Inflammatory biomarkers and symptom presence in pediatric corrosive substance ingestion: a retrospective study

Abstract

Background

Corrosive substance ingestion is a significant clinical problem in the pediatric population, with challenges in early assessment due to the inconsistent relationship between symptoms and the severity of esophageal injury. Easily accessible inflammatory biomarkers have been proposed as adjunctive tools for early clinical evaluation. This study aimed to evaluate the association between inflammatory biomarkers and symptom presence in pediatric patients with corrosive substance ingestion and to assess their discriminative performance.

Methods

This retrospective study included 213 pediatric patients (aged 0–18 years) with corrosive substance ingestion. Patients were classified according to the type of ingested substance and the presence of symptoms. Inflammatory biomarkers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune-inflammation value (PIV) were calculated, and their association with symptom presence was analyzed.

Results

The proportion of symptomatic patients was 8.5% (n = 18), with vomiting and hypersalivation being the most common symptoms. Neutrophil levels were higher (P = 0.016) and lymphocyte levels were lower (P = 0.007) in symptomatic patients, resulting in significantly elevated NLR (P = 0.002). PLR (P = 0.006), SII (P = 0.004), SIRI (P = 0.020), and PIV (P = 0.019) were also higher. NLR showed the best discriminative performance (AUC = 0.723; 95% CI: 0.557–0.888), with 61.1% sensitivity and 90.3% specificity at a cut-off of 2.15. Logistic regression confirmed a significant association between elevated NLR and symptom presence.

Conclusions

Inflammatory biomarkers, particularly NLR, were associated with symptom presence; however, their diagnostic or prognostic value is limited. They should not replace endoscopic evaluation. Further prospective studies are needed to validate their clinical utility.

Introduction

Lesions formed in the esophagus as a result of ingesting corrosive substances (acid or alkali) in liquid or solid form are called corrosive esophagitis [1, 2]. Such accidents are common in the pediatric age group and constitute a significant health problem in our country. Corrosive substances are divided into two main groups according to their chemical content: basic and acidic. Acidic substances cause coagulation necrosis in the affected tissue, resulting in more superficial damage, whereas alkaline substances lead to liquefactive necrosis, causing deeper and more extensive injury [3, 4]. Full-thickness burns, perforation, and stricture development, particularly in the thoracic esophagus, contribute to significant morbidity and mortality. Long-term complications include esophageal stricture formation and gastrointestinal morbidity, with reported rates ranging from 7% to 25% [5, 6].

Corrosive esophageal injuries are most commonly classified using the Zargar endoscopic grading system, which categorizes mucosal damage from Grade 0 (normal mucosa) to Grade 3 (severe necrosis, subdivided into 3 A and 3B) and Grade 4 (perforation). This classification provides important prognostic information and guides clinical management decisions [7]. In addition to endoscopic grading, the clinical course of corrosive esophagitis is typically divided into three phases: the acute phase (days 1–10), characterized by necrosis and inflammation; the subacute phase (days 10–20), marked by ulceration and increased tissue fragility; and the chronic phase (after 3 weeks), during which fibrosis and stricture formation may occur. Understanding these phases is critical in determining the timing and safety of interventions such as endoscopy [8].

The unresolved debate surrounding the management of corrosive substance ingestion poses a significant problem for both patients and healthcare systems. The clinical management of corrosive substance ingestion is directly related to the extent of damage and the risk of complications. Current guidelines recommend endoscopic evaluation within 24–48 h after exposure [9, 10]. However, some researchers argue that endoscopy may yield a high rate of normal findings and should be selectively performed based on clinical criteria [11–13]. The current literature highlights the mismatch between symptom severity and the extent of esophageal injury as a major clinical challenge [14].

In recent years, alternative imaging modalities such as computed tomography (CT)-based classifications have also been proposed to assess the depth and extent of injury, particularly in cases where endoscopy may be contraindicated or inconclusive. However, these approaches are not yet standardized and remain complementary rather than definitive diagnostic tools [8].

Determining the severity of injury and predicting clinical outcomes based solely on clinical presentation or the chemical nature of the ingested substance remains difficult. Therefore, there is an ongoing need for reliable, rapid, and non-invasive biomarkers that may assist in the initial assessment of these patients.

Recently, parameters derived from complete blood count (CBC) have gained attention as accessible and cost-effective markers of systemic inflammation. These include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune-inflammation value (PIV), which have been investigated in various inflammatory and gastrointestinal conditions [15–17].

A review of the literature revealed no studies evaluating NLR, PLR, SII, SIRI, and PIV together in pediatric patients with corrosive substance ingestion. However, several recent studies and meta-analyses in pediatric gastrointestinal diseases have demonstrated the potential diagnostic and prognostic relevance of these indices, particularly in conditions such as acute appendicitis and inflammatory disorders, supporting their potential utility as adjunctive markers in clinical decision-making [17]. In this context, rather than replacing established diagnostic methods such as endoscopy, these biomarkers may provide supportive information in the early clinical assessment of patients.

In our study, we aimed to evaluate the association between inflammatory biomarkers (NLR, PLR, SII, SIRI, and PIV) and the presence of symptoms in pediatric patients who ingested corrosive substances, and to assess their discriminative performance in distinguishing symptomatic from asymptomatic patients. Given the current limitations in predicting esophageal injury based solely on clinical findings, our study seeks to contribute to the growing body of evidence exploring the role of easily accessible laboratory parameters in the initial evaluation of these patients.

Materials and methods

Study design and population

This retrospective study included 213 pediatric patients (aged 0–18 years) who presented with corrosive substance ingestion between December 2018 and 2023 at a tertiary care center. Ethical approval was obtained from the Institutional Ethics Committee of Hitit University Faculty of Medicine (date: 03.01.2024, decision number: 2023-22).

Inclusion and exclusion criteria

Patients aged between 0 and 18 years with a documented history of corrosive substance ingestion and available clinical and laboratory data were included in the study.

Patients with incomplete medical records, missing laboratory data, or coexisting conditions that could affect inflammatory markers (such as active infection, chronic inflammatory disease, or hematological disorders) were excluded.

Clinical definitions

Patients were classified into three groups according to the type of ingested substance: detergents, bleach and other corrosive substances, and drain cleaners and limescale removers. Patients were further categorized into two groups based on the presence of symptoms at admission. Symptomatic patients were defined as those presenting with clinical findings such as vomiting, hypersalivation, dysphagia, or oropharyngeal irritation. Patients without these findings were classified as asymptomatic.

Data collection and laboratory analysis

Demographic data (age and sex), type of ingested substance, clinical findings, and laboratory parameters were obtained from hospital records. Laboratory parameters included hemoglobin, white blood cell count (WBC), neutrophils, lymphocytes, monocytes, platelets, and albumin levels.

The following inflammatory indices were calculated:

Statistical analysis

Statistical analyses were performed using SPSS software (IBM Corp., Armonk, NY, USA), and graphical visualizations were generated using the ggplot2 package in R software (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics were presented as frequency (n) and percentage (%) for categorical variables. Continuous variables were expressed as mean ± standard deviation (SD) for normally distributed data and as median (Q1–Q3) for non-normally distributed data. The normality of continuous variables was assessed using the Shapiro–Wilk test.

Group comparisons were performed using the chi-square test for categorical variables. For continuous variables, Student’s t-test or one-way ANOVA was used for normally distributed data, while the Mann–Whitney U test or Kruskal–Wallis test was applied for non-normally distributed data. Dunn–Bonferroni post hoc analysis was conducted when appropriate.

Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of inflammatory indices to discriminate between symptomatic and asymptomatic patients. The area under the curve (AUC) and 95% confidence intervals were calculated. Optimal cut-off values were determined using the Youden index, and the corresponding sensitivity and specificity values were reported together with their 95% confidence intervals.

Univariate and multivariate logistic regression analyses were performed to evaluate the association between selected variables and the presence of symptoms. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

All statistical tests were two-tailed. A P-value < 0.05 was considered statistically significant.

Results

Patient characteristics

A total of 213 patient records were analyzed in the study. The median age of the study population was 2 years (range: 0–18). Of the patients, 106 (49.8%) were female and 107 (50.2%) were male. When classified according to the type of ingested substances, 68 patients (31.9%) ingested detergents, 98 patients (46%) ingested bleach and other corrosive substances, and 47 patients (22.1%) ingested drain cleaners and limescale removers.

The proportion of patients without symptoms was 91.5% (n = 195), while 8.5% (n = 18) developed symptoms. Among symptomatic patients, vomiting was observed in 9 patients (4.2%) and hypersalivation in 7 patients (3.3%). Dysphagia was reported in 5 patients (2.3%), and oropharyngeal irritation in 4 patients (1.9%). On physical examination, hyperemia was present in 6 patients (2.8%) and edema in 5 patients (2.3%).

The mean length of hospital stay was 0.51 ± 2.67 days, with a maximum duration of 35 days. The median length of hospital stay was 0 (0–0), reflecting that the majority of patients were managed on an outpatient basis and discharged on the same day.

Comparison according to substance type

Comparative findings of demographic characteristics, laboratory parameters, and inflammation indices between the substance groups are presented in Table 1.

Table 1.

Comparison of demographic, laboratory parameters, and inflammation indices between the research groups

Variable		Detergents (n = 68) (1)	Bleach and Other Corrosive Substances (n = 98) (2)	Drain Openers and Lime Removers (n = 47) (3)	P	Post-hoc P
Gender	F	35 (51.5%)	46 (46.9%)	25 (53.2%)	0.736a	-
	M	33 (48.5%)	52 (53.1%)	22 (46.8%)
Age (years)		2 (1–12.5)	2 (1–9)	2 (1–5)	0.928c	-
Length of Hospital Stay (days)		0 (0–0)	0 (0–0)	0 (0–0)	0.187c	-
Monocyte (×10³/µL)		1.77 ± 0.81	1.76 ± 0.74	1.84 ± 0.8	0.813b	-
Hb (g/dL)		12.8 (12.5–13.2)	12.7 (12.5–13.4)	12.5 (12.3–12.7)	0.014 c	1–2: 1.000 1–3: 0.037 2–3: 0.017
Neutrophil (×10³/µL)		6.41 ± 2.78	6.25 ± 2.8	5.66 ± 2.49	0.331b	-
Lymphocyte (×10³/µL)		5.81 ± 2.49	5.81 ± 2.67	5.95 ± 2.26	0.944b	-
PLT (×10³/µL)		307.8 ± 66.17	309.6 ± 59.77	305 ± 71.58	0.922b	-
Albumin (g/L)		42 (41–45)	43 (41-45.25)	43 (41–45)	0.831c	-
WBC (×10³/µL)		10.6 ± 2.6	10.35 ± 2.34	10.89 ± 2.31	0.444b	-
NLR		1.05 (0.73–1.67)	1.02 (0.68–1.68)	0.94 (0.68–1.37)	0.367c
PLR		59.02 (43.22–76.81)	59.21 (38.05–84.67)	53.17 (39.25–71.35)	0.668c
SII		304.1 (210.9-497.1)	321 (190.7-483.5)	296.4 (186.8 -400.8)	0.371c
SIRI		1.92 (1.08–3.22)	1.77 (0.95–3.12)	1.49 (0.97–2.74)	0.571c
PIV		568.8 (343.1–1007)	502.9 (260.9–963.5)	454 (262.2–773)	0.534c

F Female, M Male, Hb Hemoglobin, PLT Platelets, WBC White Blood Cell, NLR Neutrophil-to-Lymphocyte Ratio, PLR Platelet-to-Lymphocyte Ratio, SII Systemic Immune-Inflammation Index, SIRI Systemic Inflammatory Response Index, PIV Pan-Immune-Inflammation Value

^aChi-Square with n (%)

^bOne-way ANOVA with mean ± standard deviation (SD)

^cKruskal wallis test followed Dunn-Bonferroni post-hoc tests with median (Q1-Q3)

Values below P < 0.05 were shown bold

No significant differences were found between the groups in terms of gender distribution, age, length of stay, monocytes, neutrophils, lymphocytes, platelets, albumin, WBC, NLR, PLR, SII, SIRI, and PIV (all P > 0.05, Table 1). However, a significant difference was observed in hemoglobin levels (P = 0.014).

Post-hoc analyses showed that hemoglobin values were significantly higher in the detergents group (P = 0.037) and the bleach and other corrosive substances group (P = 0.017) compared to the drain openers and limescale removers group.

Comparison according to symptom presence

Comparisons based on symptom presence are presented in Table 2. Neutrophil levels were significantly higher (P = 0.016), whereas lymphocyte levels were significantly lower (P = 0.007) in the symptomatic group. Consequently, NLR was significantly elevated in the symptomatic group (P = 0.002). Similarly, PLR (P = 0.006), SII (P = 0.004), SIRI (P = 0.020), and PIV (P = 0.019) values were also significantly higher in symptomatic patients.

Table 2.

Statistical comparison of demographic characteristics, laboratory parameters, and inflammation indices among symptom groups

		Groups		P values
		Asymptomatic (n = 195)	Symptomatic (n = 18)
Gender	F	98 (50.3%)	8 (44.4%)	0.637a
	M	97 (49.7%)	10 (55.6%)
Age (years)		2 (1–9)	2 (1–6)	0.909e
Length of Hospital Stay (days)		0 (0–0)	0 (0–1)	0.267e
Monocyte (×10³/µL)		1.77 ± 0.76	1.85 ± 0.91	0.710d
Hb (g/dL)		12.7 (12.4–13.2)	12.65 (12.5–13.25)	0.992e
Neutrophil (×10³/µL)		6.03 ± 2.64	7.64 ± 3.27	0.016 d
Lymphocyte (×10³/µL)		5.98 ± 2.48	4.31 ± 2.46	0.007 d
PLT (×10³/µL)		307 ± 63.1	318.7 ± 77.4	0.462d
Albumin (g/L)		43 (41–45)	43.5 (41–46.25)	0.741e
WBC (×10³/µL)		10.5 ± 2.44	10.8 ± 2.18	0.605d
NLR		1 (0.68–1.57)	2.84 (0.83–3.74)	0.002 e
PLR		54.3 (39.6–77.1)	77.5 (60.8–146.7)	0.006 e
SII		300.3 (199–453.8)	785.8 (214.1–1282)	0.004 e
SIRI		1.72 (0.97–2.85)	5.04 (0.99–8.23)	0.020 e
PIV		498.1 (273–839.7)	1469.4 (202.9–2632)	0.019 e

F Female, M Male, Hb Hemoglobin, PLT Platelets, WBC White Blood Cell, NLR Neutrophil-to-Lymphocyte Ratio, PLR Platelet-to-Lymphocyte Ratio, SII Systemic Immune-Inflammation Index, SIRI Systemic Inflammatory Response Index, PIV Pan-Immune-Inflammation Value

^aChi-square test

^dStudent’s t test

^eMann-Whitney U test

Values below P < 0.05 were shown bold

No significant differences were observed between the groups in terms of gender, age, length of stay, monocytes, hemoglobin, platelets, albumin, and WBC (all P > 0.05, Table 2).

ROC analysis of inflammatory indices

The discriminative performance of inflammation indices for symptom presence was evaluated using ROC analysis (Table 3).

Table 3.

Results of ROC analysis for inflammation indices in predicting symptoms, with cut-off values and corresponding sensitivity and specificity

Variables	AUC (95% CI)	Cut-off	Sensitivity (95% CI)	Specificity (95% CI)
NLR	0.723 (0.557–0.888)	2.15	61.1% (38.6–79.7)	90.3% (85.3–93.7)
PLR	0.695 (0.545–0.845)	65.87	77.8% (54.8–91.0)	63.1% (56.1–69.5)
SII	0.705 (0.534–0.876)	738.5	61.1% (38.6–79.7)	92.3% (87.7–95.3)
SIRI	0.666 (0.486–0.845)	5.01	55.6% (33.7–75.4)	94.9% (90.8–97.2)
PIV	0.667 (0.483–0.851)	1186	61.1% (38.6–79.7)	88.2% (82.9–92.0)

NLR Neutrophil-to-Lymphocyte Ratio, PLR Platelet-to-Lymphocyte Ratio, SII Systemic Immune-Inflammation Index, SIRI Systemic Inflammatory Response Index, PIV Pan-Immune-Inflammation Value, AUC Area Under the Curve, CI Confidence Interval

According to ROC analysis, NLR showed the highest AUC value (AUC = 0.723; 95% CI: 0.557–0.888). At the optimal cut-off value of 2.15, NLR demonstrated a sensitivity of 61.1% (95% CI: 38.6–79.7) and a specificity of 90.3% (95% CI: 85.3–93.7). PLR (AUC = 0.695), SII (AUC = 0.705), SIRI (AUC = 0.666), and PIV (AUC = 0.667) also demonstrated modest discriminative performance.

Sensitivity values ranged from 55.6% to 77.8%, while specificity values ranged from 63.1% to 94.9% across the evaluated biomarkers. The distributions of NLR and SII according to symptom groups are illustrated in Fig. 1.

Fig. 1.

Violin plots with overlaid jittered individual data points and interquartile ranges illustrating the distribution of NLR and SII according to symptom groups. A Distribution of NLR according to symptom groups B Distribution of SII according to symptom groups

Logistic regression analysis

The results of the logistic regression analyses are presented in Table 4. In univariate analyses, gender and age were not significantly associated with symptom presence (P = 0.638 and P = 0.612, respectively).

Table 4.

Results of univariate and multivariate binary logistic regression analyses to determine the effect of risk factors on predicting symptoms

	Univariate		Multivariate
	P values	OR (CI 95%)	P values	OR (CI 95%)
Gender (Male vs. female)	0.638	1.26 (0.48–3.34)	0.543	1.41 (0.46–4.3)
Age (years)	0.612	0.978 (0.897–1.066)	0.619	0.976 (0.888–1.073)
Substance Type
Bleach and other corrosive substances vs. detergents	0.069	4.17 (0.89–19.47)	0.083	4.27 (0.83–22.1)
Drain openers and lime removers vs. detergents	0.111	3.93 (0.73–21.18)	0.046	6.66 (1.04–42.9)
NLR (≥ 2.15 vs. < 2.15)	< 0.001	14.6 (5.05–41.9)	< 0.001	17.6 (5.6–55.5)
Multivariate model: Nagelkerke R Square = 0.305, Classification accuracy: 92.5%

OR Odds ratio, CI Confidence interval, NLR Neutrophil-to-Lymphocyte Ratio

Values below P < 0.05 were shown bold

Compared to the detergent group, the association between bleach and corrosive substance ingestion and symptom presence did not reach statistical significance (P = 0.069).

The presence of NLR ≥ 2.15 was significantly associated with symptom development (OR = 14.6; 95% CI: 5.05–41.9; P < 0.001).

In the multivariate model, the likelihood of symptom presence was significantly higher in the drain openers and limescale removers group compared to the detergent group (OR = 6.66; 95% CI: 1.04–42.9; P = 0.046). Similarly, NLR ≥ 2.15 remained significantly associated with symptom presence (OR = 17.6; 95% CI: 5.6–55.5; P < 0.001). The explanatory power of the multivariate model was moderate (Nagelkerke R² = 0.305), with an overall classification accuracy of 92.5%.

Discussion

In this study, we found that inflammatory biomarkers, particularly NLR, were significantly associated with the presence of symptoms in pediatric patients with corrosive substance ingestion. However, their discriminative performance was modest, and these markers cannot be considered reliable tools for clinical decision-making. Although corrosive substance ingestion is a rare health problem in developed countries due to safety regulations, it remains a significant cause of morbidity and mortality in developing countries [18]. Injuries related to corrosive substance ingestion are particularly common in the pediatric age group. Although there are no definitive recorded data for Turkey, the annual number of cases is estimated to be between 3,000 and 5,000 [19]. However, previous studies have reported that the incidence of corrosive ingestion remains considerable worldwide, with thousands of pediatric cases reported annually despite preventive measures [20, 21]. Accidental ingestion of household cleaning products remains a preventable but common clinical problem [22].

When the ingested substances are evaluated, it is evident that many of these substances are transferred into accessible containers during household cleaning, increasing the risk of accidental ingestion by children [22, 23]. In our study, the most common presenting symptoms were vomiting and hypersalivation, and physical examination findings revealed hyperemia and edema of the oral mucosa. Similar findings have been reported in previous studies [24]. The relationship between clinical presentation and the severity of esophageal injury remains controversial. While some studies suggest that symptoms are not reliable predictors of injury severity, others report a correlation between clinical findings and esophageal damage [25–27]. Furthermore, it has been reported that the absence of clinical findings does not exclude significant gastrointestinal injury [28–30]. This discrepancy represents a major challenge in clinical decision-making.

Current guidelines recommend endoscopic evaluation within 24–48 h after corrosive substance ingestion [9, 10]. However, previous studies have reported that a substantial proportion of endoscopic examinations are normal, raising concerns regarding the necessity of routine endoscopy in all patients [31, 32]. In addition, several studies suggest that significant esophageal injury is unlikely in asymptomatic patients and that endoscopy may be avoided in selected cases [11, 33–38]. Urganci et al. also reported that no pathological findings were detected in a considerable proportion of patients undergoing endoscopy [39]. On the other hand, some studies have demonstrated that severe oropharyngeal findings do not reliably predict esophageal injury [40].

In this context, our findings suggest that inflammatory biomarkers may be associated with the presence of clinical symptoms; however, they should not be interpreted as indicators of injury severity or as substitutes for endoscopic evaluation. Consistent with the literature, few studies have confirmed the predictive value of laboratory tests for corrosive substance-related morbidity [41]. Chen et al. reported that leukocyte counts may be useful in assessing esophageal injury severity but are not reliable predictors of long-term outcomes such as stricture formation [42, 43]. In our study, neutrophil levels were significantly higher and lymphocyte levels were lower in symptomatic patients, resulting in increased NLR values. Similarly, PLR, SII, SIRI, and PIV values were also significantly elevated in symptomatic patients. Among these biomarkers, NLR demonstrated the highest discriminative performance (AUC = 0.723), although this level indicates only moderate diagnostic accuracy.

Although ROC analysis allowed the identification of an optimal cut-off value, the sensitivity and specificity values suggest that these markers alone are insufficient for clinical decision-making and should be interpreted cautiously. Furthermore, logistic regression analysis demonstrated a significant association between elevated NLR levels and symptom presence. However, the wide confidence intervals observed in the regression models indicate limited precision and should be interpreted with caution. In addition to NLR, the multivariate analysis revealed that ingestion of drain openers and limescale removers was significantly associated with a higher likelihood of symptom development compared to detergents (OR = 6.66; 95% CI: 1.04–42.9; P = 0.046). This finding suggests that certain types of corrosive substances may have a stronger clinical impact. However, the wide confidence interval indicates limited precision, likely due to the relatively small number of symptomatic cases, and this result should therefore be interpreted cautiously.

This study has several limitations. First, its retrospective and single-center design may limit the generalizability of the findings. Second, the relatively small number of symptomatic patients may have affected the statistical power of the analyses. In addition, the cut-off values identified in this study were determined using the study dataset and may therefore be subject to threshold overfitting, potentially leading to optimistic estimates of diagnostic performance. External validation in independent cohorts is required to confirm these findings [44]. Moreover, although odds ratios were used to evaluate associations, it should be noted that odds ratios do not directly reflect diagnostic or predictive performance, and their interpretation in this context has important limitations [45]. Finally, the lack of endoscopic grading data (such as Zargar classification) limits the ability to evaluate the relationship between biomarkers and the severity of esophageal injury.

Conclusion

Corrosive substance ingestion remains a significant cause of morbidity in children due to its potential to cause severe gastrointestinal injury and long-term complications. Inflammatory biomarkers such as NLR, PLR, SII, SIRI, and PIV were associated with symptom presence in pediatric patients with corrosive substance ingestion. However, these biomarkers should not be considered as diagnostic or prognostic tools or as substitutes for endoscopic evaluation. Further prospective studies with larger sample sizes and external validation are needed.

Authors’ contributions

All authors contributed to the study conception and design. All authors read and approved the final manuscript. Hİ: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. GD: Conceptualization, Data curation, Methodology, Resources, Validation, Writing – review & editing. MM: Conceptualization, Formal analysis, Methodology, Validation, Writing – review & editing. NÇ: Conceptualization, Methodology, Validation, Writing – review & editing. ÇEA: Conceptualization, Methodology, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing.

Funding

The authors received no specific funding for this work.

Data availability

Data can be obtained by contacting the corresponding author.

Declarations

Ethics approval and consent to participate

This retrospective study was approved by the Institutional Ethics Committee of Hitit University Faculty of Medicine (date: 03.01.2024, decision number: 2023-22). This study was conducted in accordance with the principles of the Declaration of Helsinki. Due to the retrospective nature of the study, the requirement for informed consent was waived.

Competing interests

The authors declare no competing interests.