Evaluation of the diagnostic value of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in diagnosing uncomplicated and complicated appendicitis in children aged 3 to 18 years in patients referred to Ali Ibn Abi Taleb Hospital in Zahedan in 2024-2025

Evaluation of the diagnostic value of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in diagnosing uncomplicated and complicated appendicitis in children aged 3 to 18 years in patients referred to Ali Ibn Abi Taleb Hospital in Zahedan in 2024-2025 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of the diagnostic value of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in diagnosing uncomplicated and complicated appendicitis in children aged 3 to 18 years in patients referred to Ali Ibn Abi Taleb Hospital in Zahedan in 2024-2025 Hosein Ali Danesh, Mohammad Aref Emami, Mahdi Mohammadi, Seyed Sajad Arfaei Chitkar This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8676392/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Appendicitis is one of the most frequent abdominal emergencies in children, and making an early and accurate diagnosis is essential to avoid complications like perforation and peritonitis. Because routine lab tests are not always reliable in determining the severity of appendicitis, there is growing interest in finding simple and practical markers that can help distinguish uncomplicated cases from those that are already complicated. Among these markers, the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) have recently gained attention as inexpensive and easily obtainable indicators of inflammation. In this study, we aimed to assess how useful NLR and PLR are in differentiating simple from complicated appendicitis in children admitted to Ali Ibn Abitaleb Hospital in Zahedan. Methods: This prospective cross-sectional study was conducted on 385 children, aged 3 to 18 years, with acute appendicitis. Based on histopathological findings following appendectomy, the patients were categorized into two groups: uncomplicated and complicated appendicitis. Data on neutrophil, lymphocyte, and platelet counts were extracted from pre-operative complete blood count (CBC) tests, and the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) were calculated. Data analysis was performed using Receiver Operating Characteristic (ROC) curve analysis to determine the optimal cut-off values and to calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results : 385 pediatric patients aged 3-18 years were diagnosed with complicated appendicitis (n=185) and uncomplicated appendicitis (n=200). The area under the curve (AUC) for NLR and PLR was 0.883 and 0.768, respectively. The optimal cutoff point of NLR for predicting appendicitis was 3.075 with a sensitivity of 75.1%, specificity of 87.5%, and NPV and PPV of 79.2% and 84.8%, respectively. The optimal cutoff point of PLR was 102.185 with a sensitivity of 65.4% and specificity of 80%, and NPV and PPV of 71.4% and 75.2%, respectively. Conclusions: The use of inflammatory indices such as NLR and PLR, due to their easy accessibility and low cost, can help improve diagnostic accuracy and facilitate faster decision-making in the management of pediatric appendicitis when used alongside clinical and paraclinical findings. appendicitis neutrophil lymphocyte platelet Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Appendicitis is an acute process that involves the appendix. It is the number one surgical emergency and one of the most common causes of abdominal pain, especially in children. Up to 250,000 cases of appendicitis are reported annually. The estimated lifetime risk is 12% for men and 25% for women. Although appendicitis can occur at any age, it is most common between the ages of 10 and 19 ( 1 ). The etiopathogenesis is still unknown, but it is probably multifactorial ( 2 ). It has been suggested that intraductal obstruction by lymphoid hyperplasia, foreign bodies, parasites, tumors, or feces is responsible for the initiation of inflammation. Here, the accumulation of intestinal secretions and dilation of the appendiceal lumen, which compromises capillary blood flow and weakens the mucoepithelial barrier, potentially allows bacterial invasion of the appendiceal wall ( 3 ). Despite the well-known classic symptoms and clinical findings of acute appendicitis, early diagnosis can sometimes be challenging. It includes a combination of clinical, laboratory, and radiological findings ( 4 ). The diagnosis of acute appendicitis is primarily based on clinical features with radiological examinations reserved for selected cases as an auxiliary diagnostic tool ( 5 ). The 2020 World Society of Emergency Surgery (WSES) guidelines include gangrene, perforation, and abscess in the definition of complicated appendicitis ( 4 ) . Furthermore, the rate of perforated appendicitis generally varies between 16 and 40%, is higher in younger age groups, varying between 40 and 57%, and is associated with diagnostic delay ( 6 ). Failure to diagnose acute appendicitis in the early stages may lead to adverse outcomes, including perforation, which can be associated with significant complications and even mortality( 7 ). There are several screening and scoring tools to help diagnose acute appendicitis, including the Alvarado score ( 8 ), RIPASA (Raja Isteri Pengiran Anak Saleha Appendicitis) score and more recently, RIFT (Right Iliac Fossa Pain Treatment) score ( 9 , 10 ) Although each of these scores differs in the clinical parameters used ( 11 ). Diagnostic workup can be improved by using clinical scoring systems that include physical examination findings and inflammatory markers ( 4 ). Furthermore, these scoring tools lack sensitivity and specificity in predicting the severity of acute appendicitis, although low scores can help classify patients as low risk. Therefore, scoring tools are not routinely used or recommended by the WSES ( 4 ). In addition, several blood tests are used to predict appendicitis and its severity. The white blood cell (WBC) count is predominantly increased in patients with appendicitis ( 12 ), however, the increased WBC count has no predictive value in differentiating simple from complicated appendicitis ( 13 , 14 ). Elevated serum bilirubin has been shown to be a potential marker for appendiceal perforation, but it lacks sufficient sensitivity and specificity ( 15 , 16 ) .C-reactive protein (CRP) is superior to bilirubin for predicting perforation in acute appendicitis ( 17 ). Identifying a tool or marker that can predict the diagnosis of acute appendicitis and can distinguish between uncomplicated and complicated appendicitis with good sensitivity and specificity is still a topic of interest for many researchers. The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are simple, inexpensive markers of inflammation that are easily obtained ( 18 ). Neutrophilia and lymphocytopenia are elements of the cellular response in systemic inflammation. An increased difference between neutrophils and lymphocytes indicates the severity of the inflammatory response. Therefore, the NLR has been used as a marker in many pathological conditions such as malignancies, chronic inflammatory diseases, and postoperative complications for many years( 19 ). The NLR provides information about two different immune and inflammatory pathways, which may make it a potential marker for predicting appendicitis and its severity. A recent meta-analysis showed that the NLR predicts both the diagnosis and severity of appendicitis ( 18 ). Methods This prospective study was conducted at Ali Ibn Abi Taleb Hospital in Zahedan (AS) in 2024–2025. This study was approved by the Ethics Committee of Zahedan University of Medical Sciences (IR.ZAUMS.REC.1403.430). The study population included children aged 3 to 18 years who were referred to the hospital with a diagnosis of acute appendicitis and underwent appendectomy. Inclusion criteria included: diagnosis of acute appendicitis based on histopathological examination of the appendectomy specimen and age 3 to 18 years. Exclusion criteria included: negative appendectomy report after surgery, long-term use of steroids or NSAIDs, all patients who had symptoms similar to appendicitis but had undergone surgery due to concurrent ovarian cysts or diverticulitis, or had a history of antibiotic use in the past 24 hours. In addition, patients with a diagnosis of perforated peptic ulcer, diabetes, hypo/hyperthyroidism, hematological disorder, any other inflammatory disease, kidney infection, and kidney stones were also excluded from the study. Sample size Based on the study of Celik et al. ( 20 ), using the unit ratio estimation formula with a confidence level of 95% and a precision of 5% (d = 0.05) and considering a sensitivity of about 50% to maximize the sample size, the required number of 385 patients was calculated. Consecutive convenient sampling method was used to provide the target sample size. Based on the pathology results, 200 patients were included in the uncomplicated appendicitis group and 185 patients were included in the complicated appendicitis group. Data and variables were collected using convenient and convenient sampling based on patient referral using a data collection form. Venous blood was collected from all eligible patients before antibiotic administration or surgery. Complete blood cell count (CBC) with differential was performed using an automated hematology analyzer. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. The type of appendicitis was divided into two groups based on definitive histopathological examination: uncomplicated appendicitis and complicated appendicitis. Finally, the data were analyzed using Roc Curve to determine cut-off values, NLR and PLR, and to calculate sensitivity, specificity, and positive and negative predictive values ​​using SPSS version 27 software. Results In this study, 385 children aged 3 to 18 years with a mean age (standard deviation) of 10.07 (4.699) years with a definitive diagnosis of appendicitis were included in the study. Of these, 200 (51.9%) patients had uncomplicated appendicitis and 185 (48.1%) had complicated appendicitis. The gender distribution was almost balanced, including 191 (49.6%) girls and 194 (50.4%) boys. (Table 1) The optimal cut-off point for the NLR index was calculated as 3.075. At this point, the sensitivity was 75.1%, specificity was 87.5%, positive predictive value was 84.8% (PPV), and negative predictive value was 79.2% (NPV). For the PLR index, the optimal cutoff point was determined to be 102.185, which yielded a sensitivity of 65.4%, specificity of 80%, positive predictive value of 75.2%, and negative predictive value of 71.4%. To evaluate the ROC curve, the area under the curve (AUC) value for the NLR index was 0.883 (with a 95% confidence interval: 0.851-0.915) (Figure 1) and for the PLR index was 0.768 (with a 95% confidence interval: 0.719-0.817) (Figure 2). Examining the performance of these indices in the two genders using the Mann-Whitney test showed that there was no significant difference between the performance of PLR in girls and boys (P=0.547). (Figure 3) Similarly, the performance of NLR did not show a statistically significant difference between the two genders (P=0.363) (Figure 4). Table 1 Demographic Information Value Variable 10.07 ± 4.75 Age( SD ± mean) 191 ( %49.6 ) Gender – Female n(%) 194 ( 50.4% ) Gender – male n(%) 185 ( 48.1% ) Complicated Appendicitis n(%) 200 ( 51.9% ) Uncomplicated Appendicitis n(%) Discussion Diagnostic imaging, accurate diagnosis of complex appendicitis and prediction of complications such as perforation and peritonitis in the pediatric population remain challenging (21-23). Considering this, there is a growing need to investigate simple and inexpensive biochemical laboratory parameters that can be useful in the diagnosis of acute appendicitis (22). The present study was designed and conducted with the aim of evaluating the diagnostic value of two inflammatory indices NLR and PLR in this context. The results of the study showed that the CUT-OFF NLR >= 3.075 (sensitivity: 75.1%, specificity: 87.5%, positive and negative predictive values: 84.8% and 79.2, respectively) and for PLR >= 102.185 (sensitivity: 65.4%, specificity: 80% and positive and negative predictive values: 75.2 and 71.4%, respectively) were obtained. Previous studies, including Shimizu et al.(24) suggest a cut-off value of 5.0 with a sensitivity of 44% and a specificity of 22%. Ishizuka et al. (25) determined a cut-off value of 8.0 for NLR to differentiate gangrenous appendicitis from catarrhal appendicitis, with a sensitivity of 73% and a specificity of 39%. Kahramanka et al. (21) reported two NLR cut-off values of 4.68 (sensitivity of 65%, specificity of 55%) and 5.74 (sensitivity of 71%, specificity of 49%) to differentiate acute appendicitis from normal appendicitis, and complicated appendicitis from uncomplicated appendicitis, respectively. Also, in a study by Hosseinpour et al. (26), a cut-off point of 3.5 (sensitivity 74%, specificity 67%, positive predictive value 94%, and negative predictive value 25%) was obtained, and in the study by M. Biatas et al. (27), a sensitivity of 77.5% and a specificity of 73.3% were obtained for NLR ≤ 3.5. In the study by Pahlavanli and Aydin (19), PLR> 140.45 had a sensitivity of 71.4% and a specificity of 88.9% for differentiating between appendicitis and normal appendicitis, while PLR> 163.27 had a sensitivity of 71.4% and a specificity of 88.9% for differentiating complicated appendicitis from simple appendicitis. Also, in another study by AYENI et al. (28), the cut-off value for simple appendicitis was 8.86 for NLR and 8.86 for complex appendicitis (sensitivity 70.3%, specificity 70%) and for PLR a cut-off point of 149.25 was found in simple appendicitis and 193.67 for complex appendicitis (sensitivity 64% with specificity 61%). In a meta-analysis conducted by EUN et al. (29), the optimal cut-off values for NLR for the diagnosis of acute appendicitis in children varied and ranged from 2.5 to 6.14. Our study was in line with the results of these studies. One reason for the variation in cut-off values could be that they differed depending on the characteristics of the patient and control group, clinical settings, laboratory methods, and reference standards. In this study, all included studies used histological findings as the reference standard for the diagnosis of acute appendicitis, but the definition of the control groups varied (i.e., healthy children or patients with negative appendectomy). In addition, the included studies were conducted in different clinical settings and countries. Therefore, all of these factors could lead to variations in the cut-off value. To date, the optimal NLR cutoff value for diagnosing acute pediatric appendicitis has not been determined; however, similar cumulative sensitivities and specificities were found in studies that used a cutoff value of ≤3.7 (range: 2.5–3.66) compared with studies that used a cutoff value of >3.7 (range: 4.0–6.14). Therefore, if an NLR value ≥2.5 is found in pediatric patients with acute appendicitis, it can be assumed that NLR will show similar moderate sensitivity and specificity for diagnosing acute pediatric appendicitis. However, clinicians should apply these results with caution in practice due to the heterogeneous characteristics of the included studies. (29) The data obtained in our study are also consistent with the findings of a meta-analysis conducted by Eun et al. (29) that included 19 studies with a total of 5974 pediatric cases, which reported that NLR had moderate sensitivity (0.82) and moderate specificity (0.76) for diagnosing appendicitis in pediatric patients, with an area under the curve (AUC) of 0.86 (29). This suggests that when NLR and PLR are considered simultaneously, the reliability of distinguishing complicated from simple appendicitis is significantly increased. Therefore, NLR and PLR can be used synergistically to identify more severe cases of acute appendicitis and these indices can be valuable tools in clinical decision-making related to pediatric appendicitis. However, due to the limitations of single-center and differences in sampling time and different time of onset of clinical symptoms and hospital admission, it is possible that NLR and PLR values may have been affected. Both of these biomarkers can be easily calculated from complete blood cell count (CBC DIFFERENTIAL) and are therefore considered low-cost markers. This provides easy clinical application and eliminates the need to rely on complex scoring systems that usually require the use of online calculators or text-based scoring systems.(28) Conclusions According to the findings of this study, NLR and PLR are promising indicators that can both diagnose and predict the severity of pediatric appendicitis, and when interpreted simultaneously, they can have acceptable sensitivity and specificity. NLR and PLR have the potential to help in prioritizing patients with clinically or imaging-confirmed appendicitis who are waiting for emergency appendectomy in busy general surgery departments. They can also be used to monitor patients with imaging-confirmed uncomplicated appendicitis who are treated conservatively. These indicators can also be used to monitor children with appendicitis who are treated non-surgically by confirming the diagnosis in patients in whom CT is not justified, such as children and pregnant women. Given the accuracy and simplicity of these indices, their use, along with other tests, can help make faster decisions about surgery, and training the medical staff on the correct interpretation of these indices can lead to their correct use in clinical diagnosis. Given the continuous changes in NLR and PLR during hospitalization and the course of treatment, it can be useful to monitor the patient's response to treatment by examining serial changes in these indices. Also, conducting multicenter studies with a larger sample size and a combined study with other inflammatory markers or clinical scoring systems to create a stronger predictive model to more accurately examine the relationship between PLR, NLR and the severity of inflammation is recommended. Recommendations Given the accuracy and simplicity of these indices, their use, along with other tests, can help make faster decisions about surgery, and training the medical staff on the correct interpretation of these indices can lead to their correct use in clinical diagnosis. Given the continuous changes in NLR and PLR during hospitalization and the course of treatment, it can be useful to monitor the patient's response to treatment by examining serial changes in these indices. It is also recommended to conduct multicenter studies with larger sample sizes and combined studies with other inflammatory markers or clinical scoring systems to create a more robust prediction model to more accurately examine the relationship between PLR, NLR, and inflammation severity. Abbreviations NLR Neutrophil-to-Lymphocyte Ratio PLR Platelet-to-Lymphocyte Ratio CBC Complete Blood Count ROC Receiver Operating Characteristic AUC Area Under the Curve PPV Positive Predictive Value NPV Negative Predictive Value WBC White Blood Cell RIPASA Raja Isteri Pengiran Anak Saleha Appendicitis Score RIFT Right Iliac Fossa Pain Treatment Score Declarations Acknowledgements The authors would like to thank all the patients who participated in this study. Authors’ contributions: HAD, MAE, and SSAC conceptualized and designed the study, and contributed to drafting and editing the manuscript. SSAC collected the data, participated in the experiments, reviewed the manuscript, and supervised the project. MM performed data analysis. All authors critically reviewed and revised the manuscript drafts. All authors read and approved the final manuscript and agreed to its submission. Ethics approval and consent to participate This prospective study was approved by the Ethics Committee of Zahedan University of Medical Sciences (IR.ZAUMS.REC.1403.430). Written informed consent was obtained from the parents or legal guardians of all participating children prior to their inclusion in the study. All methods were performed in accordance with the relevant guidelines and regulations. Clinical trial number: Not applicable Availability of data and materials The datasets generated and analyzed during the current study are not publicly available due to patient privacy concerns but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author details ¹ Associate Professor of Plastic Surgery, Zahedan University of Medical Sciences, Zahedan, Iran.² Assistant Professor of Surgery, Zahedan University of Medical Sciences, Zahedan, Iran.³ Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.⁴ Department of General Surgery, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. References Waseem M, Wang CF. Pediatric Appendicitis. StatPearls. Treasure Island FL ineligible companies. Disclosure: Cecily Wang declares no relevant financial relationships with ineligible companies.: © 2025, StatPearls Publishing LLC.; 2025. Humes DJ, Simpson J. Acute appendicitis. BMJ (Clinical research ed). 2006 Sep 9;333(7567):530-4. PubMed PMID: 16960208. Pubmed Central PMCID: PMC1562475. Epub 2006/09/09. eng. Schülin S, Schlichting N, Blod C, Opitz S, Suttkus A, Stingu CS, et al. The intra- and extraluminal appendiceal microbiome in pediatric patients: A comparative study. 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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-8676392","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":586469882,"identity":"06923505-5176-4860-805b-8b46b8e05ec5","order_by":0,"name":"Hosein Ali Danesh","email":"","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hosein","middleName":"Ali","lastName":"Danesh","suffix":""},{"id":586469886,"identity":"48dcafeb-9142-48a3-ab92-5f93b6c8c9c4","order_by":1,"name":"Mohammad Aref Emami","email":"","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Aref","lastName":"Emami","suffix":""},{"id":586469887,"identity":"f698540d-5551-4b1e-922e-664a8279cb42","order_by":2,"name":"Mahdi Mohammadi","email":"","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mahdi","middleName":"","lastName":"Mohammadi","suffix":""},{"id":586469890,"identity":"a204bc52-35bd-45eb-b656-bd1e3510aaf4","order_by":3,"name":"Seyed Sajad Arfaei Chitkar","email":"data:image/png;base64,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","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Seyed","middleName":"Sajad Arfaei","lastName":"Chitkar","suffix":""}],"badges":[],"createdAt":"2026-01-23 07:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8676392/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8676392/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102209324,"identity":"5cf2e356-9c59-4af0-81cd-c2be4cc6436d","added_by":"auto","created_at":"2026-02-09 12:12:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53939,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for NLR in differentiating complicated from uncomplicated appendicitis\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8676392/v1/888c0c37824761cc838ede19.png"},{"id":102297051,"identity":"a89d8192-1506-4390-a7a1-17cee7058b2d","added_by":"auto","created_at":"2026-02-10 10:25:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":51969,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for PLR in differentiating complicated from uncomplicated appendicitis\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8676392/v1/836e08c876e62ae3e4006c52.png"},{"id":102209430,"identity":"6c51cb53-ad16-4c50-bace-caa3d898c6e0","added_by":"auto","created_at":"2026-02-09 12:13:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":62187,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for PLR based on gender\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8676392/v1/dd67033c373bcd6cc06b8e98.png"},{"id":102209514,"identity":"03648136-9b92-495e-8c23-f9c1d6750daf","added_by":"auto","created_at":"2026-02-09 12:13:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":57747,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for NLR based on gender\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8676392/v1/c2e2c0a35e5e6042f57cfb50.png"},{"id":103734770,"identity":"192508cb-73a6-4f10-b2e2-1a038e53215e","added_by":"auto","created_at":"2026-03-02 09:42:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":721627,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8676392/v1/c86f48bc-14b8-4924-a36b-917aac1b1a84.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of the diagnostic value of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in diagnosing uncomplicated and complicated appendicitis in children aged 3 to 18 years in patients referred to Ali Ibn Abi Taleb Hospital in Zahedan in 2024-2025","fulltext":[{"header":"Background","content":"\u003cp\u003eAppendicitis is an acute process that involves the appendix. It is the number one surgical emergency and one of the most common causes of abdominal pain, especially in children. Up to 250,000 cases of appendicitis are reported annually. The estimated lifetime risk is 12% for men and 25% for women. Although appendicitis can occur at any age, it is most common between the ages of 10 and 19 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe etiopathogenesis is still unknown, but it is probably multifactorial (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It has been suggested that intraductal obstruction by lymphoid hyperplasia, foreign bodies, parasites, tumors, or feces is responsible for the initiation of inflammation. Here, the accumulation of intestinal secretions and dilation of the appendiceal lumen, which compromises capillary blood flow and weakens the mucoepithelial barrier, potentially allows bacterial invasion of the appendiceal wall (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite the well-known classic symptoms and clinical findings of acute appendicitis, early diagnosis can sometimes be challenging. It includes a combination of clinical, laboratory, and radiological findings (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The diagnosis of acute appendicitis is primarily based on clinical features with radiological examinations reserved for selected cases as an auxiliary diagnostic tool (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The 2020 World Society of Emergency Surgery (WSES) guidelines include gangrene, perforation, and abscess in the definition of complicated appendicitis (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) .\u003c/p\u003e \u003cp\u003eFurthermore, the rate of perforated appendicitis generally varies between 16 and 40%, is higher in younger age groups, varying between 40 and 57%, and is associated with diagnostic delay (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Failure to diagnose acute appendicitis in the early stages may lead to adverse outcomes, including perforation, which can be associated with significant complications and even mortality(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere are several screening and scoring tools to help diagnose acute appendicitis, including the Alvarado score (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), RIPASA (Raja Isteri Pengiran Anak Saleha Appendicitis) score and more recently, RIFT (Right Iliac Fossa Pain Treatment) score (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) Although each of these scores differs in the clinical parameters used (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDiagnostic workup can be improved by using clinical scoring systems that include physical examination findings and inflammatory markers (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Furthermore, these scoring tools lack sensitivity and specificity in predicting the severity of acute appendicitis, although low scores can help classify patients as low risk. Therefore, scoring tools are not routinely used or recommended by the WSES (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition, several blood tests are used to predict appendicitis and its severity. The white blood cell (WBC) count is predominantly increased in patients with appendicitis (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), however, the increased WBC count has no predictive value in differentiating simple from complicated appendicitis (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eElevated serum bilirubin has been shown to be a potential marker for appendiceal perforation, but it lacks sufficient sensitivity and specificity (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) .C-reactive protein (CRP) is superior to bilirubin for predicting perforation in acute appendicitis (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIdentifying a tool or marker that can predict the diagnosis of acute appendicitis and can distinguish between uncomplicated and complicated appendicitis with good sensitivity and specificity is still a topic of interest for many researchers. The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are simple, inexpensive markers of inflammation that are easily obtained (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Neutrophilia and lymphocytopenia are elements of the cellular response in systemic inflammation. An increased difference between neutrophils and lymphocytes indicates the severity of the inflammatory response. Therefore, the NLR has been used as a marker in many pathological conditions such as malignancies, chronic inflammatory diseases, and postoperative complications for many years(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The NLR provides information about two different immune and inflammatory pathways, which may make it a potential marker for predicting appendicitis and its severity. A recent meta-analysis showed that the NLR predicts both the diagnosis and severity of appendicitis (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis prospective study was conducted at Ali Ibn Abi Taleb Hospital in Zahedan (AS) in 2024\u0026ndash;2025. This study was approved by the Ethics Committee of Zahedan University of Medical Sciences (IR.ZAUMS.REC.1403.430).\u003c/p\u003e \u003cp\u003eThe study population included children aged 3 to 18 years who were referred to the hospital with a diagnosis of acute appendicitis and underwent appendectomy. Inclusion criteria included: diagnosis of acute appendicitis based on histopathological examination of the appendectomy specimen and age 3 to 18 years. Exclusion criteria included: negative appendectomy report after surgery, long-term use of steroids or NSAIDs, all patients who had symptoms similar to appendicitis but had undergone surgery due to concurrent ovarian cysts or diverticulitis, or had a history of antibiotic use in the past 24 hours. In addition, patients with a diagnosis of perforated peptic ulcer, diabetes, hypo/hyperthyroidism, hematological disorder, any other inflammatory disease, kidney infection, and kidney stones were also excluded from the study.\u003c/p\u003e \u003cp\u003eSample size Based on the study of Celik et al. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), using the unit ratio estimation formula with a confidence level of 95% and a precision of 5% (d\u0026thinsp;=\u0026thinsp;0.05) and considering a sensitivity of about 50% to maximize the sample size, the required number of 385 patients was calculated. Consecutive convenient sampling method was used to provide the target sample size. Based on the pathology results, 200 patients were included in the uncomplicated appendicitis group and 185 patients were included in the complicated appendicitis group.\u003c/p\u003e \u003cp\u003eData and variables were collected using convenient and convenient sampling based on patient referral using a data collection form. Venous blood was collected from all eligible patients before antibiotic administration or surgery. Complete blood cell count (CBC) with differential was performed using an automated hematology analyzer. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated.\u003c/p\u003e \u003cp\u003eThe type of appendicitis was divided into two groups based on definitive histopathological examination: uncomplicated appendicitis and complicated appendicitis. Finally, the data were analyzed using Roc Curve to determine cut-off values, NLR and PLR, and to calculate sensitivity, specificity, and positive and negative predictive values ​​using SPSS version 27 software.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, 385 children aged 3 to 18 years with a mean age (standard deviation) of 10.07 (4.699) years with a definitive diagnosis of appendicitis were included in the study. Of these, 200 (51.9%) patients had uncomplicated appendicitis and 185 (48.1%) had complicated appendicitis. The gender distribution was almost balanced, including 191 (49.6%) girls and 194 (50.4%) boys. (Table 1)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The optimal cut-off point for the NLR index was calculated as 3.075. At this point, the sensitivity was 75.1%, specificity was 87.5%, positive predictive value was 84.8% (PPV), and negative predictive value was 79.2% (NPV). For the PLR index, the optimal cutoff point was determined to be 102.185, which yielded a sensitivity of 65.4%, specificity of 80%, positive predictive value of 75.2%, and negative predictive value of 71.4%.\u003c/p\u003e\n\u003cp\u003eTo evaluate the ROC curve, the area under the curve (AUC) value for the NLR index was 0.883 (with a 95% confidence interval: 0.851-0.915) (Figure 1) \u0026nbsp;and for the PLR index was 0.768 (with a 95% confidence interval: 0.719-0.817) (Figure 2).\u003c/p\u003e\n\u003cp\u003eExamining the performance of these indices in the two genders using the Mann-Whitney test showed that there was no significant difference between the performance of PLR in girls and boys (P=0.547). (Figure 3) Similarly, the performance of NLR did not show a statistically significant difference between the two genders (P=0.363) (Figure 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e Demographic Information\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eValue\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eVariable\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e10.07\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e4.75\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eAge( SD \u0026plusmn; mean)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e191\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e%49.6\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eGender \u0026ndash; Female n(%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e194\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e50.4%\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eGender \u0026ndash; male n(%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e185\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e48.1%\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eComplicated Appendicitis n(%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e200\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003e51.9%\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003eUncomplicated Appendicitis n(%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eDiagnostic imaging, accurate diagnosis of complex appendicitis and prediction of complications such as perforation and peritonitis in the pediatric population remain challenging (21-23). Considering this, there is a growing need to investigate simple and inexpensive biochemical laboratory parameters that can be useful in the diagnosis of acute appendicitis (22). The present study was designed and conducted with the aim of evaluating the diagnostic value of two inflammatory indices NLR and PLR in this context.\u003c/p\u003e\n\u003cp\u003eThe results of the study showed that the CUT-OFF NLR \u0026gt;= 3.075 (sensitivity: 75.1%, specificity: 87.5%, positive and negative predictive values: 84.8% and 79.2, respectively) and for PLR \u0026gt;= 102.185 (sensitivity: 65.4%, specificity: 80% and positive and negative predictive values: 75.2 and 71.4%, respectively) were obtained.\u003c/p\u003e\n\u003cp\u003ePrevious studies, including Shimizu et al.(24) suggest a cut-off value of 5.0 with a sensitivity of 44% and a specificity of 22%. Ishizuka et al. (25) determined a cut-off value of 8.0 for NLR to differentiate gangrenous appendicitis from catarrhal appendicitis, with a sensitivity of 73% and a specificity of 39%. Kahramanka et al. (21) reported two NLR cut-off values of 4.68 (sensitivity of 65%, specificity of 55%) and 5.74 (sensitivity of 71%, specificity of 49%) to differentiate acute appendicitis from normal appendicitis, and complicated appendicitis from uncomplicated appendicitis, respectively. Also, in a study by Hosseinpour et al. (26), a cut-off point of 3.5 (sensitivity 74%, specificity 67%, positive predictive value 94%, and negative predictive value 25%) was obtained, and in the study by M. Biatas et al. (27), a sensitivity of 77.5% and a specificity of 73.3% were obtained for NLR ≤ 3.5. In the study by Pahlavanli and Aydin (19), PLR\u0026gt; 140.45 had a sensitivity of 71.4% and a specificity of 88.9% for differentiating between appendicitis and normal appendicitis, while PLR\u0026gt; 163.27 had a sensitivity of 71.4% and a specificity of 88.9% for differentiating complicated appendicitis from simple appendicitis. Also, in another study by AYENI et al. (28), the cut-off value for simple appendicitis was 8.86 for NLR and 8.86 for complex appendicitis (sensitivity 70.3%, specificity 70%) and for PLR a cut-off point of 149.25 was found in simple appendicitis and 193.67 for complex appendicitis (sensitivity 64% with specificity 61%). In a meta-analysis conducted by EUN et al. (29), the optimal cut-off values for NLR for the diagnosis of acute appendicitis in children varied and ranged from 2.5 to 6.14. Our study was in line with the results of these studies.\u003c/p\u003e\n\u003cp\u003eOne reason for the variation in cut-off values could be that they differed depending on the characteristics of the patient and control group, clinical settings, laboratory methods, and reference standards. In this study, all included studies used histological findings as the reference standard for the diagnosis of acute appendicitis, but the definition of the control groups varied (i.e., healthy children or patients with negative appendectomy). In addition, the included studies were conducted in different clinical settings and countries. Therefore, all of these factors could lead to variations in the cut-off value. To date, the optimal NLR cutoff value for diagnosing acute pediatric appendicitis has not been determined; however, similar cumulative sensitivities and specificities were found in studies that used a cutoff value of ≤3.7 (range: 2.5–3.66) compared with studies that used a cutoff value of \u0026gt;3.7 (range: 4.0–6.14). Therefore, if an NLR value ≥2.5 is found in pediatric patients with acute appendicitis, it can be assumed that NLR will show similar moderate sensitivity and specificity for diagnosing acute pediatric appendicitis. However, clinicians should apply these results with caution in practice due to the heterogeneous characteristics of the included studies. (29)\u003c/p\u003e\n\u003cp\u003eThe data obtained in our study are also consistent with the findings of a meta-analysis conducted by Eun et al. (29) that included 19 studies with a total of 5974 pediatric cases, which reported that NLR had moderate sensitivity (0.82) and moderate specificity (0.76) for diagnosing appendicitis in pediatric patients, with an area under the curve (AUC) of 0.86 (29).\u003c/p\u003e\n\u003cp\u003eThis suggests that when NLR and PLR are considered simultaneously, the reliability of distinguishing complicated from simple appendicitis is significantly increased. Therefore, NLR and PLR can be used synergistically to identify more severe cases of acute appendicitis and these indices can be valuable tools in clinical decision-making related to pediatric appendicitis. However, due to the limitations of single-center and differences in sampling time and different time of onset of clinical symptoms and hospital admission, it is possible that NLR and PLR values may have been affected. Both of these biomarkers can be easily calculated from complete blood cell count (CBC DIFFERENTIAL) and are therefore considered low-cost markers. This provides easy clinical application and eliminates the need to rely on complex scoring systems that usually require the use of online calculators or text-based scoring systems.(28)\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAccording to the findings of this study, NLR and PLR are promising indicators that can both diagnose and predict the severity of pediatric appendicitis, and when interpreted simultaneously, they can have acceptable sensitivity and specificity. NLR and PLR have the potential to help in prioritizing patients with clinically or imaging-confirmed appendicitis who are waiting for emergency appendectomy in busy general surgery departments. They can also be used to monitor patients with imaging-confirmed uncomplicated appendicitis who are treated conservatively. These indicators can also be used to monitor children with appendicitis who are treated non-surgically by confirming the diagnosis in patients in whom CT is not justified, such as children and pregnant women. Given the accuracy and simplicity of these indices, their use, along with other tests, can help make faster decisions about surgery, and training the medical staff on the correct interpretation of these indices can lead to their correct use in clinical diagnosis. Given the continuous changes in NLR and PLR during hospitalization and the course of treatment, it can be useful to monitor the patient's response to treatment by examining serial changes in these indices. Also, conducting multicenter studies with a larger sample size and a combined study with other inflammatory markers or clinical scoring systems to create a stronger predictive model to more accurately examine the relationship between PLR, NLR and the severity of inflammation is recommended.\u003c/p\u003e\n\u003ch3\u003eRecommendations\u003c/h3\u003e\n\u003cp\u003eGiven the accuracy and simplicity of these indices, their use, along with other tests, can help make faster decisions about surgery, and training the medical staff on the correct interpretation of these indices can lead to their correct use in clinical diagnosis. Given the continuous changes in NLR and PLR during hospitalization and the course of treatment, it can be useful to monitor the patient's response to treatment by examining serial changes in these indices. It is also recommended to conduct multicenter studies with larger sample sizes and combined studies with other inflammatory markers or clinical scoring systems to create a more robust prediction model to more accurately examine the relationship between PLR, NLR, and inflammation severity.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNLR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeutrophil-to-Lymphocyte Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePLR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePlatelet-to-Lymphocyte Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCBC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComplete Blood Count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eROC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReceiver Operating Characteristic\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eAUC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eArea Under the Curve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePPV\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePositive Predictive Value\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNPV\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNegative Predictive Value\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eWBC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWhite Blood Cell\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eRIPASA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRaja Isteri Pengiran Anak Saleha Appendicitis Score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eRIFT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRight Iliac Fossa Pain Treatment Score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the patients who participated in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHAD, MAE, and SSAC conceptualized and designed the study, and contributed to drafting and editing the manuscript. SSAC collected the data, participated in the experiments, reviewed the manuscript, and supervised the project. \u0026nbsp;MM performed data analysis. All authors critically reviewed and revised the manuscript drafts. \u0026nbsp;All authors read and approved the final manuscript and agreed to its submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective study was approved by the Ethics Committee of Zahedan University of Medical Sciences (IR.ZAUMS.REC.1403.430). Written informed consent was obtained from the parents or legal guardians of all participating children prior to their inclusion in the study. All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003eClinical trial number: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to patient privacy concerns but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026sup1; Associate Professor of Plastic Surgery, Zahedan University of Medical Sciences, Zahedan, Iran.\u0026sup2; Assistant Professor of Surgery, Zahedan University of Medical Sciences, Zahedan, Iran.\u0026sup3; Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.⁴ Department of General Surgery, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWaseem M, Wang CF. Pediatric Appendicitis. StatPearls. Treasure Island FL ineligible companies. Disclosure: Cecily Wang declares no relevant financial relationships with ineligible companies.: \u0026copy; 2025, StatPearls Publishing LLC.; 2025.\u003c/li\u003e\n\u003cli\u003eHumes DJ, Simpson J. Acute appendicitis. BMJ (Clinical research ed). 2006 Sep 9;333(7567):530-4. PubMed PMID: 16960208. Pubmed Central PMCID: PMC1562475. Epub 2006/09/09. eng.\u003c/li\u003e\n\u003cli\u003eSch\u0026uuml;lin S, Schlichting N, Blod C, Opitz S, Suttkus A, Stingu CS, et al. The intra- and extraluminal appendiceal microbiome in pediatric patients: A comparative study. Medicine. 2017 Dec;96(52):e9518. PubMed PMID: 29384958. Pubmed Central PMCID: PMC6393148. Epub 2018/02/01. eng.\u003c/li\u003e\n\u003cli\u003eDi Saverio S, Podda M, De Simone B, Ceresoli M, Augustin G, Gori A, et al. Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World journal of emergency surgery : WJES. 2020 Apr 15;15(1):27. PubMed PMID: 32295644. Pubmed Central PMCID: PMC7386163. Epub 2020/04/17. eng.\u003c/li\u003e\n\u003cli\u003eBhangu A, S\u0026oslash;reide K, Di Saverio S, Assarsson JH, Drake FT. Acute appendicitis: modern understanding of pathogenesis, diagnosis, and management. Lancet (London, England). 2015 Sep 26;386(10000):1278-87. PubMed PMID: 26460662. Epub 2015/10/16. eng.\u003c/li\u003e\n\u003cli\u003eLivingston EH, Woodward WA, Sarosi GA, Haley RW. Disconnect between incidence of nonperforated and perforated appendicitis: implications for pathophysiology and management. Annals of surgery. 2007 Jun;245(6):886-92. PubMed PMID: 17522514. Pubmed Central PMCID: PMC1876946. Epub 2007/05/25. eng.\u003c/li\u003e\n\u003cli\u003eRajalingam VR, Mustafa A, Ayeni A, Mahmood F, Shammout S, Singhal S, et al. The Role of Neutrophil-Lymphocyte-Ratio (NLR) and Platelet-Lymphocyte-Ratio (PLR) as a Biomarker for Distinguishing Between Complicated and Uncomplicated Appendicitis. Cureus. 2022 Jan;14(1):e21446. PubMed PMID: 35223231. Pubmed Central PMCID: PMC8857869. Epub 2022/03/01. eng.\u003c/li\u003e\n\u003cli\u003eAlvarado A. A practical score for the early diagnosis of acute appendicitis. Annals of emergency medicine. 1986 May;15(5):557-64. PubMed PMID: 3963537. Epub 1986/05/01. eng.\u003c/li\u003e\n\u003cli\u003eChong CF, Adi MI, Thien A, Suyoi A, Mackie AJ, Tin AS, et al. Development of the RIPASA score: a new appendicitis scoring system for the diagnosis of acute appendicitis. Singapore medical journal. 2010 Mar;51(3):220-5. PubMed PMID: 20428744. Epub 2010/04/30. eng.\u003c/li\u003e\n\u003cli\u003eBhangu A. Evaluation of appendicitis risk prediction models in adults with suspected appendicitis. The British journal of surgery. 2020 Jan;107(1):73-86. PubMed PMID: 31797357. Pubmed Central PMCID: PMC6972511. Epub 2019/12/05. eng.\u003c/li\u003e\n\u003cli\u003eKulik DM, Uleryk EM, Maguire JL. Does this child have appendicitis? A systematic review of clinical prediction rules for children with acute abdominal pain. Journal of clinical epidemiology. 2013 Jan;66(1):95-104. PubMed PMID: 23177898. Epub 2012/11/28. eng.\u003c/li\u003e\n\u003cli\u003eGuraya SY, Al-Tuwaijri TA, Khairy GA, Murshid KR. Validity of leukocyte count to predict the severity of acute appendicitis. Saudi medical journal. 2005 Dec;26(12):1945-7. PubMed PMID: 16380778. Epub 2005/12/29. eng.\u003c/li\u003e\n\u003cli\u003eColeman C, Thompson JE, Jr., Bennion RS, Schmit PJ. White blood cell count is a poor predictor of severity of disease in the diagnosis of appendicitis. The American surgeon. 1998 Oct;64(10):983-5. PubMed PMID: 9764707. Epub 1998/10/09. eng.\u003c/li\u003e\n\u003cli\u003eSand 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. American journal of surgery. 2009 Aug;198(2):193-8. PubMed PMID: 19306980. Epub 2009/03/25. eng.\u003c/li\u003e\n\u003cli\u003eJamaluddin M, Hussain SM, Ahmad H. Hyperbilirubinaemia a predictive factor for complicated acute appendicitis: a study in a tertiary care hospital. JPMA The Journal of the Pakistan Medical Association. 2013 Nov;63(11):1374-8. PubMed PMID: 24392522. Epub 2014/01/08. eng.\u003c/li\u003e\n\u003cli\u003eFR S, MI dR, BR S, C S, MC A, LR M, et al. Hyperbilirubinaemia alone cannot distinguish a perforation in acute appendicitis. ANZ J Surg. 2016 2016 Apr;86(4):255-9. Epub 2015 Feb 2.\u003c/li\u003e\n\u003cli\u003eMuller S, Falch C, Axt S, Wilhelm P, Hein D, K\u0026ouml;nigsrainer A, et al. Diagnostic accuracy of hyperbilirubinaemia in anticipating appendicitis and its severity. Emergency medicine journal : EMJ. 2015 Sep;32(9):698-702. PubMed PMID: 25476715. Epub 2014/12/06. eng.\u003c/li\u003e\n\u003cli\u003eHajibandeh S, Hajibandeh S, Hobbs N, Mansour M. Neutrophil-to-lymphocyte ratio predicts acute appendicitis and distinguishes between complicated and uncomplicated appendicitis: A systematic review and meta-analysis. American journal of surgery. 2020 Jan;219(1):154-63. PubMed PMID: 31056211. Epub 2019/05/06. eng.\u003c/li\u003e\n\u003cli\u003ePehlivanlı F, Aydin O. Role of Platelet to Lymphocyte Ratio as a Biomedical Marker for the Pre-Operative Diagnosis of Acute Appendicitis. Surgical infections. 2019 Dec;20(8):631-6. PubMed PMID: 31120412. Epub 2019/05/24. eng.\u003c/li\u003e\n\u003cli\u003eCelik 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. Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma \u0026amp; emergency surgery : TJTES. 2019 May;25(3):222-8. PubMed PMID: 31135939. Epub 2019/05/29. Pediatrik acil serviste komplike apandisitin belirlenmesinde n\u0026ouml;trofil-lenfosit oranı ve trombosit-lenfosit oranının rol\u0026uuml;. eng.\u003c/li\u003e\n\u003cli\u003eKahramanca S, Ozgehan G, Seker D, G\u0026ouml;kce EI, Seker G, Tun\u0026ccedil; G, et al. Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma \u0026amp; emergency surgery : TJTES. 2014 Jan;20(1):19-22. PubMed PMID: 24639310. Epub 2014/03/19. eng.\u003c/li\u003e\n\u003cli\u003eAtema JJ, van Rossem CC, Leeuwenburgh MM, Stoker J, Boermeester MA. Scoring system to distinguish uncomplicated from complicated acute appendicitis. The British journal of surgery. 2015 Jul;102(8):979-90. PubMed PMID: 25963411. Epub 2015/05/13. eng.\u003c/li\u003e\n\u003cli\u003eSchellekens DH, Hulsew\u0026eacute; KW, van Acker BA, van Bijnen AA, de Jaegere TM, Sastrowijoto SH, et al. Evaluation of the diagnostic accuracy of plasma markers for early diagnosis in patients suspected for acute appendicitis. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2013 Jul;20(7):703-10. PubMed PMID: 23859584. Epub 2013/07/19. eng.\u003c/li\u003e\n\u003cli\u003eShimizu T, Ishizuka M, Kubota K. A lower neutrophil to lymphocyte ratio is closely associated with catarrhal appendicitis versus severe appendicitis. Surgery today. 2016 Jan;46(1):84-9. PubMed PMID: 25686778. Epub 2015/02/18. eng.\u003c/li\u003e\n\u003cli\u003eIshizuka M, Shimizu T, Kubota K. Neutrophil-to-lymphocyte ratio has a close association with gangrenous appendicitis in patients undergoing appendectomy. International surgery. 2012 Oct-Dec;97(4):299-304. PubMed PMID: 23294069. Pubmed Central PMCID: PMC3727267. Epub 2013/01/09. eng.\u003c/li\u003e\n\u003cli\u003eHosseinpour M, Arbabi M, Nezadi S, Hamsaye M. Evaluation of the Diagnostic Value of Neutrophil-to-Lymphocyte Ratio in the Diagnosis of Acute and Complicated Appendicitis in Adults. Iranian Journal of Surgery 2012;20(4):33-9.\u003c/li\u003e\n\u003cli\u003eBiałas M, Taran K, Gryszkiewicz M, Modzelewski B. [Evaluation of neutrophil-lymphocyte ratio usefulness in the diagnosis of appendicitis]. Wiadomosci lekarskie (Warsaw, Poland : 1960). 2006;59(9-10):601-6. PubMed PMID: 17338113. Epub 2007/03/07. Wartość wskaźnika neutrofilowo-limfocytarnego w diagnostyce zapalenia wyrostka robaczkowego. pol.\u003c/li\u003e\n\u003cli\u003eAyeni A, Mahmood F, Mustafa A, McLeish B, Kulkarni V, Singhal S, et al. Predicting the Severity of Acute Appendicitis in Children Using Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR). Cureus. 2022 Aug;14(8):e28619. PubMed PMID: 36185898. Pubmed Central PMCID: PMC9523736. Epub 2022/10/04. eng.\u003c/li\u003e\n\u003cli\u003eEun S, Ho IG, Bae GE, Kim H, Koo CM, Kim MK, et al. Neutrophil-to-lymphocyte ratio for the diagnosis of pediatric acute appendicitis: a systematic review and meta-analysis. European review for medical and pharmacological sciences. 2021 Nov;25(22):7097-107. PubMed PMID: 34859875. Epub 2021/12/04. eng.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","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":"appendicitis, neutrophil, lymphocyte, platelet","lastPublishedDoi":"10.21203/rs.3.rs-8676392/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8676392/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Appendicitis is one of the most frequent abdominal emergencies in children, and making an early and accurate diagnosis is essential to avoid complications like perforation and peritonitis. Because routine lab tests are not always reliable in determining the severity of appendicitis, there is growing interest in finding simple and practical markers that can help distinguish uncomplicated cases from those that are already complicated. Among these markers, the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) have recently gained attention as inexpensive and easily obtainable indicators of inflammation.\u003c/p\u003e\n\u003cp\u003eIn this study, we aimed to assess how useful NLR and PLR are in differentiating simple from complicated appendicitis in children admitted to Ali Ibn Abitaleb Hospital in Zahedan.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This prospective cross-sectional study was conducted on 385 children, aged 3 to 18 years, with acute appendicitis. Based on histopathological findings following appendectomy, the patients were categorized into two groups: uncomplicated and complicated appendicitis. Data on neutrophil, lymphocyte, and platelet counts were extracted from pre-operative complete blood count (CBC) tests, and the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) were calculated. Data analysis was performed using Receiver Operating Characteristic (ROC) curve analysis to determine the optimal cut-off values and to calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: 385 pediatric patients aged 3-18 years were diagnosed with complicated appendicitis (n=185) and uncomplicated appendicitis (n=200). The area under the curve (AUC) for NLR and PLR was 0.883 and 0.768, respectively. The optimal cutoff point of NLR for predicting appendicitis was 3.075 with a sensitivity of 75.1%, specificity of 87.5%, and NPV and PPV of 79.2% and 84.8%, respectively. The optimal cutoff point of PLR was 102.185 with a sensitivity of 65.4% and specificity of 80%, and NPV and PPV of 71.4% and 75.2%, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The use of inflammatory indices such as NLR and PLR, due to their easy accessibility and low cost, can help improve diagnostic accuracy and facilitate faster decision-making in the management of pediatric appendicitis when used alongside clinical and paraclinical findings.\u003c/p\u003e","manuscriptTitle":"Evaluation of the diagnostic value of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in diagnosing uncomplicated and complicated appendicitis in children aged 3 to 18 years in patients referred to Ali Ibn Abi Taleb Hospital in Zahedan in 2024-2025","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 12:10:02","doi":"10.21203/rs.3.rs-8676392/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":"8d2a94b7-f7db-42b9-93ce-3ad48acd2be9","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T09:40:53+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-09 12:10:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8676392","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8676392","identity":"rs-8676392","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}