Skip to main content
Top
Published in: Pediatric Surgery International 1/2023

01-12-2023 | Appendicitis | Commentary

The role of IL-6, thiol–disulfide homeostasis, and inflammatory biomarkers in the prediction of acute appendicitis in children: a controlled study

Authors: Ceyhan Şahin, Eray Metin Güler, H. Nihan Karaman Ayyıldız, Zeliha Akış Yıldız, Mehmet Arpacık, Zekeriya İlçe

Published in: Pediatric Surgery International | Issue 1/2023

Login to get access

Abstract

Purpose

This study aimed to examine the diagnostic value of IL-6, thiol–disulfide homeostasis, complete blood count and inflammatory biomarkers in the prediction of acute appendicitis in children.

Methods

The study was designed as a prospective and controlled study in children—the study was conducted at a tertiary referential university hospital between May 2020 and April 2021. Patients were divided between study groups and one control group (CG): 1: confirmed acute appendicitis group (AAP); 2: perforated appendicitis group (PAP); and 3: non-specified abdominal pain (NAP). The age and gender of the patients were determined. The following listed laboratory parameters were compared between groups: TOS: total oxidative status, TAS: total antioxidant status, OSI: oxidative stress index, TT: total thiol, NT (µmol/L): native thiol, DIS: disulfide, IL-6: interleukin 6, TNF-a: tumor necrosis factor-alpha, WBC: white blood cell, NEU: neutrophil, NEU%: neutrophil percentage, LY: lymphocyte, LY%: lymphocyte percentage, PLT: platelet, MPV: mean platelet volume NLR: neutrophil lymphocyte ratio, CRP: C-reactive protein, LCR: lymphocyte CRP ratio, and serum lactate.

Results

The TOS level of the PAP group was found to be significantly higher than that in the AAP, NAP and control groups (p = 0.006, < 0.001 and p < 0.001). TAS, TT, and NT levels in the PAP group were significantly lower than those in the AAP, NAP and control groups. OSI was significantly higher in the PAP group than in the other groups. The TT and NT levels of the NAP group were both similar to those of the control group. Serum DIS level was similar between the AAP and PAP groups, AAP and NAP groups, and NAP and control groups. Serum IL-6 and TNF-α levels were found to be significantly higher in the PAP group compared to those in all groups. The WBC, NEU, and NEU% values were found to be significantly higher in the PAP group than those in the NAP and control groups, while LY and LY% values were found to be significantly lower. PAP and AAP groups were found to be similar in terms of WBC, NEU, LYM, NEU%, and LYM% values. PLT and MPV values and serum lactate values did not show a significant difference between the groups. NLR was similar in the AAP and PAP groups. A significant increase in CRP versus a decrease in LCR was detected in the PAP group compared to that in the AAP group. Multivariate analysis demonstrated that only IL-6 has significant estimated accuracy rates as 80% for the control group, 78.8% for AAP, 96.9% for PAP, and 81.6% for NAP.

Conclusion

Rather than AAP, PAP caused significantly higher oxidative stress (increased TOS and OSI), and lower antioxidation capacity (decreased TT and NT). IL-6 levels can provide a significant stratification. Nevertheless, simply detecting WBC or CRP is not enough to distinguish the specific pathology in acute appendicitis and related conditions.
Literature
1.
go back to reference Becker C, Kharbanda A (2019) Acute appendicitis in pediatric patients: an evidence-based review. Pediatr Emerg Med Pract 16(9):1–20PubMed Becker C, Kharbanda A (2019) Acute appendicitis in pediatric patients: an evidence-based review. Pediatr Emerg Med Pract 16(9):1–20PubMed
2.
go back to reference Aydin E, Türkmen İU, Namli G, Öztürk Ç, Esen AB, Eray YN et al (2020) A novel and simple machine learning algorithm for preoperative diagnosis of acute appendicitis in children. Pediatr Surg Int 36(6):735–742CrossRefPubMed Aydin E, Türkmen İU, Namli G, Öztürk Ç, Esen AB, Eray YN et al (2020) A novel and simple machine learning algorithm for preoperative diagnosis of acute appendicitis in children. Pediatr Surg Int 36(6):735–742CrossRefPubMed
4.
go back to reference Hodge SVL, Mickiewicz B, Lau M, Jenne CN, Thompson GC (2021) Novel molecular biomarkers and diagnosis of acute appendicitis in children. Biomark Med 15(12):1055–1065CrossRefPubMed Hodge SVL, Mickiewicz B, Lau M, Jenne CN, Thompson GC (2021) Novel molecular biomarkers and diagnosis of acute appendicitis in children. Biomark Med 15(12):1055–1065CrossRefPubMed
5.
go back to reference Guaitoli E, Gallo G, Cardone E, Conti L, Famularo S, Formisano G et al (2021) Consensus statement of the Italian Polispecialistic Society of Young Surgeons (SPIGC): diagnosis and treatment of acute appendicitis. J Investig Surg 34(10):1089–1103CrossRef Guaitoli E, Gallo G, Cardone E, Conti L, Famularo S, Formisano G et al (2021) Consensus statement of the Italian Polispecialistic Society of Young Surgeons (SPIGC): diagnosis and treatment of acute appendicitis. J Investig Surg 34(10):1089–1103CrossRef
6.
go back to reference Malia L, Sturm JJ, Smith SR, Timothy Brown R, Campbell B, Chicaiza H (2021) Predictors for acute appendicitis in children. Pediatr Emerg Care 37(12):E962–E968CrossRefPubMed Malia L, Sturm JJ, Smith SR, Timothy Brown R, Campbell B, Chicaiza H (2021) Predictors for acute appendicitis in children. Pediatr Emerg Care 37(12):E962–E968CrossRefPubMed
7.
go back to reference Sevinç MM, Kınacı E, Çakar E, Bayrak S, Özakay A, Aren A et al (2016) Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis: an analysis of 3392 cases. Ulus Travma Acil Cerrahi Derg 22(2):155–162PubMed Sevinç MM, Kınacı E, Çakar E, Bayrak S, Özakay A, Aren A et al (2016) Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis: an analysis of 3392 cases. Ulus Travma Acil Cerrahi Derg 22(2):155–162PubMed
8.
go back to reference Başkıran A, İnce V, Çiçek E, Şahin T, Dirican A, Balıkçı Çiçek İ, Işık B, Yılmaz S (2018) Efficacy of laboratory tests and ultrasonography in the diagnosis of acute appendicitis in gravid patients according to the stages of pregnancy. Ulus Travma Acil Cerrahi Derg 24(4):333–336PubMed Başkıran A, İnce V, Çiçek E, Şahin T, Dirican A, Balıkçı Çiçek İ, Işık B, Yılmaz S (2018) Efficacy of laboratory tests and ultrasonography in the diagnosis of acute appendicitis in gravid patients according to the stages of pregnancy. Ulus Travma Acil Cerrahi Derg 24(4):333–336PubMed
9.
go back to reference Peeters T, Martens S, D’Onofrio V, Stappers MHT, van der Hilst JCH, Houben B et al (2020) An observational study of innate immune responses in patients with acute appendicitis. Sci Rep 10(1):1–15CrossRef Peeters T, Martens S, D’Onofrio V, Stappers MHT, van der Hilst JCH, Houben B et al (2020) An observational study of innate immune responses in patients with acute appendicitis. Sci Rep 10(1):1–15CrossRef
10.
go back to reference Kharbanda AB, Cosme Y, Liu K, Spitalnik SL, Dayan PS (2011) Discriminative accuracy of novel and traditional biomarkers in children with suspected appendicitis adjusted for duration of abdominal pain. Acad Emerg Med 18(6):567–574CrossRefPubMedPubMedCentral Kharbanda AB, Cosme Y, Liu K, Spitalnik SL, Dayan PS (2011) Discriminative accuracy of novel and traditional biomarkers in children with suspected appendicitis adjusted for duration of abdominal pain. Acad Emerg Med 18(6):567–574CrossRefPubMedPubMedCentral
11.
go back to reference Filiz AI, Aladag H, Akin ML, Sucullu I, Kurt Y, Yucel E et al (2010) The role of D-lactate in differential diagnosis of acute appendicitis. J Investig Surg 23(4):218–223CrossRef Filiz AI, Aladag H, Akin ML, Sucullu I, Kurt Y, Yucel E et al (2010) The role of D-lactate in differential diagnosis of acute appendicitis. J Investig Surg 23(4):218–223CrossRef
12.
go back to reference Birben B, Akkurt G, Akın T, Surel AA, Tez M (2021) Efficacy of bilirubin values in diagnosing acute appendicitis in patients with normal white blood cell count and predicting complicated appendicitis. Ulus Travma Acil Cerrahi Derg 27(1):50–54PubMed Birben B, Akkurt G, Akın T, Surel AA, Tez M (2021) Efficacy of bilirubin values in diagnosing acute appendicitis in patients with normal white blood cell count and predicting complicated appendicitis. Ulus Travma Acil Cerrahi Derg 27(1):50–54PubMed
13.
go back to reference Ozer OF, Yigit M, Guler EM, Kocyigit A, Meral I, Gultepe BS et al (2018) Raftlin, presepsin levels and thiol-disulphide homeostasis in acute appendicitis: a pilot study. J Pak Med Assoc 68(11):1660–1665PubMed Ozer OF, Yigit M, Guler EM, Kocyigit A, Meral I, Gultepe BS et al (2018) Raftlin, presepsin levels and thiol-disulphide homeostasis in acute appendicitis: a pilot study. J Pak Med Assoc 68(11):1660–1665PubMed
14.
go back to reference Anand S, Pakkasjärvi N, Bajpai M, Krishnan N, Goswami C, Suominen JS et al (2022) Utility of pentraxin-3 as a biomarker for diagnosis of acute appendicitis: a systematic review and meta-analysis. Pediatr Surg Int 38(8):1105–1112CrossRefPubMedPubMedCentral Anand S, Pakkasjärvi N, Bajpai M, Krishnan N, Goswami C, Suominen JS et al (2022) Utility of pentraxin-3 as a biomarker for diagnosis of acute appendicitis: a systematic review and meta-analysis. Pediatr Surg Int 38(8):1105–1112CrossRefPubMedPubMedCentral
15.
go back to reference Ates U, Bahadir K, Ergun E, Gollu G, Durmaz M, Gunay F et al (2020) Determination of pentraxin 3 levels in diagnosis of appendicitis in children. Pediatr Int 62(5):624–628CrossRefPubMed Ates U, Bahadir K, Ergun E, Gollu G, Durmaz M, Gunay F et al (2020) Determination of pentraxin 3 levels in diagnosis of appendicitis in children. Pediatr Int 62(5):624–628CrossRefPubMed
16.
go back to reference Ulusoy E, Çitlenbik H, Akgül F, Öztürk A, Şık N, Ulusoy O et al (2020) Is ischemia-modified albumin a reliable marker in accurate diagnosis of appendicitis in children? World J Surg 44(4):1309–1315CrossRefPubMed Ulusoy E, Çitlenbik H, Akgül F, Öztürk A, Şık N, Ulusoy O et al (2020) Is ischemia-modified albumin a reliable marker in accurate diagnosis of appendicitis in children? World J Surg 44(4):1309–1315CrossRefPubMed
17.
go back to reference Hou J, Feng W, Liu W, Hou J, Die X, Sun J et al (2022) The use of the ratio of C-reactive protein to albumin for the diagnosis of complicated appendicitis in children. Am J Emerg Med 52:148–154CrossRefPubMed Hou J, Feng W, Liu W, Hou J, Die X, Sun J et al (2022) The use of the ratio of C-reactive protein to albumin for the diagnosis of complicated appendicitis in children. Am J Emerg Med 52:148–154CrossRefPubMed
18.
go back to reference Yap TL, Fan JD, Ho MF, Choo CSC, Ong LY, Chen Y (2020) Salivary biomarker for acute appendicitis in children: a pilot study. Pediatr Surg Int 36(5):621–627CrossRefPubMed Yap TL, Fan JD, Ho MF, Choo CSC, Ong LY, Chen Y (2020) Salivary biomarker for acute appendicitis in children: a pilot study. Pediatr Surg Int 36(5):621–627CrossRefPubMed
19.
go back to reference Alizadeh S, Ghazavi A, Ganji A, Mosayebi G (2018) Diagnostic value of high-mobility group box 1 (HMGB1) protein in acute and perforated appendicitis. J Investig Surg 31(1):9–13CrossRef Alizadeh S, Ghazavi A, Ganji A, Mosayebi G (2018) Diagnostic value of high-mobility group box 1 (HMGB1) protein in acute and perforated appendicitis. J Investig Surg 31(1):9–13CrossRef
20.
go back to reference Güney C, Coskun A (2019) Can fetuin-A, CRP, and WBC levels be predictive values in the diagnosis of acute appendicitis in children with abdominal pain? Healthcare (Basel) 7(4):110CrossRefPubMed Güney C, Coskun A (2019) Can fetuin-A, CRP, and WBC levels be predictive values in the diagnosis of acute appendicitis in children with abdominal pain? Healthcare (Basel) 7(4):110CrossRefPubMed
21.
go back to reference Yücel Ç, Fırat Oğuz E, Er S, Balamir İ, Turhan T, Tez M (2020) Diagnostic value of GCP-2/CXCL-6 and hs-CRP in the diagnosis of acute appendicitis. Ulus Travma Acil Cerrahi Derg 26(2):191–196PubMed Yücel Ç, Fırat Oğuz E, Er S, Balamir İ, Turhan T, Tez M (2020) Diagnostic value of GCP-2/CXCL-6 and hs-CRP in the diagnosis of acute appendicitis. Ulus Travma Acil Cerrahi Derg 26(2):191–196PubMed
22.
go back to reference Elmas B, Yildiz T, Yazar H, İlçe Z, Bal C, Özbek B, Yürümez Y (2020) New oxidative stress markers useful in the diagnosis of acute appendicitis in children: thiol/disulfide homeostasis and the asymmetric dimethylarginine level. Pediatr Emerg Care 36(8):362–367CrossRefPubMed Elmas B, Yildiz T, Yazar H, İlçe Z, Bal C, Özbek B, Yürümez Y (2020) New oxidative stress markers useful in the diagnosis of acute appendicitis in children: thiol/disulfide homeostasis and the asymmetric dimethylarginine level. Pediatr Emerg Care 36(8):362–367CrossRefPubMed
23.
go back to reference Gökhan S, Aydın İE, Günaydın GP, Yıldırım Ç, Tanrıverdi F, Gürü S et al (2020) Comparison of thiol/disulphide homeostasis with modified Alvarado and RIPASA scores in the diagnosis of acute appendicitis. Ulus Travma Acil Cerrahi Derg 26(3):389–395PubMed Gökhan S, Aydın İE, Günaydın GP, Yıldırım Ç, Tanrıverdi F, Gürü S et al (2020) Comparison of thiol/disulphide homeostasis with modified Alvarado and RIPASA scores in the diagnosis of acute appendicitis. Ulus Travma Acil Cerrahi Derg 26(3):389–395PubMed
26.
go back to reference Erel O, Neselioglu S (2014) A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 47(18):326–332CrossRefPubMed Erel O, Neselioglu S (2014) A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 47(18):326–332CrossRefPubMed
27.
go back to reference Erel Ö, Erdoğan S (2020) Thiol–disulfide homeostasis: an integrated approach with biochemical and clinical aspects. Turkish J Med Sci 50(SI-2):1728–1738CrossRef Erel Ö, Erdoğan S (2020) Thiol–disulfide homeostasis: an integrated approach with biochemical and clinical aspects. Turkish J Med Sci 50(SI-2):1728–1738CrossRef
28.
go back to reference Uǧur C, Madenci H, Kurku H, Neśelioǧlu S (2020) The use of thiol/disulfide homeostasis parameters in the diagnosis of acute appendicitis in children. J Pediatr Infect Dis 15(4):195–199CrossRef Uǧur C, Madenci H, Kurku H, Neśelioǧlu S (2020) The use of thiol/disulfide homeostasis parameters in the diagnosis of acute appendicitis in children. J Pediatr Infect Dis 15(4):195–199CrossRef
29.
go back to reference Tullavardhana T, Sanguanlosit S, Chartkitchareon A (2021) Role of platelet indices as a biomarker for the diagnosis of acute appendicitis and as a predictor of complicated appendicitis: a meta-analysis. Ann Med Surg (Lond) 66:102448PubMed Tullavardhana T, Sanguanlosit S, Chartkitchareon A (2021) Role of platelet indices as a biomarker for the diagnosis of acute appendicitis and as a predictor of complicated appendicitis: a meta-analysis. Ann Med Surg (Lond) 66:102448PubMed
30.
go back to reference Prasetya D, Rochadi, Gunadi (2019) Accuracy of neutrophil lymphocyte ratio for diagnosis of acute appendicitis in children: a diagnostic study. Ann Med Surg (Lond) 48:35–38CrossRefPubMed Prasetya D, Rochadi, Gunadi (2019) Accuracy of neutrophil lymphocyte ratio for diagnosis of acute appendicitis in children: a diagnostic study. Ann Med Surg (Lond) 48:35–38CrossRefPubMed
32.
go back to reference Acar E, Özcan Ö, Deliktaş H, Beydilli H, Kırlı İ, Alataş ÖD et al (2016) Laboratory markers has many valuable parameters in the discrimination between acute appendicitis and renal colic. Ulus Travma Acil Cerrahi Derg 22(1):17–22PubMed Acar E, Özcan Ö, Deliktaş H, Beydilli H, Kırlı İ, Alataş ÖD et al (2016) Laboratory markers has many valuable parameters in the discrimination between acute appendicitis and renal colic. Ulus Travma Acil Cerrahi Derg 22(1):17–22PubMed
33.
go back to reference Kahramanca Ş, Özgehan G, Şeker D, Ismail Gökce E, Şeker G, Tunç G et al (2014) Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg 20(1):19–22CrossRefPubMed Kahramanca Ş, Özgehan G, Şeker D, Ismail Gökce E, Şeker G, Tunç G et al (2014) Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg 20(1):19–22CrossRefPubMed
34.
go back to reference Daldal E, Dagmura H (2020) The correlation between complete blood count parameters and appendix diameter for the diagnosis of acute appendicitis. Healthcare (Basel) 8(1):39CrossRefPubMed Daldal E, Dagmura H (2020) The correlation between complete blood count parameters and appendix diameter for the diagnosis of acute appendicitis. Healthcare (Basel) 8(1):39CrossRefPubMed
35.
go back to reference Pehlivanll F, Aydin O (2019) Role of platelet to lymphocyte ratio as a biomedical marker for the pre-operative diagnosis of acute appendicitis. Surg Infect (Larchmt) 20(8):631–636CrossRef Pehlivanll F, Aydin O (2019) Role of platelet to lymphocyte ratio as a biomedical marker for the pre-operative diagnosis of acute appendicitis. Surg Infect (Larchmt) 20(8):631–636CrossRef
36.
go back to reference Haghi AR, Pourmohammad P, Rabiee MAS (2019) Accuracy of mean platelet volume (MPV) and red cell distribution width (RDW) for the diagnosis of acute appendicitis: evaluation of possible new biomarkers. Adv J Emerg Med 4(2):e20PubMedPubMedCentral Haghi AR, Pourmohammad P, Rabiee MAS (2019) Accuracy of mean platelet volume (MPV) and red cell distribution width (RDW) for the diagnosis of acute appendicitis: evaluation of possible new biomarkers. Adv J Emerg Med 4(2):e20PubMedPubMedCentral
37.
go back to reference Boshnak N, Boshnaq M, Elgohary H (2018) Evaluation of platelet indices and red cell distribution width as new biomarkers for the diagnosis of acute appendicitis. J Investig Surg 31(2):121–129CrossRef Boshnak N, Boshnaq M, Elgohary H (2018) Evaluation of platelet indices and red cell distribution width as new biomarkers for the diagnosis of acute appendicitis. J Investig Surg 31(2):121–129CrossRef
38.
go back to reference Shommu NS, Jenne CN, Blackwood J, Joffe AR, Martin DA, Thompson GC et al (2018) Metabolomic and inflammatory mediator based biomarker profiling as a potential novel method to aid pediatric appendicitis identification. PLoS ONE 13(3):1–13CrossRef Shommu NS, Jenne CN, Blackwood J, Joffe AR, Martin DA, Thompson GC et al (2018) Metabolomic and inflammatory mediator based biomarker profiling as a potential novel method to aid pediatric appendicitis identification. PLoS ONE 13(3):1–13CrossRef
39.
go back to reference Köylüoğlu G, Arpacik M, Arici D, Ceran C, Kivanç F (2002) Akut apandisit tanısında inflamatuvar belirteçlerin yeri. Pediatrik Cerrahi Derg 16(1):33–37 Köylüoğlu G, Arpacik M, Arici D, Ceran C, Kivanç F (2002) Akut apandisit tanısında inflamatuvar belirteçlerin yeri. Pediatrik Cerrahi Derg 16(1):33–37
Metadata
Title
The role of IL-6, thiol–disulfide homeostasis, and inflammatory biomarkers in the prediction of acute appendicitis in children: a controlled study
Authors
Ceyhan Şahin
Eray Metin Güler
H. Nihan Karaman Ayyıldız
Zeliha Akış Yıldız
Mehmet Arpacık
Zekeriya İlçe
Publication date
01-12-2023
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Surgery International / Issue 1/2023
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-023-05366-5

Other articles of this Issue 1/2023

Pediatric Surgery International 1/2023 Go to the issue