268-021-06093-5.
  16. Gonzalez DO, Lawrence AE, Cooper JN, et al. Can ultrasound reliably identify compli- cated appendicitis in children? J Surg Res. 2018;229:76-81. j.jss.2018.03.012.
  17. Ashkenazi I, Zeina AR, Olsha O. Early ultrasound in acute appendicitis avoids CT in most patients but delays surgery and increases complicated appendicitis if nondiag- nostic – a retrospective study. Am J Surg. 2020;219(4):683-9. 1016/j.amjsurg.2019.05.013.
  18. Caruso AM, Pane A, Garau R, et al. Acute appendicitis in children: not only surgical treatment. J Pediatr Surg. 2017;52(3):444-8. 2016.08.007.
  19. Yu CW, Juan LI, Wu MH, Shen CJ, Wu JY, Lee CC. Systematic review and meta- analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis. Br J Surg. 2013;100(3):322-9.
  20. Cameron DB, Williams R, Geng Y, et al. Time to appendectomy for acute appendici- tis: a systematic review. J Pediatr Surg. 2018;53(3):396-405. 1016/j.jpedsurg.2017.11.042.
  21. Bonadio W. Time to appendectomy and risk of complicated appendicitis and adverse outcomes in children. JAMA Pediatr. 2018;172(1):94. jamapediatrics.2017.4095.
  22. Cordemans C, De Laet I, Van Regenmortel N, et al. fluid management in critically ill patients: the role of extravascular lung water, abdominal hypertension, capillary leak, and fluid balance. Ann Intensive Care. 2012;2(Suppl. 1):S1. 1186/2110-5820-2-S1-S1 Diagnosis and management of intra-abdominal hyperten.
  23. Kayabasi S, Hizli O, Cayir S. A novel predictor parameter for active recurrent Aphthous stomatitis: C-reactive protein to albumin ratio. Cureus. 2019.;11(10): e5965.
  24. Svensson JF, Patkova B, Almstrom M, et al. nonoperative treatment with antibiotics versus surgery for acute nonperforated appendicitis in children: a pilot randomized controlled trial. Ann Surg. 2015;261(1):67-71. 0000000000000835.
  25. Vitetta L, Chen J, Clarke S. The vermiform appendix: an immunological organ sus- taining a microbiome inoculum. Clin Sci (Lond). 2019;133(1):1-8. 10.1042/CS20180956.