Predictive Role of the C-Reactive Protein/Albumin Ratio in Identifying Complicated Acute Appendicitis: A Retrospective Study

Predictive Role of the C-Reactive Protein/Albumin Ratio in Identifying Complicated Acute Appendicitis: A Retrospective Study | 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 Article Predictive Role of the C-Reactive Protein/Albumin Ratio in Identifying Complicated Acute Appendicitis: A Retrospective Study Ramazan Topcu, Mustafa Şahin, İsmail Sezikli, Orhan Aslan, Mahmut Arif Yüksek, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6264751/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 Introduction: This study investigates the predictive value of the C-reactive protein/albumin ratio (CAR) in distinguishing complicated acute appendicitis (CAA) from non-complicated acute appendicitis (NCAA), aiming to enhance diagnostic accuracy and improve clinical decision-making. Methods: A retrospective analysis was conducted on patients diagnosed with acute appendicitis who underwent appendectomy between January 2016 and May 2020. Demographic, clinical, and laboratory data, including age, sex, white blood cell (WBC) count, neutrophil count (NE), lymphocyte count (LY), hemoglobin (Hb), mean platelet volume (MPV), platelet count (PLT), serum albumin (Alb) levels, and C-reactive protein (CRP) levels, were extracted from hospital records. Additionally, ASA scores and operative durations were recorded. Patients were classified into CAA and NCAA groups based on pathology reports and surgical notes. The CAR and other hematological parameters were compared between groups, and their diagnostic performance was evaluated. Results: The median CAR was significantly higher in the CAA group (5.53; range: 0.63–115.19) compared to the NCAA group (2.24; range: 0.59–97.50) (p < 0.001). The optimal CAR cut-off value for predicting CAA was 2.06, yielding a sensitivity of 72.61% and a specificity of 48.46%. The positive predictive value (PPV) was 46.20%, whereas the negative predictive value (NPV) was 74.40%. Furthermore, a CAR level exceeding 2.06 was associated with a 1.48-fold increased risk of complications (p = 0.001). Conclusion: Our findings suggest that CAR is a significant biomarker for predicting complicated acute appendicitis, offering valuable clinical insights for early risk stratification. When used in conjunction with other hematological parameters, CAR may enhance diagnostic accuracy and guide clinical decision-making, potentially reducing unnecessary interventions. Further large-scale, prospective studies are essential to validate the clinical utility of the CAR in the managem Health sciences/Biomarkers/Predictive markers Health sciences/Biomarkers/Prognostic markers Appendicitis C-Reactive Protein Albumin Hemogram Parameters Biomarker Complicated Appendicitis Figures Figure 1 Figure 2 INTRODUCTION Acute appendicitis is one of the most common causes of acute abdominal pain in emergency surgical practice, with a lifetime prevalence of approximately 7% [1]. The timing of surgical intervention in acute appendicitis is of critical importance. Early surgical intervention can lead to unnecessary appendectomies, with normal appendix resection rates ranging from 15–30%. However, delaying surgery increases the risk of perforation, which significantly elevates morbidity and mortality rates ( 1 ). Therefore, optimizing preoperative evaluations is crucial to reduce unnecessary surgeries, lower perforation rates, and minimize hospital stays for patients presenting with acute appendicitis symptoms ( 2 ). The diagnosis of acute appendicitis relies on clinical evaluation and laboratory tests, often supplemented by imaging techniques such as ultrasonography (USG), computed tomography (CT), magnetic resonance imaging (MRI), and diagnostic laparoscopy ( 3 – 5 ). However, USG is operator-dependent and requires expertise, while other imaging methods involve high costs and limited accessibility, complicating routine clinical practice. The diagnostic accuracy of USG in acute appendicitis ranges from 71–95% ( 6 ). Since a definitive diagnosis can only be confirmed histopathologically, incorporating a highly predictive, cost-effective, widely accessible, and rapidly applicable biomarker into the diagnostic algorithm would significantly improve clinical decision-making. A standardized preoperative method for distinguishing between complicated (CAA) and non-complicated acute appendicitis (NCAA) has yet to be established. The ability to predict appendiceal perforation preoperatively is of paramount importance for guiding treatment decisions, determining the need for intraoperative drainage, and adjusting the dosage and duration of antibiotic therapy. C-reactive protein (CRP) is an acute-phase protein that increases in response to infection, ischemia, trauma, and inflammatory conditions. Elevated CRP levels are strongly associated with adverse clinical outcomes and increased mortality in critically ill patients ( 7 – 9 ). Similarly, hypoalbuminemia is widely recognized as a poor prognostic indicator in both acute and chronic illnesses, frequently occurring in severely ill patients and linked to higher mortality rates ( 10 ). The C-reactive protein/albumin ratio (CAR) has recently emerged as an inflammation-based prognostic biomarker demonstrating clinical utility in various conditions, including infections, malignancies, and critically ill patients. CAR has also been investigated as an effective tool in the management of acute cholecystitis, acute pancreatitis, cancer, polycystic ovary syndrome, and intensive care patients ( 11 – 13 ). In the literature, studies similar to ours are limited in number, with most studies involving small populations ( 14 – 16 ). The aim of our study is to demonstrate how CAR can be integrated into the clinical decision-making process by determining a specific cut-off value, based on a large patient population, even though the diagnostic value of CAR has been investigated in previous studies. MATERIALS AND METHODS This retrospective study was conducted at the Hitit University Faculty of Medicine Çorum Erol Olçok Training and Research Hospital, encompassing patients who underwent appendectomy. Ethical approval was granted by the Hitit University Faculty of Medicine Non-Interventional Studies Ethics Committee on April 7, 2021 (Institutional Review Board approval No: 2021/383). Study Population Patients aged 18 years and older who were diagnosed with acute appendicitis and subsequently underwent appendectomy after clinical evaluation, abdominal ultrasonography (USG), and abdominal computed tomography (CT) between January 2016 and May 2020 were retrospectively identified from hospital records. An initial cohort of 2156 patients was identified.Patients were excluded if they had a documented history of hematologic or oncologic disorders, incomplete laboratory data, concurrent infectious or inflammatory conditions unrelated to appendicitis, or malignant/non-appendicitis findings in pathology reports. Following the application of these exclusion criteria, a total of 2001 patients were included in the final analysis ( Fig. 1 ). Demographic and laboratory parameters, including age, sex, white blood cell (WBC) count, neutrophil count (NE), lymphocyte count (LY), hemoglobin (Hb), mean platelet volume (MPV), platelet count (PLT), serum albumin (Alb) level, and serum C-reactive protein (CRP) level, were obtained from hospital records at the time of emergency department admission. Additionally, emergency American Society of Anesthesiologists (ASA) scores, operative duration, intraoperative complications (as documented in operative notes), postoperative pathology reports, and length of postoperative hospitalization were recorded. Furthermore, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-albumin ratio (CAR) were calculated based on the corresponding hematological parameters. Classification of Appendicitis Cases Pathology reports and operative notes were systematically reviewed to classify patients into complicated and uncomplicated appendicitis groups. In histopathological evaluations, cases presenting with perforation, abscess formation, necrosis, gangrene, phlegmon, or intraoperative perforation were categorized as complicated appendicitis (CAA) (n = 711). In contrast, cases demonstrating no significant inflammation, only mild edema, reactive lymphoid hyperplasia, or fibrous obliteration were classified as non-complicated appendicitis (NCAA) (n = 1290). To assess the potential of CAR, NLR, PLT, MPV, and other hematological parameters as predictive markers for complicated appendicitis, a comparative analysis was performed between the two groups. The relationship between these biomarkers and appendicitis severity was statistically evaluated to determine their diagnostic and prognostic significance."* Statistical Analysis All statistical analyses were conducted using IBM SPSS Statistics for Windows (version 26; IBM Corp., Armonk, NY, USA). Descriptive statistics were reported as frequencies and percentages for categorical variables, while continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range, minimum–maximum), depending on the distribution of the data. The normality of data distribution was assessed using the Shapiro-Wilk test. For comparisons of continuous variables between independent groups, either the independent samples t-test (Student's t-test) or the Mann-Whitney U test was applied, contingent on the normality assumption. Correlations between continuous variables were analyzed using Pearson’s correlation coefficient for normally distributed data and Spearman’s rank correlation coefficient for non-normally distributed data. Categorical variables were compared using the Chi-squared test (χ² test) or Fisher’s exact test, as appropriate. All statistical tests were two-tailed, and results were interpreted within a 95% confidence interval (CI). Statistical significance was set at p < 0.05. RESULTS Among the 2001 patients included in the study, 1197 (59.8%) were male and 804 (40.2%) were female. The mean age of the cohort was 37.24 ± 14.52 years, with an age range of 18 to 97 years. The distribution of ASA classifications was as follows: 967 patients (48.32%) were ASA1, 886 (44.28%) were ASA2, 130 (6.50%) were ASA3, and 18 (0.90%) were ASA4. The mean values for white blood cell (WBC) count, neutrophil count (NE), and lymphocyte count (LY) were 12.74 ± 4.19 ×10⁹/L, 9.70 ± 4.04 ×10⁹/L, and 1.99 ± 0.90 ×10⁹/L, respectively. The mean hemoglobin level was 13.94 ± 1.82 g/dL, and the mean platelet count was 236.06 ± 63.41 fL. The mean albumin level was 4.31 ± 0.39 g/dL, and the median C-reactive protein (CRP) level was 13.05 mg/L (range: 3.02–374 mg/L). The mean neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-albumin ratio (CAR) were 6.54 ± 5.75, 147.44 ± 94.51, and 3.36 (0.59–97.50), respectively. The mean surgical procedure duration, measured from anesthesia initiation to completion, was 51.23 ± 13.63 minutes. The mean postoperative hospital stay was 2.52 ± 1.42 days. A total of 75 patients were classified as negative appendectomy cases, as their pathology reports indicated only the presence of the appendix vermiformis with no evidence of appendicitis. Reactive lymphoid hyperplasia was identified in 148 patients, whereas fibrous obliteration was detected in 40 patients. A definitive diagnosis of acute appendicitis was established in 1027 patients. The complicated appendicitis group included 303 cases of phlegmonous appendicitis, 139 cases of gangrenous appendicitis, 69 cases of necrotizing appendicitis, 112 cases of suppurative appendicitis, and 88 cases of perforated appendicitis. The demographic and clinical characteristics of all patients are presented in Table 1 . Comparison Between Uncomplicated and Complicated Appendicitis Groups Patients were stratified into complicated and uncomplicated appendicitis groups, and their clinical and laboratory parameters were compared (Table 1 ). A statistically significant difference was observed in gender distribution, with a higher proportion of males in the complicated appendicitis group (p < 0.001). The mean age of patients in the complicated appendicitis group was significantly higher than that of the uncomplicated group (p < 0.001). However, no statistically significant difference was found between the two groups in terms of ASA score distribution (p = 0.097). Significant differences were observed in WBC count, neutrophil count, and lymphocyte levels between the groups. The complicated appendicitis group exhibited significantly higher leukocytosis and neutrophilia, while lymphopenia was more pronounced (p < 0.001 for all comparisons). Platelet levels were significantly lower in the complicated appendicitis group (p = 0.002). Additionally, the mean albumin level was significantly lower, while CRP levels were significantly higher in the complicated appendicitis group (p = 0.041 and p < 0.001, respectively). However, there were no statistically significant differences in hemoglobin levels and mean platelet volumes between the two groups (p = 0.349 and p = 0.372, respectively). The mean NLR was 5.88 ± 5.44 in the uncomplicated appendicitis group and 7.74 ± 6.10 in the complicated appendicitis group, with a statistically significant difference (p < 0.001). Similarly, the PLR was significantly higher in the complicated appendicitis group (p < 0.001). The CAR was 7.21 ± 11.29 in the uncomplicated appendicitis group and 12.72 ± 17.46 in the complicated appendicitis group, demonstrating a statistically significant difference (p < 0.001). Furthermore, significant differences were noted in surgical duration and postoperative hospital stay, with both being significantly longer in the complicated appendicitis group (p = 0.014 and p < 0.001, respectively). ROC Curve Analysis and Cut-Off Values To determine the optimal cut-off values for NLR, PLR, and CAR in distinguishing uncomplicated from complicated appendicitis, receiver operating characteristic (ROC) curve analysis was performed using the area under the curve (AUC) and Youden index (Fig. 2 ). The optimal CAR cut-off was determined as 2.06, with 72.61% sensitivity, 48.46% specificity, 46.20% positive predictive value, and 74.40% negative predictive value (OR: 2.48, 95% CI: 1.90–3.25, p < 0.001). The optimal NLR cut-off was 3.64, with 80.40% sensitivity, 40.92% specificity, 43.80% positive predictive value, and 79.70% negative predictive value (OR: 3.06, 95% CI: 2.47–3.79, p < 0.001). The optimal PLR cut-off was 144.87, with 45.23% sensitivity, 63.23% specificity, 40.40% positive predictive value, and 67.60% negative predictive value (OR: 1.39, 95% CI: 1.15–1.68, p < 0.001). A CAR exceeding 2.06 mm increased the likelihood of complicated appendicitis by approximately 1.048 times, while an NLR exceeding 3.64 increased the likelihood by 2.06 times. Additionally, a PLR greater than 144.87 increased the risk of complicated appendicitis by 39% (all p-values < 0.001; see Table 2 ). Table 1 Assessment of all patients and univariate comparison between uncomplicated and complicated appendicitis Variables Whole Group (n = 2001) Uncomplicated (n = 1290) Complicated (n = 711) Statistical Significance Gender Male 1197 (59.82%) 734 (56.90%) 463 (65.12%) < 0.001 Female 804 (40.18%) 556 (43.10%) 248 (34.88%) Age 37.24 ± 14.52 35.72 ± 13.23 39.99 ± 16.23 < 0.001 ASA I 967 (48.32%) 620 (48.06%) 347 (48.80%) 0.097 II 886 (44.28%) 588 (45.58%) 298 (41.91%) III 130 (6.50%) 72 (5.58%) 58 (8.16%) IV 18 (0.90%) 10 (0.78%) 8 (1.13%) WBC 12.74 ± 4.19 12.18 ± 4.24 13.76 ± 3.91 < 0.001 NE 9.70 ± 4.04 9.10 ± 4.09 10.79 ± 3.71 < 0.001 LY 1.99 ± 0.90 2.07 ± 0.90 1.83 ± 0.88 < 0.001 Hb 13.94 ± 1.82 13.90 ± 1.89 14.02 ± 1.69 0.349 MPV 9.61 ± 1.12 9.60 ± 1.11 9.64 ± 1.13 0.372 Plt 236.05 ± 63.41 238.92 ± 63.84 230.83 ± 62.34 0.002 Alb 4.34 ± 0.39 4.34 ± 0.39 4.31 ± 0.39 0.041 CRP 13.05 (3.02–374.00) 8.92 (3.02–312.00) 21.30 (3.02–374.00) < 0.001 NLR 6.54 ± 5.75 5.88 ± 5.44 7.74 ± 6.10 < 0.001 PLR 147.44 ± 94.51 142.60 ± 94.95 156.20 ± 93.12 < 0.001 CAR 3.36 (0.59-115.19) 2.24 (0.59–97.50) 5.53 (0.63-115.19) < 0.001 Operation Duration 51.23 ± 13.63 53.49 ± 13.62 55.48 ± 13.57 0.014 Length of Stay 2.52 ± 1.42 2.38 ± 1.28 2.77 ± 1.63 < 0.001 Histopathological Type Appendix Vermiformis 75 (3.75%) Reactive Lymphoid Hyperplasia 148 (7.40%) Fibrous Obliteration 40 (2.00%) Acute Appendicitis 1027 (51.32%) Phlegmonous Appendicitis 303 (15.14%) Gangrenous Appendicitis 139 (6.95%) Necrotizing Appendicitis 69 (3.45%) Suppurative Appendicitis 112 (5.60%) Perforation 88 (4.40%) Complication 711 (35.53%) Table 2 CAR, NLR, PLR Cut-off Values Cut-off Diagnostic Values ROC Analysis Odds Ratio (95% CI) Sensitivity Specificity PPV NPV Area (SE) 95% CI p OR (95% CI) p CAR 2.06 72.61% 48.46% 46.20% 74.40% 0.630 (0.01) 0.596–0.664 0.001 2.48 (95% CI 1.90–3.25) 0.001 NLR 3.64 80.40% 40.92% 43.80% 79.70% 0.618 (0.01) 0.583–0.652 0.001 3.06 (95% CI 2.47–3.79) 0.001 PLR 144.87 45.23% 63.23% 40.40% 67.30% 0.542 (0.01) 0.506–0.578 0.022 1.39 (95% CI 1.15–1.68) 0.001 DISCUSSION Acute appendicitis (AA) remains one of the most common causes of acute abdomen. In early-stage surgical interventions, the presence of a normal appendix has been reported in 15–30% of cases. Prolonged preoperative observation in AA has been associated with an increased risk of complicated appendicitis, leading to higher morbidity and mortality rates ( 1 ). Therefore, identifying a cost-effective, repeatable, and widely accessible biomarker with high predictive value could facilitate more accurate diagnoses and improve clinical decision-making. Predicting appendiceal perforation preoperatively, particularly through blood-based biomarkers, could significantly influence treatment strategies, including the necessity for surgical drainage, the selection and duration of antibiotic therapy, and overall patient management. Numerous studies have evaluated laboratory markers for the diagnosis of AA. Parameters such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume, red cell distribution width, and C-reactive protein (CRP) have been extensively investigated in this context ( 17 , 18 ). Beyond diagnosing AA, distinguishing between complicated and uncomplicated appendicitis is of critical importance due to the significant differences in associated morbidity and mortality. Previous studies have demonstrated that CRP levels are markedly elevated in complicated appendicitis compared to uncomplicated cases ( 19 ). Similarly, high leukocyte counts have been reported in cases of necrotic or perforated appendicitis ( 20 ). Kim et al. ( 13 ) found that both CRP and international normalized ratio (INR) were predictive of complicated appendicitis. Additionally, a study by Shelton et al. ( 21 ) established a direct association between elevated preoperative CRP levels and increased postoperative complications. Moreover, elevated NLR and PLR levels have been implicated in higher complication rates among AA patients ( 22 ). Our study corroborates these findings, demonstrating significantly higher levels of neutrophils (NE), CRP, white blood cell (WBC) count, NLR, and PLR in patients with complicated AA compared to those with uncomplicated AA (p < 0.001). Conversely, platelet, albumin, and lymphocyte levels were significantly lower in complicated AA cases (p < 0.001). These findings align with the existing literature, reinforcing the diagnostic utility of these biomarkers in clinical practice. The C-reactive protein-to-albumin ratio (CAR) has increasingly been recognized as an independent prognostic marker in various inflammatory and malignant conditions ( 11 , 12 ). Elevated CAR levels are expected in inflammatory states and have been shown to aid in the early diagnosis and management of acute cholecystitis, acute pancreatitis, malignancies, polycystic ovary syndrome, and critically ill patients ( 11 , 12 , 13 ). Despite its emerging importance, studies investigating the relationship between CAR and acute appendicitis (AA) remain limited. To date, only a few studies have evaluated CAR in AA patients. One of these studies suggests that an increasing CAR may serve as a valuable biomarker for distinguishing complicated from uncomplicated AA ( 14 – 16 , 23 ). Another study demonstrated that CAR provided superior predictive value for complicated appendicitis in pediatric populations compared to other biomarkers ( 24 ). In our study, the optimal CAR cut-off value for predicting complicated AA was determined to be 2.06, yielding a sensitivity of 72.61% and specificity of 48.46%, with positive and negative predictive values of 46.20% and 74.40%, respectively. A CAR level exceeding 2.06 was associated with a 1.48-fold increased risk of complications (p = 0.001). These findings are consistent with previous studies that have identified CAR cut-off values for complicated appendicitis. Doğan et al. ( 23 ) reported a CAR cut-off value of 4.4, which was associated with a 10.624-fold increased risk of complicated AA. Similarly, Feng et al. ( 25 ) found an optimal CAR cut-off value of 1.43, which was associated with a 102.22-fold increased risk of complicated appendicitis. These studies corroborate our findings and highlight the potential of CAR as a diagnostic and prognostic marker ( 14 – 16 , 23 , 24 ). CAR values > 2.06 in patients indicate a higher risk of complications. Therefore, more intensive monitoring should be implemented. This involves closely tracking clinical signs, laboratory results, and imaging findings to identify any deterioration or progression of the condition promptly. Furthermore, antibiotic therapy should be initiated early to reduce the risk of infection and sepsis, particularly in patients at risk for complicated appendicitis. In some cases, the timing of surgery may need to be expedited to prevent the development of further complications, such as perforation or abscess formation, which can significantly increase morbidity and mortality. These measures aim to optimize patient outcomes by proactively addressing potential complications. Additionally, we determined the optimal cut-off values for NLR (3.64; sensitivity: 80.40%, specificity: 40.92%) and PLR (144.87; sensitivity: 45.23%, specificity: 63.23%). An NLR value exceeding 3.64 was associated with a 2.06-fold increased risk of complications (p = 0.001). Previous studies have reported varying cut-off values for NLR, ranging from 4.68 to 8.0, with sensitivities ranging from 65–73% and specificities from 39–55% ( 26 , 27 ). For PLR, our results align with those of Çelik et al. ( 22 ), who reported a cut-off value of 284 (sensitivity: 42%, specificity: 86%) for diagnosing complicated AA. Additionally, Pehlivanli et al.( 29 ) found that PLR was valuable in differentiating normal appendix cases from AA and in distinguishing uncomplicated from complicated AA. A comparative analysis of our study groups revealed that male gender, older age, elevated WBC and NE counts, lower lymphocyte and platelet counts, reduced albumin levels, and increased CRP, CAR, PLR, and NLR levels were significantly associated with complicated AA. These findings are consistent with multiple studies in the literature ( 22 , 23 , 29 , 30 ). Due to the relatively low specificity, the management of false positives needs to be discussed. For instance, "In patients with CAR > 2.06, further evaluation using NLR and PLR can help minimize the likelihood of false positives." This would involve using additional biomarkers to confirm or refine the diagnosis, ensuring that patients at higher risk for complications are appropriately treated, while avoiding unnecessary interventions for those with false positive results. Combining CAR with other parameters, such as NLR and PLR, enhances diagnostic accuracy, offering a more comprehensive approach to patient management. Limitations This study has several limitations, primarily its retrospective design, which may introduce selection bias and limit the ability to establish causal relationships. Additionally, the absence of preoperative imaging comparisons restricts the ability to assess the role of imaging modalities in conjunction with CAR for the diagnosis of complicated appendicitis. Furthermore, the reliance on data obtained from the hospital information system may limit the accuracy and completeness of some clinical variables. Future prospective studies incorporating imaging techniques, such as ultrasound, CT, or MRI, along with larger and more diverse patient cohorts, are needed to validate these findings and assess the utility of CAR CONCLUSION Our findings suggest that elevated levels of WBC, NE, CRP, NLR, and CAR, along with reduced levels of LY, Plt, and albumin, can serve as valuable biomarkers for distinguishing between complicated and uncomplicated acute appendicitis (AA) when used in conjunction with clinical and radiological assessments. Laboratory-based cut-off values may help refine diagnostic accuracy and optimize treatment planning. Notably, CAR emerged as a potentially superior biomarker for predicting complicated AA compared to other hematological markers. Since these laboratory parameters do not incur additional financial costs, their application could be particularly advantageous in resource-limited settings where access to advanced diagnostic tools is constrained. Further large-scale, prospective studies are necessary to establish the clinical utility of CAR in managing AA. Declarations Ethics approval and consent to participate This exploratory, retrospective, single-center cohort study was conducted in accordance with the most recent version of the Declaration of Helsinki. The study received approval from the local ethics committee of the Hitit University Faculty of Medicine (2021/383). Given the retrospective design of the study, the ethics committee granted a waiver for written informed consent. The informed consent was waived by IRB (Clinical Research Ethics Committee of Hitit University Faculty of Medicine) The data collection and manuscript preparation processes were conducted in accordance with the guidelines set forth by the Committee on Publication Ethics (COPE) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. Author İnformation Authors and Affiliations 1.Hitit University Faculty of Medicine, Department of General Surgery, 19030, Çorum, Turkey İsmail SEZİKLİ, Ramazan TOPCU, Mahmut Arif YÜKSEK, Orhan ASLAN, Aşkın Kadir PERÇEM 2. Hitit University Faculty of Medicine, Department of Medical Biochemistry, 19030, Çorum, Turkey Mustafa ŞAHİN 3. Alaca State Hospital, Department of General Surgery, Çorum, Turkey Mehmet Berksun TUTAN Author Contributions: RT: Writing – review & editing, Supervision, Methodology, MBT : Conceptualization, Project administration MŞ: Data curation, Formal analysis, Software, Writing–original draft, AKP: Investigation, Visualization, Project administration. İS: Investigation, Project administration. MAY: Investigation, Resources Validation. OA: Investigation, Project administration, Software, Visualization All authors approved the final version of the manuscript to be published. Source of funding: This research received no external funding and This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflict of interest: The authors have no conflict of interest to declare. Data availability statement: The data that support the findings of this study are not openly available due to reasons of sensitivity and privacy are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Hitit University Faculty of Medicine Department of General Surgery. References Shogilev D.J., et al. Diagnosing appendicitis: evidence-based review of the diagnostic approach in 2014. West J Emerg Med. 2014. 15(7): p. 859-871. Brogden T. and C Streets, The management of acute appendicitis. Journal of the Royal Naval Medical Service, 2013. 99(3). Alvarado, A., A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med, 1986. 15(5): p. 557-564. Karul, M., et al., Imaging of appendicitis in adults. Rofo, 2014. 186(6): p. 551-8. Navez, B. and J. Navez, Laparoscopy in the acute abdomen. Best Pract Res Clin Gastroenterol, 2014. 28(1): p. 3-17. Rao, P.M. and G.W. 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Doğan S, Dorter M, Kalafat UM, et al.Diagnostic Value of C-Reactive Protein/Albumin Ratio to Differentiate Simple Versus Complicated Appendicitis. Eurasian J Emerg Med 2020;19:178-183. Feng W, Yang Q, Zhao X,et al.The use of the ratio of C-reactive protein to albumin for the diagnosis of complicated appendicitis in children. Research Square; 2020. Ishizuka M, Shimizu T, Kubota K. Neutrophil-to-lymphocyte ratio has a close association with gangrenous appendicitis in patients undergoing appendectomy. Int Surg 2012; 97: 299-304 Kahramanca S, Ozgehan G, Seker D, et al. Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2014; 20: 19–22 Mehmet Ü, Ertuğrul K, Murat O, et al. The role of neutrophils/lymphocyte ratio, platelet/lymphocyte ratio and platelet distribution width values in acute appendicitis diseases. Biomedical Research 2017; 28(17):7514–7518 Pehlivanli F, Aydin O. Role of Platelet to Lymphocyte Ratio as a Biomedical Marker for the Pre-Operative Diagnosis of Acute Appendicitis. Surgical infections 2019 Bedel C.Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis. Turk J Clin Lab 2018; 4: 266-271. Shahab H, Shahin H, Nicholas H, Moustafa M, Neutrophil-to-lymphocyte ratio predicts acute appendicitis and distinguishes between complicated and uncomplicated appendicitis: A systematic review and meta-analysis, The American Journal of Surgery, 2020; 154-163. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-6264751","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":431412997,"identity":"bbb1bfbd-2931-4ea7-b36d-bb0e17ad5c77","order_by":0,"name":"Ramazan Topcu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYPCCf3L8ICqhgAi1PBDqgLFkA0iLAQlaEjccANHEaLFn7z34mXfPHWPj86sTPzwwYJDnFztAwBaec8nSPM+eyZndeLtZAugww5mzEwhokcgxY+Y5wGxsduPsBpCWBIPbRGpJ3Dzj7OYfpGg5nLiBv3cbkbacOZcsOedAmrHEDd5tFgkGEoT9wt7ee/DDmwM2cvz9Zzff/FFhI88vTUALPGYYJMAqJQgpR9bCf4AY1aNgFIyCUTASAQAZkULpcuaMfAAAAABJRU5ErkJggg==","orcid":"","institution":"Hitit University","correspondingAuthor":true,"prefix":"","firstName":"Ramazan","middleName":"","lastName":"Topcu","suffix":""},{"id":431412998,"identity":"773c4c93-b44c-4861-ac79-470ed81d5bc0","order_by":1,"name":"Mustafa Şahin","email":"","orcid":"","institution":"Hitit University","correspondingAuthor":false,"prefix":"","firstName":"Mustafa","middleName":"","lastName":"Şahin","suffix":""},{"id":431412999,"identity":"2ad63f00-cd87-42d2-a34f-c04a5658f958","order_by":2,"name":"İsmail Sezikli","email":"","orcid":"","institution":"Hitit University","correspondingAuthor":false,"prefix":"","firstName":"İsmail","middleName":"","lastName":"Sezikli","suffix":""},{"id":431413000,"identity":"d2d386ac-d351-4cb3-9fde-6739b0eeab60","order_by":3,"name":"Orhan Aslan","email":"","orcid":"","institution":"Hitit University","correspondingAuthor":false,"prefix":"","firstName":"Orhan","middleName":"","lastName":"Aslan","suffix":""},{"id":431413001,"identity":"f0ccfe08-13cb-4fca-9009-a163fae14b6c","order_by":4,"name":"Mahmut Arif Yüksek","email":"","orcid":"","institution":"Hitit University","correspondingAuthor":false,"prefix":"","firstName":"Mahmut","middleName":"Arif","lastName":"Yüksek","suffix":""},{"id":431413002,"identity":"f6bbcda0-eff1-4c37-ae4a-9bad97839b9c","order_by":5,"name":"Aşkın Kadir Perçem","email":"","orcid":"","institution":"Hitit University","correspondingAuthor":false,"prefix":"","firstName":"Aşkın","middleName":"Kadir","lastName":"Perçem","suffix":""},{"id":431413003,"identity":"40dbaa80-c87a-4090-9843-00db8bc4fde2","order_by":6,"name":"Mehmet Berksun Tutan","email":"","orcid":"","institution":"Alaca State Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"Berksun","lastName":"Tutan","suffix":""}],"badges":[],"createdAt":"2025-03-19 22:38:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6264751/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6264751/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79216550,"identity":"f7024053-0912-4297-ace3-b3be6df4d1e5","added_by":"auto","created_at":"2025-03-25 18:58:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":305618,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart diagram of data collection\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6264751/v1/4d88a38e8ed48b98accb8537.png"},{"id":79216551,"identity":"5b72bfe8-0b6f-4668-b65d-14f95fd0f6eb","added_by":"auto","created_at":"2025-03-25 18:58:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":38165,"visible":true,"origin":"","legend":"\u003cp\u003eCAR, NLR, PLR ROC Curve analysis\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6264751/v1/6c5d2dc6d06ca08ac3d362bc.png"},{"id":79218253,"identity":"1425332b-4825-4154-a45e-886b84bf6e6e","added_by":"auto","created_at":"2025-03-25 19:30:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1099556,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6264751/v1/c2045486-bb70-4518-9d67-89824f2adf94.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive Role of the C-Reactive Protein/Albumin Ratio in Identifying Complicated Acute Appendicitis: A Retrospective Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAcute appendicitis is one of the most common causes of acute abdominal pain in emergency surgical practice, with a lifetime prevalence of approximately 7% [1]. The timing of surgical intervention in acute appendicitis is of critical importance. Early surgical intervention can lead to unnecessary appendectomies, with normal appendix resection rates ranging from 15\u0026ndash;30%. However, delaying surgery increases the risk of perforation, which significantly elevates morbidity and mortality rates (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Therefore, optimizing preoperative evaluations is crucial to reduce unnecessary surgeries, lower perforation rates, and minimize hospital stays for patients presenting with acute appendicitis symptoms (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe diagnosis of acute appendicitis relies on clinical evaluation and laboratory tests, often supplemented by imaging techniques such as ultrasonography (USG), computed tomography (CT), magnetic resonance imaging (MRI), and diagnostic laparoscopy (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). However, USG is operator-dependent and requires expertise, while other imaging methods involve high costs and limited accessibility, complicating routine clinical practice. The diagnostic accuracy of USG in acute appendicitis ranges from 71\u0026ndash;95% (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Since a definitive diagnosis can only be confirmed histopathologically, incorporating a highly predictive, cost-effective, widely accessible, and rapidly applicable biomarker into the diagnostic algorithm would significantly improve clinical decision-making.\u003c/p\u003e \u003cp\u003eA standardized preoperative method for distinguishing between complicated (CAA) and non-complicated acute appendicitis (NCAA) has yet to be established. The ability to predict appendiceal perforation preoperatively is of paramount importance for guiding treatment decisions, determining the need for intraoperative drainage, and adjusting the dosage and duration of antibiotic therapy.\u003c/p\u003e \u003cp\u003eC-reactive protein (CRP) is an acute-phase protein that increases in response to infection, ischemia, trauma, and inflammatory conditions. Elevated CRP levels are strongly associated with adverse clinical outcomes and increased mortality in critically ill patients (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Similarly, hypoalbuminemia is widely recognized as a poor prognostic indicator in both acute and chronic illnesses, frequently occurring in severely ill patients and linked to higher mortality rates (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe C-reactive protein/albumin ratio (CAR) has recently emerged as an inflammation-based prognostic biomarker demonstrating clinical utility in various conditions, including infections, malignancies, and critically ill patients. CAR has also been investigated as an effective tool in the management of acute cholecystitis, acute pancreatitis, cancer, polycystic ovary syndrome, and intensive care patients (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In the literature, studies similar to ours are limited in number, with most studies involving small populations (\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe aim of our study is to demonstrate how CAR can be integrated into the clinical decision-making process by determining a specific cut-off value, based on a large patient population, even though the diagnostic value of CAR has been investigated in previous studies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThis retrospective study was conducted at the Hitit University Faculty of Medicine \u0026Ccedil;orum Erol Ol\u0026ccedil;ok Training and Research Hospital, encompassing patients who underwent appendectomy. Ethical approval was granted by the Hitit University Faculty of Medicine Non-Interventional Studies Ethics Committee on April 7, 2021 (Institutional Review Board approval No: 2021/383).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003ePatients aged 18 years and older who were diagnosed with acute appendicitis and subsequently underwent appendectomy after clinical evaluation, abdominal ultrasonography (USG), and abdominal computed tomography (CT) between January 2016 and May 2020 were retrospectively identified from hospital records. An initial cohort of 2156 patients was identified.Patients were excluded if they had a documented history of hematologic or oncologic disorders, incomplete laboratory data, concurrent infectious or inflammatory conditions unrelated to appendicitis, or malignant/non-appendicitis findings in pathology reports. Following the application of these exclusion criteria, a total of 2001 patients were included in the final analysis \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003eDemographic and laboratory parameters, including age, sex, white blood cell (WBC) count, neutrophil count (NE), lymphocyte count (LY), hemoglobin (Hb), mean platelet volume (MPV), platelet count (PLT), serum albumin (Alb) level, and serum C-reactive protein (CRP) level, were obtained from hospital records at the time of emergency department admission.\u003c/p\u003e \u003cp\u003eAdditionally, emergency American Society of Anesthesiologists (ASA) scores, operative duration, intraoperative complications (as documented in operative notes), postoperative pathology reports, and length of postoperative hospitalization were recorded. Furthermore, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-albumin ratio (CAR) were calculated based on the corresponding hematological parameters.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClassification of Appendicitis Cases\u003c/h3\u003e\n\u003cp\u003ePathology reports and operative notes were systematically reviewed to classify patients into complicated and uncomplicated appendicitis groups. In histopathological evaluations, cases presenting with perforation, abscess formation, necrosis, gangrene, phlegmon, or intraoperative perforation were categorized as complicated appendicitis (CAA) (n\u0026thinsp;=\u0026thinsp;711). In contrast, cases demonstrating no significant inflammation, only mild edema, reactive lymphoid hyperplasia, or fibrous obliteration were classified as non-complicated appendicitis (NCAA) (n\u0026thinsp;=\u0026thinsp;1290).\u003c/p\u003e \u003cp\u003eTo assess the potential of CAR, NLR, PLT, MPV, and other hematological parameters as predictive markers for complicated appendicitis, a comparative analysis was performed between the two groups. The relationship between these biomarkers and appendicitis severity was statistically evaluated to determine their diagnostic and prognostic significance.\"*\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were conducted using IBM SPSS Statistics for Windows (version 26; IBM Corp., Armonk, NY, USA). Descriptive statistics were reported as frequencies and percentages for categorical variables, while continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median (interquartile range, minimum\u0026ndash;maximum), depending on the distribution of the data. The normality of data distribution was assessed using the Shapiro-Wilk test. For comparisons of continuous variables between independent groups, either the independent samples t-test (Student's t-test) or the Mann-Whitney U test was applied, contingent on the normality assumption. Correlations between continuous variables were analyzed using Pearson\u0026rsquo;s correlation coefficient for normally distributed data and Spearman\u0026rsquo;s rank correlation coefficient for non-normally distributed data. Categorical variables were compared using the Chi-squared test (χ\u0026sup2; test) or Fisher\u0026rsquo;s exact test, as appropriate. All statistical tests were two-tailed, and results were interpreted within a 95% confidence interval (CI). Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eAmong the 2001 patients included in the study, 1197 (59.8%) were male and 804 (40.2%) were female. The mean age of the cohort was 37.24\u0026thinsp;\u0026plusmn;\u0026thinsp;14.52 years, with an age range of 18 to 97 years. The distribution of ASA classifications was as follows: 967 patients (48.32%) were ASA1, 886 (44.28%) were ASA2, 130 (6.50%) were ASA3, and 18 (0.90%) were ASA4. The mean values for white blood cell (WBC) count, neutrophil count (NE), and lymphocyte count (LY) were 12.74\u0026thinsp;\u0026plusmn;\u0026thinsp;4.19 \u0026times;10⁹/L, 9.70\u0026thinsp;\u0026plusmn;\u0026thinsp;4.04 \u0026times;10⁹/L, and 1.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90 \u0026times;10⁹/L, respectively. The mean hemoglobin level was 13.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82 g/dL, and the mean platelet count was 236.06\u0026thinsp;\u0026plusmn;\u0026thinsp;63.41 fL.\u003c/p\u003e \u003cp\u003eThe mean albumin level was 4.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39 g/dL, and the median C-reactive protein (CRP) level was 13.05 mg/L (range: 3.02\u0026ndash;374 mg/L). The mean neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-albumin ratio (CAR) were 6.54\u0026thinsp;\u0026plusmn;\u0026thinsp;5.75, 147.44\u0026thinsp;\u0026plusmn;\u0026thinsp;94.51, and 3.36 (0.59\u0026ndash;97.50), respectively. The mean surgical procedure duration, measured from anesthesia initiation to completion, was 51.23\u0026thinsp;\u0026plusmn;\u0026thinsp;13.63 minutes. The mean postoperative hospital stay was 2.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42 days.\u003c/p\u003e \u003cp\u003eA total of 75 patients were classified as negative appendectomy cases, as their pathology reports indicated only the presence of the appendix vermiformis with no evidence of appendicitis. Reactive lymphoid hyperplasia was identified in 148 patients, whereas fibrous obliteration was detected in 40 patients. A definitive diagnosis of acute appendicitis was established in 1027 patients. The complicated appendicitis group included 303 cases of phlegmonous appendicitis, 139 cases of gangrenous appendicitis, 69 cases of necrotizing appendicitis, 112 cases of suppurative appendicitis, and 88 cases of perforated appendicitis. The demographic and clinical characteristics of all patients are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003eComparison Between Uncomplicated and Complicated Appendicitis Groups\u003c/h3\u003e\n\u003cp\u003ePatients were stratified into complicated and uncomplicated appendicitis groups, and their clinical and laboratory parameters were compared (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A statistically significant difference was observed in gender distribution, with a higher proportion of males in the complicated appendicitis group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean age of patients in the complicated appendicitis group was significantly higher than that of the uncomplicated group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, no statistically significant difference was found between the two groups in terms of ASA score distribution (p\u0026thinsp;=\u0026thinsp;0.097).\u003c/p\u003e \u003cp\u003eSignificant differences were observed in WBC count, neutrophil count, and lymphocyte levels between the groups. The complicated appendicitis group exhibited significantly higher leukocytosis and neutrophilia, while lymphopenia was more pronounced (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all comparisons). Platelet levels were significantly lower in the complicated appendicitis group (p\u0026thinsp;=\u0026thinsp;0.002). Additionally, the mean albumin level was significantly lower, while CRP levels were significantly higher in the complicated appendicitis group (p\u0026thinsp;=\u0026thinsp;0.041 and p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively). However, there were no statistically significant differences in hemoglobin levels and mean platelet volumes between the two groups (p\u0026thinsp;=\u0026thinsp;0.349 and p\u0026thinsp;=\u0026thinsp;0.372, respectively).\u003c/p\u003e \u003cp\u003eThe mean NLR was 5.88\u0026thinsp;\u0026plusmn;\u0026thinsp;5.44 in the uncomplicated appendicitis group and 7.74\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10 in the complicated appendicitis group, with a statistically significant difference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, the PLR was significantly higher in the complicated appendicitis group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The CAR was 7.21\u0026thinsp;\u0026plusmn;\u0026thinsp;11.29 in the uncomplicated appendicitis group and 12.72\u0026thinsp;\u0026plusmn;\u0026thinsp;17.46 in the complicated appendicitis group, demonstrating a statistically significant difference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eFurthermore, significant differences were noted in surgical duration and postoperative hospital stay, with both being significantly longer in the complicated appendicitis group (p\u0026thinsp;=\u0026thinsp;0.014 and p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eROC Curve Analysis and Cut-Off Values\u003c/h2\u003e \u003cp\u003eTo determine the optimal cut-off values for NLR, PLR, and CAR in distinguishing uncomplicated from complicated appendicitis, receiver operating characteristic (ROC) curve analysis was performed using the area under the curve (AUC) and Youden index (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The optimal CAR cut-off was determined as 2.06, with 72.61% sensitivity, 48.46% specificity, 46.20% positive predictive value, and 74.40% negative predictive value (OR: 2.48, 95% CI: 1.90\u0026ndash;3.25, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThe optimal NLR cut-off was 3.64, with 80.40% sensitivity, 40.92% specificity, 43.80% positive predictive value, and 79.70% negative predictive value (OR: 3.06, 95% CI: 2.47\u0026ndash;3.79, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The optimal PLR cut-off was 144.87, with 45.23% sensitivity, 63.23% specificity, 40.40% positive predictive value, and 67.60% negative predictive value (OR: 1.39, 95% CI: 1.15\u0026ndash;1.68, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eA CAR exceeding 2.06 mm increased the likelihood of complicated appendicitis by approximately 1.048 times, while an NLR exceeding 3.64 increased the likelihood by 2.06 times. Additionally, a PLR greater than 144.87 increased the risk of complicated appendicitis by 39% (all p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.001; see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssessment of all patients and univariate comparison between uncomplicated and complicated appendicitis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWhole Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2001)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUncomplicated\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1290)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eComplicated\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;711)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eStatistical Significance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1197 (59.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e734 (56.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e463 (65.12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e804 (40.18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e556 (43.10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e248 (34.88%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.24\u0026thinsp;\u0026plusmn;\u0026thinsp;14.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.72\u0026thinsp;\u0026plusmn;\u0026thinsp;13.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.99\u0026thinsp;\u0026plusmn;\u0026thinsp;16.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eASA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e967 (48.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e620 (48.06%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e347 (48.80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e886 (44.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e588 (45.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e298 (41.91%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130 (6.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (5.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58 (8.16%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (0.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (0.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (1.13%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.74\u0026thinsp;\u0026plusmn;\u0026thinsp;4.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.18\u0026thinsp;\u0026plusmn;\u0026thinsp;4.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.76\u0026thinsp;\u0026plusmn;\u0026thinsp;3.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.70\u0026thinsp;\u0026plusmn;\u0026thinsp;4.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.10\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.79\u0026thinsp;\u0026plusmn;\u0026thinsp;3.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePlt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e236.05\u0026thinsp;\u0026plusmn;\u0026thinsp;63.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e238.92\u0026thinsp;\u0026plusmn;\u0026thinsp;63.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e230.83\u0026thinsp;\u0026plusmn;\u0026thinsp;62.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAlb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.05 (3.02\u0026ndash;374.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.92 (3.02\u0026ndash;312.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.30 (3.02\u0026ndash;374.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.54\u0026thinsp;\u0026plusmn;\u0026thinsp;5.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.88\u0026thinsp;\u0026plusmn;\u0026thinsp;5.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.74\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e147.44\u0026thinsp;\u0026plusmn;\u0026thinsp;94.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e142.60\u0026thinsp;\u0026plusmn;\u0026thinsp;94.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e156.20\u0026thinsp;\u0026plusmn;\u0026thinsp;93.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCAR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.36 (0.59-115.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.24 (0.59\u0026ndash;97.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.53 (0.63-115.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eOperation Duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.23\u0026thinsp;\u0026plusmn;\u0026thinsp;13.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53.49\u0026thinsp;\u0026plusmn;\u0026thinsp;13.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.48\u0026thinsp;\u0026plusmn;\u0026thinsp;13.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLength of Stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.77\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eHistopathological Type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAppendix Vermiformis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (3.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" morerows=\"8\" nameend=\"c6\" namest=\"c4\" rowspan=\"9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReactive Lymphoid Hyperplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e148 (7.40%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFibrous Obliteration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (2.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcute Appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1027 (51.32%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhlegmonous Appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e303 (15.14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGangrenous Appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139 (6.95%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNecrotizing Appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (3.45%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuppurative Appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112 (5.60%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerforation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88 (4.40%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eComplication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e711 (35.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCAR, NLR, PLR Cut-off Values\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eCut-off\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eDiagnostic Values\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eROC Analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003eOdds Ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSpecificity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePPV\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNPV\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eArea (SE)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.61%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.46%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46.20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e74.40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.630 (0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.596\u0026ndash;0.664\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.48 (95% CI 1.90\u0026ndash;3.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.92%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79.70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.618 (0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.583\u0026ndash;0.652\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.06 (95% CI 2.47\u0026ndash;3.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.23%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.23%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67.30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.542 (0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.506\u0026ndash;0.578\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.39 (95% CI 1.15\u0026ndash;1.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eAcute appendicitis (AA) remains one of the most common causes of acute abdomen. In early-stage surgical interventions, the presence of a normal appendix has been reported in 15\u0026ndash;30% of cases. Prolonged preoperative observation in AA has been associated with an increased risk of complicated appendicitis, leading to higher morbidity and mortality rates (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Therefore, identifying a cost-effective, repeatable, and widely accessible biomarker with high predictive value could facilitate more accurate diagnoses and improve clinical decision-making. Predicting appendiceal perforation preoperatively, particularly through blood-based biomarkers, could significantly influence treatment strategies, including the necessity for surgical drainage, the selection and duration of antibiotic therapy, and overall patient management.\u003c/p\u003e \u003cp\u003eNumerous studies have evaluated laboratory markers for the diagnosis of AA. Parameters such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume, red cell distribution width, and C-reactive protein (CRP) have been extensively investigated in this context (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Beyond diagnosing AA, distinguishing between complicated and uncomplicated appendicitis is of critical importance due to the significant differences in associated morbidity and mortality. Previous studies have demonstrated that CRP levels are markedly elevated in complicated appendicitis compared to uncomplicated cases (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Similarly, high leukocyte counts have been reported in cases of necrotic or perforated appendicitis (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Kim et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) found that both CRP and international normalized ratio (INR) were predictive of complicated appendicitis. Additionally, a study by Shelton et al. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) established a direct association between elevated preoperative CRP levels and increased postoperative complications. Moreover, elevated NLR and PLR levels have been implicated in higher complication rates among AA patients (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur study corroborates these findings, demonstrating significantly higher levels of neutrophils (NE), CRP, white blood cell (WBC) count, NLR, and PLR in patients with complicated AA compared to those with uncomplicated AA (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Conversely, platelet, albumin, and lymphocyte levels were significantly lower in complicated AA cases (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These findings align with the existing literature, reinforcing the diagnostic utility of these biomarkers in clinical practice.\u003c/p\u003e \u003cp\u003eThe C-reactive protein-to-albumin ratio (CAR) has increasingly been recognized as an independent prognostic marker in various inflammatory and malignant conditions (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Elevated CAR levels are expected in inflammatory states and have been shown to aid in the early diagnosis and management of acute cholecystitis, acute pancreatitis, malignancies, polycystic ovary syndrome, and critically ill patients (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Despite its emerging importance, studies investigating the relationship between CAR and acute appendicitis (AA) remain limited. To date, only a few studies have evaluated CAR in AA patients. One of these studies suggests that an increasing CAR may serve as a valuable biomarker for distinguishing complicated from uncomplicated AA (\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Another study demonstrated that CAR provided superior predictive value for complicated appendicitis in pediatric populations compared to other biomarkers (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, the optimal CAR cut-off value for predicting complicated AA was determined to be 2.06, yielding a sensitivity of 72.61% and specificity of 48.46%, with positive and negative predictive values of 46.20% and 74.40%, respectively. A CAR level exceeding 2.06 was associated with a 1.48-fold increased risk of complications (p\u0026thinsp;=\u0026thinsp;0.001). These findings are consistent with previous studies that have identified CAR cut-off values for complicated appendicitis. Doğan et al. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) reported a CAR cut-off value of 4.4, which was associated with a 10.624-fold increased risk of complicated AA. Similarly, Feng et al. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) found an optimal CAR cut-off value of 1.43, which was associated with a 102.22-fold increased risk of complicated appendicitis. These studies corroborate our findings and highlight the potential of CAR as a diagnostic and prognostic marker (\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCAR values\u0026thinsp;\u0026gt;\u0026thinsp;2.06 in patients indicate a higher risk of complications. Therefore, more intensive monitoring should be implemented. This involves closely tracking clinical signs, laboratory results, and imaging findings to identify any deterioration or progression of the condition promptly. Furthermore, antibiotic therapy should be initiated early to reduce the risk of infection and sepsis, particularly in patients at risk for complicated appendicitis. In some cases, the timing of surgery may need to be expedited to prevent the development of further complications, such as perforation or abscess formation, which can significantly increase morbidity and mortality. These measures aim to optimize patient outcomes by proactively addressing potential complications.\u003c/p\u003e \u003cp\u003eAdditionally, we determined the optimal cut-off values for NLR (3.64; sensitivity: 80.40%, specificity: 40.92%) and PLR (144.87; sensitivity: 45.23%, specificity: 63.23%). An NLR value exceeding 3.64 was associated with a 2.06-fold increased risk of complications (p\u0026thinsp;=\u0026thinsp;0.001). Previous studies have reported varying cut-off values for NLR, ranging from 4.68 to 8.0, with sensitivities ranging from 65\u0026ndash;73% and specificities from 39\u0026ndash;55% (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). For PLR, our results align with those of \u0026Ccedil;elik et al. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), who reported a cut-off value of 284 (sensitivity: 42%, specificity: 86%) for diagnosing complicated AA. Additionally, Pehlivanli et al.(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) found that PLR was valuable in differentiating normal appendix cases from AA and in distinguishing uncomplicated from complicated AA.\u003c/p\u003e \u003cp\u003eA comparative analysis of our study groups revealed that male gender, older age, elevated WBC and NE counts, lower lymphocyte and platelet counts, reduced albumin levels, and increased CRP, CAR, PLR, and NLR levels were significantly associated with complicated AA. These findings are consistent with multiple studies in the literature (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDue to the relatively low specificity, the management of false positives needs to be discussed. For instance, \"In patients with CAR\u0026thinsp;\u0026gt;\u0026thinsp;2.06, further evaluation using NLR and PLR can help minimize the likelihood of false positives.\" This would involve using additional biomarkers to confirm or refine the diagnosis, ensuring that patients at higher risk for complications are appropriately treated, while avoiding unnecessary interventions for those with false positive results. Combining CAR with other parameters, such as NLR and PLR, enhances diagnostic accuracy, offering a more comprehensive approach to patient management.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eThis study has several limitations, primarily its retrospective design, which may introduce selection bias and limit the ability to establish causal relationships. Additionally, the absence of preoperative imaging comparisons restricts the ability to assess the role of imaging modalities in conjunction with CAR for the diagnosis of complicated appendicitis. Furthermore, the reliance on data obtained from the hospital information system may limit the accuracy and completeness of some clinical variables. Future prospective studies incorporating imaging techniques, such as ultrasound, CT, or MRI, along with larger and more diverse patient cohorts, are needed to validate these findings and assess the utility of CAR\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eOur findings suggest that elevated levels of WBC, NE, CRP, NLR, and CAR, along with reduced levels of LY, Plt, and albumin, can serve as valuable biomarkers for distinguishing between complicated and uncomplicated acute appendicitis (AA) when used in conjunction with clinical and radiological assessments. Laboratory-based cut-off values may help refine diagnostic accuracy and optimize treatment planning. Notably, CAR emerged as a potentially superior biomarker for predicting complicated AA compared to other hematological markers. Since these laboratory parameters do not incur additional financial costs, their application could be particularly advantageous in resource-limited settings where access to advanced diagnostic tools is constrained. Further large-scale, prospective studies are necessary to establish the clinical utility of CAR in managing AA.\u003c/p\u003e"},{"header":"Declarations","content":"\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis exploratory, retrospective, single-center cohort study was conducted in accordance with the most recent version of the Declaration of Helsinki. The study received approval from the local ethics committee of the Hitit University Faculty of Medicine (2021/383). Given the retrospective design of the study, the ethics committee granted a waiver for written informed consent. The informed consent was waived by IRB (Clinical Research Ethics Committee of Hitit University Faculty of Medicine)\u0026nbsp;The data collection and manuscript preparation processes were conducted in accordance with the guidelines set forth by the Committee on Publication Ethics (COPE) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor İnformation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.Hitit University Faculty of Medicine, Department of General Surgery, 19030, \u0026Ccedil;orum, Turkey\u003c/p\u003e\n\u003cp\u003eİsmail SEZİKLİ, Ramazan TOPCU, Mahmut Arif Y\u0026Uuml;KSEK, Orhan ASLAN, Aşkın Kadir PER\u0026Ccedil;EM\u003c/p\u003e\n\u003cp\u003e2. Hitit University Faculty of Medicine, Department of Medical Biochemistry, 19030, \u0026Ccedil;orum, Turkey\u003c/p\u003e\n\u003cp\u003eMustafa ŞAHİN\u003c/p\u003e\n\u003cp\u003e3. Alaca State Hospital, Department of General Surgery, \u0026Ccedil;orum, Turkey\u003c/p\u003e\n\u003cp\u003eMehmet Berksun TUTAN\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRT:\u003c/strong\u003e Writing \u0026ndash; review \u0026amp; editing, Supervision, Methodology, \u003cstrong\u003eMBT\u003c/strong\u003e: Conceptualization, Project administration \u003cstrong\u003eMŞ:\u003c/strong\u003e Data curation, Formal analysis, Software, Writing\u0026ndash;original draft, \u003cstrong\u003eAKP:\u003c/strong\u003e Investigation, Visualization, Project administration. \u003cstrong\u003eİS:\u003c/strong\u003e Investigation, Project administration. \u003cstrong\u003eMAY:\u003c/strong\u003e Investigation, Resources Validation. \u003cstrong\u003eOA:\u003c/strong\u003e Investigation, Project administration, Software, Visualization\u003c/p\u003e\n\u003cp\u003eAll authors approved the final version of the manuscript to be published.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSource of funding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding and This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflict of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not openly available due to reasons of sensitivity and privacy are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Hitit University Faculty of Medicine Department of General Surgery.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShogilev D.J., et al. Diagnosing appendicitis: evidence-based review of the diagnostic approach in 2014. West J Emerg Med. 2014. 15(7): p. 859-871.\u003c/li\u003e\n\u003cli\u003eBrogden T. and C Streets, The management of acute appendicitis. Journal of the Royal Naval Medical Service, 2013. 99(3).\u003c/li\u003e\n\u003cli\u003eAlvarado, A., A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med, 1986. 15(5): p. 557-564.\u003c/li\u003e\n\u003cli\u003eKarul, M., et al., Imaging of appendicitis in adults. Rofo, 2014. 186(6): p. 551-8.\u003c/li\u003e\n\u003cli\u003eNavez, B. and J. Navez, Laparoscopy in the acute abdomen. Best Pract Res Clin Gastroenterol, 2014. 28(1): p. 3-17.\u003c/li\u003e\n\u003cli\u003eRao, P.M. and G.W. Boland, Imaging of acute right lower abdominal quadrant pain. Clin Radiol, 1998. 53(9): p. 639-649.\u003c/li\u003e\n\u003cli\u003eThijs, L.G. and C.E. Hack, Time course of cytokine levels in sepsis. Intensive Care Med, 1995. 21 Suppl 2: p. S258-263.\u003c/li\u003e\n\u003cli\u003eHo, K.M., et al., C-reactive protein concentration as a predictor of in-hospital mortality after ICU discharge: a prospective cohort study. Intensive care medicine, 2008. 34(3): p. 481-487.\u003c/li\u003e\n\u003cli\u003eVillacorta H., A.C. Masetta E.T. Mesquita, C-reactive protein: an inflammatory marker with prognostic value in patients with decompensated heart failure. Arq Bras Cardiol, 2007. 88(5): p. 585-589.\u003c/li\u003e\n\u003cli\u003eArtero, A., et al., Prognostic factors of mortality in patients with community-acquired bloodstream infection with severe sepsis and septic shock. J Crit Care, 2010. 25(2): p. 276-281.\u003c/li\u003e\n\u003cli\u003eKim, M.H., et al., The C-reactive protein/albumin ratio as an independent predictor of mortality in patients with severe sepsis or septic shock treated with early goal-directed therapy. PLoS One, 2015. 10(7)\u003c/li\u003e\n\u003cli\u003eRanzani, O.T., et al., C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLoS One, 2013. 8(3)\u003c/li\u003e\n\u003cli\u003eKim, M., S.J. Kim, and H.J. Cho, International normalized ratio and serum C-reactive protein are feasible markers to predict complicated appendicitis. World J Emerg Surg, 2016. 11: p. 31.\u003c/li\u003e\n\u003cli\u003eHou, J., Feng, W., Liu, W., Hou, J., Die et al. The use of the ratio of C-reactive protein to albumin for the diagnosis of complicated appendicitis in children. The American Journal of Emergency Medicine.2022. 52, 148-154.\u003c/li\u003e\n\u003cli\u003eDin\u0026ccedil; T, and Sapmaz A. Albumin to C-Reactive Protein Ratio: A New Inflammation-Based Score That Can be Used to Predict the Severity of Appendicitis .Surgical Chronicles. (2021) 26.4 \u003c/li\u003e\n\u003cli\u003eZhao, Xin, Jian Yang, and Jun Li.The predictive value of the C-reactive protein/albumin ratio in adult patients with complicated appendicitis.Journal of Laboratory Medicine 47.5 (2023): 211-215.\u003c/li\u003e\n\u003cli\u003eAl-Abed YA, Alobaid N, Myint F. Diagnostic markers in acute appendicitis. Am J Surg. 2015; 209:1043-1047.\u003c/li\u003e\n\u003cli\u003eAydin OU, Soylu L, Dandin O, et al. Laboratory in complicated appendicitis prediction and predictive value of monitoring. Bratisl Lek Listy. 2016; 117: 697-701.\u003c/li\u003e\n\u003cli\u003eEddama M, Fragkos KC, Renshaw S, et al. Logistic regression model to predict acute uncomplicated and complicated appendicitis. Ann R Coll Surg Engl. 2019;5: 107-118.\u003c/li\u003e\n\u003cli\u003ePham XD, Sullins VF, Kim DY, et al. Factors predictive of complicated appendicitis in children. J Surg Res. 2016; 206 :62-66.\u003c/li\u003e\n\u003cli\u003eShelton JA, Brown JJ, Young JA. Preoperative C-reactive protein predicts the severity and likelihood of complications following appendicectomy. Ann R Coll Surg Engl. 2014 ;96: 369-372.\u003c/li\u003e\n\u003cli\u003eCelik B, Nalcacioglu H, Ozcatal M, et al.Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department. Ulus Travma Acil Cerrahi Derg. 2019 May;25(3):222-228. \u003c/li\u003e\n\u003cli\u003eDoğan S, Dorter M, Kalafat UM, et al.Diagnostic Value of C-Reactive Protein/Albumin Ratio to Differentiate Simple Versus Complicated Appendicitis. Eurasian J Emerg Med 2020;19:178-183.\u003c/li\u003e\n\u003cli\u003eFeng W, Yang Q, Zhao X,et al.The use of the ratio of C-reactive protein to albumin for the diagnosis of complicated appendicitis in children. Research Square; 2020. \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. Int Surg 2012; 97: 299-304\u003c/li\u003e\n\u003cli\u003eKahramanca S, Ozgehan G, Seker D, et al. Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2014; 20: 19\u0026ndash;22\u003c/li\u003e\n\u003cli\u003eMehmet \u0026Uuml;, Ertuğrul K, Murat O, et al. The role of neutrophils/lymphocyte ratio, platelet/lymphocyte ratio and platelet distribution width values in acute appendicitis diseases. Biomedical Research 2017; 28(17):7514\u0026ndash;7518\u003c/li\u003e\n\u003cli\u003ePehlivanli F, Aydin O. Role of Platelet to Lymphocyte Ratio as a Biomedical Marker for the Pre-Operative Diagnosis of Acute Appendicitis. Surgical infections 2019 \u003c/li\u003e\n\u003cli\u003eBedel C.Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis. Turk J Clin Lab 2018; 4: 266-271.\u003c/li\u003e\n\u003cli\u003eShahab H, Shahin H, Nicholas H, Moustafa M, Neutrophil-to-lymphocyte ratio predicts acute appendicitis and distinguishes between complicated and uncomplicated appendicitis: A systematic review and meta-analysis, The American Journal of Surgery, 2020; 154-163.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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, C-Reactive Protein, Albumin, Hemogram Parameters, Biomarker, Complicated Appendicitis","lastPublishedDoi":"10.21203/rs.3.rs-6264751/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6264751/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eThis study investigates the predictive value of the C-reactive protein/albumin ratio (CAR) in distinguishing complicated acute appendicitis (CAA) from non-complicated acute appendicitis (NCAA), aiming to enhance diagnostic accuracy and improve clinical decision-making.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective analysis was conducted on patients diagnosed with acute appendicitis who underwent appendectomy between January 2016 and May 2020. Demographic, clinical, and laboratory data, including age, sex, white blood cell (WBC) count, neutrophil count (NE), lymphocyte count (LY), hemoglobin (Hb), mean platelet volume (MPV), platelet count (PLT), serum albumin (Alb) levels, and C-reactive protein (CRP) levels, were extracted from hospital records. Additionally, ASA scores and operative durations were recorded. Patients were classified into CAA and NCAA groups based on pathology reports and surgical notes. The CAR and other hematological parameters were compared between groups, and their diagnostic performance was evaluated.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eThe median CAR was significantly higher in the CAA group (5.53; range: 0.63\u0026ndash;115.19) compared to the NCAA group (2.24; range: 0.59\u0026ndash;97.50) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The optimal CAR cut-off value for predicting CAA was 2.06, yielding a sensitivity of 72.61% and a specificity of 48.46%. The positive predictive value (PPV) was 46.20%, whereas the negative predictive value (NPV) was 74.40%. Furthermore, a CAR level exceeding 2.06 was associated with a 1.48-fold increased risk of complications (p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eOur findings suggest that CAR is a significant biomarker for predicting complicated acute appendicitis, offering valuable clinical insights for early risk stratification. When used in conjunction with other hematological parameters, CAR may enhance diagnostic accuracy and guide clinical decision-making, potentially reducing unnecessary interventions. Further large-scale, prospective studies are essential to validate the clinical utility of the CAR in the managem\u003c/p\u003e","manuscriptTitle":"Predictive Role of the C-Reactive Protein/Albumin Ratio in Identifying Complicated Acute Appendicitis: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-25 18:58:52","doi":"10.21203/rs.3.rs-6264751/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":"d2a195aa-4146-4d26-8da4-a686f3dbe55c","owner":[],"postedDate":"March 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":45949862,"name":"Health sciences/Biomarkers/Predictive markers"},{"id":45949863,"name":"Health sciences/Biomarkers/Prognostic markers"}],"tags":[],"updatedAt":"2025-06-17T12:59:38+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-25 18:58:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6264751","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6264751","identity":"rs-6264751","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}