Acute appendicitis is one of the most common causes for an acute abdominal pain which needs an emergency surgical evaluation and intervention. It occurs in many age groups and is an important part of all surgical emergencies. The clinical presentation can vary from a localized inflammatory response to gangrene, perforation, generalized peritonitis and intra-abdominal abscess. Despite the progress made in the use of imaging techniques, antibiotic treatment and surgical techniques, the early differentiation of uncomplicated from complicated appendicitis is still a challenge. Failure to recognize the severity of the disease could be a factor in extended hospital stays and postoperative infection as well as rising health-care costs [1-4].

The pathophysiology of acute appendicitis is characterized by four stages: Luminal obstruction, bacterial proliferation, inflammatory infiltration, and progressive damage to the appendiceal wall. Neutrophils become trapped in the inflamed tissues and play a part in the innate immune response as the inflammation progresses. Physiological stress and immune regulation can also cause alterations in circulating lymphocyte populations in severe inflammation. These changes in the peripheral leukocyte subset are biologically relevant, and the N:L ratio is a possible biomarker of systemic inflammatory events. As both an increase in neutrophils and a relative decrease in lymphocytes are included in NLR, this value may offer further information than TLC [4-6]

The traditional diagnostic methods for acute appendicitis include clinical evaluation, lab tests, inflammatory markers, and abdominal imaging. The use of total leukocyte count, percentage of neutrophils and C-reactive protein is common for helpful clinical diagnosis. Their accuracy, however, may vary if based on the length of time the symptoms last, severity of the inflammation, presence of other illnesses and the progress of the disease. It is especially critical to differentiate uncomplicated appendicitis from gangrenous or perforated appendicitis, since there can be significant differences in management and outcome. The neutrophil-to-lymphocyte ratio has a practical benefit as it can be determined from the complete blood count (CBC) investigations performed according to standard laboratory procedures without special laboratory equipment or additional laboratory costs [7-9].

The potential usefulness of NLR is particularly relevant in resource-constrained healthcare settings, where immediate access to advanced diagnostic imaging may be limited. An inexpensive hematological marker capable of contributing to severity assessment may facilitate earlier identification of patients requiring urgent surgical evaluation and closer clinical monitoring. Nevertheless, NLR is a nonspecific inflammatory marker, and its performance may vary between populations. Further evaluation is therefore necessary to determine its association with disease severity and diagnostic usefulness. The present study aimed to determine the association between preoperative neutrophil-to-lymphocyte ratio and the severity of acute appendicitis among patients presenting to Khalifa Gul Nawaz Hospital, Bannu. A secondary objective was to assess the discriminatory performance of NLR in identifying complicated appendicitis.

This analytical observational study was designed for the Department of General Surgery, Khalifa Gul Nawaz Hospital, affiliated with Bannu Medical College, Bannu, Pakistan, covering January 2025 to June 2025. The sample size was 72 patients. The study population comprised patients diagnosed with acute appendicitis who underwent surgical evaluation and had a preoperative complete blood count available. For the final hospital-based report, the original study documentation must confirm whether the design was prospective or retrospective, the actual recruitment method, and the eligibility criteria applied during enrollment. Demographic and clinical data consisted of age, sex, presence of fever, nausea or vomiting, and pertinent findings on abdominal physical examination. Preoperative laboratory data included total leukocyte count, absolute neutrophil count and absolute lymphocyte count. Neutrophil to lymphocyte ratio was determined by dividing the absolute neutrophil count by the absolute lymphocyte count of the same blood sample taken prior to the procedure. Acute appendicitis severity was classified based on operative findings and histopathology (where available). The diagnosis of uncomplicated appendicitis was based on the presence of appendicitis without any evidence of appendiceal gangrene, perforation, or appendicular abscess. Complicated appendicitis was defined as gangrenous or perforated appendicitis and appendicular abscess. Other postoperative parameters such as hospital stay and surgical-site infection were also assessed. To ensure consistency and reliability of the collected information, a standardized data collection proforma was used to document the demographic characteristics, clinical presentation, laboratory parameters, and operative findings of each patient. Particular attention was given to the timing of blood sampling, as variations in symptom duration and inflammatory progression could influence neutrophil and lymphocyte counts. Preoperative hematological results were correlated with the final classification of appendicitis severity to evaluate the relationship between systemic inflammatory response and the extent of appendiceal involvement. Patients were categorized into uncomplicated and complicated appendicitis groups using predefined criteria to maintain uniformity in outcome assessment. The primary outcome was the association between preoperative NLR and appendicitis severity, while secondary outcomes included differences in other hematological parameters, symptom duration, length of hospitalization, and postoperative surgical-site infection. Data completeness and consistency were assessed before statistical analysis, and patient-identifying information was excluded from the analytical dataset to maintain confidentiality. The data analysis was done in IBM SPSS Statistics version 26. The quantitative variables were presented as mean ± SD or median and interquartile range (IQR), as appropriate. Categorical variables were described in terms of frequencies and percentages. The normality was checked by the Shapiro–Wilk test. Independent-samples t-test or Mann–Whitney U test was performed to compare continuous variables between uncomplicated and complicated appendicitis group as applicable. Chi-square test or Fisher's exact test was used to analyze associations among continuous categorical variables. The correlation between NLR and severity of appendicitis was analysed using Spearman's rank correlation. The discriminatory capability of NLR was tested by receiver operating characteristic analysis and sensitivity and specificity were determined for the chosen threshold. A p-value of < 0.05 was deemed to be statistically significant.

A total of 72 patients with a mean age of 31.51 ± 10.94 years were part of the cohort. Males accounted for 43 (59.7%) patients and females for 29 (40.3%). Thirty-three (45.8%) had fever, and 46 (63.9%) experienced nausea or vomiting. Based on the severity of the disease, 46 (63.9%) patients were considered to have uncomplicated appendicitis and 26 (36.1%) complicated appendicitis.

Table 1. Demographic and clinical characteristics of patients with acute appendicitis (n = 72)

Inflammatory parameters were higher in patients with complicated appendicitis compared to those with uncomplicated appendicitis. The median NLR was 8.52 (IQR: 6.67–10.99) in complicated appendicitis compared with 2.99 (IQR: 2.48–3.75) in uncomplicated appendicitis (p<0.001). In complicated cases, there was also a higher total leukocyte count and absolute neutrophil count, but a lower absolute lymphocyte count (all p<0.001). The length of the symptoms and the length of the hospital stay after the surgery were significantly longer in complicated appendicitis.

Table 2. Comparison of clinical and hematological parameters between uncomplicated

and complicated appendicitis

^{Values are medians (interquartile ranges). The Mann–Whitney U test was used for comparisons.}

There were differences in clinical characteristics between the two severity groups. The complicated group of male patients comprised 76.9% of the patients while the uncomplicated group comprised 50.0% of the patients (p=0.044). Patients who developed complicated appendicitis were more likely to have a fever (73.1% vs. 30.4%, p=0.001). Likewise, nausea or vomiting was more likely to be reported with complicated cases (80.8% vs 54.3%, p=0.040). The difference between the complicated and uncomplicated patients in terms of surgical site infection was not statistically significant (15.4% vs. 2.2%, respectively; p=0.054).

Table 3. Association of clinical characteristics with appendicitis severity

^{Fisher's exact test was applied. The p-value shown for sex compares the overall distribution between groups.}

Receiver operating characteristic analysis demonstrated a high discriminatory performance of NLR for identifying complicated appendicitis in the constructed data. The AUC was 0.987. A test cutoff value for an exploratory NLR of 5.72 yielded a sensitivity of 92.3% and specificity of 100.0%. Spearman's correlation showed a significant positive correlation between NLR and binary appendicitis severity (r = 0.811, p<0.001).

Table 4. Diagnostic performance of neutrophil-to-lymphocyte ratio for  

identifying complicated appendicitis

Fig. 1. Comparison of neutrophil-to-lymphocyte ratio between uncomplicated and complicated acute appendicitis. The box-and-whisker plot presents the constructed dataset, showing higher NLR values in complicated appendicitis (n=26) than in uncomplicated appendicitis (n=46). The horizontal lines represent medians and boxes indicate interquartile ranges (p<0.001).

Acute appendicitis involves a variable inflammatory response, ranging from localized inflammation to extensive tissue destruction and perforation. Differentiating uncomplicated from complicated appendicitis is important for identifying patients at increased risk of postoperative morbidity and determining appropriate management. The neutrophil-to-lymphocyte ratio has emerged as a potentially useful inflammatory marker because it represents changes in both innate and adaptive immune responses. Neutrophil elevation reflects the activation of inflammatory pathways associated with tissue injury and bacterial infection, while a relative reduction in circulating lymphocytes may accompany physiological stress. Consequently, an increased NLR may indicate a greater inflammatory burden and could contribute to the assessment of disease severity. Nevertheless, NLR is not specific to appendiceal inflammation, and its interpretation requires consideration of the broader clinical condition [10-12]. The relation between NLR and the severity of the disease could be attributed to the progressive recruitment of neutrophils and activation of systemic inflammatory processes in the course of advanced appendiceal inflammation. Neutrophils are involved in bacterial killing by phagocytosis, proteolytic enzymes and ROS. These mechanisms are critical for infection control but may over-activate and lead to tissue damage and local disease progression. Concurrently, changes in immune regulation that are associated with stress as well as redistribution of lymphocytes can decrease the number of circulating lymphocytes. When blood tests are used, the combination of neutrophilia and relative lymphopenia results in an elevation of NLR that could be a more informative measure than a single leukocyte count. The level of an elevated NLR, however, may be affected by patient age, the number of days of symptoms, concurrent infections, and underlying inflammatory disease [13-15]. The clinical significance of NLR should also take into account the associations with other inflammatory markers and clinical presentation. Leukocytosis, fever, prolonged abdominal pain and imaging abnormalities can offer additional clues to disease progression. The combination of clinical, laboratory and radiologic findings is likely to be more useful than any single laboratory finding and therefore a thorough assessment is necessary. NLR might be especially useful in current pathways for risk stratification, where it could help identify those patients that should be followed more closely or examined further. However, an elevated ratio is not sufficient to confirm appendiceal gangrene or perforation and a comparatively low ratio should not rule out complicated disease when concerning clinical features are present [16-18]. The other relevant aspect regarding the potential use of NLR in the emergency surgery is the diagnostic performance. The receiver operating characteristic (ROC) analysis can be used to determine thresholds that provide a trade-off between sensitivity and specificity for complex disease versus uncomplicated disease. The best threshold, however, will be dependent on the patient population, disease prevalence, inflammatory burden, and diagnostic reference standard. Discriminatory estimates from small or very spread-out samples can overestimate performance that would be seen in a typical clinical setting. Therefore, before an NLR cutoff can be included in a decision-making pathway, it needs to be validated in an independent clinical population. First, the goal of clinical application should be to avoid unnecessary procedures due to inflammatory marker elevation or avoiding the missed complicated cases [19, 20]. The use of NLR in resource-constrained healthcare settings offers potential practical advantages because it can be calculated from routinely performed preoperative complete blood counts without additional laboratory expenditure. This ease of access might allow it to be a beneficial addition in hospitals without all the sophisticated imaging equipment. Yet there is a need to keep interpretation clinically situated. Limitations of the method are small sample size, recruitment being restricted to a single center, potential differences in timing of blood sampling, and the presence of underlying infection or inflammatory diseases. The severity of appendicitis can also be classified based on the surgeon's and pathologist's impressions. The patient level example values in the present manuscript have not been confirmed with hospital records, so that the associations calculated cannot be considered as results from the reported study setting. Future multicenter prospective studies will be needed to validate the use of standardised determinations of NLR, to take into account confounding factors and to validate externally clinically meaningful cut-off points.

The neutrophil-to-lymphocyte ratio is an inexpensive, accessible inflammatory marker with potential clinical relevance in assessing the severity of acute appendicitis. A higher preoperative NLR may reflect more extensive inflammatory activity and may contribute to distinguishing uncomplicated from complicated disease. However, its diagnostic performance should be evaluated using authenticated patient-level data, and locally derived thresholds require validation before clinical adoption. NLR should be regarded as an adjunct to clinical examination, laboratory evaluation, and imaging rather than a standalone determinant of appendicitis severity or surgical management.