July 2025
Prediction of serious clinical outcomes in patients presenting with syncope in the short-term follow-up: Which variables to use?
İbrahim Ertaş 1, Derya Abuşka 2, Özgür Karcıoğlu 3
1 Department of Emergency Medicine, Faculty of Medicine, University of Yıldırım Beyazıt, Yenimahalle Research and Training Hospital, Ankara, 2 Department of Emergency Medicine, Istanbul Research and Training Hospital, Istanbul, 3 Department of Emergency Medicine, Taksim Research and Training Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.22175 Received: 2024-03-10 Accepted: 2024-05-06 Published Online: 2025-02-07 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):460-464
Corresponding Author: İbrahim Ertaş, Department of Emergency Medicine, Faculty of Medicine, University of Yıldırım Beyazıt, Yenimahalle Research and Training Hospital, Ankara, Turkey. E-mail: ertasibrahim0880@gmail.com P: +90 506 440 08 80 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9375-4298
Other Authors ORCID ID: Derya Abuşka, https://orcid.org/0000-0003-3527-2682 . Özgür Karcıoğlu, https://orcid.org/0000-0002-8814-6164
This study was approved by the Ethics Committee of Istanbul Training and Research Hospital (Date: 2020-10-16, No: 2556)
Aim: This study aims to identify patient groups diagnosed with syncope in the emergency department (ED) based on initial evaluation, distinguish those whose etiology remains unclear necessitating hospitalization, and assess factors influencing serious clinical outcomes (SCOs) within 30 days post-ED admission for suspected syncope.
Material and Methods: This prospective, single-center observational study included patients presenting to the ED with suspected syncope over a six-month period. Subjects were categorized into three groups: those diagnosed and discharged following initial testing in the ED, those requiring hospitalization, and those undiagnosed in the ED but discharged for outpatient follow-up within 24 hours. The study’s primary endpoint was the incidence of SCO, with secondary analysis focusing on determinants of SCO.
Results: The study encompassed 257 patients, among whom 22 (8.6%) experienced serious clinical outcomes (SCOs). The incidence of SCO was significantly higher at 22.2% among Group 2 patients, who required hospitalization, compared to those discharged directly from the emergency department (ED) (p=0.013). Notably, 62.9% of the hospitalized patients (Group 2) were diagnosed with cardiac syncope, while 11.1% had an undetermined cause of syncope despite ED evaluation. Abnormalities in electrocardiogram (ECG) were observed in 59.1% (n=13) of the patients who experienced SCOs (p<0.001).
Discussion: The data indicates a statistically significant increase in SCOs among patients admitted to the hospital compared to those discharged from the ED. Moreover, the presence of a normal ECG appears to correlate with a lower likelihood of experiencing SCOs, underscoring the value of ECG as a predictive tool in the assessment of syncope.
Keywords: Emergency Department, Electrocardiogram, Syncope, Serious Clinical Outcome
Introduction
Syncope, defined as a transient loss of consciousness due to a brief reduction in cerebral perfusion, is marked by an abrupt onset and spontaneous resolution without the need for medical intervention [1-3]. This prevalent condition accounts for approximately 1-3% of emergency department (ED) visits annually, with one in four individuals experiencing at least one episode of syncope in their lifetime [4, 5].
The management of syncope is tailored to its underlying cause. In cases of cardiac syncope, the primary objective is to prevent sudden cardiac death. Conversely, when dealing with reflex syncope presented in the ED, the goals shift towards preventing future episodes, safeguarding against potential injury from falls during subsequent attacks, and enhancing the patient’s quality of life [6].
Given the critical nature of timely and accurate patient assessments in emergency settings, the noisy and crowded environment of the ED can impair the evaluation process of patients at risk, underscoring the importance of utilizing algorithms in the assessment of such patients [7-9]. This approach not only streamlines patient care but also enhances the accuracy and efficiency of emergency medical interventions.
In the ED, accurately assessing a syncope patient’s risk for serious clinical outcomes (SCOs) is crucial. The European Society of Cardiology (ESC) 2018 Syncope Guidelines categorize patients based on their SCO risk into three levels: low-risk, high-risk, and intermediate-risk (neither high nor low) [10]. For low-risk patients, discharge from the ED is typically deemed safe. In contrast, high-risk patients are recommended for immediate emergency intervention and hospitalization. The intermediate-risk group warrants further investigations to address the potential for syncope recurrence.
This study aims to segregate patients admitted to the ED with a preliminary diagnosis of syncope into these risk categories based on initial evaluation, to analyze their 30-day SCO rates, and to identify factors influencing SCOs.
Material and Methods
This prospective observational study was conducted in the ED of a tertiary care hospital. Eligible participants were individuals aged 18 years and older who presented to the ED with a preliminary diagnosis of syncope between August 1, 2019, and February 1, 2020. Exclusion criteria included patients presenting with other causes of transient loss of consciousness such as seizures, vertigo, trauma, cerebrovascular events, drug intoxication, hypoglycemia, as well as pregnant women, individuals under 18 years of age, and those unwilling to provide consent for participation. Consent was obtained from all subjects participating in the study.
Upon presentation to the ED, all patients underwent a standardized initial evaluation, including a medical history review, physical examination, electrocardiography (ECG), and measurements of blood pressure in both supine and standing positions. Neuroimaging was conducted as needed for individuals suspected of experiencing a cerebrovascular event. Consistent with the ESC 2018 Syncope Guidelines, patients were stratified into three distinct groups for analysis [10]. The first group comprised patients who were evaluated, diagnosed, and discharged directly from the ED. The second group included those who were either diagnosed with conditions requiring in-hospital treatment or undiagnosed but considered high risk for adverse outcomes, necessitating hospitalization. Criteria for high risk were established according to the ESC guidelines. The third group consisted of patients who remained undiagnosed after ED assessment but were clinically stable enough to be discharged within 24 hours for outpatient follow-up.
The primary outcome of interest was the occurrence of a SCO within 30 days of the ED visit. SCOs were defined as a recurrence of syncope, readmission to the ED, or mortality within this period. Follow-up for determining the 30-day SCOs was conducted via telephone calls to the patients or their relatives, using contact information collected at the time of ED admission. The analysis also explored factors potentially influencing the likelihood of an SCO, considered as a secondary endpoint.
Statistical analysis
Descriptive statistics of the dataset included mean, standard deviation, median, range (lowest to highest values), frequency, and proportion. The distribution normality of variables was assessed using the Kolmogorov-Smirnov test. For the analysis of independent quantitative data, the Kruskal-Wallis and Mann-Whitney U tests were employed. Independent qualitative data were evaluated using the Chi-square test, with Fisher’s Exact test applied in instances where Chi-square test assumptions did not hold. All statistical analyses were conducted using SPSS software for Windows (Version 26, Chicago, IL, USA). Statistical significance was determined at a p-value of less than 0.05.
Ethical Approval
This study was approved by the Ethics Committee of Istanbul Training and Research Hospital (Date: 2020-10-16, No: 2556).
Results
After applying the exclusion criteria, 257 patients remained eligible for inclusion. Notably, the proportion of female patients was higher in Group 1 compared to the other two groups, and the mean age in this group was statistically significantly lower. The distribution of age and gender across the groups, along with vital signs analyses, is detailed in Table 1. Among the study participants, reflex syncope was identified in 51% (n=131) of patients, orthostatic syncope in 25.3% (n=65), and cardiac syncope in 10.9% (n=28). For 12.8% (n=33) of the patients, the type of syncope remained unspecified. Serious clinical outcomes were observed in 8.6% (n=22) of cases. The overall 30-day mortality rate across the cohort was 1.6% (n=4). Notably, the incidence of SCO was significantly higher in the group requiring hospitalization (p=0.013). The categorization of syncope types across the patient groups is detailed in Table 2. The mean age of patients experiencing SCO was 59.05±19.68 years, significantly older than those without SCO (p=0.017). Additionally, 68% (n=15) of patients with SCO were male; however, gender was not found to be a statistically significant factor in comparison to patients without SCO (p=0.078).
A prodromal period, characterized by symptoms such as dizziness, nausea, and sweating before syncope, was reported in 71.9% (n=185) of patients. SCOs occurred in only 3.2% (n=6) of patients with these prodromal symptoms, compared to 22.2% (n=16) of patients without them, indicating a significant association between the absence of a prodromal period and increased SCO risk (p<0.001). Electrocardiogram (ECG) results were normal in 73.5% (n=189) of study participants but showed abnormalities in 26.5% (n=68). The most frequent ECG abnormalities included atrial fibrillation (AF) at 7% (n=18), sinus bradycardia at 4.7% (n=12), and sinus tachycardia at 3.9% (n=10). ECG abnormalities were significantly more common in patients with SCOs (59.1%, n=13) than in those without (p<0.001). The distribution of ECG abnormalities and their correlation with SCOs are detailed in Table 3.
Among patients experiencing SCOs, 59.1% (n=13) had ECG abnormalities, with AF being the predominant finding (18.2%, n=4). Of the four deceased patients, ECGs revealed right bundle branch block (RBBB) in one case, AF in two, and sinus tachycardia in the remaining patient.
Analysis of comorbid diseases among study participants revealed that hypertension (HT) at 28% (n=71), diabetes mellitus (DM) at 18.3% (n=47), and coronary artery disease (CAD) at 12.8% (n=33) were the most common. Among patients experiencing SCOs, the presence of HT, DM, CAD, and chronic obstructive pulmonary disease (COPD) did not significantly impact SCO incidence. However, patients with malignancy exhibited a notably higher SCO rate at 30% (n=4 out of 13), which was statistically significant (p=0.017).
Echocardiography (ECHO) was performed for 20.6% (n=53) of patients, revealing mild heart failure in 3.9% (n=10), moderate heart failure in 0.4% (n=1), severe heart failure in 3.5% (n=9), very severe heart failure in 0.8% (n=2), and normal findings in 12.1% (n=31). The necessity for ECHO and the mean ejection fraction (EF) did not significantly predict SCOs, with no discernible difference in distribution across the groups (p=0.37).
In the evaluation of laboratory results, blood lactate levels were assessed in 70 patients from Group 1, showing a significant relationship with SCOs. The average lactate level in patients without SCOs was 1.67±0.76 (n=65), compared to 2.06±1.59 in patients with SCOs (n=5), indicating higher lactate levels in those experiencing SCOs (p=0.032).
Discussion
Our study highlighted an increased incidence of serious clinical outcomes (SCOs) among hospitalized patients, predominantly those with cardiac syncope or undetermined syncope etiology in the emergency department (ED). This observation mirrors the findings of a large-scale multicenter study by Krishan RJ et al., which also reported a heightened SCO rate in hospitalized patients, attributed to both non-fatal arrhythmic events and serious non-arrhythmic complications [11]. Notably, 82.3% of our hospitalized patients who experienced SCOs presented with abnormal ECGs, reinforcing the significance of ECG abnormalities as a predictor of adverse outcomes.
These results align with the European Society of Cardiology (ESC) 2018 syncope guidelines, which recommend hospitalization for patients with syncope of unclear etiology due to the associated high risk of SCOs. An additional aspect explored in our study was the SCO rate among patients discharged with recommendations for outpatient follow-up within 24 hours. The absence of a significant increase in SCOs in this group suggests effective patient selection for discharge, highlighting the feasibility of outpatient management for those at lower risk of SCOs.
Mortality rates significantly increase in elderly patients presenting with syncope, primarily due to the multifaceted nature of potential causes and a higher prevalence of underlying cardiac conditions [12]. This correlation is supported by the research of Grossman et al., who monitored the 30-day outcomes of 293 syncope patients. Their findings revealed a mean age of 57.8±24.2 years across the cohort, with patients experiencing SCOs having a mean age of 70.2±21.4 years. Importantly, an age exceeding 75 years was significantly associated with SCOs [13]. Similarly, our study observed that advanced age correlated with an increased risk of SCOs, mirroring the mean age trend and reinforcing the critical consideration of age in syncope prognosis.
In a prospective analysis of syncope patients by Sarasin FP et al., 69% were found to have cardiac syncope, while the etiology remained undetermined in 14% despite comprehensive evaluations including computerized tomography (CT), troponin, plasma D-dimer, Doppler ultrasonography (USG), lung imaging, echocardiography (ECHO), and 24-hour Holter monitoring [14]. Similarly, in our study, despite employing a range of diagnostic tools such as CBT, high-sensitivity troponin T (Hs-TnT), D-Dimer, Doppler USG, and ECHO, the etiology of syncope remained elusive in 12.8% of patients following initial ED evaluation. The notably higher incidence of SCOs in hospitalized patients underscores the importance of hospitalization for those at risk, even when the specific syncope type remains unidentified through advanced ED diagnostics.
Reed MW’s analysis on syncope management, supplemented by case studies, highlights the necessity for further arrhythmia investigations in patients presenting without a prodromal period, atypical syncope triggers, or facial injuries, even among younger populations [15]. This recommendation is based on the distinction between arrhythmic syncope—often lacking a prodrome or featuring a very brief prodrome of less than 3 seconds—and reflex syncope, which may have a prodrome lasting up to 3 minutes. Consistent with Reed MW’s findings, our study observed a significantly higher SCO rate in patients who did not experience a prodromal period, suggesting a potential link between the absence of prodrome and increased risk of arrhythmic events.
Previous research has shown varying rates of ECG abnormalities in syncope patients, with one prospective study identifying abnormalities in 36% of cases [16], and another study reporting a 31% abnormality rate in the context of short-term SCOs [17]. Our findings align with these observations, as abnormal ECGs were detected in 26.5% of our study participants, correlating with an increased likelihood of SCOs. This concurrence with existing literature underscores the pivotal role of ECG evaluation in identifying patients at elevated risk of adverse outcomes following syncope episodes.
A comprehensive study involving 1,920 patients aged 65 and over reported that hypertension (HT) was present in 66% of the cohort, hyperlipidemia in 32%, and coronary artery disease (CAD) in another 32% [15]. Another investigation highlighted that among its participants, 32% had HT, 10% were diagnosed with diabetes mellitus (DM), 12% had CAD, and 3.9% suffered from congestive heart failure (CHF) [18]. In line with these findings, our study also identified HT, DM, CAD, and CHF among the syncope patients. However, unlike previous studies, we found no significant association between these comorbid conditions and the occurrence of SCOs in our patient population. Interestingly, our analysis did reveal that patients with malignancy were more likely to experience adverse clinical outcomes.
In a prospective study evaluating 84 patients discharged from the ED, 11% experienced a serious outcome within 7 days, identifying abnormal ECG, hematocrit below 30%, blood pressure (BP) under 90 mmHg, and a history of congestive heart failure (CHF) as key warning signs for adverse events [17]. Our study, with a higher SCO rate of 26%, also underscores the significance of ECG abnormalities and comorbidities in influencing SCOs. However, unlike the referenced study, our analysis did not find admission vital signs, hematocrit levels, or a history of CHF to be predictive of SCOs. Instead, ECG abnormalities were a more pronounced indicator of risk in our cohort. In another study focusing on ECG monitoring of 5,581 patients presenting with syncope to the ED, 7.5% encountered SCOs, attributed to various arrhythmias and device issues [19]. Consistent with these findings, AF was identified as the most frequent ECG abnormality leading to SCOs in our study, followed by ischemic ECG changes. Notably, one of the patients with a fatal outcome in our study had RBBB.
A significant study involving 282,311 individuals reported a 30-day readmission rate of 9.3%, with male gender and cardiovascular diseases highlighted as risk factors. Cardiac issues were the primary cause of readmission, accounting for 17.2% of cases [20]. While our study focused on SCOs including ED readmissions and syncope relapses within 30 days, specific causes of rehospitalization were not explored in detail. Nevertheless, cardiac etiologies were identified as the prevalent reason for initial hospital admissions in our cohort, aligning with the broader literature emphasizing cardiac conditions as a critical concern in syncope management.
Serum lactate is increasingly recognized for its role in distinguishing between syncope and other conditions causing transient loss of consciousness, such as epileptic seizures and psychogenic non-epileptic states. Matz O et al. underscored serum lactate as an exceptional biomarker for differentiating these events, advocating for its inclusion in standard evaluations [12]. Consistent with this perspective, our study found that lactate levels exceeding 2 mmol/L were significantly associated with SCOs in patients initially diagnosed with syncope after excluding those with epilepsy. This highlights the diagnostic and prognostic importance of measuring serum lactate in the acute assessment of syncope.
Limitation
This study’s limitations include its single-center design, which may limit the generalizability of the findings to broader populations and healthcare settings. Additionally, the observational nature of the study cannot establish causality between identified risk factors and serious clinical outcomes (SCOs). The reliance on initial ED evaluations and follow-up via phone calls may also introduce recall bias and underestimate the incidence of SCOs. Furthermore, the exclusion of certain patient groups, such as those under 18 and those unable to give consent, may skew the study population. Finally, the study did not account for all potential confounding variables, such as medication use or detailed medical history, which could influence the risk of SCOs.
Conclusion
This study highlights that hospitalization rates and SCOs are significantly higher among patients with cardiac syncope, abnormal ECG findings, advanced age, absence of prodromal symptoms, presence of malignancy, and elevated lactate levels at admission. These findings suggest a need for careful reevaluation of patients in the emergency department, particularly those displaying these risk factors, to improve patient outcomes. Identifying and addressing these key predictors of SCOs can guide clinicians in making more informed decisions regarding the need for hospitalization and further investigation, ultimately enhancing patient safety and care quality.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Morris J. Emergency department management of syncope. Emerg Med Pract. 2021;23(6):1-24.
2. Tatliparmak AC, Yilmaz S. Diagnostic accuracy of high sensitivity troponin and association of electrocardiogram findings for mortality in syncope patients: A retrospective cohort study. Medicine (Baltimore). 2023;102(25):e34064.
3. Canakci ME, Sevik OE, Acar N. How Should We Approach Syncope in the Emergency Department? Current Perspectives. Open Access Emerg Med. 2022;14(1):299-309.
4. Erdoğan YE, Şeker MY, Gündüz ŞG, Başkaya N, Ak R, Seyhan AU. Comparison of Canadian and San Francisco syncope rules in patients admitted to emergency department with syncope. Intercont J Emerg Med. 2023;1(4):71-6.
5. El-Hussein MT, Cuncannon A. syncope in the emergency department: A guide for clinicians. J Emerg Nurs. 2021;47(2):342-51.
6. Sutton R. Syncope presenting to the emergency department. J Intern Med. 2021;290(3):755-6.
7. Tatliparmak AC, Yilmaz S. Agreement of Oscillometric and Auscultatory blood pressure measurement methods: An ambulance noise simulation study. Am J Emerg Med. 2023;67(5):120-5.
8. Yılmaz S, Cetinkaya R, Ozel M, Tatliparmak AC, Ak R. Enhancing triage and management in earthquake-related ınjuries: The SAFE-QUAKE scoring system for predicting dialysis requirements. Prehosp Disaster Med. 2023;38(6):716-24.
9. Ak R, Kurt E, Bahadirli S. Comparison of 2 risk prediction models specific for COVID-19: The Brescia-COVID Respiratory Severity Scale Versus the Quick COVID-19 Severity Index. Disaster Med Public Health Prep. 2021;15(4):e46-e50.
10. Brignole M, Moya A, de Lange FJ, Deharo JC, Elliott PM, Fanciulli A, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018;39(21):1883-1948.
11. Krishnan RJ, Mukarram M, Ghaedi B, Sivilotti MLA, Sage NL, Yan JW, et al. Benefit of hospital admission for detecting serious adverse events among emergency department patients with syncope: A propensity-score-matched analysis of a multicentre prospective cohort. CMAJ. 2020;192(41):E1198-E1205.
12. Bastani A, Su E, Adler DH, Baugh C, Catarino JM, Clark CL, et al. Comparison of 30-day serious adverse clinical events for elderly patients presenting to the emergency department with near-syncope versus syncope. Ann Emerg Med. 2019;73(3):274-80.
13. Grossman SA, Fischer C, Lipsitz LA, Mottley L, Sands K, Thompson S, et al. Predicting adverse outcomes in syncope. J Emerg Med. 2007;33(3):233-239.
14. Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Rajeswaran A, Metzger JT, et al. Prospective evaluation of patients with syncope: A population-based study. Am J Med. 2001;111(3):177-84.
15. Reed MJ. Approach to syncope in the emergency department. Emerg Med J. 2019;36(2):108-16.
16. Kariman H, Harati S, Safari S, Baratloo A, Pishgahi M. Validation of EGSYS score in prediction of cardiogenic syncope. Emerg Med Int. 2015;2015(1):515370.
17. Quinn JV, Stiell IG, McDermott DA, Sellers KL, Kohn MA, Wells GA. Derivation of the San Francisco Syncope Rule to predict patients with short-term serious outcomes. Ann Emerg Med. 2004;43(2):224-32.
18. Thiruganasambandamoorthy V, Taljaard M, Stiell IG, Sivilotti MLA, Murray H, Vaidyanathan A, et al. Emergency department management of syncope: Need for standardization and improved risk stratification. Intern Emerg Med. 2015;10(5):619-27.
19. Thiruganasambandamoorthy V, Rowe BH, Sivilotti MLA, McRae AD, Arcot K, Nemnom MJ, et al. Duration of electrocardiographic monitoring of emergency department patients with syncope. Circulation. 2019;139(11):1396-406.
20. Kadri AN, Abuamsha H, Nusairat L, Kadri N, Abuissa H, Masri A, et al. Causes and predictors of 30-day readmission in patients with syncope/collapse: A nationwide cohort study. J Am Heart Assoc. 2018;7(18):e009746.
21. Matz O, Zdebik C, Zechbauer S, Bündgens L, Litmathe J, Willmes K, et al. Lactate as a diagnostic marker in transient loss of consciousness. Seizure. 2016;40(7):71-5.
Download attachments: 10.4328.ACAM.22175
İbrahim Ertaş, Derya Abuşka, Özgür Karcıoğlu. Prediction of serious clinical outcomes in patients presenting with syncope in the short-term follow-up: Which variables to use? Ann Clin Anal Med 2025;16(7):460-464
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The place of echinocandins in the treatment of recurrent vulvovaginal candidiasis: Case series
Mustafa Uğuz 1, Berfin Çirkin Doruk 1, İrem Yengel 2
1 Department of Infectious Disease, Mersin City Hospital, Mersin, 2 Department of Private Obstetrics and Gynecology Clinic, School of Medicine, Medipol University, Istanbul, Turkey
DOI: 10.4328/ACAM.22372 Received: 2024-08-17 Accepted: 2024-12-16 Published Online: 2025-01-29 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):465-468
Corresponding Author: Mustafa Uğuz, Department of Infectious Disease, Mersin City Hospital, Mersin, Turkey. E-mail: drmustafauguz@gmail.com P: +90 505 369 44 08 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3428-6137
Other Authors ORCID ID: Berfin Çirkin Doruk, https://orcid.org/0000-0002-5370-4197 . İrem Yengel, https://orcid.org/0000-0002-1971-4092
This study was approved by the Ethics Committee of Toros University (Date: 2024-01-18, No: 16)
Aim: Recurrent vulvovaginal candidiasis (RVVC) is a chronic infection that affects women worldwide and affects the quality of life. We aimed to evaluate echinocandin treatment at RVVC.
Material and Methods: The patients who were diagnosed with RVVC between 2022 and 2023 were retrospectively examined. Patients who continued to experience unresolved symptoms despite prophylactic treatment and showed persistent growth of resistant Candida species in culture were selected. In total, eight patients who met the criteria were included in the study.
Results: All of the patients had previously received local and oral treatment for vaginal candidiasis. The vaginal cultures obtained azole-resistant candida species. All patients received treatment with echinocandin derivatives, and clinical and microbiological response was achieved.
Discussion: Azole resistance is frequently observed in women with RVVC. Ibrexafungerp, a new oral glucan synthase inhibitor, has received FDA approval for treatment but is not available in our country. Antifungal echinocandins showing similar fungicidal activity were used in our cases, and clinical and microbiological response was found to be high. Our findings show that echinocandins may be successful in the treatment of recurrent vaginal candidiasis.
Keywords: Vulvovaginal Candidiasis, Echinocandin, Reccurent Vulvovaginal Candidiasis
Introduction
Recurrent vulvovaginal candidiasis (RVVC) is a common infection with a significant morbidity in women. European guidelines define RVVC as four or more symptomatic episodes of VVC over one year [1]. The global prevalence is about 4 thousand per 100,000 women [2]. The most common symptoms are vulvar itching, pain, dysuria or dyspareunia, and cheese-like vaginal discharge [3]. Microscopic examination of the vagina using light or phase contrast microscopy with saline or 10% KOH is required to confirm Candida infection. The gold standard method for diagnosis is still culture [4]. In clinical practice, the most common agent is C. albicans. However, rarely C. glabrata, C. parapsilosis, C. lusitaniae, C. tropicalis, C. krusei, C. kefyr, and C. dubliniensis can be seen as causative agents. Treatment resistance is more prevalent in non-albicans strains, presenting a challenge for clinicians [5, 6].
The first-line treatment for RVVC is induction therapy with topical antifungals or oral fluconazole followed by 150 mg oral fluconazole for six months. However, due to the high rate of resistance to fluconazole, alternative treatment regimens for RVVC are on the agenda [1].
In the treatment of RVVC, there is often azole resistance due to the long-term use of oral fluconazole and/or topical clotrimazole. In treatment-resistant VVC strains, 25-45% of the causative agents are non-albicans strains [7]. As a result, due to the variations in pathogenicity and resistance profiles against current antifungal medications, recent studies have proposed new treatment strategies for azole-resistant Candida strains [8].
Echinocandins exhibit fungicidal activity against various Candida species, including those resistant to fluconazole. Both echinocandins and ibrexafungerp seem to maintain efficacy against Candida species embedded in biofilms. Because of their fungicidal effects, echinocandins have a high therapeutic response in fluconazole-resistant albicans and non-albicans strains. Echinocandins are drugs with a high safety interval due to their low allergic potential and less toxicity to the liver and kidney compared to other antifungals. Ibrexafungerp is approved for the treatment of VVC and RVVC [9]. It is still not used in Turkey. The systemic administration of echinocandins and their ineffectiveness for oral use restrict their application in the treatment of vulvovaginal candidiasis. The approval of the new drug suggests that echinocandins, which have a similar drug mechanism, may have a role in rescue therapy. In this study, patients who received echinocandin treatment for RVVC were evaluated retrospectively.
Material and Methods
The patients who were diagnosed with RVVC between 2022 and 2023 were retrospectively screened. All patients were asked to provide informed consent. Demographic data, along with clinical and laboratory findings, treatment approaches, and outcomes, were assessed. The patient group received oral and local antifungal treatment for six months. Patients whose complaints did not resolve despite prophylaxis and resistant Candida species persisted in culture growths were selected. In total, eight patients who met the criteria were included in the study. Recurrent VVC was defined as three or more episodes of symptomatic VVC within a year by the Centre for Disease Control and Prevention [10].
Ethical Approval
This study was approved by the Ethics Committee of Toros University (Date: 2024-01-18, No: 16).
Results
The mean age was 35.2±3.4 (28-39) years. Of the patients, 87.5% were married, while 12.5% were single. All our patients had recurrent fluconazole use. Considering comorbid diseases and risk factors, one patient had IUD use (12.5%), one patient had diabetes mellitus (12.5%), and one patient had hypothyroidism (12.5%). Co-treatment was applied to only one patient. The characteristics of the patients are shown in Table 1.
The clinical samples were inoculated using conventional methods, and the isolated colonies were processed. The identification and the antifungal susceptibility profiles of the isolates have been made using VITEK 2 (bioMérieux, France), and the susceptibility findings were evaluated according to EUCAST criteria [11].
C. albicans was detected in five patients (62.5%), C. krusei (25%) was detected in two cases, and C. glabrata (12.5%) was detected in a patient. Azole resistance was detected in all cultures. Echinocandin was used as a treatment regimen of anidulafungin in four (50%) patients, micafungin in three (37.5%) patients, and caspofungin in a (12.5%) patient. All patients were treated for ten days. No growth was detected in control cultures taken at the end of treatment. The patients were considered clinically cured. No recurrence was detected in the 8-week clinical follow-up.
Discussion
There is no clear data about the incidence of recurrent vulvovaginal candidiasis in our country. As it is not a notifiable condition in most parts of the world, estimating its incidence is challenging. It is estimated that at least 75% of healthy women will experience a vulvovaginal candidiasis episode at some point in their lives [12]. The diagnosis is usually made with complaints and symptoms, and treatment is started, laboratory support is usually not needed in first-line treatment. Consequently, identifying the causative microorganisms and their sensitivity patterns in vulvovaginal candidiasis is highly challenging [12]. The rate of symptomatic vulvovaginal candidiasis in women can be considered between 17-42% [12, 13]. Obesity, impaired glucose tolerance, IUD use, hormonal deficiencies, carrier status in the partner, and oral contraceptive use are accepted risk factors for RVVC [14]. Although some studies suggest that oral contraceptive use is a significant factor in vulvovaginal candidiasis, there is also evidence indicating that it does not increase Candida colonization [14].
Candidal vaginosis is typically diagnosed by isolating the causative agent through culture. Serological tests are not thought to be useful [12]. Although C. albicans is the most common agent, C. glabrata is more prevalent during the premenopausal and perimenopausal periods. In a study examining cervical and vaginal smear samples using the PCR method, C. albicans was detected at a rate of 89%, C.glabrata at 7.9%, and other Candida species at a rate of less than 2% [15].
Acute VVC can be treated locally with polyenes (such as nystatin and amphotericin B), imidazoles (including clotrimazole, miconazole nitrate, and fenticonazole nitrate), or ciclopiroxolamine. Among the oral treatment options, Triazoles include fluconazole and itraconazole. Post-treatment cure rates are 85% within 1-2 weeks. The literature lacks clear data on the effectiveness of treatment for addressing penile or sperm carrier status in asymptomatic sexual partners [12]. Today, it is accepted that oral and vaginal treatments containing fluconazole are inadequate in cases of vaginitis caused by C. glabrata [13]. Therefore, it has been recommended 600 mg of boric acid, Amphotericin B, for 14 days. However, in the presence of resistance, treatment success remains at 17% [15]. In case of treatment failure, fluconazole 800 mg is recommended for 2-3 weeks of treatment, but it is stated that treatment failure is gradually increasing with this treatment method [12]. For this reason, it was put forward that echinocandin and micafungin treatment can be applied in the presence of life-threatening clinical conditions, and it was also stated that this treatment is an unapproved off-label treatment [15].
In our study, patients had previously received oral and topical treatment. Microbiological diagnosis was obtained by detecting causative organisms with cultures. Upon examining the resistance patterns, azole resistance was observed in all cases. The treatment regimen was anidulafungin in four (50%) patients, micafungin in three (37.5%) patients, and caspofungin in a (12.5%) patient. With echinocandin treatment, the clinical and microbiological response was achieved completely, and no early relapse was detected during follow-up. Since the drugs we use are not in the RVVC indication and are used systemically, they are not suitable for use in every patient. However, it can be considered as an alternative treatment in selected cases and in cases where recurrent antifungal use is required due to chronic vaginitis clinic and a cure cannot be achieved. Our study is not sufficient to represent the patient population, and larger, more homogeneous studies are needed. We think that future studies with a larger sample size will provide more definitive guidance.
Limitation
The present study is a limited investigation that demonstrates the efficacy of echinocandin treatment in selected cases based on culture and antifungal susceptibility results. Due to the relatively small sample size, more extensive and controlled studies are needed.
Conclusion
When evaluating treatment options in the RVVC clinic, it is important to consider the patient’s previous antifungal regimens, underlying risk factors, and future treatment needs. Azole resistance, particularly in the non-Albicans group, results in non-response to treatment. The infrequent use of vaginal culture in routine practice or the inability of culture results to differentiate between infectious agents and colonization are among the underlying factors for treatment non-response. In selected cases with RVVC clinic, as in our study, echinocandins may be considered as an alternative treatment regimen for cases that are refractory to other treatments or have frequent recurrences.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Donders G, Sziller IO, Paavonen J, Hay P, de Seta F, Bohbot JM, et al. Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion. Front Cell Infect Microbiol. 2022;12:934353.
2. Denning DW, Kneale M, Sobel JD, Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect Dis. 2018;18(11):e339-47.
3. Linhares IM, Witkin SS, Miranda SD, Fonseca AM, Pinotti JA, Ledger WJ. Differentiation between women with vulvovaginal symptoms who are positive or negative for Candida species by culture. Infect Dis Obstet Gynecol. 2001;9:221–25.
4. Farr A, Effendy I, Frey Tirri B, Hof H, Mayser P, Petricevic L, et al. Guideline: Vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses. 2021;64(6):583-602.
5. Cooke G, Watson C, Deckx L, Pirotta M, Smith J, van Driel ML. Treatment for recurrent vulvovaginal candidiasis (thrush). Cochrane Database Syst Rev. 2022;1:CD009151.
6. Woodburn KW, Clemens LE, Jaynes J, Joubert LM, Botha A, Nazik H, et al. Designed antimicrobial peptides for recurrent vulvovaginal candidiasis treatment. Antimicrob Agents Chemother. 2019;63(11):e02690-18.
7. Nasrollahi Omran A, Vakili L, Jafarpur M. The determination of vaginal candidiasis in women referred to Shahid Rajaei Hospital in Tonekabon. Medical Laboratory Journal 5 (2011):1-7.
8. Paiva LC, Vidigal PG, Donatti L, Svidzinski TI, Consolaro ME. Assessment of in vitro biofilm formation by Candida species isolates from vulvovaginal candidiasis and ultrastructural characteristics. Micron. 2012;43(2-3):497-502.
9. Desai JV, Mitchell AP, Andes DR. Fungal biofilms, drug resistance, and recurrent infection. Cold Spring Harb Perspect Med. 2014;4(10):a019729.
10. Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 2016 Jan;214(1):15-21.
11. Douglas, Cameron M. “Fungal β(1,3)-d-glucan synthesis.” Medical Mycology 39(2001):55-66.
12. Sobel JD. Vulvovaginal candidosis. Lancet. 2007;369:1961–71.
13. Olowe OA, Makanjuola OB, Olowe R, Adekanle DA. Prevalence of vulvovaginal candidiasis, trichomoniasis, and bacterial vaginosis among pregnant women receiving antenatal care in Southwestern Nigeria. Eur J Microbiol Immunol. 2014;4:193–97.
14. Reed BD, Zazone P, Pierson LL, Gorenflo DW, Horreocks J. Candida transmission and sexual behavior as risk for a repeated episode of Candida vulvovaginitis. J Womens Health (Larchmt). 2003;12:979–89.
15. Vermitsky JP, Self MJ, Chadwick SG, Trama JP, Adelson ME, Mordechai E, et al. Survey of vaginal-flora Candida species isolates from women of different age groups by use of species-specific PCR detection. J Clin Microbiol. 2008;46(4):1501-03.
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Mustafa Uğuz, Berfin Çirkin Doruk, İrem Yengel. The place of echinocandins in the treatment of recurrent vulvovaginal candidiasis: Case series. Ann Clin Anal Med 2025;16(7):465-468
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Vitamin D levels in stable COPD patients according to the new GOLD staging
Hikmet Coban
Department of Pulmonology, Faculty of Medicine, Balıkesir University Education and Research Hospital, Balıkesir, Turkey
DOI: 10.4328/ACAM.22380 Received: 2024-08-22 Accepted: 2025-01-23 Published Online: 2025-02-14 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):469-472
Corresponding Author: Hikmet Coban, Department of Pulmonology, Faculty of Medicine, Balıkesir University Education and Research Hospital, Balıkesir, Turkey. E-mail: hikmetcoban04@gmail.com P: +90 536 652 06 94 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6730-9932
This study was approved by the Ethics Committee of Sakarya University, Faculty of Medicine Clinical Research (Date: 2015-04-15, No: 4762)
Aim: This study investigates Vitamin D3 levels in stable COPD patients according to the new GOLD stages.
Material and Methods: 320 stable COPD patients were included in the study. Staging was done according to GOLD 2023 criteria, and the relationship with Vitamin D was examined.
Results: The average Vit D3 level of the COPD patients included in the study was 18.49 ± 10.08, with 59.1% having Vit D3 deficiency and 28.1% having Vit D3 insufficiency. According to GOLD 2023 staging, 20.3% of the patients were classified as GOLD A, 26.6% as GOLD B and 53.1% as GOLD E. Significant differences were found between the groups in terms of Vit D3, %FEV1, %FVC, and age. There was a significant negative correlation between Vit D3 levels and exacerbations in the last year and the mMRC dyspnea scale (respectively r = -0.54 p < 0.0001, r = -0.43 p < 0.0001)). Positive significant correlations were found between Vit D3 levels and %FEV1 and %FVC parameters (respectively r = 0.14 p = 0.004, r = 0.23 p < 0.0001).
Discussion: In this study, in stable COPD patients according to GOLD 2023, Vitamin D levels significantly decrease as the severity of the disease increases.
Keywords: Vitamin D3, COPD, GOLD 2023
Introduction
Chronic Obstructive Pulmonary Disease (COPD) is a widespread, preventable, and treatable disease characterized by persistent airflow limitation and respiratory symptoms due to significant exposure to harmful particles or gases, leading to airway and/or alveolar abnormalities. GOLD (Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease) is the guideline used in the diagnosis and treatment follow-up of COPD. In the GOLD 2017 report, FEV1 was excluded from the COPD staging. This simplified the complex evaluation based on FEV1 and/or the number of exacerbations, as introduced in the 2011 version, by making it dependent only on ‘the number of exacerbations and the level of symptoms’ [available at: https://goldcopd.org/archived-reports-2017]. The ABCD assessment scheme, which started from GOLD 2017, has in GOLD 2023 emphasized the clinical significance of exacerbations regardless of symptom level and revised the pharmacological treatment initiation recommendation in COPD to the ABE scheme based on the individualized assessment of symptom and exacerbation risk [available at: https://goldcopd.org/archived-reports-2023].
Vitamin D exhibits anti-inflammatory effects, is effective in airway reactions against various stimuli such as gases and toxic particles, and has been shown to prevent airway inflammation [1, 2]. In lung diseases like asthma and COPD, there is a higher risk of vitamin D deficiency [3, 4]. The relationship between vitamin D deficiency and the severity of the disease in COPD patients has been identified [5].
The relationship between the new GOLD stages and Vitamin D levels has not been sufficiently investigated. This study investigates Vitamin D3 levels in stable COPD patients according to the new GOLD stages.
Material and Methods
At Sakarya Training and Research Hospital, 320 patients diagnosed with stable-stage COPD and followed for at least one year were included in the study. The study was conducted between January 2015 and January 2018. Cases without exacerbation symptoms in the three months prior to the study were considered clinically stable. Exclusion criteria included concomitant infection, pleural effusion, congestive heart failure, acute exacerbation, malignancy, rheumatic diseases, pulmonary embolism, restrictive airway disease, conditions affecting Vitamin D metabolism, and usage of Vitamin D and corticosteroids. COPD staging was done according to GOLD 2023 criteria (A, B, E) based on the mMRC dyspnea scale and records of exacerbations and/or hospital admissions in the last year. All patients underwent pulmonary function tests. Values of %FEV1, %FVC, and %FEV1/FVC were recorded. Plasma vitamin D levels in all cases were obtained from hospital records for the last three months. 25 (OH) Vitamin D level was measured using Roche Diagnostics (RD) kit on the E170 device by electrochemiluminescence method. 25 (OH) vitamin D levels of ≤20 ng/mL were defined as vitamin D3 deficiency, those between 20-30 ng/mL as vitamin D3 insufficiency (subclinical deficiency), and those ≥30 ng/mL as adequate vitamin D3 levels [6]. Approval was obtained from the Sakarya University Faculty of Medicine Ethics Committee for the study.
Statistical analyses were performed on IBM SPSS Statistics version 23.0 (IBM Corp. USA). The Shapiro-Wilk test was used to test the normality of variables. Normally distributed continuous variables were expressed as mean ± standard deviation. Non-normally distributed variables were expressed as median (min-max) values. The Kruskal-Wallis test was used for inter-group comparisons of COPD stages with vitamin D levels, and the Pearson correlation test was used for correlation analyses between Vitamin D and other variables. p<0.05 was considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of Sakarya University, Faculty of Medicine Clinical Research (Date: 2015-04-15, No: 4762).
Results
320 patients diagnosed with stable period COPD were included in the study. General characteristics of the patients are shown in Table 1. 89% of the participants were male, with an average age of 65.0 ± 9.94. The average BMI was 25.2 ± 4.63. According to GOLD 2023 staging, 20.3% of the patients were classified as GOLD A, 26.6% as GOLD B, and 53.1% as GOLD E. The Vit D3 level of the COPD patients included in the study was 18.49 ± 10.08, with 59.1% having Vit D3 deficiency and 28.1% having Vit D3 insufficiency.
Comparisons between the averages of Vit D3, %FEV1, %FVC, age, BMI according to GOLD 2023 COPD stages are shown in Table 2. Significant differences were found between the groups in terms of Vit D3, %FEV1, %FVC, and age, while no significant difference was found in BMI.
Pearson linear correlation results between Vit D3 levels and exacerbations in the last year, mMRC dyspnea scale, BMI, gender, age, %FVC, and %FEV1 in patients diagnosed with COPD are shown in Table 3. There was a significant negative correlation between Vit D3 levels and exacerbations in the last year and the mMRC dyspnea scale. Significant positive correlations were found with respiratory function parameters.
Discussion
To our knowledge, this study is the first to demonstrate the relationship between Vitamin D levels and the new COPD staging. In our study, we found that as the severity of GOLD 2023 staging in stable COPD patients, Vitamin D levels decreased. The GOLD 2023 ABE staging was based on the number of exacerbations in the last year and the mMRC dyspnea scale, and a significant negative correlation was found with Vitamin D levels. In our study, a positive relationship was found between plasma Vitamin D levels and respiratory function parameters.
Vitamin D deficiency in patients with COPD has been frequently demonstrated in many studies [7-13]. A study based in Elazığ found that Vitamin D levels in stable COPD cases were lower compared to a healthy control group [16]. Our study found a Vitamin D deficiency rate of 87.2%.
The association between Vitamin D deficiency and low FEV1 has been shown [13, 15, 16]. A significant positive correlation has also been found between serum 25(OH) Vitamin D concentration and FVC [18]. Similarly, in our study, a significant correlation was found between serum 25(OH)D concentration and FVC and FEV1.
In a study conducted by Jorde et al., correlations were found between 25(OH)D levels, systemic inflammation, disease severity, and disease progression. While exacerbation frequency showed significant differences between GOLD stages, a direct relationship was not found between exacerbations and 25(OH)D levels (15). Studies suggest that Vitamin D plays an anti-inflammatory role in the respiratory tract [17, 18]. In the lungs, Vitamin D helps the host defense functions of both the airway epithelium and immune cells. Burkes et al. reported a relationship between the likelihood of acute exacerbations of COPD in the previous year and Vitamin D deficiency in the patients included in their study, but this relationship disappeared in the following year [19]. The relationship between exacerbation frequency and Vitamin D levels in observational studies continues to be debated. However, a recently published meta-analysis revealed a negative relationship between serum Vitamin D and exacerbations. Additionally, two clinical studies emphasized that Vitamin D3 supplementation reduced the risk of moderate and severe exacerbations in COPD patients [20].
Limitation
Limitations of the study include it being single-centered, the selection of a population from a specific region, and the exclusion of additional comorbidities with COPD.
Conclusion
Vitamin D3 levels can be found to be low in COPD patients due to inflammation, inadequate oral intake, a sedentary lifestyle, and less exposure to sunlight. Our study found Vitamin D3 deficiency in 59.1% of patients and Vitamin D3 insufficiency in 28.1% of patients. Only 12.8% of COPD patients had normal Vitamin D3 levels. It was observed that Vitamin D levels decreased as the severity of the disease increased according to GOLD 2023 staging in stable COPD patients. A significant negative correlation was found between Vitamin D levels and the number of exacerbations in the last year and the mMRC dyspnea scale. Our study also found a positive relationship between plasma Vitamin D levels and respiratory function parameters.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Telcian AG, Zdrenghea MT, Edwards MR, Laza-Stanca V, Mallia P, Johnston SL, et al. Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro. Antiviral Res. 2017;137:93-101.
2. Hanson C, Rutten EP, Wouters EF, Rennard S. Diet and vitamin D as risk factors for lung impairment and COPD. Transl Res. 2013;162(4):219-36.
3. Rafiq R, Aleva FE, Schrumpf JA, Heijdra YF, Taube C, Daniels JM, et al. Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): A study protocol. BMC Pulm Med. 2015;15:106.
4. Finklea JD, Grossmann RE, Tangpricha V. Vitamin D and chronic lung disease: A review of molecular mechanisms and clinical studies. Adv Nutr. 2011;2(3):244-53.
5. Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A, Buysschaert I, et al. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the Vitamin D binding gene. Thorax. 2010;65(3):215-20.
6. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-30.
7. Heidari B, Javadian Y, Monadi M, Dankob Y, Firouzjahi A. Vitamin D status and distribution in patients with chronic obstructive pulmonary disease versus healthy controls. Caspian J Intern Med. 2015;6(2):93-7.
8. Persson LJ, Aanerud M, Hiemstra PS, Hardie JA, Bakke PS, Eagan TML. Chronic obstructive pulmonary disease is associated with low levels of vitamin D. PLoS One. 2012;7(6):38934.
9. Zhang P, Luo H, Zhu Y. Prevalence of vitamin D deficiency and impact on quality of life in patients with chronic obstructive pulmonary disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012;37(8):802-6.
10. Zhou X, Han J, Song Y, Zhang J, Wang Z. Serum levels of 25-hydroxyvitamin D, oral health and chronic obstructive pulmonary disease. J Clin Periodontol. 2012;39(4):350-6.
11. Franco CB, Paz-Filho G, Gomes PE, Nascimento VB, Kulak CAM, Boguszewski CL, et al. Chronic obstructive pulmonary disease is associated with osteoporosis and low levels of vitamin D. Osteoporos Int. 2009;20(11):1881-7.
12. Skaaby T, Husemoen LL, Thuesen BH, Pisinger C, Jorgensen T, Fenger RV, et al. Vitamin D status and chronic obstructive pulmonary disease: A prospective general population study. PLoS One. 2014;9(3):e90654.
13. Jorde I, Stegemann-Koniszewski S, Papra K, Föllner S, Lux A, Schreiber J, et al. Association of serum vitamin D levels with disease severity, systemic inflammation, prior lung function loss, and exacerbations in a cohort of patients with chronic obstructive pulmonary disease. J Thorac Dis. 2021;13(6):3597-609.
14. Telo S, Kuluozturk M, Deveci F. Stabil Dönem Kronik Obstrüktif Akciğer Hastalıklı Olgularda Vitamin D Düzeyleri [Levels of Vitamin D in Patients with Stable Period Chronic Obstructive Pulmonary Disease]. Fusabil. 2016;30(2):61-6.
15. Mulrennan S, Knuiman M, Walsh JP, Hui J, Hunter M, Divitini M, et al. Vitamin D and respiratory health in the Busselton Healthy Ageing Study. Respirology. 2018;23(6):576-82.
16. Ganji V, Al-Obahi A, Yusuf S, Dookhy Z, Shi Z. Serum vitamin D is associated with improved lung function markers but not with prevalence of asthma, emphysema, and chronic bronchitis. Sci Rep. 2020;10(1):11542.
17. Lange NE, Sparrow D, Vokonas P, Litonjua AA. Vitamin D deficiency, smoking, and lung function in the Normative Aging Study. Am J Respir Crit Care Med. 2012;186(7):616-21.
18. Szekely JI, Pataki A. Effects of vitamin D on immune disorders with special regard to asthma, COPD and autoimmune diseases: A short review. Expert Rev Respir Med. 2012;6(6):683-704.
19. Burkes RM, Ceppe AS, Doerschuk CM, Couper D, Hoffman EA, Comellas AP, et al. Associations among 25-hydroxyvitamin D levels, lung function, and exacerbation outcomes in COPD: an analysis of the SPIROMICS cohort. Chest. 2020;157(4):856-65.
20. Ferrari R, Caram LMO, Tanni SE, Godoy I, Rupp de Paiva SA. The relationship between Vitamin D status and exacerbation in COPD patients: a literature review. Respir Med. 2018;139(6):34-8.
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Hikmet Coban. Vitamin D levels in stable COPD patients according to the new GOLD staging. Ann Clin Anal Med 2025;16(7):469-472
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Investigation of parents with high-risk infant on participation in care, depression, quality of life, and anxiety according to the infant’s severity of neurologic impact
Müşerref Ebru Şen 1, Hatice Yakut 2
1 Department of Therapy and Rehabilitation, Health Services Vocational School, Gümüşhane University, Gümüşhane, 2 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Süleyman Demirel University, Isparta, Turkey
DOI: 10.4328/ACAM.22422 Received: 2024-09-26 Accepted: 2024-11-11 Published Online: 2025-02-03 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):473-477
Corresponding Author: Müşerref Ebru Şen, Department of Therapy and Rehabilitation, Health Services Vocational School, Gümüşhane University, Gümüşhane, Turkey. E-mail: m.ebrusen@gmail.com P: +90 555 713 66 66 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0964-4764
Other Authors ORCID ID: Hatice Yakut, https://orcid.org/0000-0002-0033-0144
This study was approved by the Ethics Committee of Süleyman Demirel University, Faculty of Medicine (Date: 2020-02-06, No: 72867572.050.01.04-17)
Aim: The study aims to examine the psychological consequences such as anxiety levels, quality of life, depression, and participation in the care of parents with high-risk infants who have varying levels of neurological impact severity.
Material and Methods: Forty high-risk infants and their mothers were included in the study. The infants were divided into three groups according to the Dubowitz Neurologic Assessment Scale. The State-Trait Anxiety Inventory (STAI), Edinburgh Postpartum Depression Scale (EPDS), Quality of Life Short Form 36 (SF-36), and the NICU Care Participation Scale were administered.
Results: There were significant differences in the mothers’ anxiety and depression levels (p < 0.001) and many parameters of quality of life according to the severity of neurological impact. However, it was determined that the severity of the neurological impact did not affect the mothers’ participation in care (p > 0.01).
Discussion: Although our study revealed that parents’ depression, anxiety, and quality of life levels changed according to the severity of neurological impairment in high-risk infants, care participation was not affected. The limited sample size and the inability to generalize the results to different cultural and socioeconomic groups are important limitations. Nevertheless, it can be concluded that the medical condition of the newborn seriously affects the mental health of the parents.
Keywords: Family Caregivers, Neonatal Intensive Care Unit, Postnatal Depression, Quality Of Life, Anxiety
Introduction
A high-risk infant is defined as an infant that requires more than the standard monitoring and care offered to a healthy full-term infant [1]. When a high-risk infant is born, compared to a healthy newborn, medical, psychosocial, and economic problems may occur [2]. The relationship between the parental mental health of infants hospitalized in the NICU and infant outcomes has drawn attention to numerous studies published in the last decade. These confirm the clinical observations that parents of NICU infants experience increased acute stress, anxiety, depression, and post-traumatic stress during and after NICU hospitalization. The psychosocial problems seen in mothers with infants in the NICU can be listed as sadness, guilt, and anxiety [3-5]. The results of the psychological problems experienced by mothers with infants in the NICU can be listed as difficulty in establishing the mother-infant bonding, negative development of the infant, and a decrease in the mother’s quality of life [4]. Gerstein et al. reported that increased stress and depressive symptoms in mothers with high-risk infants affect the parenting behavior of the mother even 5 years after discharge from the NICU [6].
Studies investigating parental mental health about neurodevelopmental outcomes have focused almost exclusively on cohorts of preterm infants [7-9]. Only one study has demonstrated an association between neonatal encephalopathy and maternal postpartum depression [3]. When the literature is examined, no other research has been found that distinguishes infants according to neurological deficits and examines mothers. It remains unclear how parental psychological distress relates to factors such as the infant’s risk of readmission to the hospital, length of stay, or course and severity of illness in the NICU or after discharge [10]. According to WHO, newborns are seen as biopsychosocial beings, and this new paradigm is considered to be the beginning of parents to develop a more active role in the upbringing of their children. In recent years, parents have been encouraged to participate in NICU care skills. With this participation, a lower mortality rate and severity of neurologic impact were found, as well as lower parental stress rates [11]. However, first of all, it is necessary to reveal the participation of parents in care and the affecting factors. Therefore, it was aimed to examine the levels of participation in care, depression, quality of life, and anxiety according to the severity of the neurologic impact on the parents who have a high-risk infant.
Material and Methods
Study Desing and Participants
A cross-sectional study was conducted between October 2020 and June 2021 on 40 parents and their high-risk babies in the tertiary NICU of Afyonkarahisar Health Sciences University Hospital. The sample size of the study was determined by power analysis. Using the G*Power program, the alpha value was set at 0.05, the effect size was 0.5, and the sample size was 40 with a universe representation power of 0.9281. The study included 40 infants born between 37 and 40 weeks of gestation and weighing less than 2500 g who were in the NICU for at least 10 days after birth and were diagnosed as infants with neurodevelopmental risk. Forty parents who were older than 18 years of age, had adequate communication and reading skills, and did not have a serious physical or mental illness were included. Infants of families who refused to participate in the study and infants with congenital anomalies and severe sepsis were not included in the study.
Data collection
To determine the neurological impact of infants, a Dubowitz Neurological Examination was performed by specialist health personnel 6-48 hours after birth. Clinical diagnosis and Apgar score were noted, and reflexes and muscle tone were evaluated. To obtain comparable results, all infants were tested under the most equal conditions possible, with attention to feeding time, sleep, and irritability.
Demographic information, including the parents’ age, marital status, and education level, was obtained. Additionally, participation in care, postpartum depression, quality of life, and state and trait anxiety were evaluated.
Measurement Tools Neonatal neurological examination data, including birth weight, gestational age in weeks, birth length, head circumference, Apgar scores at the 1st and 5th minutes, clinical diagnosis, diet, presence of abnormal reflexes, need for an assisted breathing device, muscle tone, presence of epileptic seizures, and information about the problem, interventions, and length of stay in the NICU, were obtained from hospital files. Values from the 5th-minute Apgar scores were categorized as follows: 0–3 as low, 4–6 as moderate, and 7–10 as normal. Since our study had no infants with low Apgar scores, they were divided into two groups: normal and moderate.
Dubowitz Neurological Examination provides a neurological evaluation of preterm and term newborns. The test evaluates the infant in six areas, including neurological and neurobehavioral components, in correlation with brain ultrasonography findings, and determines the presence of neurological problems in the infant or whether the infant is at risk for neurological issues. The examination consists of 34 items: muscle tone, tone patterns, reflexes, movements, abnormal signs, and behavior. The 5th and 10th percentiles are used as cut-off points for scoring each item. An item falling above the 10th percentile is given 1 point, 0.5 points are awarded for scores between the 5th and 10th percentiles, and 0 points are assigned for scores below the 5th percentile. The total possible score is 34. In our study, we divided newborns into three groups according to cut-off scores: low, moderate, and high exposure [12, 13].
Care Participation Scale was developed to evaluate mothers’ participation in the care of their infants during their stay in the NICU. The highest score that can be obtained from the scale is 19, while the lowest score is 0. An increase in the total score indicates that a mother’s participation in the care of her infant is increasing [14].
The Edinburgh Postpartum Depression Scale (EPDS) is intended to determine women’s risk of depression that may occur in the postpartum period. The highest score that can be obtained from the scale is 30, while the lowest score is 0. A mother with 13 points or more is considered at risk for postpartum depression [15].
Quality of Life Test Short Form-36 (SF-36) was developed by the Rand Corporation in 1992 to assess quality of life. The scale consists of 36 items evaluating the quality of life in eight dimensions: physical function (10 items), social function (2 items), role limitations due to physical problems (4 items), role limitations due to emotional problems (3 items), mental health (5 items), energy/vitality (4 items), body pain (2 items), and general health perception (5 items) [16].
State-Trait Anxiety Inventory (STAI) was developed by Spielberger et al. to evaluate state and trait anxiety. The scores obtained from both scales range from 20 to 80. As the score increases, the individual’s anxiety also increases [17].
Statistical Analysis
Data were analyzed using SPSS version 25.0 statistical software for Windows. The power of the study was found to be 0.9281, the effect size was 0.5 (medium), and the alpha value (α) was 0.05, as determined using G*Power software. Measured variables were expressed as mean ± standard deviation (X ± SD). Differences in parental involvement in care, depression, quality of life, and anxiety levels, as well as infant grouping according to Apgar and Dubowitz scores, were analyzed using independent samples t-tests and one-way ANOVA. All tests were conducted at a 95% confidence level (p < 0.05).
Ethical Approval
This study was approved by the Ethics Committee of Süleyman Demirel University, Faculty of Medicine (Date: 2020-02-06, No: 72867572.050.01.04-17).
Results
During the study period, 47 infants met the initial inclusion criteria. Four infants who could not undergo neurological examinations within the first 6 to 48 hours of life, two mothers who could not attend to the care of their infants due to health problems, and one infant who died were excluded from the study. Forty infants (26 boys and 14 girls) who were born at 37 to 40 weeks of gestation and met the inclusion criteria, along with their parents, were included in the study. Demographic information about the parents and the mean data for the infants are presented in Table 1. Maternal care and psychological outcomes classified according to the 5-minute Apgar score are presented in Table 2. When evaluating parents’ participation in care, depression, quality of life, and anxiety levels, postpartum depression (p < 0.001), physical function (p < 0.001), physical role difficulty (p < 0.001), energy and vitality (p < 0.001), mental health (p < 0.001), social functionality (p = 0.018), pain (p < 0.001), and general health (p = 0.033) were found to be statistically significant. There was no difference in care participation and anxiety levels. The depression levels of mothers who had infants with an Apgar score of 4-6 at the 5th minute were higher than those in the other groups. Additionally, it was determined that the sub-dimensions of quality of life for mothers with infants who had an Apgar score of 7-10 at the 5th minute were more advanced than those in the other groups.
Maternal care and psychological outcomes classified according to the level of severity of neurologic impact are presented in Table 3.
When the parents’ participation in care, depression, quality of life, and anxiety levels were evaluated according to the severity of the neurologic impact of the infants participating in the study: postpartum depression (p<0.001), trait anxiety (p<0.001), state anxiety (p=0.026), physical function (p<0.001), physical role difficulty (p<0.001), energy, vitality, vitality (p<0.001) 0.001), mental health (p<0.001), social functionality (p=0.022) and pain (p<0.001) dimensions were statistically significant. Depression, trait anxiety, and state anxiety levels of mothers with infants with high severity of neurologic impact: It has been determined that it is at an advanced level compared to mothers with infants with moderate and low severity of neurologic impact. It was determined that the sub-dimensions of quality of life of mothers with low and moderate levels of severity of neurologic impact were more advanced than those of mothers with infants with high severity of neurologic impact. It was found that there was no significant difference between the groups in terms of participation in care.
Discussion
Our study aimed to evaluate the participation in care, depression, quality of life, and anxiety levels of parents with a high-risk infant and to investigate whether these factors change according to the severity of the infant’s neurological impact. Our findings showed that the anxiety levels, quality of life, and depression parameters of parents with at-risk infants change according to the severity of neurological impact. On the other hand, it was concluded that parental involvement in care did not change.
Emotional and behavioral changes in parents of high-risk infants have been the subject of many studies. However, research on the psychosocial problems caused by the severity of the infant’s neurological impact on parents is limited in the literature. This study examined the anxiety levels, quality of life, and depression of mothers in the early period according to the level of severity of neurological impact in the group described as high-risk infants for the first time, along with the participation of parents in care. An infant’s unstable health status and high risk of neurodevelopmental delay and childhood disability are known to have a strong impact on parental stress and anxiety [18,19]. In our study, we demonstrated this neurodevelopmental risk using the 5th-minute Apgar score and Dubowitz score. We found that there was no difference in parental involvement and anxiety according to the infant’s Apgar score; however, we noted that parents of infants with low scores had higher depression scores. A study conducted in 2019 examined the risk factors for postpartum depression and showed that the length of labor and duration of epidural analgesia are significant risk factors for developing postpartum depression. Conversely, the relationship between the newborn’s Apgar score and postpartum depression was not significant [20]. Lucja et al. revealed that there was no significant relationship between attachment between mother and infant and the infant’s Apgar score [21]. However, it is noted that the Apgar scores of the infants in these studies were not very low. The Dubowitz assessment was preferred in our study because it encompasses various aspects of neurological function, providing a detailed profile of the infant’s neurological status with practical application. However, no evaluation of parents in terms of depression and other factors according to this scale has been made in the literature. In our study, while depression and anxiety scores were high among parents of infants with high and moderate severity of neurological impact, quality of life scores were low. According to a study similar to ours, the depression levels of mothers of infants with encephalopathy were found to be twice as high as those of mothers of other infants admitted to the NICU. However, contrary to the results of our study, no relationship was found between the severity of the disease and depression in this study [3].
The postpartum maternal psychological state has been associated with negative outcomes for the newborn. Studies have shown that mothers with postpartum depression exhibit more negative and distant behaviors, have less contact with their babies, participate less in care, breastfeed for shorter durations, experience decreased breastfeeding confidence, and face increased breastfeeding difficulties [22, 23]. While there are many different approaches to supporting an infant’s development in the NICU, it is important to include the family as part of the care and to support the parent-infant relationship [9]. When examining the effect of kangaroo care on parental outcomes, it has been shown to reduce anxiety and depressive symptoms while positively impacting parental trust and interaction with the infant [24].
Considering all of this, it is important to improve the mental health of parents with babies in the NICU, strengthen their relationships with their infants, and offer ample opportunities for meaningful experiences (such as breastfeeding, skin-to-skin holding, and talking/communicating with their babies) based on the infant’s cues. This approach is essential for optimizing both short- and long-term outcomes for the newborn. Future research is needed to better understand which strategies are most effective in optimizing infant and parent health based on neonatal and family outcomes [6,10]. Unfortunately, our study had some limitations. Post-discharge evaluations were not repeated. Another limitation was the limited time the mothers spent in the intensive care unit. Additionally, parents of premature infants were not included in the study.
Conclusion
This study provides new insights into the factors that contribute to parents’ psychological problems. In light of the findings of our study and the existing literature, the following conclusions can be drawn: The medical condition of the infant significantly affects the mental health of the parents. Having a neurologically high-risk infant can lead to anxiety and depression in the parents, independent of the severity of the neurological impact; however, the severity of these problems is influenced by the level of neurological impairment. On the other hand, it can be concluded that the neurological status of the infant does not affect the parent’s participation in care in the short term.
Acknowledgment
We are very thankful to Prof. Dr. Ahmet Afşin Kundak for their valuable contribution and support in providing personnel and environmental.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Raju TNK. The high-risk infant. In: Elzouki AY, Harfi HA, Nazer HM, Stapleton FB, Oh W, Whitley RJ, editors. Textbook of clinical pediatrics. Berlin: Springer; 2012. p.177-86.
2. Litt JS, Campbell DE. High-risk infant follow-up after NICU discharge: current care models and future considerations. Clin Perinatol. 2023;50(1):225-38.
3. Laudi A, Peeples E. The relationship between neonatal encephalopathy and maternal postpartum depression. J Matern Fetal Neonatal Med. 2020;33(19):3313-17.
4. Staver MA, Moore TA, Hanna KM. Maternal distress in the neonatal intensive care unit: a concept analysis. Adv Neonatal Care. 2019;19(5):394-401.
5. Bonacquisti A, Geller PA, Patterson CA. Maternal depression, anxiety, stress, and maternal-infant attachment in the neonatal intensive care unit. J Reprod Infant Psychol. 2020;38(3):297-310.
6. Gerstein ED, Njoroge WF, Paul RA, Smyser CD, Rogers CE. Maternal depression and stress in the neonatal intensive care unit: associations with mother-child interactions at age 5 years. J Am Acad Child Adolesc Psychiatry. 2019;58(3):350-58.
7. McManus BM, Poehlmann J. Parent-child interaction, maternal depressive symptoms, and preterm infant cognitive function. Infant Behav Dev. 2012;35(3):489-98.
8. Huhtala M, Korja R, Lehtonen L, Haataja L, Lapinleimu H, Rautava P, et al. Parental psychological well-being and behavioral outcome of very low birth weight infants at 3 years. Pediatrics. 2012;129(4):937-44.
9. Cheong JL, Burnett AC, Treyvaud K, Spittle AJ. Early environment and long-term outcomes of preterm infants. J Neural Transm. 2020;127(1):1-8.
10. Erdei C, Liu CH, Machie M, Church PT, Heyne R. Parent mental health and neurodevelopmental outcomes of children hospitalized in the neonatal intensive care unit. Early Hum Dev. 2021;154:105278.
11. Balbino FS, Balieiro MM, Mandetta MA. Measurement of family-centered care perception and parental stress in a neonatal unit. Rev Lat Am Enfermagem. 2016;24:e2753.
12. Dubowitz L, Ricciw D, Mercuri E. The Dubowitz neurological examination of the full-term newborn. Ment Retard Dev Disabil Res Rev. 2005;11(1):52-60.
13. Dubowitz L, Mercuri E, Dubowitz V. An optimality score for the neurologic examination of the term newborn. J Pediatr. 1998;133(3):406-16.
14. Karacam Z, Cakmak E. Yenidoğan yoğun bakım ünitesinde bebeği yatan anneler için bakıma katılımı değerlendirme ölçeği: ölçek geliştirme, geçerlik ve güvenirliği [Participation in care assessment scale for mothers whose babies are hospitalized in neonatal intensive care unit: Scale development, validity and reliability]. Anatol J Nurs Health Sci. 2018;21(2):69-78.
15. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression: development of the 10-item Edinburgh postnatal depression scale. Br J Psychiatry. 1987;150(6):782-86.
16. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care. 1992;30(6):473-83.
17. Spielberger CD. Manual for the state-trait anxiety inventory. Consult Psychologist. 1970.
18. Cook N, Ayers S, Horsch A. Maternal posttraumatic stress disorder during the perinatal period and child outcomes: a systematic review. J Affect Disord. 2018;225(1):18-31.
19. Brunson E, Thierry A, Ligier F, Vulliez-Coady L, Novo A, Rolland AC, et al. Prevalences and predictive factors of maternal trauma through 18 months after premature birth: A longitudinal, observational and descriptive study. PLoS One. 2021;16(2):e0246758.
20. Smorti M, Ponti L, Pancetti F. A comprehensive analysis of post-partum depression risk factors: the role of socio-demographic, individual, relational, and delivery characteristics. Front Public Health. 2019;7:295.
21. Bieleninik Ł, Lutkiewicz K, Cieślak M, Preis-Orlikowska J, Bidzan M. Associations of maternal-infant bonding with maternal mental health, infant’s characteristics and socio-demographical variables in the early postpartum period: a cross-sectional study. Int J Environ Res Public Health. 2021;18(16):8517.
22. Netsi E, Pearson RM, Murray L, Cooper P, Craske MG, Stein A. Association of persistent and severe postnatal depression with child outcomes. JAMA Psychiatry. 2018;75(3):247-53.
23. Bogen DL, Hanusa BH, Moses-Kolko E, Wisner KL. Are maternal depression or symptom severity associated with breastfeeding intention or outcomes? J Clin Psychiatry. 2010;71(8):1069-78.
24. Brett J, Staniszewska S, Newburn M, Jones N, Taylor L. A systematic mapping review of effective interventions for communicating with, supporting, and providing information to parents of preterm infants. BMJ Open. 2011;1(1):e000023.
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Müşerref Ebru Şen, Hatice Yakut. Investigation of parents with high-risk infant on participation in care, depression, quality of life, and anxiety according to the infant’s severity of neurologic impact. Ann Clin Anal Med 2025;16(7):473-477
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Importance of heart rate variability in social phobia and panic disorder patients
Mesut Mehmet Özdemir 1, Eren Abatan 2, Mehmet Fatih Özlü 3, Özden Arısoy 2
1 Department of Cardiology, Faculty of Medicine, Konya Başkent University Hospital, Konya, 2 Department of Psychiatry, Faculty of Medicine, Abant İzzet Baysal University, Bolu, 3 Department of Cardiology, Faculty of Medicine, Abant İzzet Baysal University, Bolu, Turkey
DOI: 10.4328/ACAM.22437 Received: 2024-10-04 Accepted: 2024-11-25 Published Online: 2025-01-27 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):478-481
Corresponding Author: Mesut Mehmet Özdemir, Department of Cardiology, Faculty of Medicine, Konya Başkent University Hospital, Konya, Turkey. E-mail: ozdemirmesutmehmet@gmail.com P: +90 506 351 08 82 Corresponding Author ORCID ID: https://orcid.org/0009-0000-6735-8486
Other Authors ORCID ID: Eren Abatan, https://orcid.org/0000-0003-3190-9869 . Mehmet Fatih Özlü, https://orcid.org/0009-0008-4503-2993 . Özden Arısoy, https://orcid.org/0000-0002-1422-1600
This study was approved by the Ethics Committee of Abant Izzet Baysal University, Faculty of Medicine (Date:2012-08-09, No: 2012/13)
Aim: Heart Rate Variability (HRV) is a simple and noninvasive method for measuring beat-to-beat changes in heart rate, quantified as a periodic variation in RR intervals. The association between anxiety disorders and sudden cardiac death has long been recognized and studied. In this study, the relationship between anxiety disorders and HRV was investigated.
Material and Methods: The study included 93 participants (33 with panic disorder, 25 with social phobia, and 35 controls). Psychiatric evaluation was performed using the Structured Interview Guide (SCID-I), and patient groups were formed. Groups were compared according to SDNN, SDANN, NN50, %pNN50, and RMSSD data.
Results: The mean SDNN values were statistically significantly lower in the panic disorder group than in the other groups (p=0.029 vs the social phobia group and p<0.001 vs the control group). There was no statistically significant difference between the study groups according to the average SDANN, RMSSD, and pNN50 values (p=0.065, p=0.548, and p=0.949, respectively). There was no significant difference between the social phobia group and the control group in terms of any parameter showing heart rate variability.
Discussion: The results of our study suggest that heart rate variability parameters are decreased in patients with panic disorder compared to the control group and that these patients should be evaluated more carefully in terms of sudden cardiac death and other cardiac events.
Keywords: Anxiety Disorder, Heart Rate Variability, Panic Disorder, Social Phobia
Introduction
Heart Rate Variability (HRV) is the beat-to-beat variation in heart rate, measured as the periodic variation in RR intervals, and is a simple and non-invasive method to assess sympathovagal balance at the sinoatrial (SA) level [1]. HRV is considered a measure of cardiac autonomic tone and an indicator of the cardiorespiratory system because it provides information about sympathetic and parasympathetic balance. HRV is used to objectively assess cardiovascular dysfunction and to determine sympathetic and parasympathetic effects on cardiovascular activity [2].
Sudden death is more common in individuals with anxiety disorders compared to healthy individuals. It has been shown that parasympathetic activity is suppressed, and sympathetic activity is increased in anxiety disorders, especially in panic disorder. This results in a decrease in high-frequency heart rate variability in these patients. Individuals with high levels of anxiety have a 4,5 to 6 times higher risk of sudden cardiac death compared to individuals without anxiety. This increased risk of sudden cardiac death is attributed to abnormal sympathovagal balance [3-5]. This decrease in high-frequency heart rate variability is associated with sudden cardiac death [4].
This study aims to compare the heart rate variability in patients diagnosed with social phobia and panic disorder presenting to the psychiatry outpatient clinic with anxiety complaints against healthy individuals.
Material and Methods
Working Groups and Work Plan
In the study, 33 patients diagnosed with panic disorder and 25 patients diagnosed with social phobia who applied to the psychiatry outpatient clinic of our hospital between May 25, 2012, and December 31, 2012, were evaluated. A control group of 35 people who applied to the check-up outpatient clinic and did not have any health problems was formed. Patients aged between 18 and 60 years who were literate enough to understand and respond to self-reported charts and scales, who did not have hearing or visual impairments that would make understanding and comprehension difficult, and who did not have cognitive impairments due to dementia, psychosis, or mental retardation were included in the study. Patients with any cardiac conditions, such as heart failure, valvular heart disease, coronary artery disease, and palpitations, were excluded. Consent was obtained from all patients for the study.
Heart Rate Variability Analysis
To evaluate the heart rate variability of patients in all groups, 24-hour Holter electrocardiography data were assessed using a Holter device with four leads (DMS 300-4A, MTM Multitechmed GmbH, Hunfelden-Dauborn, Germany) and Cardioscan II Premier software. For HRV analysis, heart recordings of all patients were manually evaluated to exclude artifacts. HRV parameters were determined automatically with a Holter data processing program. The time- and frequency-dependent automatic analysis method was used to determine the mean NN (cycle length between two normal beats), SDNN (standard deviation of all NN intervals throughout the examination), SDNN index (mean of standard deviations of all NN intervals in 5-minute recordings), SDANN (standard deviation of the average NN intervals in 5-minute recordings throughout the study period), NN50 (number of neighboring NN intervals with more than 50 msec difference between them during the entire recording), % pNN50 (number of NN50 divided by the total number of all NNs), and RMSSD (square root of the sum of squares of the differences of consecutive NN intervals in a 24-hour recording) parameters [6, 7].
Laboratory Analysis
Biochemical tests and complete blood counts were performed using fully automatic analyzers. Results were specified separately for each parameter.
Psychiatric Evaluation
The sociodemographic information form was filled out by the researcher, and psychiatric evaluation was performed using the Structured Interview Guide (SCID-I). The Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale were evaluated by the researcher. Self-reported Panic Agoraphobia Scale (PAAS), Hospital Anxiety and Depression Scale (HAD), State-Trait Anxiety Inventory (STAI 1-2), Bodily Sensation Exaggeration Scale (BDAQ), Anxiety Sensitivity Index-3 (ADI), and Liebowitz Symptoms of Social Phobia Scale (LSFPS) were administered to all participants. Groups were formed as a result of the psychiatric evaluation [8-10].
Statistical Analysis
Data were analyzed using the Statistical Package for Social Sciences (SPSS) for Windows 15.0 software. Categorical variables were expressed as number (n) and percentage (%) and analyzed using the Chi-square test (and/or Fisher’s exact test). Numerical variables were expressed as mean ± standard deviation, and Student’s t-test was used to compare the means of two independent groups. A value of p < 0.05 was considered statistically significant for all results.
Ethical Approval
This study was approved by the Ethics Committee of Abant Izzet Baysal University Faculty of Medicine Education, Planning, and Coordination Board (Date: 2012-08-09, No: 2012/13).
Results
A total of 33 patients with panic disorder, 25 patients with social phobia, and 35 patients in the control group were included in the study. Demographic data of the patients are summarized in Table 1. According to the data obtained, no difference was found between the groups in terms of gender, age, and smoking (p = 0.311, p = 0.756, and p = 0.424, respectively). The analysis of laboratory data of the patients is presented in Table 2. According to these data, there was no difference between the groups in terms of hemoglobin, electrolyte levels, thyroid function tests, glucose, and vitamin B12 levels (p > 0.05 for all data). The results of the parameters showing heart rate variability between groups are provided in Table 3. According to the data obtained, there was no difference between the groups in terms of minimum heart rate, maximum heart rate, and average heart rate results (p = 0.658, p = 0.201, and p = 0.508, respectively). The mean SDNN values were statistically significantly lower in the panic disorder group than in the other groups (p = 0.029 vs the social phobia group and p < 0.001 vs the control group). There was no statistically significant difference between the study groups according to the average of SDANN, RMSSD, and pNN50 values (p = 0.065, p = 0.548, and p = 0.949, respectively). However, the mean of these values was statistically significantly lower in the panic disorder group than in the control group (p = 0.013, p = 0.008, and p = 0.020, respectively). There was no significant difference between the social phobia group and the control group in terms of any parameter indicating heart rate variability.
Discussion
In this study, heart rate variability in patients diagnosed with social phobia and panic disorder who applied to the psychiatric outpatient clinic with anxiety complaints was compared with healthy individuals. Especially in patients with panic disorder, there was a significant difference in heart rate variability compared to the control group.
Findings related to cardiovascular abnormality have been known since the first studies on individuals with so-called irritable hearts in the 1870s. Publications on tachycardia and palpitations associated with severe fear and anxiety have made cardiovascular activity the focus of research [3]. It is known that an autonomic nervous system imbalance in the form of increased sympathetic activity affects cardiac electrophysiology and causes ventricular arrhythmias and sudden cardiac death. Neural remodeling in the heart affected by various diseases causes these imbalances in autonomic activity. Heart rate variability, which is an indirect indicator of tonic autonomic interactions at the sinus node level, is used as an indicator of neural control [4].
It is known that there is a close relationship between anxiety disorders and sudden death. Many complex physiological events occurring in acute anxiety states contribute to the occurrence of sudden death. In cases of persistent anxiety, the development of atherosclerosis is accelerated, and sudden death can be triggered. The acute effects of psychological stress leading to sudden death are summarized as causing myocardial ischemia, initiating arrhythmia, activating platelets, and increasing blood viscosity [11]. HRV, defined as frequency changes in sinus node velocity over time, is considered a measure of cardiac autonomic tone and an indicator of the cardiorespiratory system because it provides information about sympathetic and parasympathetic balance [3].
In the measurement of HRV, two measurement parameters are used as time and frequency dependent. In time-dependent measurement, SDNN (standard deviation of normal heartbeats), SDANN (standard deviation of the mean N-N intervals), SDNNI (mean of the standard deviation of all N-N intervals), RMSSD (square root of the mean of the sum of the squares of the differences between neighboring NNs), and pNN50 (obtained by dividing the number of N-Ns by NN50) (10). In frequency-dependent measurements, three main components are defined as very low frequency (VLF) (<0.04 Hz), low frequency (LF) (0.04-0.15 Hz), and high frequency (HF) (0.15-0.40 Hz) [6, 7].
HRV values are an important determinant of mortality after myocardial infarction. Kleigler et al. is one of the first studies showing that a decrease in the SDNN value is closely related to increased mortality [12]. In the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) study conducted in patients under 80 years of age and eligible for exercise testing, it was shown that SDNN <70, which is an indicator of parasympathetic-sympathetic imbalance, is an important independent predictor of cardiovascular mortality in patients [13]. During psychological stress in patients with anxiety disorders, a decrease in heart rate variability has been found, indicating parasympathetic inhibition. In patients with anxiety disorders, findings such as stress causing a more inadequate autonomic response, sometimes taking a long time for the autonomic changes to recover, and decreased heart rate variability are considered a serious risk for early mortality [14]. In a study conducted on 2059 patients, it was measured that SDNN and RSA [respiratory sinus arrhythmia] values of patients with anxiety disorder were significantly lower when compared with the control group. These values were found to be similar among the three types of anxiety disorder [14].
In our study, mean SDNN values were statistically significantly lower in the panic disorder group compared to the other groups (p = 0.029 vs the social phobia group and p < 0.001 vs the control group). There was no statistically significant difference between the study groups according to the mean SDANN, RMSSD, and pNN50 values (p = 0.065, p = 0.548, and p = 0.949, respectively). However, the mean of these values was statistically significantly lower in the panic disorder group than in the control group (p = 0.013, p = 0.008, and p = 0.020, respectively). There was no significant difference between the social phobia group and the control group in terms of any parameter indicating heart rate variability.
Conclusion
Our study found that HRV parameters were statistically significantly lower in patients with panic disorder compared to the control group. These patients should be followed up more closely in terms of cardiac risk since the risk of sudden cardiac death and cardiac events increases as a result of the impaired balance of parasympathetic and sympathetic activity.
Limitation
If this study is conducted in larger study groups, more significant results can be obtained. Also, the inclusion of arrhythmia patients may reveal new results. Additionally, there were no mortal patients in our study. It would be more useful to include this data in a larger series.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Ishaque S, Khan N, Krishnan S. Trends in Heart-Rate Variability Signal Analysis. Front Digit Health. 2021;3:639444.
2. Khan AA, Lip GYH, Shantsila A. Heart rate variability in atrial fibrillation: The balance between sympathetic and parasympathetic nervous system. Eur J Clin Invest. 2019;49(11):e13174.
3. Franciosi S, Perry FKG, Roston TM, Armstrong KR, Claydon VE, Sanatani S. The role of the autonomic nervous system in arrhythmias and sudden cardiac death. Auton Neurosci. 2017;205:1-11.
4. Lombardi F, Mäkikallio TH, Myerburg RJ, Huikuri HV. Sudden cardiac death: Role of heart rate variability to identify patients at risk. Cardiovasc Res. 2001;50(2):210-7.
5. Pittig A, Arch JJ, Lam CW, Craske MG. Heart rate and heart rate variability in panic, social anxiety, obsessive-compulsive, and generalized anxiety disorders at baseline and in response to relaxation and hyperventilation. Int J Psychophysiolog. 2013;87(1):19-27.
6. Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017;5:258.
7. Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996;93(5):1043-65.
8. Gaebler M, Daniels JK, Lamke JP, Friedrich T, Walter H. Heart rate variability and its neural correlates during emotional face processing in social anxiety disorder. Biol Psychol. 2013;94(2):319-30.
9. Servant D, Logier R, Mouster Y, Goudemand M. La variabilité de la fréquence cardiaque. Intérêts en psychiatrie [Heart rate variability. Applications in psychiatry]. Encephale. 2009;35(5):423-8.
10. Åhs F, Sollers III JJ, Furmark T, Fredrikson M, Thayer JF. High-frequency heart rate variability and cortico-striatal activity in men and women with social phobia. NeuroImage. 2009;47(3):815-20.
11. Abrignani MG, Renda N, Abrignani V, Raffa A, Novo S, Lo Baido R. Panic disorder, anxiety, and cardiovascular diseases. Clinical Neuropsychiatry. 2014;11(5):130-144.
12. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987;59(4):256-62.
13. La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI Investigators. Lancet. 1998;351(9101):478-84.
14. Licht CM, de Geus EJ, van Dyck R, Penninx BW. Association between anxiety disorders and heart rate variability in The Netherlands Study of Depression and Anxiety (NESDA). Psychosom Med. 2009;71(5):508-18.
Download attachments: 10.4328.ACAM.22437
Mesut Mehmet Özdemir, Eren Abatan, Mehmet Fatih Özlü, Özden Arısoy.Importance of heart rate variability in social phobia and panic disorder patients.Ann Clin Anal Med 2025;16(7):478-481
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Promising hepatorenal protective effects of pumpkin (Cucurbita pepo L.) And watermelon (Citrullus lanatus L.) Seed oils against diazinon-induced acute toxicity in rats
Abeer A. Banjabi1, Fares K. Khalifa 1, 2, Maha M. Al-Bazi 1, Sahar A. Alkhodair 1, Huda A. Al Doghaither 1, Aliaa M. Sabban 3, Salma M. Aljahdali 1, Hayat M. Albishi 1
1 Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia, 2 Department of Biochemistry and Nutrition, Faculty of Women for Arts Science and Education, Ain Shams University, Cairo, Egypt, 3 Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
DOI: 10.4328/ACAM.22439 Received: 2024-10-06 Accepted: 2024-11-10 Published Online: 2025-02-11 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):482-487
Corresponding Author: Fares Khairy Khalifa, Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. E-mail: fkkhalifa@kau.edu.sa P: +90 966 53 156 9236 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6320-2297
Other Authors ORCID ID: Abeer A. Banjabi, https://orcid.org/0000-0002-8303-9351 . Maha M. Al-Bazi, https://orcid.org/0000-0002-6447-4833 . Sahar A. Alkhodair, https://orcid.org/0000-0002-6376-955X . Huda A. Al Doghaither, https://orcid.org/0000-0002-6192-8326 . Aliaa M. Sabban, https://orcid.org/0000-0002-0558-4354 Salma M. Aljahdali, https://orcid.org/0009-0002-0812-7244 . Hayat M. Albishi, https://orcid.org/0009-0004-9349-9986
This study was approved by the Ethics Committee of Ain Shams University (Date: 2024-04-01, No: sci1432409001)
Aim: The present study aimed to evaluate the toxicity of DZN in the liver and kidney. We also tested the protective effect of pumpkin seed oil (PSO) and/or watermelon seed oil (WSO) against diazinon toxicity.
Material and Methods: Fifty adult male Sprague–Dawley rats were classified into five groups: G1 [control]; G2 [DZN-50 mg/kg b.w]; G3 [DZN + PSO (1.5 ml/kg b.w)]: G4 [DZN + WSO (1.5 ml/kg b.w), and G5 [ DZN + PSO+ WSO].
Results: Diazinon toxicity altered serum kidney and liver function biomarkers. These effects were pronouncedly alleviated by treatment with PSO and WSO.
Discussion: PSO and WSO have a protective role against nephrotoxicity and hepatotoxicity induced by diazinon. PSO was more effective in reducing DZN nephrotoxicity, while WSO was more potent than PSO in reducing DZN hepatoxicity. Moreover, the antioxidant properties of these oils support the bioactive roles of their protective effects on DZN toxicity. This study, therefore, suggests that these oils could be used as preventive factors against the toxicity of DZN due to its antioxidant properties.
Keywords: Pumpkin Seed Oil, Watermelon Seed Oil, Diazinon, Hepatotoxicity, Nephrotoxicity
Introduction
Organophosphorus compounds are one of the most common types of organic pollutants found in the environment [1]. Toxicities of organophosphorous insecticides cause adverse effects on many organs. Systems that could be affected by organophosphorus insecticides are the nervous system, immune system, liver, muscles, urinary system, reproductive system, and hematological system [2].
Diazinon (DZN) is an organophosphorus insecticide that is widely and effectively used throughout the world with applications in agriculture and cultivation for controlling insects in crops and other food products [3]. Several investigations have shown that DZN was capable of inducing biochemical and physiological alterations [4].
In recent years, interest has increased in using natural products for pharmacological purposes as a form of complementary or replacement therapy [5]. The pumpkin (Cucurbita Pepo L.) is a common conventional food in many countries. Pumpkin seeds contain about 42 to 54% oil. Pumpkin seed oil contains fatty acids (mainly linoleic acid, oleic acid, palmitic acid, and stearic acid). It has high amounts of antioxidant vitamins such as α- and γ-tocopherol, β carotene, and vitamin E. Pumpkin seed oil also contains phenolic compounds such as vanillic acid and vanillin and high levels of selenium and lutein. In comparison to other seed oils, PSO is rich in squalene, which is a carbon organic compound that has many commercial uses. It is an affluent source of phytosterols and proteins [6]. The presence of all these constituents in pumpkin seed oil clarifies their useful and valuable effects on human health. Nowadays, it is used in the treatment of many diseases, such as hypertension and hypercholesterolemia [7].
Watermelon (Citrullus lanatus L.) is a widely popular fruit used across the world for its numerous nutritional and health-promoting benefits. Watermelon has traditionally been used to help treat a diverse range of diseases in Africa and Asia, including erectile dysfunction, dehydration, and renal disease [8]. Watermelon seeds have great nutritional value due to their high protein, oil, citrulline, carotenoids, and lycopene content, and as a strong source of vitamin C, niacin, folate, and dietary fiber [9]. The large majority of research studies on watermelon’s health benefits have concentrated on the juice [10], but the seeds have also attracted significant attention in recent years [11]. Citrullus lanatus seed extracts have also been shown to have antihyperglycemic and hypolipidemic potential in diabetic rats [12]. In addition, seed extracts have been demonstrated to protect against aspartame-induced oxidative stress [13]. There is presently no research showing that WSO can protect rats from diazinon-induced liver and kidney damage. As a result, the study aimed to examine the protective potential of watermelon seed oil alone or mixed with pumpkin seed oil against hepatorenal toxicity induced by long-term diazinon administration in rats.
Material and Methods
Chemicals
Diazinon (O, O-Diethyl O-[4-methyl-6-(propane-2-yl)pyrimidin-2-yl] phosphorothioate; purity 100%) was purchased from Sigma-Aldrich (St. Louis, MO, USA). All other reagents were commercial products of standard chemical grade. Pumpkin seed oil was purchased from Now Foods Co., Bloomingdale, IL., USA. Watermelon seed oil was purchased from Sweet Essential, imported from Egypt.
Experimental Animals and Design
Adult male albino rats (Sprague-Dawley) were used in this study, initially weighing 136±5 g. Rats were divided and housed in environmentally controlled cages (22±1 0C, 50±5% humidity, and 12 h light/dark cycle). Rats were fed a balanced standard diet and allowed water ad libitum throughout the whole experiment (35 days).
The study was conducted between May 2024 and July 2024 at Central Laboratory Unit – Ain Shams University. Fifty male rats were classified into five groups (10 rats/group) as follows:
Group 1 (Control): Rats were untreated and received the standard diet.
Group 2 (diazinon intoxicated group- DZN): Rats were orally administrated with 50 mg/kg body weight of DZN in corn oil by gastric tube daily for 5 weeks.
Group 3 (pumpkin seed oil group- PSO + DZN): Rats received the standard diet with pumpkin seed oil at a dose of 1.5 ml/kg b.w/ day orally by gastric tube and after six h exposed to DZN at the same dose given to group 2, daily for 5 weeks.
Group 4 (watermelon seed oil group-WSO+DZN): Rats received the standard diet with watermelon seed oil at a dose of 1.5 ml/kg b.w./ day orally by gastric tube and after six h exposed to DZN at the same dose given to group 2, daily for 5 weeks.
Group 5 (PSO+ WSO+ DZN group): Rats received the standard diet with pumpkin seed oil and watermelon seed oil at the same dose given to groups 3 and 4, respectively, and after six h exposed to DZN at the same dose given to group 2, daily for 5 weeks.
Analytical Procedures
On the last day of the experimental period, rats were fasted overnight and then anesthetized with ether, blood samples were drawn from the hepatic portal vein and then transported into centrifuge tubes. Tubes were centrifuged at 5000 x g for 15 minutes at 23°C to collect serum for the biochemical examination. Serum samples were stored at -20°C until used for various biochemical analyses. To determine hematological parameters, additional blood samples (approximately 1 ml) were collected into test tubes containing EDTA.
The kits of urea, creatinine, total proteins, total bilirubin, Cystatin-C, neutrophil gelatinase-associated lipocalin (NGAL), total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA), and reduced glutathione (GSH) were obtained from Bio diagnostics Co. (Cairo, Egypt). Meanwhile, nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were determined using enzyme-linked immunosorbent assay kits (ELISA) according to the manufacturer Kamiya Biomedical Co. (CA, USA). Alanine transaminase (ALT), aspartate transaminase (AST), paraoxonase-1 (PON1), and gamma-glutamyl transferase (GGT) activities were determined using commercial kits (Biovision, CA, USA). Platelet counts were evaluated using a hematology analyzer (Beckman Coulter, USA).
Prothrombin time (PT) measurement: PT is measured by Quick’s method. The reagent used in PT testing is thromboplastin. The time in seconds taken for the formation of a fibrin clot is measured as PT.
Statistical Analysis
Statistical significance tests were performed using SPSS (v.24, IBM SPSS Statistics, US) at p≤0.01 using one-way analysis of variance (ANOVA) followed by LSD post hoc multiple comparisons. All data were expressed as mean ± SE for ten rats of each group using Microsoft Excel.
Ethical Approval
This study was approved by the Ethics Committee of Ain Shams University (Date: 2024-04-01, No: sci1432409001).
Results
Results presented in Table 1 revealed that administration of diazinon results in an increase (p≤0.01) in values of ALT, AST, GGT, and PON1 compared with untreated control rats. The administration of PSO and WSO reduced these levels significantly (p≤0.01) and reduced them to nearly control levels. Diazinon exposure was associated with hepatotoxicity in male rats, as revealed by a decrease in total proteins and an increase in serum levels of total bilirubin. An improvement was detected following treatment with PSO combined with WSO. Results revealed a correlation between DZN-induced hepatotoxicity and the increased time of prothrombin (by 58.5%) and reduced platelets count (by -52.5%). Treatment with PSO and WSO caused an increase in platelet count and significantly improved the prothrombin time (Table 2). Rats who received DZN demonstrated a significant reduction in SOD, GSH, and TAC levels (by -48.0 %, -61.9 %, and -60.0 % for SOD, GSH, and TAC respectively, as compared to the control group (P ≤ 0.01). On the other hand, the serum level of MDA was higher in the DZN-intoxicated group (by 72.5 % as compared with the control group. WSO or PSO effectively reversed these effects during oxidant damage. Treatment with PSO maintained TAC and GSH levels higher than WSO (Figure 1). Diazinon exposure induced nephrotoxicity, which is displayed by significant changes in biomarkers of serum kidney function values. DZN increased urea, cystatin C, NGAL, and creatinine as compared to the normal control group. These effects were pronouncedly alleviated by treatment with PSO (by -22.0%, -35.49%, -55.7%, and -48.7% for NGAL, cystatin C, urea, and creatinine, respectively) compared with the DZN group. The nephroprotective effect was more apparent when WSO was administered in combined with PSO as a protective agents (by -34.6%, -47.4%, -57.9%, and -66.6%, for NGAL, cystatin C, urea. and creatinine respectively) compared with the DZN group. (Table 3). Treatment with PSO (G3) and WSO (G4) caused a significant reduction in inflammatory biomarker levels when compared to the DZN-intoxicated group. Results revealed a correlation between DZN-induced nephrotoxicity and the elevated serum levels of CRP and TNF-α, thus indicating toxicity of renal cells. An improvement of these biomarker levels was detected following treatment with PSO mixed with WSO (Figure 2).
Discussion
Diazinon (DZN) is an insecticide extensively used to control pests in crops and animals. However, its indiscriminate use may lead to liver and kidney damage in animals and humans. The present study was designed to evaluate whether pre-treatment with PSO and WSO would have protective influences on DZN-induced hepatorenal injury in male rats.
The results of the current study demonstrated a significant increase in serum levels of AST, ALT, and GGT activities in DZN-treated rats. The increases in enzyme activities may be owing to hepatic cell damage or dysfunction, which results in the leakage of these enzymes from hepatocytes into the blood and/or to the disturbance in the balance between biosynthesis and degradation. Meanwhile, DZN treatment also caused a significant increase in serum bilirubin levels, arising from the toxic effect of DZN by destroying red blood cells. However, serum bilirubin increases could also be of hepatic origin [14]. The administration of PSO and WSO reduced these levels significantly (p≤0.01) and reduced them to nearly control levels. An improvement was detected following treatment with PSO mixed with WSO. A possible explanation is that PSO had hepatoprotective effects on DZN toxicity by scavenging free radicals, reducing their damaging effects, and remedying liver injury.
Studies have revealed that oxidative stress can be an important component of the mechanism of DZN intoxication. Treatment of rats with DZN significantly promotes a decrease in the level of GSH, events that may be related to the renal toxicity of DZN mediated by oxidative stress. The present results showed that the administration of DZN caused significant decreases in levels of serum GSH, TAC, and SOD, while the level of serum MDA was significantly increased. These findings are consistent with previous investigations, which indicated that DZN and other pesticides [15].
The results of the current study showed that PSO effectively reversed these effects during oxidant damage. Pumpkin seed oil can play a major role in protecting the liver against alcohol-induced hepatotoxicity and oxidative stress. Pre-treatment with PSO showed hepatoprotective effects, including antioxidant protection and enhanced detoxification [24]. Treatment with PSO counteracts oxidative parameters. The strong antioxidant activity of constituents of pumpkin led to an effective protection of the mitochondrial membrane, as underscored by a significant decline in MDA value. These were in line with Eraslan et al. [16], where PSO led to biochemical alterations in the antioxidant enzyme action due to its potential to eliminate reactive oxygen species produced under normal conditions.
Another study by Xu [17] found that polysaccharides from pumpkin may increase the activity of GSH-Px while decreasing serum MDA content in mice tumors due to its high vitamin A and tannin content, particularly present in the oil, which possesses antioxidant activity. Vitamin E and tocopherols prevent damage caused by free radicals; suppressed lipid peroxidation enhances GSH activity and improves membrane integrity.
Que et al. [18] have reported that PSO is rich in phenolic and flavonoid compounds. These components are said to possess many functional groups, including hydroxyl groups, which have very strong antioxidant potential. Polyphenols and flavonoids can scavenge hydroxyl radicals and superoxide radicals. This is why pumpkin is a plant that has been frequently used as a functional food or medicine. In addition, PSO supplementation ameliorated the non-enzymatic GSH and the enzymatic antioxidant activities of SOD. This rebalance of the antioxidant status is certainly related to the high antioxidant potential of PSO, which contains polyphenols, flavonoids, acids, and tannins detected in its phytochemical study. The PSO is also known to contain high amounts of tocopherols and selenium, which are powerful antioxidants [19]. In the same way, the pre-treatment of rats with pumpkin seed oil induced a noticeable reduction in lipid peroxidation and boosted the antioxidant status represented by hepatic TAC and GSH.
The present results demonstrated that the treatment of rats with watermelon seed oil improved the biochemical alterations induced by DZN intoxication. This indicated the effectiveness of WSO in the prevention of DZN toxicity. The possible mechanism of WSO as a protective factor may be due to its antioxidant effects, which impair the activation of DZN into the reactive form. Dietary intake of antioxidants can inhibit or delay the oxidation of susceptible cellular substrates to prevent oxidative stress [20].
Watermelon seed oil significantly (p≤0.01) reduced MDA levels while SOD activity and TAC increased in all treated groups (G4, G5). The antioxidant properties of WSO could be attributed to the presence of flavonoids, predominantly catechin, alkaloids, oxalates, and saponin in WSO. Flavonoids have been reported to act as powerful antioxidants that can protect the human body from free radicals and reactive oxygen species [21].
In response to inflammation and cell damage, the serum level of C-reactive protein (CRP) rapidly and significantly increases. CRP could be involved in the regulation of renal function. TNF-α and NF-κB levels were raised in DZN-induced rats in response to these pro-inflammatory cytokines, which in turn raised CRP levels. The antioxidants and anti-inflammatory potential of the Citrullus lanatus seeds were investigated by Logaraj [22], who confirmed that watermelon seeds are a good source of linoleic acid (18:2 ω-6) as a major fatty acid.
The results of the present study showed that WSO lowered the serum CRP level because of its confirmed anti-inflammatory effect, and this was due to the presence of established polyphenolic compounds such as tannin and flavonoids. Flavonoids like fisetin and quercetin have been shown to activate NF-κB. The activation of NF-κB is critical for the production of pro-inflammatory cytokines [23].
The goal of the current study was to determine if the flavonoid extract from Citrullus lanatus seed might protect against diazinon-induced kidney damage. The outcomes of this research indicated that diazinon-induced kidney damage was connected with increased oxidative stress and renal biochemical markers. In the present study, renal dysfunction was detected by significant increases in serum creatinine, NGAL, cystatin C, and urea levels in rats exposed to DZN. The present decreases in total serum proteins and albumin are generally due to the findings of several studies showing increases in these parameters in experimental animals exposed to DZN and other pesticides [24]. An increase in levels of serum creatinine and urea revealed damaged kidney function or kidney disorder. This disorder will cause the creatinine level in the blood to rise due to the inability of the kidneys to clear creatinine [25]. Treatment with WSO significantly (p≤0.01) reduced urea and creatinine concentrations when compared to the DZN-intoxicated group (G2). The significant decrease in creatinine concentration after treatment may be due to the strength of the WSO to ameliorate kidneys, thereby stimulating the rate of filtration by kidneys.
According to the authors` knowledge, there is no previous studies have investigated the valuable effect of pumpkin seed oil mixed with watermelon seed oil for prevention and/or reduction of toxicity induced by diazinon.
Limitations of the study
The most significant limitation of this study is the lack of previous research studies on the topic and time constraints.
Conclusion
Based on the present study, it can be concluded that pumpkin seed oil and watermelon seed oil improve the hepatorenal alterations induced by DZN intoxication. Moreover, the most protective effects were observed in rats treated with PSO mixed with WSO. Additionally, the antioxidant properties of these oils support the bioactive roles of their protective effects on DZN toxicity. To strengthen these findings, further experimental studies are needed to evaluate the effect of different doses of these oils as protective factors against the toxicity of DZN.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Worek F, Thiermann H, Wille T. Organophosphorus compounds and oximes: A critical review. Arch. Toxicol. 2020;94(7):2275-92.
2. Ore OT, Adeola AO, Bayode AA, Adedipe DT, Nomngongo PN. Organophosphate pesticide residues in environmental and biological matrices: Occurrence, distribution, and potential remedial approaches. Environ. Chem. Ecotoxicol. 2023;5(1):9-23.
3. Siddiqua A, Hahladakis JN, Al-Attiya WA. An overview of the environmental pollution and health effects associated with waste landfilling and open dumping. Environ. Sci. Poll. Res. 2022(39):58514-36.
4. Girón-Pérez MI, Mary VS, Rubinstein HR, Toledo-Ibarra GA, Theumer MG. Diazinon toxicity in hepatic and spleen mononuclear cells is associated with early induction of oxidative stress. Int J Environ Health Res. 2022;32(10):2309-23.
5. Madkhali JY, Hussein RH, Alnahdi HS. The therapeutic effect of bromelain and papain on intestinal injury induced by indomethacin in male rats. Int J Health Sci. 2023;17(5):23-30.
6. Siegmund B, Murkovic M. Changes in the chemical composition of pumpkin seeds during the roasting process for production of pumpkin seed oil (Part 2: volatile compounds). Food Chem. 2004;84(3):367-74.
7. Wal A, Singh MR, Gupta A, Rathore S, Rout RR, Wal P. Pumpkin Seeds (Cucurbita spp.) as a Nutraceutical Used in Various Lifestyle Disorders. Nat. Prod. J. 2024;14(1):118-37.
8. Michael OS, Bamidele O, Ogheneovo P, Ariyo TA, Adedayo LD, Oluranti OI, et al. Watermelon rind ethanol extract exhibits hepato-renal protection against lead-induced-impaired antioxidant defenses in male Wistar rats. Curr. Res. Physiol. 2021;4(1):252-59.
9. Benmeziane F, Derradji. Composition, bioactive potential and food applications of watermelon (Citrullus lanatus) seeds–a review. J. Food Meas. Character. 2023;17(5):5045-61.
10. Ajiboye BO, Shonibare MT, Oyinloye BE. Antidiabetic activity of watermelon (Citrullus lanatus) juice in alloxan-induced diabetic rats. J Diabetes Metab Disord. 2020;19(1):343-52.
11. Elaine E, Jess W, Nyam K. Watermelon seeds: nutritional profile, bioactivities, and application in the food industry." Valorization of Fruit Seed Waste from Food Processing Industry. Academic Press; 2024.183-213.
12. DI I. Effect of Aqueous Extract of Citrullus lanatus (Watermelon) Seed on Lipid Profile and Electrolyte Function in Alcohol-induced Toxicity in Male Rats. Euro. J. Med. Plants. 2024;35(6):132-8.
13. Ikpeme EV, Udensi OU, Ekerette EE, Okon UH. The potential of ginger (Zingiber officinale) rhizome and watermelon (Citrullus lanatus) seeds in mitigating aspartame-induced oxidative stress in a rat model. Res J Med Plant. 2016;10(1):55-66.
14. Mansouri RA, Alshaibi HF, Alqurashi MM, Shaikh MM, Bahaidrah KA, Alzahrani NA. Sulforaphane protects against LPS-induced liver injury in mice by antagonizing oxidative stress and apoptosis through AMPK activation. Int J Health Sci (Qassim). 2024;18(3):39-47.
15. Moradi A, Ziamajidi N, Ghafourikhosroshahi A, Abbasalipourkabir R. Effects of vitamin A and vitamin E on attenuation of titanium dioxide nanoparticles-induced toxicity in the liver of male Wistar rats. Mol. Biology Rep. 2019;46(3):2919-32.
16. Eraslan G, Kanbur M, Aslan Ö, Karabacak M. The antioxidant effects of pumpkin seed oil on subacute aflatoxin poisoning in mice. Enviro. Toxicol.. 2013;28(12):681-8.
17. Xu GH. A study of the possible antitumor effect and immune competence of pumpkin polysaccharide. J Wuhan Prof Med Coll. 2000;28(4):1-4.
18. Que F, Mao L, Fang X, Wu T. Comparison of hot air‐drying and freeze‐drying on the physicochemical properties and antioxidant activities of pumpkin (Cucurbita moschata Duch.) flours. IJFST. 2008;43(7):1195-201.
19. Wong A, Viola D, Bergen D, Caulfield E, Mehrabani J, Figueroa A. The effects of pumpkin seed oil supplementation on arterial hemodynamics, stiffness and cardiac autonomic function in postmenopausal women. Complement. Ther. Clin. Practice. 2019;37(1):23-26.
20. Al Doghaither HA, Elmorsy EM. Assessment of antipsychotic-induced cytotoxic effects on isolated CD1 mouse pancreatic beta cells. Int J Health Sci (Qassim). 2023;17(4):11-21.
21. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: Food sources and bioavailability. Am J Clin Nutr. 2004;79(5):727-47.
22. Logaraj TV (2011) Watermelon Citrullus lanatus (Thunb) Matsumura and Nakai seed oils and their use in health. Nuts and seeds in health and disease prevention. (1st ed), Cambridge, Massachusetts (USA): Academic Press. P.1149-1157.
23. Gabriel AF, Igwemmar NC, Sadam AA, Babalola SA. Characterization of seed oil from Citrullus lanatus (Watermelon). Direct Res. J. Public Health and Environ. Technol. 2018;3(2):34-40.
24. Al-Attar AM. Effect of grapeseed oil on diazinon-induced physiological and histopathological alterations in rats. Saudi J. Biol. Sci.2015;22(3):284-92.
25. Alkhattabi NA, Khalifa FK, Al Doghaither HA, Al-Ghafari AB, Tarbiah NI, Sabban A. Protective effects of N-acetylcysteine and S-adenosyl-Methionine against nephrotoxicity and immunotoxicity induced by ochratoxin A in rats. Int J Health Sci (Qassim). 2024;18(2):17-24.
Download attachments: 10.4328.ACAM.22439
Abeer A. Banjabi, Fares K. Khalifa, Maha M. Al-Bazi, Sahar A. Alkhodair, Huda A. Al Doghaither, Aliaa M. Sabban, Salma M. Aljahdali, Hayat M. Albishi. Promising hepatorenal protective effects of pumpkin (Cucurbita pepo L.) And watermelon (Citrullus lanatus L.) Seed oils against diazinon-induced acute toxicity in rats. Ann Clin Anal Med 2025;16(7):482-487
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Temporomandibular dysfunction in patients with diabetic foot ulcers: What could be the predictors?
Fatih Enzin 1, Hazel Çelik Güzel 2
1 Department of Physiotherapy, Faculty of Health Sciences, Harran University, Şanlıurfa, 2 Department of Physiotherapy, Vocatıonal School of Health Servıces, Bandırma Onyedı Eylul Unıversıty, Balıkesir, Turkiye
DOI: 10.4328/ACAM.22506 Received: 2024-11-30 Accepted: 2025-01-13 Published Online: 2025-02-05 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):488-493
Corresponding Author: Fatih Enzin, Department of Physiotherapy, Faculty of Health Sciences, Harran University, Şanlıurfa, Turkiye. E-mail: fatihenzin@harran.edu.tr P: +90 543 458 74 83 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9836-3787
Other Authors ORCID ID: Hazel Çelik Güzel, https://orcid.org/0000-0001-6510-5012
This study was approved by the Ethics Committee of Harran University (Date: 2022-11-28, No: HRÜ/22.23.34)
Aim: This study aimed to investigate the factors that contribute to temporomandibular dysfunction in individuals with diabetic foot ulcers.
Material and Methods: A total of 84 people were studied in the foot ulcer and control groups. Ulcer evaluation, oral health status, quality of life, mandibular functionality, pain, and oropharyngeal swallowing problems were evaluated. Multiple logistic regression and analysis structural equation modeling were performed for temporomandibular dysfunction predictors.
Results: Patients with foot ulcers had a higher incidence of oral problems and swallowing disorders (p=0.000) and a more severe temporomandibular dysfunction (p=0.010). It was observed that increasing rest pain, diabetes duration, and age by 1 unit caused temporomandibular dysfunction to increase by 0.391, 0.552, and 0.205 units, respectively. A decrease of 1 unit in temporomandibular dysfunction was found to cause a loss of 0.618 units in swallowing. Similarly, it was observed that a loss of 1 unit in temporomandibular dysfunction and swallowing values led to a reduction of 0.515 and 0.371 units in the quality of life. Longer diabetes duration increases temporomandibular dysfunction probability by 2.691 per year.
Discussion: With prolonged duration of diabetes and increasing oral health problems, it has been determined that the presence of ulceration increases temporomandibular dysfunction. Swallowing disorder, mandibular dysfunction, and decreased quality of life were detected, along with an increase in ulcer area.
Keywords: Diabetes Mellitus, Diabetic Foot Ulcer, Temporomandibular Joint, Oral Health, Complication, Quality Of Life
Introduction
Approximately 500 million people globally are living with diabetes, and this number is expected to rise by 25% by 2030 and 51% by 2045 [1]. Neuropathy is one of the most common complications of DM, affecting over half of patients with a disease duration of 10 years or more and serving as the leading cause of foot ulcers [2]. The prevalence of foot ulcers in individuals with diabetes ranges from 3% to 13%, with a global average estimated at 6.4% [3].
Studies have shown that diabetic neuropathy can affect all parts of the nervous system, including the head and neck region. Common oral symptoms of diabetes include xerostomia, taste disturbances, dental caries, periodontal disease, fungal infections, sensory loss, numbness, and burning mouth sensation [4]. Furthermore, it has been demonstrated that the rate of complications increases with the duration of diabetes [5]. Diabetic neuropathy can lead to the loss of protective plantar sensation [6]. Studies have demonstrated that sensory and motor deficits associated with DPN contribute to gait alterations, resulting in balance impairments and an increased risk of falls [7]. Furthermore, adaptive gait patterns have been observed, particularly in individuals with diabetes suffering from ulceration, along with reduced plantar pressure sensation and postural control, negatively impacting balance [8, 9].
Studies have shown a reciprocal interaction between temporomandibular dysfunction (TMD) and body posture, where changes in mandibular position influence posture, and postural changes affect mandibular position [10, 11]. However, literature exploring the relationship between temporomandibular joint (TMJ) disorders and foot structure remains limited. Studies have shown that changes in the plantar arch, in particular, affect the masseter and temporal muscles secondarily and change posture with compensatory muscle chain activities [12, 13]. Likewise, studies have shown that gait stability is impaired by changing the position of the mandible, and the loading surface and plantar pressure of the feet change under altered occlusion conditions in individuals with TMD [14]. A study conducted with healthy individuals found that static plantar pressure was influenced by maximum mouth opening, and postural stability improved when the teeth were in maximum occlusion [15].
Based on this information, we can infer that changes in foot structure in individuals with diabetic foot ulcers (DFUs) may negatively impact the TMJ due to the biomechanical, neurophysiological, and fascial relationships outlined in the literature. However, the literature review did not find any study examining how an ulcerated foot structure affects TMJ in individuals with DM. Given this gap, the authors suggest that further research should investigate how the type, area, and duration of ulceration, which leads to changes in foot structure, correspond with alterations in the TMJ. Additionally, it is essential to examine how factors such as the duration of diabetes, oral health issues, and the status of ulceration influence TMD. Therefore, this study aims to explore the impact of ulceration type, area, and duration on jaw pain, limitations in mandibular function, TMD symptoms, swallowing, and the determinants of TMD in individuals with DFU.
Material and Methods
Study Design
The study was conducted as an observational case-control study between January and June 2023. Participants’ rights were protected, and informed consent was obtained (ClinicalTrials.gov:NCT06067022).
Participants
The study group consisted of individuals aged 46-80 years diagnosed with type 2 DM and DFU, while the control group included healthy individuals aged 37-85 years without a DM diagnosis. Exclusion criteria included a Mini-Mental Test score below 24, a history of psychiatric or systemic diseases, neurological and musculoskeletal disorders, cancer, congenital anomalies, facial paralysis, recent surgeries involving the spine, abdomen, or TMJ, and treatments related to these regions within the last six months.
The sample size was calculated as 74 participants (n=37) to achieve an effect size of 0.6 with 5% Type I error, 20% Type II error, 80% statistical power, and a 95% confidence interval. A total of 84 participants were included in the study, with 42 in the DFU group and 42 in the control group. The study flowchart is given in Figure 1.
Study Protocol
In individuals with DFU, diabetes and ulcer assessments included A1C levels, diabetes duration, glycemic control, and ulcer duration and area. Ulcer area was measured using ImageJ software through the analysis of digital photographs [16], while sensory evaluation was performed using the monofilament test. Oral health assessments covered xerostomia, burning mouth syndrome, tooth loss, and oral lesions. Quality of life, mandibular function, pain, and dysfunction were evaluated using validated scales:
Ferrans&Powers Quality of Life Index Diabetes Version (FPQLI): A 68-item scale evaluating health, socioeconomic status, psychological beliefs, and overall quality of life, where higher scores indicate better quality of life [17].
Numerical Rating Scale (NRS): TMJ pain was rated on a scale from 0 (no pain) to 10 (unbearable pain).
The Mandibular Function Disorder Questionnaire (MFIQ): MFIQ is a 17-item scale with higher scores indicating greater jaw dysfunction [18].
Fonseca Anamnestic Index (FAI): A 10-item scale for TMJ disorders, with scores of 25 or above indicating the presence of dysfunction [19].
Eating Assessment Tool (EAT-10): A 10-item scale for evaluating oropharyngeal dysphagia, where total scores of 3 or higher suggest swallowing difficulties [20].
Data Analysis
Parametric variables were expressed as mean±SD, nonparametric variables as median (min-max), and categorical data as percentages.
Normality was assessed with the Shapiro-Wilk test. Group comparisons were made using Independent T, Mann-Whitney U, and Chi-Square tests. Correlations between diabetes duration, ulcer area, TMD parameters, and quality of life were analyzed with Spearman’s correlation.
Multiple logistic regression analysis was applied to determine whether the relevant variables were a statistically significant determinant of TMD (FAI?25) in individuals with DFU. We calculated odds ratios (ORs), 95% confidence intervals for ORs, and Wald statistics for each independent variable. We also used the Nagelkerke R2 to determine how much of the TMD probability of the variables included in the models could be explained. The statistical significance level was determined as p<0.05.
Path analysis via Structural Equation Modeling (AMOS 23) explored relationships between TMD, swallowing disorders, quality of life, and variables such as age, ulcer area, pain, and diabetes duration. A significance level of p<0.05 was applied.
Ethical Approval
This study was approved by the Ethics Committee of Harran University (Date: 2022-11-28, No: HRÜ/22.23.34).
Results
The mean age of the DFU group was 61.31 (46-80), while the mean age of the control group was 61.88 (37-85). The frequency of burning mouth syndrome (p=0.000), xerostomia (p=0.000), oral lesions (p=0.002), and swallowing disorders (p=0.000) was significantly higher in individuals with DFU compared to healthy individuals. Although there was no significant difference in TMD frequency (p=0.297), TMD severity was higher in the DFU group (p=0.010). The DFU group scored significantly higher than the control group on NRS (p=0.010), FAI (p=0.000), EAT-10 (p=0.000), and MFQI (p=0.000) (Table 1).
In individuals with Wagner 2 ulcers, FAI (p=0.013) and EAT-10 (p=0.039) scores were significantly higher.
In individuals with ulcer duration >30 days, FAI scores were significantly higher (p=0.010).
The ulcer area showed a significant positive correlation with FAI (p=0.005), EAT-10 (p=0.046), MFIQ (p=0.036), and FPQLI (p=0.003).
Diabetes duration showed a significant positive correlation with NRS (p=0.011), FAI (p=0.000), EAT-10 (p=0.002), and MFIQ (p=0.000).
The data considered as predictors of TMD presence in individuals with DFU and found to show significant differences in earlier analyses were examined using multivariate logistic regression analysis in three models, as shown in Table 2.
Model I: For each additional year of diabetes duration, the odds of having TMD increased significantly by 2.691 times (95% CI: 1.120-6.467, p=0.027).
Model II: In individuals with burning mouth syndrome, the odds of having TMD were 8.374 times higher compared to those without the syndrome (95% CI: 0.801-87.557, p=0.046).
Model III: In individuals with ulcer duration >30 days, the risk of having TMD was 11.707 times higher compared to those with shorter ulcer durations (95% CI: 1.182-115.937, p=0.035).
In this study, a Structural Equation Model (SEM) was employed to investigate the relationship between age, ulcer area, pain (during activity and at rest), and diabetes duration with TMD. Additionally, the association of TMD with swallowing disorders and quality of life was examined. The results of the analysis indicate that the established model meets the validity criteria. These findings are shown in Figure 2.
The patients’ age, ulcer area, pain during activity and rest, and diabetes duration explained 62.9% of the total FAI score, while the total FAI score explained 38.2% of the change in EAT-10. The combined evaluation of FAI and EAT-10 scores accounted for 63.9% of the change in quality of life.A one-unit increase in age results in a 0.205 unit increase in the FAI score for patients with diabetes (B = 0.205; P = 0.031). A one-unit increase in rest pain leads to a 0.391-unit change in the FAI score (B=0.391, P<0.001). With each additional year of diabetes, FAI caused a deterioration of 0.552 units (B=0.552; P<0.001). A one-unit increase in patients’ FAI score results in a 0.618-unit change in EAT-10 (B=0.618; p<0.001). A unit decrease in FAI and EAT-10 scores causes a reduction of 0.515 and 0.371 units in the quality of life, respectively (B=-0.515; p<0.001; B=-0.371; p<0.001) (Table 3).
Discussion
This study aims to examine the effects of neuropathy-induced oral health problems and ulcer-related foot structural impairments on the temporomandibular joint (TMJ) from a holistic perspective using biomechanical pathways. The findings indicate that individuals with diabetic foot ulcers (DFU) have a high prevalence of oral health issues, jaw pain, mandibular dysfunction, and swallowing disorders. TMJ complaints were found to increase with greater ulcer depth, duration, and area. Additionally, the duration of diabetes, burning mouth syndrome, and the duration of ulcers were identified as significant predictors of temporomandibular disorders (TMD).
Structural Equation Modeling revealed that factors such as age, ulcer area, pain, and diabetes duration accounted for 62.9% of the variability in TMD. Furthermore, TMD and swallowing disorders explained 63.9% of the decline in quality of life.
A recent worldwide meta-analysis (29 studies with 50,112 participants) showed that the prevalence of DPN in individuals with type 2 diabetes was 31.5% [21]. Furthermore, the prevalence of DPN varies by country and can be as high as 66% [22]. Diabetic neuropathy can impact various parts of the nervous system, including the head and neck region. Common oral symptoms experienced by individuals with DM include dry mouth (xerostomia), taste disturbances, dental caries, and burning mouth syndrome. Additionally, the prevalence and severity of these complications tend to increase with a longer duration of the disease [4].
A study reported that 18.8% of individuals with DM experienced burning mouth syndrome. It was reported that 46% to 92.5% had xerostomia, and 45% to 82.5% had intraoral mucosal lesions [4]. In the present study, among individuals with DFU, 52.3% reported burning mouth syndrome, 85.7% had xerostomia, and 61.9% exhibited intraoral lesions, with these rates being higher than those observed in healthy individuals. The high prevalence of oral health issues is attributed to the long duration of diabetes. The average duration of diabetes in the study participants was 17.62 years. The high prevalence of oral health problems observed in this study is believed to be related to the longer duration of diabetes.
In the regression model that examines how burning mouth syndrome, dry mouth, and intraoral lesions influence the presence of TMD, it was found that the probability of TMD is 8.37 times higher in individuals with burning mouth syndrome. A previous study revealed that 55% of patients with burning mouth syndrome experienced persistent symptoms throughout the day, significantly impacting their quality of life. [23]. Burning mouth syndrome has a strong impact on TMJ disorder due to pain, burning, and taste changes affecting mandibular functions.
Numerous studies have shown a bidirectional interaction between mandibular position and body posture, where changes in mandibular position can affect posture and vice versa, changes in posture can influence mandibular position [10, 11]. This interaction involves not only the muscles and fascia surrounding the TMJ but also the entire body structure [24]. Specifically, alterations in the plantar arch have been shown to affect the activity of the masseter and temporal muscles, thereby altering posture. For instance, when the plantar arch flattens, mechanoreceptors are stimulated, leading to the realignment of head and neck position and the body’s center of mass [12, 13]. Additionally, in healthy individuals, static plantar pressure has been found to be influenced by maximum mouth opening, and the maximum occlusion position enhances postural stability [15]. These findings suggest that changes in foot structure in individuals with DFU may negatively impact the TMJ, highlighting the need to investigate the relationship between the type, duration, and area of foot ulceration and TMJ alterations.
In this study, it was observed that individuals with deeper ulcers experienced a higher incidence of TMD. Additionally, individuals with ulcers lasting longer than thirty days exhibited higher TMD scores. Structural equation modeling analysis revealed that each unit increase in the ulcer area was associated with a 0.088 unit increase in TMD scores. When the ulcer duration exceeded thirty days, the likelihood of developing TMD increased by 11.7 times. The type, duration, and area of the ulcer are thought to affect the temporomandibular joint through changes in the foot’s loading surface and plantar pressure. Particularly, extensive and deep ulcerations, as well as long-term ulcerations, may increase the risk of TMD due to adaptive gait and decreased postural control.
In this study, each year of increased diabetes duration was found to increase the risk of TMD by 2.69 times and lead to a 0.552 unit increase in TMD scores. These results emphasize the importance of effective monitoring and management of diabetes in preventing or reducing the development of TMD.
This study found that diabetes duration, ulceration, and oral health issues are significant factors in the development of TMD in individuals with DFU. Regression analyses revealed that diabetes duration was the best predictor of TMD likelihood, followed by the type, area, and duration of ulceration, as well as oral health problems. Structural equation modeling showed that increases in age, resting pain, and oral health issues were associated with higher TMD scores, which in turn were linked to a reduction in quality of life.
Conclusion
The present study found that oral health problems were common in individuals with DFU, and jaw pain, mandibular dysfunction, and swallowing disorders were high due to TMD. It was observed that TMJ complaints increased as the depth, duration, and surface area of ulceration increased, and complaints about swallowing disorders increased as the depth and area of ulceration increased. Results of this study showed that diabetes duration, burning mouth syndrome, and ulcer duration are essential determinants of TMD in individuals with DFU. When evaluating oral health problems in individuals with DFU, it may be necessary to assess them holistically, including TMD and swallowing problems. It should be considered that rehabilitation success in individuals may increase by evaluating TMD and swallowing problems, which reduce the individual’s quality of life physically, psychologically, and socially in these patients.
Limitation
The most significant limitation of the present study is the lack of postural evaluation. It was necessary to evaluate the general body posture and the anterior posture of the head, primarily associated with TMD.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4-14.
2. Feldman EL, Nave KA, Jensen TS, Bennett DL. New horizons in diabetic neuropathy: Mechanisms, bioenergetics, and pain. Neuron. 2017;93(6):1296-1313.
3. Yazdanpanah L, Nasiri M, Adarvishi S. Literature review on the management of diabetic foot ulcer. World J Diabetes. 2015;6(1):37-53.
4. Ahmad R, Haque M. Oral health messiers: Diabetes mellitus relevance. Diabetes Metab Syndr Obes. 2021;1(1):3001-15.
5. Einarson TR, Acs A, Ludwig C, Panton UH. The economic burden of cardiovascular disease in type 2 diabetes: A systematic review. Value Health. 2018;21(7):881-90.
6. Bretan O, Pinheiro RM, Corrente JE. Balance and plantar cutaneous sensitivity functional assessment in community-dwelling elderly. Braz J Otorhinolaryngol. 2010;76(2):219-24.
7. Reeves ND, Orlando G, Brown SJ. Sensory-motor mechanisms increasing fall risk in diabetic peripheral neuropathy. Medicina. 2021;57(5):457-71.
8. Jorgetto JV, Oggiam DS, Gamba MA, Kusahara DM. Factors associated with changes in plantar pressure of people with peripheral diabetic neuropathy. J Diabetes Metab Disord. 2022;21(2):1577-89.
9. Fernando ME, Crowther RG, Lazzarini PA, Sangla KS, Buttner P, Golledge J. Gait parameters of people with diabetes-related neuropathic plantar foot ulcers. Clin Biomech. 2016;37(1):98-107.
10. Tardieu C, Dumitrescu M, Giraudeau A, Blanc JL, Cheynet F, Borel L. Dental occlusion and postural control in adults. Neurosci Lett. 2009;450(2):221-4.
11. Nota A, Tecco S, Ehsani S, Padulo J, Baldini A. Postural stability in subjects with temporomandibular disorders and healthy controls: A comparative assessment. J Electromyogr Kinesiol. 2017;37(7):21-4.
12. Mielcarek M, Złotnicka K, Jaranowska K, Borek J, Malak R, Samborski W. Impact of temporomandibular joint disorders on body posture. J Educ Health Sport. 2019;9(10):160-5.
13. Souza JA, Pasinato F, Corrêa ECR, Da Silva AMT. Global body posture and plantar pressure distribution in individuals with and without temporomandibular disorder: A preliminary study. J Manipulative Physiol Ther. 2014;37(6):407-14.
14. Tecco S, Tetè S, D’Attilio SM, Festa F. The analysis of walking in subjects with and without temporomandibular joint disorders. A cross-sectional analysis. Minerva Stomatol. 2008;57(9):399-411.
15. Amaricai E, Onofrei RR, Suciu O, Marcauteanu C, Stoica E, Negrutiu ML, et al. Do different dental conditions influence the static plantar pressure and stabilometry in young adults? PLoS One. 2020;15(2):1-10.
16. Jeffcoate W, Musgrove A, Lincoln N. Using Image J to document healing in ulcers of the foot in diabetes. Int Wound J. 2017;14(6):1137-9.
17. Ferrans CE, Powers MJ. Psychometric assessment of the quality of life index. Res Nurs Health. 1985;15(1):29-38.
18. Yıldız NT, Alkan A, Külünkoglu BA. Validity and reliability of the Turkish version of Mandibular Function Impairment Questionnaire. Cranio. 2024;42(2):160-70.
19. Yap AU, Zhang MJ, Lei J, Fu KY. Accuracy of the Fonseca Anamnestic Index for identifying pain-related and/or intra-articular temporomandibular disorders. J Craniomand Sleep. 2024;42(3):259-66.
20. Belafsky PC, Kuhn MA, editors. The clinician’s guide to swallowing fluoroscopy. New York: Springer; 2014.p.59.
21. Sun J, Wang Y, Zhang X, Zhu S, He H. Prevalence of peripheral neuropathy in patients with diabetes: A systematic review and meta-analysis. Prim care diabetes. 2020;14(5):435-44.
22. Lu Y, Xing P, Cai X, Luo D, Li R, Lloyd C, et al. Prevalence and risk factors for diabetic peripheral neuropathy in type 2 diabetic patients from 14 countries: estimates of the INTERPRET-DD study. Front Public Health. 2020;8:534372.
23. Souza FT, Santos TP, Bernardes VF, Teixeira AL, Kümmer AM, Silva TA, et al. The impact of burning mouth syndrome on health-related quality of life. Health Qual Life Outcomes. 2011;9(1):1-5.
24. Munhoz WC, Marques AP. Body posture evaluations in subjects with internal temporomandibular joint derangement. Cranio. 2009;27(4):231-5.
Download attachments: 10.4328.ACAM.22506
Fatih Enzin, Hazel Çelik Güzel. Temporomandibular dysfunction in patients with diabetic foot ulcers: what could be the predictors? Ann Clin Anal Med 2025;16(7):488-493
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The relationship between materialism and anger: The mediating role of depression and anxiety
Onur Gökçen 1, Kader Semra Karataş 1, Merve Akkuş 1, Feyza Dönmez 1, Çiğdem Aydoğan 2, Elif Aydoğan 3
1 Department of Psychiatry, Faculty of Medicine, Kutahya Health Sciences University, Kütahya, 2 Department of Emergency Health, Bursa Center Emergency Health Services Station Number 03, Bursa, 3 Department of Emergency Health, Afyonkarahisar Basmakci District State Hospital, Afyonkarahisar, Turkiye
DOI: 10.4328/ACAM.22510 Received: 2024-12-02 Accepted: 2025-01-13 Published Online: 2025-01-26 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):494-499
Corresponding Author: Onur Gökçen, Department of Psychiatry, Faculty of Medicine, Kutahya Health Sciences University, Kütahya, Turkiye. E-mail: onur.gokcen@ksbu.edu.tr P: +90 507 201 52 21 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2058-9855
Other Authors ORCID ID: Kader Semra Karataş, https://orcid.org/0000-0003-3595-8019 . Merve Akkuş, https://orcid.org/0000-0003-3046-2815 . Feyza Dönmez, https://orcid.org/0000-0002-1293-165X . Çiğdem Aydoğan, https://orcid.org/0009-0000-9575-1277 . Elif Aydoğan, https://orcid.org/0000-0002-2638-7659
This study was approved by the Ethics Committee of Kutahya Health Sciences University (Date: 2023-07-10, No: 2023/08-23)
Aim: Materialism has been previously reported in the literature to reduce individual well-being and to be associated with depression and anxiety. The aim of this study was to examine the relationship between materialism and anger and to examine the possible mediating role of depression and anxiety in this relationship.
Material and Methods: An online survey of 513 university students was conducted including questions about demographics and income status, the Material Values Scale (MVS), the Trait Anger and Anger Expression Style Scale (STAI), and the Hospital Anxiety Depression Scale (HADS).
Results: Material Values Scale (MVS) scores and the Trait Anger and Anger Expression Style Scale (STAI) scores were statistically significantly correlated. Depression and anxiety were also found to be statistically significantly associated with the MVS total score. When anxiety and depression are included in the significant relationship between the Material Values Scale (MVS) total score and “trait anger”, both have been shown to play a mediating role.
Discussion: This is the first study to examine the relationship between materialism and anger. Depression and anxiety seem to have a mediating role in this relationship. This relationship can be important for designing interventions that enhance individual and societal well-being. Further research is needed to better understand the relationship between materialism and anger.
Keywords: Materialism, Anger, Depression, Anxiety
Introduction
“Enjoy material comforts if they’re there, but don’t miss them if they aren’t there. Treat the things you don’t have as nonexistent. Look at what you have and think how much you’d want them if you didn’t have them.”
Marcus Aurelius, Meditations
Billions of people from almost every culture are exposed on a daily basis to mass messages regarding the importance of money, possessions, status, and correct image. On the other hand, the tendency to acquire money and possessions has been widely criticized from many philosophical and religious perspectives throughout history [1]. In a number of these criticisms, it is seen as a shallow goal or a bad human trait that leads to the neglect of higher values [2]. In the psychoanalytic criticisms that emerged in later periods, purchasing and possessing behavior as a means of happiness were thought to stem from fixation or regression in psychological development [2]. In recent decades, materialism has emerged as a topic of great interest among researchers; empirical research on materialism has been conducted since the mid-1980s [3].
Belk defined materialism as ‘the importance that the consumer attaches to worldly possessions’ and saw it as a personality trait consisting of the desire to possess, a lack of generosity, and envy [4]. According to Richins and Dawson, materialism is not a personality trait but a set of social values that can change throughout life [5]. They see materialism as a ‘set of centrally held beliefs about the importance of possessions in one’s life’. They state that materialism has three dimensions; centrality, success, and happiness. According to them, materialism has three dimensions: centrality, success, and happiness. ‘Centrality’ is when the acquisition of possessions becomes a central focus in one’s life. ‘Success’ is the use of one’s possessions as the primary indicators of success and achievement in life, both in evaluating oneself and others. ‘Happiness’ is their belief that the acquisition of possessions is the greatest source of their well-being and life satisfaction. Many authors in the literature also think of materialism as a set of values and goals that people have for money, possessions, power, status, and image [6].
Prioritizing materialistic values at the expense of not prioritizing certain other values has been reported to have negative well-being consequences [3, 6, 7]. In a meta-analysis focusing on the relationship between materialism and various well-being indicators, Dittmar et al. also suggest that the negative relationship between materialism and well-being is mediated by poor psychological need satisfaction [3]. The evidence base highlighted by this meta-analysis is based more on correlation data [7]. In addition, longitudinal and experimental studies have also shown that materialism can lead to changes in personal well-being. Studies on well-being have used indicators such as life satisfaction, subjective well-being, physical health, loneliness, happiness, and frustration of the basic psychological needs [1, 6, 8, 9]. In addition, materialism in the literature has been associated with psychiatric symptoms such as depression, anxiety, compulsive buying, and risky behavior such as alcohol or substance abuse [3, 10, 11] Another condition that can be related to well-being is anger [12]. Anger is a species-typical response to perceived threat, frustration, or social provocation. It is not considered as a unitary construct [12]. The authors distinguish between various dissociable subcomponents such as trait and state anger, anger expression, and anger control [13]. Among these subcomponents, trait anger is defined as ‘individual differences in the disposition to perceive a wide range of situations as annoying or frustrating and by the tendency to respond to situations with elevations in state anger [13]. High levels of anger can be associated with maladaptive behavior, resulting in impaired social relationships, negative health outcomes, and lower quality of life [12]. It has also been reported in the literature that anger is significantly associated with risky behavior such as alcohol or drug abuse and with depression, anxiety, and many other psychiatric disorders [14].
Materialism has been found to be associated with a number of situations that may cause anger, such as loneliness, low happiness [15], and frustration [8]. Furthermore, while both anger and materialism have been found to be associated with psychiatric symptoms such as anxiety and depression, to the best of our knowledge, no study has focused on the relationship between anger and materialism. We predict that individuals who shape their social relations and expectations with materialistic values have higher levels of anger. The aim of this study is to examine the relationship between materialism and anger (trait anger and its subcomponents) and to examine the possible mediating role of depression and anxiety in this relationship.
Material and Methods
Participants and procedure
The participants of this study were students of Kutahya University aged between 18-26 years. The study was conducted online. Within the scope of the study, the participants were asked questions about their sociodemographic characteristics and income status.
Measures
Material Values Scale (MVS): Materialism was measured using the 9-item, 3-dimension ‘Material Values Scale’ (Centrality, Success, and Happiness) on a 5-point Likert scale [16]. In the Turkish version, high correlation between Centrality and Success indicated overlapping constructs. Confirmatory factor analyses supported a two-factor structure: Happiness and Centrality/Success [15].
Trait Anger and Anger Expression Style Scale (STAI): The STAI measures anger emotion and expression [17], adapted to Turkish [18]. It has 34 items and four subscales: Trait Anger, Anger-in, Anger-out, and Anger Control. High scores in Trait Anger indicate high anger levels; Anger Control indicates controlled anger; Anger-out indicates easily expressed anger; Anger-in indicates suppressed anger.
The Hospital Anxiety Depression Scale (HADS): The HADS measures anxiety and depression symptoms via self-report [19]. Its validity and reliability have been established in Turkey [20]. It is used for quick diagnosis and identifying at-risk groups.
Statistical Analysis
Statistical analyses were conducted using IBM SPSS version 25.0 (SPSS Inc., Chicago, USA). Continuous variables are presented as means ± standard deviations (Mean ± SD), and categorical variables as numbers and percentages. Normality was confirmed based on a sample size of over 200 [19] and Skewness/Kurtosis within ± 3.29. Independent Samples t-test and One-Way ANOVA were used for comparisons of two-group and multi-group variables, respectively. Pearson correlation analysis, a parametric test, was used to determine the relationship between the scale and subscale scores. The Chi-square test was used for categorical variables, with p < 0.05 indicating significance.
Ethical Approval
This study was approved by the Ethics Committee of Kutahya Health Sciences University (Date: 2023-07-10, No: 2023/08-23).
Results
513 people participated in the study. Two dummy questions (attention control items: e.g. please select ‘5’ for this question) were added to improve the quality of the monument in the study [9]. The answers of four people who gave incorrect answers to these questions were not evaluated. Table 1 shows the frequency analysis of sociodemographics and various variables of the participants.
A significant positive correlation was observed between the MVS total score and ‘STAI-Trait Anger’ (r = 0.372), ‘STAI-Anger-in’ (r = 0.232), ‘STAI-Anger-out’ (r = 0.315), ‘HADS-Anxiety’ (r = 0.262), and ‘HADS-Depression’ (r = 0.129), and a negative correlation with ‘STAI-Anger Control’ (r = -0.183) (all p < 0.001).
The ‘MVS-Happiness’ score correlated positively with ‘STAI-Trait Anger’ (r = 0.245), ‘STAI-Anger-in’ (r = 0.247), ‘STAI-Anger-out’ (r = 0.215), ‘HADS-Anxiety’ (r = 0.245), and ‘HADS-Depression’ (r = 0.187), and negatively with ‘STAI-Anger Control’ (r = -0.088, p = 0.048).
The ‘MVS-Centrality-Success’ score showed positive correlations with ‘STAI-Trait Anger’ (r = 0.377), ‘STAI-Anger-in’ (r = 0.169), ‘STAI-Anger-out’ (r = 0.313), and ‘HADS-Anxiety’ (r = 0.212), and a negative correlation with ‘STAI-Anger Control’ (r = -0.209) (all p < 0.001).
‘STAI-Trait Anger’ correlated positively with ‘HADS-Anxiety’ (r = 0.341) and ‘HADS-Depression’ (r = 0.208), while ‘STAI-Anger-in’ correlated with ‘HADS-Anxiety’ (r = 0.334) and ‘HADS-Depression’ (r = 0.336). ‘STAI-Anger-out’ was positively correlated with ‘HADS-Anxiety’ (r = 0.247) and ‘HADS-Depression’ (r = 0.168), whereas ‘STAI-Anger Control’ showed negative correlations with both ‘HADS-Anxiety’ (r = -0.216) and ‘HADS-Depression’ (r = -0.188) (all p < 0.001).
There was no difference between the males and females in terms of the Material Values Scale scores. Furthermore, there was no difference in the Material Values Scale scores between those with and those without psychiatric diagnosis (Table 3).
The Material Values Scale scores were found to be statistically significantly higher in those with a monthly income of 3,000 TL and above (Table 3).
The Mediation Analysis
The PROCESS v2.16.3 macro, which can work within the SPSS 25.0 program, was used to examine the relationship between the MVS total score and the ‘STAI- Trait Anger’ score with the mediation model of the ‘HADS-Depression’ and the ‘HADS-Anxiety’ scores ( www.afhayes.com). It is argued that the bootstrap method is more reliable than Baron and Kenny’s traditional method and the Sobel Test.
The mediating effect of the ‘HADS-Depression’ and the ‘HADS-Anxiety’ scores on the association between the total score of the material values scale and the ‘STAI- Trait Anger’ score was determined according to the confidence intervals obtained with the Bootstrap technique. In the current analyses, the bootstrap method and 5,000 resamplings were chosen. In the mediation analyses that were conducted using the bootstrap method, to support the research hypothesis, it was seen as necessary that there should be no zero (0) included between the values in a 95% confidence interval (CI).
The MVS total scores significantly predicted ‘HADS-Anxiety’ (a path; b = 0.18, t = 6.08, p < 0.001, CI [0.12, 0.24]), and ‘HADS-Anxiety’ significantly predicted ‘STAI-Trait Anger’ (b path; b = 0.34, t = 6.37, p < 0.001, CI [0.24, 0.45]). The total effect of MVS scores on ‘STAI-Trait Anger’ was significant (c path; b = 0.34, t = 9.03, p < 0.001, CI [0.27, 0.42]), with ‘HADS-Anxiety’ mediating this relationship (c’ path; b = 0.28, t = 7.38, p < 0.001, CI [0.20, 0.35]). The model explained 20% of the variance, and the indirect effect was significant (CI [0.03, 0.09]) (Figure 1).
Similarly, MVS total scores significantly predicted ‘HADS-Depression’ (a path; b = 0.08, t = 2.93, p = 0.034, CI [0.02, 0.14]), and ‘HADS-Depression’ significantly predicted ‘STAI-Trait Anger’ (b path; b = 0.22, t = 3.96, p = 0.001, CI [0.11, 0.34]). The total effect of MVS scores on ‘STAI-Trait Anger’ was significant (c path; b = 0.34, t = 9.03, p < 0.001, CI [0.27, 0.42]), with ‘HADS-Depression’ mediating this relationship (c’ path; b = 0.32, t = 8.57, p < 0.001, CI [0.25, 0.40]). The model explained 16.5% of the variance, and the indirect effect was significant (CI [0.003, 0.041]) (Figure 2).
Discussion
This study examined the relationship between materialism, anger, anxiety, and depression among 509 university students. The Material Values Scale (MVS) scores, which we used to assess materialism, and ‘trait anger’ and other components of anger were found to be associated.
It is known that people purchase products as a means of increasing their happiness, improving their image, and achieving a certain social status, which can have negative consequences [7]. It is argued that individuals who are oriented towards materialistic values for such purposes have unrealistically high expectations [21]. Unrealistically high expectations can lead to frustration and unsatisfied psychological needs [3, 21]. The concept of frustration is often used to define anger and is associated with anger Individuals whose expectations are not adequately met may experience frustration and anger [22].
Based on research, it can be argued that increased materialism not only reduces individual well-being but also increases the likelihood of behaving in ways that undermine other people’s well-being [6, 7]. Materialism is suggested to be negatively associated with engaging in pro-social activities and positively associated with engaging in anti-social behavior [6]. In terms of close interpersonal relationships, it has also been suggested that people who prioritize materialistic values have lower quality romantic and friendship relationships [1, 6]. Anger can also negatively affect relationships with other people. Anger and its various separable subcomponents, such as trait anger, anger expression, and anger control, are known to be associated with impaired social relations, antisocial behavior, and low-quality interpersonal relationships [12, 14, 22]. People who prioritize materialistic values make the acquisition of money and material goods their main goal in order to achieve happiness, success, and social status consequences [5-7]. They may project their anger at not achieving these goals, or at the lack of satisfaction in achieving them, onto the people around them or other members of society. We think that the relationship between materialism and anger may be a factor in why people who prioritize materialistic values behave in ways that harm the well-being of the people around them. More research is needed on this relationship.
In the study, depression and anxiety are found to be associated with the MVS total score. Previous studies have shown that materialistic people can experience a lack of happiness [15]. It has also been reported in the literature that prioritizing materialistic values is associated with depression and anxiety [3, 23, 24]. This result seems to be consistent with the results of previous studies in the literature.
This study examines the mediating effect of anxiety and depression on the association between materialism and anger. A statistically significant association was found between the Material Values Scale (MVS) total score and ‘trait anger’. When anxiety and depression are included in the association, both have been shown to play a mediating role. This indicates that the effect of materialism on trait anger is partially mediated by depression and anxiety, which means that interventions or strategies for anxiety and depression may help to reduce trait anger in students both directly and indirectly.
In our study, there was no difference in the Material Values Scale (MVS) scores in terms of gender and having a diagnosis of psychiatric disorder. Age was not considered in the analysis as the participants were close in age. Previous studies also indicate that there are no consistent differences in materialism by gender [3, 25]. Having a diagnosis of a psychiatric disorder and having psychiatric symptoms are two different things. A diagnosed individual may show fewer psychiatric symptoms (depression, anxiety, and such conditions) while still under treatment. The reverse is also possible. An individual with psychiatric symptoms may not yet be diagnosed, or the individual’s symptoms may be below the threshold for clinical diagnosis. For these reasons, there may not have been a relationship between self-reported psychiatric diagnoses and MVS.
When the participants were divided according to their monthly income for personal expenditure, it was observed that students with higher incomes had higher MVS scores. In the literature, there are studies indicating that lower socioeconomic status is associated with higher materialism and that there is no significant relationship between socioeconomic variables and materialism [3, 7]. We believe that this difference in the literature is related to sociocultural variables.
Limitation
This study has several limitations and provides important directions for future research. Variables such as personality traits, social support, and self-esteem, which could mediate the relationship between materialism and anger beyond anxiety and depression, were not considered in this study. Furthermore, anger could be a symptom resulting from the depression process or a facilitating factor for the development of depression. The cross-sectional design limits causal inferences, highlighting the need for longitudinal and experimental studies. Finally, the sample consists solely of university students within a similar age range, and further research with populations of different demographic characteristics is necessary to enhance the generalizability of the findings.
Conclusion
Despite limitations, this study is the first to explore the materialism-anger relationship, showing that depression and anxiety mediate this link. Consistent with prior research [6], materialism negatively affects personal and social well-being [6]. Addressing these effects is crucial [7]. Interventions to enhance well-being must consider emotions and social responses. Understanding the materialism-anger relationship can guide future research and intervention models to improve individual well-being and happiness.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Kasser T. Materialistic values and goals. Annu Rev Psychol. 2016;67:489-514.
2. Belk RW. Worldly possessions: Issues and criticisms. ACR North Am Adv. 1983;10:514-9.
3. Dittmar H, Bond R, Hurst M, Kasser T. The relationship between materialism and personal well-being: A meta-analysis. J Per Soc Psychol. 2014;107(5):879-924.
4. Belk RW. Materialism: Trait aspects of living in the material world. J Consum Res. 1985;12(3):265-80.
5. Richins ML, Dawson S. A consumer values orientation for materialism and its measurement: Scale development and validation. J Consum Res. 1992;19(3):303-16.
6. Kasser T. Materialism and living well. In: Handbook of well-being. Salt Lake City, UT: DEF Publishers; 2018.p.860-71.
7. Dittmar H, Isham A. Materialistic value orientation and well-being. Curr Opin Psychol. 2022;46(101337):1-6.
8. Reyes V, Unanue W, Gómez M, Bravo D, Unanue J, Araya-Veliz C et al. Dispositional gratitude as an underlying psychological process between materialism and the satisfaction and frustration of basic psychological needs: A longitudinal mediational analysis. J Happiness Stud. 2022;23(2):561-86.
9. Ohno H, Lee KT, Maeno T. The Japanese version of the Material Values Scale: Construct assessment and relationship with age, personality, and subjective well-being. BMC Psychol. 2022;10(1):200-1.
10. Wang R, Liu H, Jiang J, Song Y. Will materialism lead to happiness? A longitudinal analysis of the mediating role of psychological needs satisfaction. Personality and Individual Differences. 2017;105:312-317.
11. Jalees T, Khan S, Zaman SI, Miao M. The effect of religiosity, materialism, and self-esteem on compulsive and impulsive buying behavior. J Islam Mark. 2024;15(11):2697-731.
12. Phillips LH, Henry JD, Hosie JA, Milne AB. Age, anger regulation and well-being. Aging Ment Health. 2006;10(3):250-6.
13. Spielberger C. State-trait anger expression inventory STAXI professional manual. FL. Psychological Assessment Resources Inc. 1988.p.1781.
14. de Bles NJ, Rius Ottenheim N, van Hemert AM, Pütz AM, van der Does, Penninx BW et al. Trait anger and anger attacks in relation to depressive and anxiety disorders. J Affect Disord. 2019;2:259-65.
15. Gazanfer A. Maddi değerler ölçeği’nin Türkçe’ye uyarlanması [Adaptation of the Material Values Scale into Turkish]. Afyon Kocatepe Univ Soc Sci. 2020;22(3):624-34.
16. Richins ML. The material values scale: Measurement properties and development of a short form. J Consum Res. 2004;31(1):209-19.
17. Spielberger C, Jacobs G, Russell S, Crane R. Assessment of anger: The state-trait anger scale. Adv Pers Assess. 1983;2:161-9.
18. Özer AK. Sürekli öfke (SL-Öfke) ve öfke ifade tarzı (Öfke-tarz) ölçekleri ön çalışması [Preliminary study of trait anger (SL-Anger) and anger expression style (Anger-Style) scales]. Turk Psikol Derg. 1994;9(31):26-35.
19. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361-70.
20. Aydemir Ö. Hastane anksiyete ve depresyon ölçeği Türkçe formunun geçerlilik ve güvenilirliği [Validity and reliability of hospital anxiety and depression scale Turkish form]. Turk Psikiyatri Derg. 1997;8:187-280.
21. Tsang J-A, Carpenter TP, Roberts JA, Frisch MB, Carlisle RD. Why are materialists less happy? The role of gratitude and need satisfaction in the relationship between materialism and life satisfaction. Pers Individ Differ. 2014;64:62-6.
22. Blair RJR. Traits of empathy and anger: Implications for psychopathy and other disorders associated with aggression. Philos Trans R Soc Lond B Biol Sci. 2018;373:1744-5.
23. Azibo DA. Unmasking materialistic depression as a mental health problem: its effect on depression and materialism in an African-United States undergraduate sample. J Affect Disord. 2013;150(2):623-8.
24. Mueller A, Mitchell JE, Peterson LA, Faber RJ, Steffen KJ, Crosby RD et al. Depression, materialism, and excessive Internet use in relation to compulsive buying. Compr Psychiatry. 2011;52(4):420-4.
25. Muñiz-Velázquez JA, Gomez-Baya D, Lopez-Casquete M. Implicit and explicit assessment of materialism: Associations with happiness and depression. Pers Individ Differ. 2017;116:123-32.
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Onur Gökçen, Kader Semra Karataş, Merve Akkuş, Feyza Dönmez, Çiğdem Aydoğan, Elif Aydoğan. The relationship between materialism and anger: The mediating role of depression and anxiety. Ann Clin Anal Med 2025;16(7):494-499
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Does inguinal hernia surgery affect sexual function in men?
Ali Karabulut 1, Melih Yetemen 2
1 Department of General Surgery, 2 Department of Urology, Siirt Education and Research Hospital, Siirt, Turkiye
DOI: 10.4328/ACAM.22527 Received: 2024-12-20 Accepted: 2025-01-23 Published Online: 2025-02-11 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):500-504
Corresponding Author: Ali Karabulut, Department of General Surgery, Siirt Education and Research Hospital, Siirt, Turkiye. E-mail: alikarabulut7676@gmail.com P: +90 554 340 90 57 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6690-2152
Other Authors ORCID ID: Melih Yetemen, https://orcid.org/0000-0003-4404-5932
This study was approved by the Ethics Committee of Siirt University (Date: 2024-12-10, No: 8086)
Aim: It was aimed to reveal the relationship between inguinal hernia surgery and erectile function using an internationally valid, standardized patient questionnaire.
Material and Methods: In this retrospective study, data from 133 male patients who underwent the Lichtenstein hernioplasty technique for inguinal hernia surgery were examined. Patients who gave their consent for the study and whose data were available were asked the 5-question IIEF-5 (International Index of Erectile Function) questionnaire to determine their sexual functions preoperatively and at 1, 6, and 12 months postoperatively, and the answers were recorded. Patients’ age, body mass index, hernia, type, size, and side were statistically evaluated.
Results: IIEF-5 results were revealed to be as follows:17.26 before surgery: 17.62 in the first month after surgery, 18.02 in the sixth month after surgery, and 18.14 in the twelfth month after surgery. A statistically notable variation was found in the preoperative and postoperative scores of the patients. When the IIEF-5 results of the patients were investigated, it was seen that the results of the patients were boosted after the surgery.
Discussion: As a result of inguinal hernia surgery, the swelling in the groin area decreases, cosmetic concerns are eliminated, and pain is reduced, resulting in improved sexual functions.
Keywords: Inguinal Hernia, Lichtenstein Technique, Erectile Dysfunction, Sexual Functions
Introduction
Inguinal hernia (IH) surgeries are among the most frequently performed procedures in general surgery clinics. IH surgeries are extremely important because they are anatomically close to the genital area and are a very common operation in general surgery. Nearly 1 million IH surgeries are conducted each year in the United States [1]. The Lichtenstein hernioplasty (LH) technique is a surgery that repairs hernias with mesh and is the most commonly used method [2].
Erectile dysfunction (ED) is a disease that is increasingly seen among male patients today and negatively affects patients both physically and mentally. The definition of sexual dysfunction was defined in 1992 at the National Institutes of Health (NIH) meeting as the incapacity to initiate penile erection required for adequate sexual intercourse for 6 months and the inability to continue. Sexuality is essential in life both psychologically and in the transfer of human genetics. Sexual function can be affected by many factors. One of these factors is surgery [1].
When we look at the studies on IH surgeries in the literature, it is seen that factors that may occur after surgery, such as pain, which is one of the most feared complications, and wound healing problems are examined, but there are few studies examining sexual functions after surgery.
Since IH surgeries are performed in the groin area, where structures significant for sexual function are located, it is substantial to appraise the sexual lives of patients after these surgeries [3, 4].
In IH surgery, the sexual functions of patients may change owing to tissue hardening caused by foreign body reactions due to the Mesh used for tissue repair, cosmetic reasons, and pain due to the incision scar after surgery [5].
In this research, we intended to assess the preoperative and postoperative sexual functions of male patients who underwent surgery with the IH LH technique using the internationally accepted, standardized IIEF-5 score.
Material and Methods
This study is retrospective research conducted by the Departments of General Surgery and Urology of Siirt Education and Research Hospital. The study was conducted using data between November 2023 and November 2024. After obtaining permission for the study, 239 male IH cases who were operated on with the LH and 6×11 cm propylene mesh were retrospectively added to the study. The exclusion requirements for the study were determined as patients who underwent surgery with a different surgical method for inguinal hernia, patients who did not have a sexual partner, patients who had recurrent surgery, people below the age of 20 and above the age of 65, people who did not consent to take part in the research, and people whose data could not be accessed. The study was conducted with 133 patients after excluding 106 patients whose information could not be reached in the pre-surgery and post-surgery first, sixth, and twelfth months and who did not answer the questions.
The International Index of Sexual Function (IIEF) is one of the most commonly used forms developed by Rosen and used today in men presenting with sexual complaints. Patients presenting with complaints of sexual dysfunction are questioned with the IIEF-5 form, a variant of this form. Pre- and post-treatment evaluations of patients followed up for sexual dysfunction can be made more accurately and reliably with this form. Patients who approved the study were asked the IIEF-5 scoring system form questionnaire by phone pre-surgery and at the first, sixth, and twelfth months post-surgery. This questionnaire consisted of 5 questions. The IIEF-5 questionnaire is divided into five categories: No Erectile Dysfunction (ED) (score 22-25), Mild ED (score 17-21), Mild-Moderate ED (score 12-16), Moderate ED (score 8-11), Severe ED (score 5-7). Age, body mass index, hernia, type, size, and side of the people participating in the research were determined.
Statistical analyses
The statistical analyses of the research were carried out using JASP (Version 0.19.0, University of Amsterdam, Netherlands). The normality assumption was tested with Kolmogorov-Smirnov and Shapiro-Wilk tests. Descriptive statistics of the variables are given as mean, ?standard deviation, Median (25th-75th percentiles), and frequencies as n (%). The pre-and post-operative International Sexual Function Index (IIEF-5) values of the patients were contrasted using the Wilcoxon Signed Rank Test. P<.05 was regarded as statistically meaningful throughout the study.
Ethical Approval
This study was approved by the Ethics Committee of Siirt University (Date: 2024-12-10, No: 8086).
Results
Data of the people participating in the study are given in Table 1. The average age of the people was 46.16±13.55 years, with a median age of 47.0 (20.0-65.0) years. When the patients were grouped according to the median age, 68(51.1%) of the patients were less than or equal to 47 years old, and 65(48.9%) were older than 47 years old. The mean BMI was 30.73±4.06 kg/m2, the median BMI was 31.1(19.9-37.4). According to the median BMI value, 67(50.4%) of the patients had a BMI value equal to or less than 31.1, and 66(49.6%) had a BMI value greater than 31.1. In 81 (60.9%) of the patients, the hernia was on the right side, in 46 (34.6%) on the left side, and 6 (4.5%) bilateral. The number of patients with direct hernia type was 19 (14.3%), indirect hernia type was 62 (46.6%), and combined hernia type was 52 (39.1%). In 58 (43.6%) of the patients, the hernia size was less than or equal to 2 cm, and in 75 (56.4%) it was greater than 2 cm.
Table 2 shows the IIEF-5 results for the pre-surgery and post-surgery first, sixth, and twelfth months of inguinal hernia surgery and the scores of the five questions on the scale. According to these results, the patients’ Q1 (What was your level of confidence in achieving and maintaining erection?) scores increased in the 1st and 6th months post-surgery relative to before surgery. The variation between pre-surgery and post-surgery 1st month, post-surgery 6th month, and post-surgery 12th month is statistically meaningful (p=0.000). The differences between post-surgery 1st month- post-surgery 6th month and post-surgery 1st month- post-surgery 12th month in terms of Q1 are also statistically meaningful (p=0.005). The differences between post-surgery 6th month- and post-surgery 12th month are also not statistically meaningful (p=1.000).
When the results of the answers to the question Q2 (When you achieved an erection with sexual stimulation, how often was this erection sufficient to enter the vagina/reservoir?) were examined, it was found that the patients’ scores rose. The difference between the pre-surgery and post-surgery 1st-month scores is statistically meaningful (p=0.002). The difference between pre-surgery – post-surgery 6th month, pre-surgery – post-surgery 12th month, post-surgery 1st month – post-surgery 6th month, post-surgery 1st month – post-surgery 12th month is statistically meaningful (p=0.000). The differences between post-surgery 6th month – and post-surgery 12th month in terms of Q2 are also not statistically meaningful (p=0.317).
When the results of the answers given to question Q3 (How often were you able to maintain the erection you had before intercourse after penetration (vagina/reservoir)?) were compared, it was found that the scores of the patients rose. The difference between the pre-surgery and post-surgery 1st-month scores is statistically meaningful (p=0.011). The difference between pre-surgery – post-surgery 6th month, pre-surgery – post-surgery 12th month, post-surgery 1st month- post-surgery 6th month, post-surgery 1st month – post-surgery 12th month is statistically meaningful (p=0.000). The differences between post-surgery 6th month – and post-surgery 12th month in terms of Q3 are also not statistically meaningful (p=0.317).
When the results of the answers to question Q4 (How difficult did you have to maintain an erection during sexual intercourse until the end of intercourse?) were examined, it was found that the patients’ scores rose. The difference between pre-surgery and post-surgery 1st month, pre-surgery – post-surgery 6th month, pre-surgery – post-surgery 12th month, post-surgery 1st month – post-surgery 6th month, post-surgery 1st month – post-surgery 12th month is statistically meaningful (p=0.000). The differences between post-surgery 6th month – and post-surgery 12th month in terms of Q4 are also not statistically meaningful (p=0.655).
When the results of the answers to the question Q5 (How often did you find your sexual intercourse attempts satisfactory?) were examined, it was found that the patients’ scores rose. The difference between the pre-surgery and post-surgery 1st-month scores was statistically meaningful (p=0.002). The difference between pre-surgery – post-surgery 6th month, pre-surgery – post-surgery 12th month, post-surgery 1st month – post-surgery 6th month, post-surgery 1st month – post-surgery 12th month was statistically meaningful (p=0.000). The differences between post-surgery 6th month – and post-surgery 12th month in terms of Q5 were also statistically significant (p=0.004).
When the total scores of the people were examined, it was found that the results of the patients increased after the operation. The difference between pre-surgery and post-surgery 1st month, pre-surgery – post-surgery 6th month, pre-surgery – post-surgery 12th month, post-surgery 1st month – post-surgery 6th month, post-surgery 1st month – post-surgery 12th month is statistically meaningful (p=0.000). The differences between post-surgery 6th month – and post-surgery 12th month are also statistically meaningful (p=0.007).
Discussion
Pain caused by IH and the cosmetic appearance of the body due to the hernia may adversely influence sexual functions in patients. In addition, during IH surgeries, important structures such as arterial injury, vein injury, nerve injury, spermatic cord, testicles, and scrotum may be affected, and as a result, sexual functions may be impaired. Patients may develop hematoma, seroma, and orchitis as complications. Irreversible complications may occur due to testicular damage. All these reasons may affect sexual functions [6, 7].
When previous studies in the literature were examined, ED was detected in 95.8% of preoperative patients in the research by Aykanat et al. [8]. In the research by Sonmez et al., it was revealed that 85.1% of the patients had sexual dysfunction [4]. In the research of Ertan et al. and El-awady et al., it was noticed that there was no sexual dysfunction in the patients in the pre-surgery period, but in the postoperative study of Ertan et al., 85.1% and the research of El-awady et al., 90% of the patients reported significant improvement in sexual function [9, 10].
In the literature, Cantay et al. found the erectile function score to be 18.04 preoperatively, 19.53 postoperatively at 1 month, and 21.26 at 6 months postoperatively in their study using the IIEF-15 score [1]. In the research conducted by El-Awady et al. using the IIEF-15 score, the erectile function results of the people were shown to be 20.24 preoperatively, 21.54 in the third postoperative month, and 21.44 in the ninth postoperative month [9]. In the research conducted by Giray et al. using the IIEF-15 score, it was shown to be 18.04 preoperatively, 19.53 in the first month postoperatively, and 21.26 in the sixth month postoperatively [4]. In the research conducted by Tamer et al. using the IIEF-15 score, it was found to be 21.14 preoperatively and 22.85 in the third month postoperatively [10]. The findings in our research are parallel to the studies in the literature, and since it includes fewer questions in the evaluation of erectile function and patients can answer them more easily, IIEF-5 scoring was used, and erectile function results were shown to be 17.26 preoperatively, 17.62 in the first postoperative month, 18.02 in the sixth postoperative month, and 18.14 in the twelfth postoperative month. When the preoperative and postoperative scores were compared, a statistically significant difference was noticed. When the IIEF-5 scores of the patients were examined, it was determined that the results of the postoperative patients increased. The differences between pre-surgery and post-surgery 1st, 6th, and 12th months, post-surgery 1st, 6th, and 12th months, and post-surgery 6th and 12th months were found to be statistically significant.
When the answers given to the questions in the IIEF-5 score were statistically examined, for Q1, the differences between pre-surgery and post-surgery 1st, 6th, and 12th months, post-surgery 1st month and post-surgery 6th and 12th months were found to be statistically significant, while the differences between post-surgery 6th month and post-surgery 12th month were not observed to be statistically significant.
For Q2, the differences between pre-surgery and post-surgery 1st, 6th, and 12th months and post-surgery 1st month and post-surgery 6th and 12th months were statistically meaningful, while the differences between post-surgery 6th month and post-surgery 12th month were not statistically meaningful.
For Q3, the differences between pre-surgery and post-surgery 1st, 6th, and 12th months and post-surgery 1st month and post-surgery 6th and 12th month were statistically meaningful, while the differences between post-surgery 6th month and post-surgery 12th month were not statistically meaningful.
For Q4, the differences between pre-surgery and post-surgery 1st, 6th, and 12th months, post-surgery 1st month, and post-surgery 6th and 12th months were found to be statistically significant, while the differences between post-surgery 6th month and post-surgery 12th month were not observed to be statistically significant.
For Q5, the differences between pre-surgery and post-surgery 1st, 6th, and 12th months and between post-surgery 1st month and post-surgery 6th and 12th months and between post-surgery 6th month and post-surgery 12th month were observed to be statistically significant.
We think that the inclusion criteria for the research were patients of sexually active age and that the exclusion of patients with recurrent hernia from the study may have caused an increase in the scores. When the complications and benefits of IH surgery are examined in the literature, it is seen that the positive results of surgery on sexual functions are more. We think that this is because of the decrease in preoperative pain and the removal of aesthetic issues.
Limitation
Except for physical disorders, sexual functions can be affected by many psychological, social, and cultural factors. It was not possible to analyze these factors in this study. Patients were contacted retrospectively by phone, and their information was obtained and the answers given during the phone interview may differ from the answers given by the patient alone. The number of patients in the research was not large enough to separately evaluate subgroups of diseases that may cause erectile dysfunction. Therefore, prospective studies with bigger case series are needed to show results with higher levels of scientific findings.
Conclusion
Even though sexual functions might be affected because of complications that may occur owing to inguinal hernia surgery, IH surgery provides an improvement in sexual functions by eliminating the swelling before the surgery, eliminating the patient’s cosmetic concerns, and reducing pain. IH surgery has a positive impact on sexual functions before the surgery.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Cantay H, Ezer M, Binnetoglu K, Uslu M, Anuk T, Bayram H. What Is the Effect of Inguinal Hernia Operations on Sexual Functions? Cureus. 2022;14(4):e24137.
2. Messias BA, Nicastro RG, Mocchetti ER, Waisberg J, Roll S, Junior MAFR. Lichtenstein technique for inguinal hernia repair: ten recommendations to optimize surgical outcomes. Hernia. 2024;28(4):1467-76.
3. Gutlic N, Petersson U, Rogmark P, Montgomery A. The Relevance of Sexual Dysfunction Related to Groin Pain After Inguinal Hernia Repair – The SexIHQ Short Form Questionnaire Assessment. Front Surg. 2018;5:15.
4. Sonmez MG, Sonbahar BÇ, Bora G, Ozalp N, Kara C. Does inguinal hernia repair have an effect on sexual functions? Cent European J Urol. 2016;69(2):212-6.
5. Jangjoo A, Mahboub MRD, Bahar MM, Afzalaghaee M, Jalali AN, Aliakbarian M. Sexual function after Stoppa hernia repair in patients with bilateral inguinal hernia. Med J Islam Repub Iran. 2014;28:48.
6. Asuri K, Mohammad A, Prajapati OP, Sagar R, Kumar A, Sharma M, et al. A prospective randomized comparison of sexual function and semen analysis following laparoscopic totally extraperitoneal (TEP) and transabdominal pre-peritoneal (TAPP) inguinal hernia repair. Surg Endosc. 2021;35(6):2936-41.
7. Dong Z, Kujawa SA, Wang C, Zhao H. Does the use of hernia mesh in surgical inguinal hernia repairs cause male infertility? A systematic review and descriptive analysis. Reprod Health. 2018;15(1):69.
8. Aykanat IC, Er S, Senel C, Comcali B, Aslan Y, Balci M, et al. Comparison of the impact of open and laparoscopic inguinal hernia operations on male sexual function and pain during sexual activity. Andrologia. 2022;54(1):e14254.
9. El-Awady SE, Elkholy AAM. Beneficial effect of inguinal hernioplasty on testicular perfusion and sexual function. Hernia. 2009;13(3):251-8.
10. Ertan T, Keskek M, Kilic M, Dizen H, Koc M, Tez M. Recovery of sexual function after scrotal hernia repair. Am J Surg. 2007;194(3):299-303.
Download attachments: 10.4328.ACAM.22527
Ali Karabulut, Melih Yetemen. Does inguinal hernia surgery affect sexual function in men? Ann Clin Anal Med 2025;16(7):500-504
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Evaluation of the effects of three different postoperative analgesic methods on thiol/disulphide homeostasis
Cansu Ofluoğlu 1, Kübra Taşkın 2, Ceren Hazer 1, Süheyla Abitağaoğlu 3, Ahmet Kacıroğlu 4, Almila Şenat 5, Özcan Erel 6, Dilek Erdoğan 7
1 Department of Anesthesiology and Reanimation, Faculty of Health Sciences, Fatih Sultan Mehmet Trainig and Research Hospital, İstanbul, 2 Department of Anesthesiology and Reanimation, Faculty of Health Sciences, Kartal Dr. Lutfi Kirdar City Hosptial, İstanbul, 3 Department of Anesthesiology and Reanimation, Faculty of Health Science, Sultan 2. AbdulHamid Khan Educational and Research Hospital, İstanbul, 4 Department of Anesthesiology and Reanimation, Faculty of Health Science, Bursa City Hospital, Bursa, 5 Department of Medical Biochemistry, Faculty of Health Science, Taksim Training and Research Hospital, İstanbul, 6 Department of Medical Biochemistry, Faculty of Health Science, Yıldırım Beyazıt University, Ankara, 7 Department of Anesthesiology and Reanimation, Faculty of Health Science, Acıbadem Kozyatağı Hospital, İstanbul, Turkiye
DOI: 10.4328/ACAM.22528 Received: 2024-12-21 Accepted: 2025-01-23 Published Online: 2025-02-03 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):505-510
Corresponding Author: Cansu Ofluoğlu, Department of Anesthesiology and Reanimation, Faculty of Health Sciences, Fatih Sultan Mehmet Trainig and Research Hospital, İstanbul, Turkiye. E-mail: cansuakin.iu@gmail.com P: +90 535 864 05 64 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5876-7541
Other Authors ORCID ID: Kübra Taşkın, https://orcid.org/0000-0002-7023-4748 . Ceren Hazer, https://orcid.org/0000-0003-4756-480X . Süheyla Abitağaoğlu, https://orcid.org/0000-0003-4937-0080 . Ahmet Kacıroğlu, https://orcid.org/0000-0001-8911-2225 . Almila Şenat, https://orcid.org/0000-0002-5806-562X . Özcan Erel, https://orcid.org/0000-0002-2996-3236 . Dilek Erdoğan, https://orcid.org/0000-0002-3734-5323
This study was approved by the Ethics Committee of Fatih Sultan Mehmet Training and Research Hospital (Date: 2016-09-22, No: 2016/44)
Aim: Trauma increases oxidative stress at the cellular level, with thiol/disulfide homeostasis serving as a direct indicator of the cell’s oxidative state. Oxidative stress leads to a decrease in thiol levels and an increase in disulfide levels. This study aimed to investigate the correlation between total thiol, native thiol/disulfide levels, and pain scores using three different analgesic methods.
Material and Methods: Sixty patients with an ASA score of I–III undergoing proximal femoral nail (PFN) surgery under hypobaric spinal anesthesia were randomly divided into three groups. Group I received IV patient-controlled analgesia (PCA), Group II received epidural PCA, and Group III underwent USG-guided femoral–sciatic nerve block. Postoperative VAS scores at 3, 6, and 24 hours were recorded. Paracetamol (1g IV) was given when VAS exceeded 3. Total thiol, native thiol, and disulfide levels were measured preoperatively, 30 minutes perioperatively, and at 3, 6, and 24 hours postoperatively.
Results: Hypobaric spinal anesthesia increased thiol levels and decreased disulfide levels. In all groups, total and native thiol levels increased, while disulfide levels decreased postoperatively. No significant differences were noted among groups regarding thiol and disulfide levels. Similarly, VAS scores were comparable across all groups.
Discussion: Spinal anesthesia effectively reduces oxidative stress. The three analgesic methods (IV PCA, epidural PCA, and femoral–sciatic nerve block) showed no significant differences in their effects on basal thiol, native thiol, or disulfide levels. All methods provided comparable analgesia and oxidative stress control following PFN surgery.
Keywords: Thiol-Disulfide, Epidural, Spinal, Proximal Femoral Nail, Patient-Controlled Analgesia
Introduction
Elderly patients admitted to the hospital with a hip fracture have several characteristics that complicate the management of anesthesia and analgesia. These characteristics, including low cardiac/respiratory reserves, use of multiple drugs that can interact with anesthetic and analgesic agents, and sensitivity to opioids, increase the morbidity and mortality in such patients. Cardiovascular and cerebrovascular diseases, which are common in older individuals, cause increased oxidative stress [1]. Moreover, trauma, surgery, and pain lead to the activation of several neuroendocrine pathways, subsequently resulting in the exacerbation of stress responses.
Effective analgesia initiated in the pre-operative period often requires the selection of individualized agents and methods. Subjective pain scoring systems, such as the visual analog scale (VAS), are used for the personalized evaluation of pain control. However, stress markers must be used to quantitatively evaluate the oxidative state caused by surgical stress and pain.
The thiol/disulfide balance is a direct indicator of the oxidative state and damage within a cell. A decrease in the total thiol and native thiol levels in the native thiol/disulfide ratio and an increase in the disulfide levels are considered an imbalance in favor of oxidative stress [2].
In the present study, we aimed to investigate the most effective method for pain control by examining the correlation of different post-operative analgesia methods with the thiol/disulfide balance in patients operated under spinal anesthesia for a proximal femoral fracture.
Material and Methods
The present study was conducted between November 2016 and March 2018 at a tertiary referral hospital. The study included 60 patients aged >65 years who were scheduled to undergo surgery with a proximal femoral nail (PFN) at the Orthopaedics and Traumatology Clinic for a proximal femoral fracture and who had an American Society of Anaesthesiologists (ASA) score of I–III, and who agreed to participate in the study.
Before the surgery, patients with the following conditions were excluded from the study: possible need for post-operative intensive care, ASA score of IV, continuous pain medication used due to chronic pain, allergy to local anesthetics, refusal to have regional anesthesia performed, lower extremity neurological dysfunction, injection site infection, and coagulopathy.
In addition to obtaining informed consent, the relatives of the patients were provided training regarding the 10-cm VAS ruler. The patients included in the study were randomly divided into three groups using the closed-envelope method.
Group I: The patients in this group received intravenous (IV) patient-controlled analgesia (PCA) for postoperative analgesia following spinal anesthesia (20 mg/h infusion with tramadol, 20 mg IV bolus dose, and 20 min lockout time).
Group II: The patients in this group were administered a combined spinal–epidural set and received epidural PCA for postoperative analgesia (0.125% bupivacaine 4 mL/h infusion, 4 mL bolus dose, and 15 min lockout time).
Group III: The patients in this group received an ultrasound (USG)-guided combined femoral–sciatic nerve block for postoperative analgesia following spinal anesthesia (20 mL of 0.25% bupivacaine solution in each area).
The patients were taken to the operating room, and thereafter, they first underwent routine electrocardiography (ECG) and non-invasive blood pressure and peripheral oxygen saturation (SpO2) monitoring, after which the radial artery was catheterized, and a 2-mL blood sample was collected into a plain gel biochemistry tube for pre-operative (T0) thiol/disulfide level measurements.
Peak heart rate as well as invasive systolic, diastolic, and mean blood pressure values of the patients were recorded when they were taken to the operating room (T0) and every 15 minutes thereafter.
After the patients were positioned in an appropriate lateral decubitus position with their fractured leg to be operated on top, the patients in all the groups were administered spinal anesthesia with mL of hypobaric solution (3 mL was drawn into the injector from the 4 mL hypobaric solution prepared with 10 mg 0.5% bupivacaine, 40 μg fentanyl and 1.2 mL distilled water) using a combined spinal–epidural set (18 G epidural needle, 27 G spinal needle, Egemen, Turkey) in Group II and a Quincke spinal needle (25 G, Egemen, Turkey) in Groups I and III.
At 30 min after the application of spinal anesthesia, blood samples were collected from all the patients for thiol/disulfide value (T1) measurements. At the end of the surgery, USG (Esaote MyLab TM 30Gold Cardiovascular USG, Genoa)-guided combined femoral–sciatic nerve block (100-mm 21G, Locoplex, Vygon, France) was performed in Group III.
At 3(T2), 6 (T3), and 24 (T4) h post-operatively, the pain levels of the patients were evaluated using VAS, blood samples were obtained for thiol/disulfide level measurement and the peak heart rate and non-invasive systolic, diastolic and mean blood pressure values were recorded. During the post-operative follow-up, 1 g of paracetamol was intravenously administered as a rescue analgesic in patients with a VAS score of >3. The number of bolus doses administered with PCA and the need for additional analgesics were recorded.
Power Analysis
Power analysis was performed using the G*Power software based on a pilot study conducted with 5 patients from each group. When the effect size d and SD were considered 0.436 and 2.4, respectively, for the decrease in the number of native thiol levels from T0 to T1, the number of samples for a power of 0.80 and of 0.05 was determined as a minimum value of n=19 for each subgroup. Considering the possibility of data loss during follow-ups, it was decided to include 20 patients per group in the study.
Statistical Analysis
IBM SPSS Statistics 22.0 (IBM SPSS, Turkey) was used for statistical analysis of the study results. For evaluating the study data, the conformity of the parameters to normal distribution was evaluated using the Shapiro–Wilks test. In addition to descriptive statistical methods (mean, standard deviation, and frequency), one-way ANOVA was used to compare the quantitative data for intergroup comparisons of normally distributed parameters, whereas Tukey’s honestly significant difference test was used to identify the group that caused the difference. The Kruskal–Wallis test was used for intergroup comparisons of parameters not showing normal distribution, whereas the Mann–Whitney U test was used to identify the group that caused the difference. Paired sample t-test was used for intragroup comparisons of quantitative data showing normal distribution, whereas the Wilcoxon signed-rank test was used for intragroup comparisons of the parameters not showing normal distribution. The chi-square and Fisher–Freeman–Halton tests were used for the comparison of qualitative data. A p-value of <0.05 was considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of Fatih Sultan Mehmet Training and Research Hospital (Date: 2016-09-22, No: 2016/44).
Results
In the present study, gender, ASA scores, surgical duration, and patient satisfaction were similar in all the groups (p > 0.05) (Table 1). Although there was no significant difference between Groups I and II in terms of age, the mean age of the patients in Group III was higher compared with that of patients in Groups I and II (p1: 0.005; p2: 0.038; p < 0.05).
Although the peak heart rates were similar up to 6h postoperatively in all the groups, it was higher in Group II than in Group I at 6 and 24h post-operatively (Figure 1).
Intergroup comparison (one-way ANOVA p:0.008, p:0.001; p < 0.05).
●When compared with T0 in Groups I, II, and III (paired sample t-test; p < 0.05)
◊ When compared with T0 in Group II (paired sample t-test; p < 0.05).
No significant difference was observed between the groups in terms of mean arterial pressure values (p > 0.05).
No significant difference was observed between the groups in terms of the VAS scores obtained at 3 (T2), 6 (T3), and 24 h (T4) post-operatively (p > 0.05). The need for additional analgesics was similar between the groups (Table 2).
● Intergroup comparison (one-way ANOVA; p:0.037)
When compared with T0 in the groups (paired sample t-test; p<0.05).
In all three groups, the perioperative and post-operative native thiol levels were higher than pre-operative (T0) native thiol levels (p: 0.000; p: 0.000; p1: 0.001, p2−4: 0.000, p < 0.05) (Figure 2).
The native thiol levels at 24 h (T4) postoperatively were significantly higher in the epidural PCA group (Group II) than in the IV PCA group (Group 1) (p: 0.029; Tukey’s honestly significant difference test); no significant difference was observed between the other two groups.
The total thiol levels were similar in the three groups at all measurement times (p > 0.05). The perioperative and post-operative total thiol levels were higher than pre-operative total thiol levels in all three groups (p: 0.000, p: 0.000, p1: 0.009, p2–4: 0.000; p < 0.05).
● Intergroup comparison (Kruskal–Wallis test, p<0.05)
Intragroup comparison according to T0 (‡paired sample t-test).
In all three groups, the perioperative and post-operative disulfide levels were lower than the pre-operative levels (p: 0.000, p: 0.000, p: 0.000, p < 0.05) (Figure 3). The preoperative (T0), 30 min perioperative (T1), and 3 h (T2) postoperative disulfide levels were higher in the epidural PCA group (Group II) than in the IV PCA group (Group I) (p: 0.011, p: 0.005, p: 0.009; p < 0.05). The 3h (T2) post-operative disulfide levels were higher in the epidural PCA group (Group II) than in the combined femoral–sciatic nerve block group (Group III) (p: 0.042). No significant difference was observed between the groups in terms of the decrease observed in the disulfide levels from T0 to T1 and T2 (Kruskal–Wallis test, p > 0.05) (Table 3).
Discussion
The present study was conducted in elderly patients who underwent femoral nail surgery for a proximal femoral fracture, and to the best of our knowledge, this is the first study to evaluate the effects of three different postoperative analgesia methods administered following spinal anesthesia on oxidative stress by measuring the thiol/disulfide balance.
All the patients were operated on under spinal anesthesia, and they were administered IV PCA, epidural PCA, or combined femoral–sciatic nerve block for postoperative analgesia. The present study demonstrated that the application of hypobaric spinal anesthesia resulted in an increase in the thiol levels and a decrease in the disulfide levels, thereby indicating a decrease in oxidative stress. The VAS scores were similar in all the groups, and no difference was observed in the use of additional analgesics. Similar and effective levels of analgesia were ensured in all the patients. The similarity of the thiol/disulfide balance in all three groups demonstrated that there was no difference in the level of oxidative stress caused by pain among IV PCA, epidural PCA, and combined femoral–sciatic nerve block.
In aerobic organisms, free oxygen radicals are released as a result of normal oxygen metabolism. These radicals are highly reactive due to the single electron in their outer shell. Free radicals are continuously produced as a result of normal metabolic processes. The activation of several neuroendocrine, humoral, and cellular pathways in the body due to trauma, inflammation, surgical/emotional stress, and pain leads to an excessive increase in free radical production and consequently causes an increase in oxidative stress. As the body’s defense mechanism, antioxidant molecules prevent oxidative damage by forming bonds with reactive oxygen molecules [3-5]. Because reactive oxygen species are highly reactive, with a short half-life and low concentration, different indirect markers, rather than direct measurement, are used to evaluate cellular damage.
Thiol, which is an organic compound, is one of the antioxidant molecules that play a crucial role in the body’s defense mechanism against reactive oxygen derivatives. When thiol encounters oxidative stress, its sulfhydryl (-SH) group oxidizes to form a disulfide bond and protects protein structures from oxidation. Disulfide bonds can be reduced back to thiol groups. Owing to this reversible reaction, the oxidative state within a cell can be measured on the basis of the decrease in thiol levels and increase in disulfide levels [6]. Although only the thiol parameter of this balance could be measured using the Ellman method since 1979, the new method developed by Erel and Neşelioğlu allows both separate and cumulative measurement of the native thiol (-SH), dynamic disulfide (-S-S-) and total thiol [(-SH) + (-S-S-)] levels [7]. A decrease in the total thiol and native thiol levels in the native thiol/disulfide ratio and an increase in the disulfide level are considered indicative of oxidative stress [8, 9].
Regional anesthesia/analgesia reduces the stress response to surgery by ensuring both afferent sensory block and efferent sympathetic block [10-12]. Akın et al. investigated the relationship between the anesthesia technique performed in cesarean section and the thiol/disulfide balance and demonstrated that a mother and a newborn who were operated under general anesthesia experienced higher oxidative stress than a mother and a newborn who was operated under spinal anesthesia [13]. In the present study, the decreased disulfide levels and increased native thiol and total thiol levels following spinal anesthesia, which resulted in a shift of thiol/disulfide balance in the direction of thiol, support the argument that spinal anesthesia reduces oxidative stress.
In the postoperative period, pain creates emotional stress and stimulates the autonomic nervous system, thereby triggering the secretion of hormones, such as epinephrine and cortisol as well as inflammatory cytokines [14]. Several studies have reported that epidural analgesia achieved with opioids and/or local anesthetics provides better pain control than intramuscular or IV opioids [15-18]. In addition, local anesthetics administered via the epidural route are considered to exert a stronger effect in suppressing the stress response than opioids because they block both the nociceptive and non-nociceptive pathways [19]. Epidural anesthesia provides support to the cell in the prevention of oxidative damage [20, 21]. In the present study, only native thiol levels measured at post-operative 24 h were higher in the epidural PCA group (Group II) than in the IV PCA group (Group I) (p: 0.029; p < 0.05); however, the total thiol levels as well as the changes in disulphide levels were similar between the groups.
An alternative to neuraxial blocks is peripheral nerve blocks. Chelly et al. suggested that the post-operative combined femoral–sciatic nerve block provides better analgesia than epidural analgesia and morphine PCA [22]. Davies et al. considered a single-dose femoral–sciatic nerve block as a useful alternative to epidural analgesia [23]. In the present study, three different methods were used for the administration of analgesia in the postoperative period. Effective analgesia was confirmed in all the patients on the basis of the VAS scores and high patient satisfaction. In all the groups, the disulfide levels obtained at 3, 6, and 24 h post-operatively were low (p: 0.000). During the postoperative follow-ups, the decrease in the disulfide levels and increase in the native total thiol levels in all the patients demonstrated that effective analgesia was achieved and that IV PCA, epidural PCA and combined femoral–sciatic nerve block reduced oxidative stress.
Limitation
The present study had some limitations. One of the limitations was that the mean age of the patients in the combined femoral–sciatic nerve block group (Group III) was high, and it has been reported that oxidative stress increases with increasing age [24]. In addition, the present study was conducted with patients having high levels of basal oxidative stress due to the femoral fracture. Concomitant diseases and multiple drug use in geriatric patients may have been manifested with the high basal disulfide levels. Therefore, a comparison was made between the decrease in the disulfide levels obtained with anesthesia/analgesia. No significant difference was observed between the groups in terms of the changes in the disulfide and native total thiol levels.
Conclusion
The present study demonstrated that oxidative stress decreases with hypobaric spinal anesthesia in elderly patients who underwent surgery for a femoral fracture. It was concluded that it is important to provide effective analgesia in the postoperative period for managing oxidative stress, regardless of the selected analgesic method.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Koksal G. Oxidative stress and its complications in human health. Adv Biosci Biotechnol. 2012;3(8):1113-15.
2. Mirzahosseini A, Noszál B. Species-specific standard redox potential of thiol-disulfide systems: A key parameter to develop agents against oxidative stress. Sci Rep. 2016;6(1):37596.
3. Kayhan ZY. Metabolic/endocrine system and anesthesia. In: Sahinoglu AH, editor. Clinical Anesthesia. Istanbul: Logos Publishing; 2004.p.406-15.
4. Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000;85(1):109-17.
5. Gungor B, Malazgirt Z. Neuroendocrine, immune, and metabolic responses in injury. In: Sahinoglu AH, editor. Intensive Care Problems and Treatments. Istanbul: Nobel Publishing; 2011.p.661-81.
6. Oliveira PVS, Laurindo FRM. Implications of plasma thiol redox in disease. Clin Sci. 2018;132(12):1257-80.
7. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47(18):326-32.
8. Eren Y, Dirik E, Neşelioğlu S, Erel O. Oxidative stress and decreased thiol level in patients with migraine: cross-sectional study. Acta Neurol Belg. 2015;115(4):643-49.
9. Kara SS, Erel O, Demirbag DB, Yayla B, Gulhan B, Neselioglu S, et al. Alteration of thiol/disulfide homeostasis in acute tonsillopharyngitis. Redox Rep. 2015;20(6):247-52.
10. Buckley A, McQuaid S, Johnson P, Buggy DJ. Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: A pilot study. Br J Anaesth. 2014;113(Suppl.1):S56-62.
11. Hogevold HE. Changes in plasma IL-1 beta, TNF-alpha and IL-6 after total hip replacement surgery in general or regional anaesthesia. Cytokine. 2000;12(7):1156-59.
12. Khaw KS, Wang CC, Ngan Kee WD, Pang CP, Rogers MS. Effects of high inspired oxygen fraction during elective caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation. Br J Anaesth. 2002;88(1):18-23.
13. Akın F. Maternal and fetal dynamic thiol-disulfide balance pregnancies [Maternal ve fetal dinamik tiyol-disülfid dengesi gebelikleri]. Gulhane Med J. 2018;60(4):501-42.
14. Volk T, Schenk M, Voigt K, Tohtz S, Putzier M, Kox WJ, et al. Postoperative epidural anesthesia preserves lymphocyte, but not monocyte, immune function after major spine surgery. Anesth Analg. 2004;98(4):1086-92.
15. Kampe S, Randebrock G, Kiencke P, Hunseler U, Cranfield K, Konig DP, et al. Comparison of continuous epidural infusion of ropivacaine and sufentanil with intravenous patient-controlled analgesia after total hip replacement. Anaesthesia. 2001;56(12):1189-93.
16. Liu YF, Chen KB, Lin HL, Ho CH, Liu SK, Wu RS, et al. Comparison of the effect of epidural and intravenous patient-controlled analgesia on bowel activity after cesarean section: A retrospective study of 726 Chinese patients. Acta Anaesthesiol Taiwan. 2009;47(1):22-27.
17. Lee SH, Kim KH, Cheong SM, Kim S, Kooh M, Chin DK, et al. A comparison of the effect of epidural patient-controlled analgesia with intravenous patient-controlled analgesia on pain control after posterior lumbar instrumented fusion. J Korean Neurosurg Soc. 2011;50(3):205-8.
18. Schenk MR, Putzier M, Kugler B, Tohtz S, Voigt K, Schink T, et al. Postoperative analgesia after major spine surgery: patient-controlled epidural analgesia versus patient-controlled intravenous analgesia. Anesth Analg. 2006;102(4):1147-52.
19. Spencer Liu S, Carpenter L, Neal M. Epidural anesthesia and analgesia: Their role in postoperative outcome. Anesthesiology. 1995;82(5):1474-506.
20. Ezhevskaia AA, Prusakova ZB, Maksimova LP, Sholkina MN, Balmusova EA, Petrova GN, et al. Effects of epidural anesthesia on stress-induced immune suppression during major corrective spine surgery. Anesteziol Reanimatol. 2014;59(6):4-9.
21. Enohata K, Hasegawa-Moriyama M, Kuniyoshi T, Kanmura Y. Plasma levels of antioxidant markers during general anesthesia—a comparison between remifentanil- and epidural-based anesthesia. Masui. 2014;63(3):328-32.
22. Chelly JE, Greger J, Gebhard R, Coupe K, Clyburn TA, Buckle R, et al. Continuous femoral blocks improve recovery and outcome of patients undergoing total knee arthroplasty. J Arthroplasty. 2001;16(4):436-45.
23. Davies AF, Segar EP, Murdoch J, Wright DE, Wilson IH. Epidural infusion or combined femoral and sciatic nerve blocks as perioperative analgesia for knee arthroplasty. Br J Anaesth. 2004;93(3):368-74.
24. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13(1):757-72.
Download attachments: 10.4328.ACAM.22528
Cansu Ofluoğlu, Kübra Taşkın, Ceren Hazer, Süheyla Abitağaoğlu, Ahmet Kacıroğlu, Almila Şenat, Özcan Erel, Dilek Erdoğan. Evaluation of the effects of three different postoperative analgesic methods on thiol/disulphide homeostasis.Ann Clin Anal Med 2025;16(7):505-510
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Comparison of ketamine and magnesium sulphate for the prevention of postoperative shivering in gynaecological surgery: A randomized, prospective, placebo-controlled study
Ali Alkan Yılmaz 1, Ali Akdogan 2, Nesrin Erceyes 2
1 Department of Anesthesiology and Critical Care, Kanuni Training and Research Hospital, 2 Department of Anesthesiology and Critical Care, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye
DOI: 10.4328/ACAM.22550 Received: 2025-01-07 Accepted: 2025-02-11 Published Online: 2025-02-20 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):511-515
Corresponding Author: Ali Akdogan, Department of Anesthesiology and Critical Care, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye. E-mail: draliakdogan@yahoo.com P: +90 462 377 58 98 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7592-3844
Other Authors ORCID ID: Ali Alkan Yilmaz, https://orcid.org/0000-0001-9019-554X . Nesrin Erceyes, https://orcid.org/0000-0001-5692-8041
This study was approved by the Ethics Committee of Karadeniz Technical University (Date: 2010-01-08, No: 588)
Aim: Post-anaesthesia shivering is a common complication that reduces patient comfort and increases morbidity and mortality risks due to physiological stress. This study aimed to compare the effects of ketamine and MgSO4 on postoperative shivering, pain, and recovery after gynecological surgeries.
Material and Methods: In this randomized, prospective, placebo-controlled study, 60 patients (ASA I-II, aged 18-65 years) undergoing elective gynecological surgery were divided into magnesium sulfate (n = 20), ketamine (n = 20), and placebo (n = 20) groups. Heart rate, mean arterial pressure, tympanic membrane temperature, shivering scores, Aldrete recovery scores, and Visual Analog Scale (VAS) values were recorded at T1-T10 time points to evaluate drug efficacy.
Results: Magnesium and ketamine showed similar efficacy in preventing shivering, both being superior to placebo. A significant decrease in systolic and diastolic arterial pressure was observed in the magnesium group during recovery. VAS scores were significantly higher in the placebo group. Tympanic membrane temperatures decreased in the ketamine group, and all placebo group patients undergoing laparoscopic surgery experienced shivering.
Discussion: Subanaesthetic doses of ketamine and low-dose magnesium had comparable effects on shivering, hemodynamics, and recovery in gynecological surgeries under general anesthesia, and both reduced postoperative VAS scores compared to placebo.
Keywords: Postoperative Shivering, Magnesium Sulphate, Ketamine, Gynaecological Surgery
Introduction
Post-anesthesia tremor is a common complication after general and regional anesthesia. The incidence of this condition, which occurs in 5-65% of patients after general anesthesia and 33% after regional anesthesia, varies depending on the type of anesthesia used, the age and sex of the patient, and the length of the surgical period [1].
The prevention and treatment of shivering after anesthesia are critically important for both patient safety and the quality of care. Shivering can seriously reduce patient comfort and lead to a range of negative outcomes, including a 100-600% increase in oxygen consumption, elevated carbon dioxide production, tachycardia, hypertension, delayed wound healing, and an increased risk of postoperative morbidity and mortality. It is known that these complications prolong the postoperative recovery process and reduce patient satisfaction [2].
The treatment of post-anesthesia shivering includes pharmacological approaches, involving various agents from biogenic amines to NMDA receptor antagonists [3]. Among these agents, magnesium sulfate (MgSO4) and ketamine stand out due to their capacities to modulate central thermoregulatory control mechanisms. Magnesium, while taking on many important roles in physiological systems, is thought to exert its analgesic effect through calcium channel blockade and NMDA receptor antagonist properties [4]. Ketamine, as a non-competitive NMDA receptor antagonist, offers an effective option for reducing postoperative pain and preventing shivering [5].
Literature reviews indicate that there are limited studies comparing the effects of MgSO4 and ketamine on postoperative shivering. In this study, we aimed to provide information about the efficacy of these two agents by comparing the effects of ketamine and MgSO4, administered in specific doses after gynecological surgeries, on postoperative shivering, pain, and recovery.
Material and Methods
Our study was conducted prospectively as a placebo-controlled, double-blind trial. A total of 60 patients, aged 18-65, ASA I-II risk class, undergoing elective gynecological surgery under general anesthesia were included.
Exclusion criteria included patients with surgery durations shorter than 1 hour or longer than 3 hours, those with a body mass index (BMI) >35 kg/m², allergies to induction agents, severe cardiovascular or pulmonary diseases, and renal or hepatic failure. New patients were included to replace any excluded individuals.
One day before surgery, all patients underwent pre-anesthetic evaluation and written informed consent was obtained. During anesthesia, non-invasive monitoring of blood pressure (MAP), heart rate (HR), oxygen saturation (SpO2), and ECG was performed. An 18G IV catheter was placed, and a 0.9% NaCl infusion was started. Tympanic membrane temperature was measured to assess core body temperature.
After standard anesthesia induction, patients were intubated and connected to a mechanical ventilator. During fascia closure, one of three randomly assigned solutions was administered: Group M received 30 mg/kg magnesium sulfate, Group K received 0.5 mg/kg ketamine hydrochloride, and Group P received a 15 mL saline bolus. After anesthesia cessation, when spontaneous respiration was restored, patients were extubated and transferred to the recovery room.
The patients’ tympanic body temperature, Pulse oximeter, mean arterial blood pressure, as well as peripheral oxygen saturation, were measured before induction (T1), after intubation (T2), at the 30th minute of surgery (T3), and before drug administration (T4); extubation, surgery, and anesthesia durations were recorded. Postoperative measurements and recordings were made by an anesthetist who was unaware of the intraoperatively administered medication. Spontaneous eye opening, response to verbal stimuli, entry into the recovery room (T5), and at 10 (T6), 20 (T7), 30 (T8), 45 (T9), and 60 (T10) minutes, hemodynamic parameters, tympanic membrane temperatures, room temperature, and additional drug injections (meperidine, sodium diclofenac, metoclopramide) were recorded. The patients’ shivering scores, Aldrete recovery scores, anxiety scores, and pain scores (VAS) were calculated. When the Aldrete score was 8 or above, agitation scores were evaluated.
Statistical analysis
The data were analyzed using SPSS 11.5. Normal distribution was evaluated using the Kolmogorov-Smirnov test. Parametric data (age, BMI, hemodynamics, etc.) were analyzed using ANOVA, ordinal data with the X² test, and nonparametric data with the Kruskal-Wallis Variance Analysis. Within-group parametric evaluations were conducted using Repeated Measures ANOVA. Parametric data were presented as mean ± standard deviation, while nonparametric data were presented as percentages or counts. The significance level was set at <0.05.
Power analysis
In this study, power analysis was performed to increase statistical power and determine the appropriate sample size. In determining the sample size, a similar study, by Kose et al. (4) (2008), was taken as a reference.
Power analysis was performed based on the significance level (α = 0.05) and 80% power (1-β = 0.80) criteria. Considering the sample size in the study of Köse et al., the minimum sample size required to observe a similar effect was calculated. The analysis was performed using G*Power 3.1 software, and power calculations were performed according to the relevant test type (e.g. independent sample t-test, ANOVA, regression analysis, etc.).
As a result, it was determined that the sample size used in our study provided sufficient statistical power. Thus, the reliability and generalizability of the findings were increased.
Ethical Approval
This study was approved by the Ethics Committee of Karadeniz Technical University (Date: 2010-01-08, No:588).
Results
This study was conducted on 60 patients after obtaining approval from the local ethics committee and patient consent. The patients’ ages, BMI (Body Mass Index), ASA scores, anesthesia, and surgical durations among the groups are shown in Table 1; there was no statistically significant difference between the groups (p > 0.05) (Table 1).
The heart rates (beats/min) of the patients included in the study were evaluated over all time points (T1-T10) according to the groups. There was no statistically significant difference between the groups in terms of heart rates (p > 0.05) (Figure 1).
The changes in the Mean Arterial Pressure (MAP) values (mmHg) of the cases included in the study over all time points (T1-T10) according to the groups. No statistically significant difference was observed between the groups in terms of OKB values (p > 0.05) (Figure 2).
In terms of body temperature measurement values between the groups; at the 30th minute of the recovery period (T8), there was a statistically significant decrease in Group K compared to Group P. Additionally, at the 45th minute (T9), there was a statistically significant decrease in Group K compared to Group P (p < 0.05). Finally, at the 60th minute (T10), there was a statistically significant decrease in Group K compared to Group P (p < 0.05) (Figure 3).
Between the groups, in terms of the measurement values of the Tremor score during the collection period at the 10th minute (T6), there was a statistically significant increase in Group P compared to the other two groups (p < 0.05) (Table 2).
When the patients were examined in terms of postoperative visual acuity scale (VAS) values, a statistically significant higher value was found in Group P compared to the other groups at the 10th minute (T6) and 20th minute (T7) of the recovery period. (p < 0,05) (Table 3).
Discussion
This study demonstrates that magnesium sulfate (MgSO₄) and ketamine are effective options for managing postoperative shivering by influencing thermoregulation. Based on the anesthesia methods, drug applications, and hemodynamic stability observed in our study, these treatment options appear to be both safe and effective.
The literature indicates that men are more prone to shivering after anesthesia, while age can impair thermoregulatory control [6]. A higher BMI has been associated with a lower incidence of shivering [7]. In our study, since all participants were women and BMI levels were similar across groups, these factors were not considered in the analysis.
Previous studies have found a correlation between anesthesia duration and shivering, with longer procedures increasing the likelihood of shivering [6, 8]. In our study, surgeries lasting less than 60 minutes or more than 180 minutes were excluded to maintain a consistent anesthesia duration range. Our findings align with existing literature, supporting the relationship between prolonged anesthesia and increased shivering incidence.
The choice of anesthesia significantly affects shivering occurrence. Certain agents, such as halothane, isoflurane, fentanyl, and nitrous oxide, lower the thermoregulatory vasoconstriction threshold [9]. Chang et al. found that propofol-nitrous oxide anesthesia resulted in a lower incidence of postoperative shivering compared to thiopental-isoflurane-nitrous oxide anesthesia [10]. In our study, thiopental and sevoflurane were standardized for all patients. While opioids like fentanyl can influence thermoregulation and reduce shivering [11], no significant difference in shivering rates was observed with fentanyl use in our study, despite literature suggesting a potential effect [12].
MgSO₄’s cardiovascular effects are primarily due to its vasodilatory properties, which relax vascular smooth muscles [12]. Mendonca et al. reported an increase in heart rate following MgSO₄ administration to prevent hemodynamic fluctuations during intubation [13]. Our study also evaluated the cardiovascular effects of MgSO₄ and ketamine, revealing no significant differences in hemodynamic parameters between the two drugs. These findings suggest that both MgSO₄ and ketamine effectively manage postoperative shivering without compromising cardiovascular stability.
Postoperative body temperature monitoring was an essential parameter in our study. Tympanic temperature measurements in the recovery room indicated that all groups approached baseline values. The ketamine group exhibited lower body temperatures, reinforcing its potential role in thermoregulation. Both the MgSO₄ and ketamine groups had lower postoperative temperatures compared to the placebo group, suggesting a preventative effect on shivering.
Interestingly, shivering can occur even in normothermic patients [14]. While intraoperative hypothermia and postoperative vasoconstriction are key risk factors, non-thermoregulatory factors may also contribute [1]. Consistent with previous research, our study found no direct correlation between body temperature changes and postoperative shivering [6]. Tympanic temperatures in all groups gradually increased in the recovery room, indicating that shivering may not solely be temperature-dependent but influenced by other mechanisms.
MgSO₄ has been shown to lower the shivering threshold and exert central nervous system effects that aid in shivering control [15]. Dal et al. compared MgSO₄, pethidine, and saline in patients experiencing severe shivering and found that MgSO₄ and pethidine significantly reduced shivering compared to saline [15]. MgSO₄’s ability to mitigate shivering may be attributed to its neuromuscular effects and vasodilation. A meta-analysis by De Oliveira Filho et al. further highlighted that IV MgSO₄ not only reduced shivering but also decreased opioid consumption and postoperative pain intensity [16].
Ketamine’s role as an NMDA receptor antagonist is crucial in managing both pain and shivering. Studies have demonstrated its efficacy in reducing postoperative shivering in both general and regional anesthesia settings [4]. Goich et al. recommended 0.5 mg/kg ketamine for shivering control after regional anesthesia due to its effectiveness and lack of significant cardiovascular side effects [18]. Our findings support these observations, showing that both MgSO₄ (30 mg/kg) and ketamine (0.5 mg/kg) administered as IV boluses at the end of surgery were superior to placebo in reducing shivering.
Postoperative shivering may stem from perioperative hypothermia due to anesthetic-induced thermoregulatory suppression. However, non-thermoregulatory factors, such as cutaneous vasodilation and pain, can also contribute [19]. Some hypothermic patients do not shiver, while postoperative pain has been shown to increase non-thermoregulatory tremors [20]. This highlights the importance of pain management in shivering treatment.
NMDA receptor antagonists help prevent central sensitization and hypersensitivity, making them valuable in acute pain management [21]. Liu et al. reported that ketamine and magnesium inhibit NMDA receptors non-competitively, with their combined effect being greater than their individual effects [22]. This may explain the enhanced impact of MgSO₄ and ketamine on both postoperative pain and shivering.
Magnesium also exerts analgesic effects by blocking calcium channels and NMDA receptors [23]. It can reduce opioid requirements and associated side effects [24]. A meta-analysis by Avci et al. showed that MgSO₄ administration in abdominal surgeries reduced both intraoperative and postoperative opioid consumption, reinforcing its role in postoperative pain management [25].
Limitation
This study has some limitations. First, since all participants were women, the generalizability of the findings to male patients is limited. Second, while tympanic membrane temperature measurement was chosen for its ease of use, factors such as earwax, airflow, or improper placement may affect accuracy. More reliable methods, like oesophageal or oropharyngeal measurements, could provide more precise results, particularly during surgery. Additionally, although some factors such as BMI and anesthesia duration were controlled, other potentially influencing factors like genetic differences and individual pain thresholds were not taken into account. The sample size of the study may be limited in detecting rare side effects. In the future, studies conducted with larger and more diverse samples may better evaluate the efficacy and safety of these treatment options.
Conclusion
In summary, MgSO4 and ketamine’s effects on shivering and post-anesthesia recovery are in line with those of other research in the literature. Both medications in our trial decreased shivering in a comparable way and had safe side effect profiles. According to these results, ketamine and magnesium sulfate are safe and effective treatments for tremors. It is also believed that these medications could be used more clinically to treat and manage postoperative shivering.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Buggy DJ, Crossley AW. Thermoregulation, mild perioperative hypothermia and postanaesthetic shivering. Br J Anaesth. 2000;84(5):615-28.
2. Annetta MG. Postoperative shivering: Prevention or treatment? Minerva Anestesiol. 2022;88(6):425-427.
3. Jouguelet-Lacoste J, La Colla L, Schilling D, Chelly JE. The use of intravenous infusion or single dose of low-dose ketamine for postoperative analgesia: A review of the current literature. Pain Med. 2015;16(2):383-403.
4. Kose EA, Dal D, Akinci SB, Saricaoglu F, Aypar U. The efficacy of ketamine for the treatment of postoperative shivering. Anesth Analg. 2008;106(1):120-2.
5. Petskul S, Kitsiripant C, Rujirojindakul P, Chantarokorn A, Jullabunyasit A, Thinchana S. Prophylactic low-dose ketamine to prevent postanesthetic shivering in orthopedic surgery: A randomized-controlled study. J Med Assoc Thai. 2016;99(4):400-5.
6. Hoshijima H, Takeuchi R, Kuratani N, Nishizawa S, Denawa Y, Shiga T, et al. Incidence of postoperative shivering comparing remifentanil with other opioids: A meta-analysis. J Clin Anesth. 2016;32:300-12.
7. Dabir S, Jahandideh M, Abbasinazari M, Kouzekanani H, Parsa T, Radpay B. The efficacy of a single dose of pethidine, fentanyl and morphine in treating postanesthesia shivering. Pak J Pharm Sci. 2011;24(4):513-7.
8. Shirozu K, Asada M, Shiraki R, Hashimoto T, Yamaura K. Factors associated with postoperative shivering in patients with maintained core temperature after surgery. JA Clin Rep. 2024;10(1):70.
9. Sessler DI. Perioperative thermoregulation and heat balance. Lancet. 2016;387(10038):2655-64.
10. Chang M, Cho SA, Lee SJ, Sung TY, Cho CK, Jee YS. Comparison of the effects of dexmedetomidine and propofol on hypothermia in patients under spinal anesthesia: A prospective, randomized, and controlled trial. Int J Med Sci. 2022;19(5):909-15.
11. Hao C, Xu H, Du J, Zhang T, Zhang X, Zhao Z, et al. Impact of opioid-free anesthesia on postoperative quality of recovery in patients after laparoscopic cholecystectomy-a randomized controlled trial. Drug Des Devel Ther. 2023;17:3539-47.
12. Sachidananda R, Basavaraj K, Shaikh SI, Umesh G, Bhat T, Arpitha B. Comparison of prophylactic intravenous magnesium sulfate with tramadol for postspinal shivering in elective cesarean section: A placebo-controlled randomized double-blind pilot study. Anesth Essays Res. 2018;12(1):130-4.
13. Mendonça FT, de Queiroz LM, Guimarães CC, Xavier AC. Effects of lidocaine and magnesium sulfate in attenuating hemodynamic response to tracheal intubation: Single-center, prospective, double-blind, randomized study. Braz J Anesthesiol. 2017;67(1):50-6.
14. Sanchez Munoz MC, De Kock M, Forget P. What is the place of clonidine in anesthesia? Systematic review and meta-analyses of randomized controlled trials. J Clin Anesth. 2017;38:140-153.
15. Dal D, Kose A, Honca M, Akinci SB, Basgul E, Aypar U. Efficacy of prophylactic ketamine in preventing postoperative shivering. Br J Anaesth. 2005;95(2):189-92.
16. De Oliveira Filho GR, Mezzari Junior A, Bianchi GN. The effects of magnesium sulfate added to epidurally administered local anesthetic on postoperative pain: A systematic review. Braz J Anesthesiol. 2023;73(4):455-66.
17. Puliyel MM, Pillai R, Korula S. Intravenous magnesium sulphate infusion in the management of very severe tetanus in a child: A descriptive case report. J Trop Pediatr. 2009;55(1):58-9.
18. Goich K, Pastore D, Koutsenko B, Infosino B, Sgrignoli MN, Schachter T. A scoping review: Ketamine for the prevention of perioperative shivering in patients undergoing spinal anesthesia. Cureus. 2024;16(8):e66630.
19. Tsukamoto M, Hitosugi T, Esaki K, Yokoyama T. Risk factors for postoperative shivering after oral and maxillofacial surgery. J Oral Maxillofac Surg. 2016;74(12):2359-62.
20. Mullington CJ, Low DA, Strutton PH, Malhotra S. A mechanistic study of the tremor associated with epidural anaesthesia for intrapartum caesarean delivery. Int J Obstet Anesth. 2020;43:56-64.
21. Reisli R, Akkaya, ÖT, Arıcan Ş, Can ÖS, Çetingök H, Güleç, et al. Pharmachologic treatment of acute postoperative pain: A clinical practice guideline of The Turkish Society of Algology. Ağrı. 2021;33(50):1-51.
22. Liu HT, Hollmann MW, Liu WH, Hoenemann CW, Durieux ME. Modulation of NMDA receptor function by ketamine and magnesium: Part I. Anesth Analg. 2001;92(5):1173-81.
23. Brown EN, Pavone KJ, Naranjo M. Multimodal general anesthesia: Theory and practice. Anesth Analg. 2018;127(5):1246-58.
24. Herroeder S, Schönherr ME, De Hert SG, Hollmann MW. Magnesium—essentials for anesthesiologists. Anesthesiology. 2011;114(4):971-93.
25. Avci Y, Rajarathinam M, Kalsekar N, Tawfic Q, Krause S, Nguyen D, et al. Unravelling the analgesic effects of perioperative magnesium in general abdominal surgery: A systematic review and meta-analysis of randomized controlled trials. Braz J Anesthesiol. 2024;74(4):844-852.
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Ali Alkan Yılmaz, Ali Akdogan, Nesrin Erceyes. Comparison of ketamine and magnesium sulphate for the prevention of postoperative shivering in gynaecological surgery: A randomized, prospective, placebo-controlled study. Ann Clin Anal Med 2025;16(7):511-515
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Transcranial magnetic stimulation in neurological rehabilitation: A bibliometric mapping of 34 years of literature
Lütfiye Parlak
Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Selcuk University, Konya, Turkey
DOI: 10.4328/ACAM.22740 Received: 2025-05-15 Accepted: 2025-06-16 Published Online: 2025-06-26 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):516-520
Corresponding Author: Lütfiye Parlak, Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Selcuk University, Konya, Turkey. E-mail: drlutfiyeparlak@gmail.com P: +90 332 241 50 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8525-228X
Aim: This study aims to analyze the global research landscape on transcranial magnetic stimulation (TMS) in neurological rehabilitation using bibliometric methods. It investigates publication trends, key authors and institutions, international collaboration patterns, and disease-specific research distribution to highlight current progress and research gaps.
Material and Methods: A total of 2,245 English-language publications from 1991 to 2025 were retrieved from the Web of Science Core Collection (WoSCC) using a specific search strategy targeting TMS, rehabilitation, and neurological disorders. Bibliometric and scientometric analyses were conducted using Biblioshiny and VOSviewer. Analyses included productivity trends, citation metrics, keyword co-occurrence, thematic clustering, and collaboration networks.
Results: The number of TMS-related publications in neurorehabilitation showed a sharp increase after 2015, with an average annual growth rate of 13.8%. Stroke, spinal cord injury, Parkinson’s disease, and multiple sclerosis were the most studied conditions, whereas cerebral palsy, traumatic brain injury (TBI), and ALS remained underrepresented. The most prolific countries were the United States, China, Italy, Canada, and the UK. Institutional and co-authorship networks were primarily centered in North America and Western Europe. Keyword mapping revealed prominent themes, including motor recovery, neuroplasticity, and functional improvement.
Discussion: This is the first bibliometric study to offer a comprehensive overview of TMS in neurological rehabilitation across multiple disease groups. The findings reveal both significant growth in scientific activity and persistent underrepresentation of certain disorders like ALS and cerebral palsy. Future research should prioritize these gaps through multicenter, long-term studies to broaden the clinical application of TMS in neurorehabilitation.
Keywords: Transcranial Magnetic Stimulation, Neurologic Rehabilitation, Stroke, Bibliometrics, Parkinson Disease
Introduction
Transcranial magnetic stimulation (TMS) is a non-invasive, painless, and reliable neuromodulation technique that uses fluctuating magnetic fields to stimulate neural tissues, including the cerebral cortex, spinal roots, and cranial and spinal neurons, while recording the responses via an electromyography (EMG) device [1]. TMS can regulate cortical excitability by delivering magnetic pulses to targeted brain regions, promote neural plasticity, and support the improvement of motor and cognitive functions [2]. Although its exact mechanism of action has not yet been fully elucidated, TMS is suggested to be associated with synaptic plasticity, neurotransmitter regulation, ATP production, and increased vascularization in the application site and even adjacent cortical areas [3].
TMS was first introduced in 1985 and has since been increasingly utilized in both clinical and research settings. Alongside the expansion of its application areas, there has been a significant rise in scientific publications on the topic [4]. The use of TMS modalities, especially as an adjunct therapy in rehabilitation, has gained broader acceptance due to growing levels of supporting evidence [3]. Currently, TMS is clinically applied in the treatment of various neurological disorders, including stroke, amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), epilepsy, multiple sclerosis (MS), and cerebral palsy (CP) [5].
In individuals with PD, TMS applications have been shown to provide significant improvements in general motor impairment, gait, functional mobility, and balance parameters, with minimal side effects [6]. In stroke patients, moderate to high-quality evidence indicates that TMS contributes to enhanced motor functions and independence during early stages and within the first six months of recovery, thereby facilitating daily living activities [7]. Among individuals with ALS, especially those with cognitive impairment, TMS has been reported to yield short-term positive effects and potentially reduce caregiver burden [8]. In MS, the application of motor TMS in combination with exercise therapy has been reported to reduce both positive symptoms, such as spasticity, and negative symptoms such as fatigue, making it a promising approach for motor rehabilitation [9]. Additionally, another study conducted on MS patients has demonstrated that TMS induces cortical plasticity modulation and consequently improves motor functions [10]. Studies conducted in patients with CP have also confirmed that when TMS is used in conjunction with physical and occupational therapy or constraint-induced movement therapies, it leads to improvements in motor functions and reductions in spasticity [11, 12]. Furthermore, TMS appears to be a well-tolerated intervention for a wide range of symptoms and neurological sequelae following TBI [13]. TMS is also considered a promising non-invasive method for the treatment of spasticity, neuropathic pain, and somatomotor deficits that develop following spinal cord injury [14].
Bibliometric analyses are an important method for identifying publication trends, research foci, influential publications, authors, and institutions in scientific domains [15]. Despite the widespread clinical use of TMS in neurorehabilitation, comprehensive bibliometric studies specifically focused on this area are lacking. The aim of the present study is to analyze the overall trends in the application of TMS within the field of neurorehabilitation, identify research gaps, and draw attention to less-studied subfields. Compared to systematic reviews, bibliometric analysis enables an easier visual representation of publication trends. In this context, the development of TMS in the field of neurorehabilitation will be evaluated through keywords, authors, journals, publications, institutions, and countries.
Material and Methods
Data regarding the use of TMS in neurorehabilitation were obtained from the Web of Science Core Collection (WoSCC) database on May 8, 2025.
In the search strategy, a combination of keywords related to transcranial magnetic stimulation, rehabilitation, and neurological diseases (e.g., stroke, Parkinson’s disease, cerebral palsy) was used. Only publications classified as “article” or “review article” were included in the initial screening. Furthermore, only English-language publications were considered for analysis. A total of 2,245 publications were identified, and all were included in the final analysis.
The reason why the number of disease-specific publications may appear higher than the total number of publications is that a single article may be associated with more than one disease group. Therefore, frequency counts based on disease may exceed the total number of publications. The final dataset was exported in TXT format for further analysis.
Data Analysis
To identify research collaborations, author networks, and core thematic clusters, co-authorship networks and keyword co-occurrence analyses were conducted using the VOSviewer software. VOSviewer provides a robust infrastructure for the visual representation of bibliometric relationships, particularly in the context of network mapping [16]. In addition, the R-based Bibliometrix package was utilized to evaluate the scientific productivity and impact of various research institutions; trends in publication output over the years were also analyzed to reveal the developmental dynamics of the field [17]. Bibliometrix effectively supported the bibliometric analysis process by offering a comprehensive and systematic solution encompassing all stages, including data collection, preprocessing, analysis, and visualization [18].
Ethical Approval:
This study was based on publicly available bibliometric data and did not involve human or animal subjects; therefore, ethical approval was not required.
Results
In this bibliometric analysis, a total of 2,245 scientific documents published between 1991 and 2025 regarding the use of TMS in neurorehabilitation were evaluated. The average annual growth rate was calculated as 13.8%, with a notable increase particularly after 2015 (Figure 1A). The average document age was 7.68 years, and the average number of citations per document was 3.16. The average annual citation trend peaked in studies published between 1999 and 2003, whereas publications from 2023 onward have, as expected, received fewer citations to date.
Among the publishing institutions, the University of Toronto (n=166), the University of Louisville (n=133), and the University of Minnesota (n=131) stood out. The most productive authors included Edgerton VR (n=27), Liu Y (n=23), Kirton A (n=22), and Fregni F (n=21), indicating a publication network predominantly centered in North America (Figure 1B).
At the international level, the United States, China, Italy, Canada, and the United Kingdom were the countries with the highest number of publications (Figure 2A). Moreover, the United States was positioned at the center of the collaboration network, both in terms of publication volume and its strong partnerships with numerous countries.
In the keyword analysis, the most frequently encountered terms included “transcranial magnetic stimulation” (n=429), “deep brain stimulation” (n=244), “recovery” (n=191), and “rehabilitation” (n=184) (Figure 2B). These concepts were frequently studied in conjunction with themes such as neuroplasticity, motor cortex, spasticity, and functional improvement (Figure 2B).
The bibliometric analysis of the applications of TMS in neurological rehabilitation reveals notable differences in research intensity among various neurological disorders. According to the search conducted in the Web of Science database, stroke appears as the most frequently studied condition. With a total of 2,743 publications, stroke constitutes the most extensively investigated disease group concerning the rehabilitative use of TMS. This can be attributed to the widespread and promising use of TMS in addressing motor and cognitive impairments that develop following stroke.
Following stroke, the other most frequently studied disease groups include spinal cord injury (552 publications), PD (447 publications), and MS (431 publications). These are chronic neurological disorders characterized by motor and cognitive dysfunction, representing important areas of research for TMS in terms of symptom control and functional improvement.
Groups with fewer publications, such as CP (229 publications) and TBI (205 publications), demonstrate the potential of TMS applications in pediatric rehabilitation and acquired brain injury, respectively. Although these areas remain underexplored, they offer significant opportunities for future research.
On the other hand, ALS is represented by only 14 publications, making it the least studied group among the conditions included in this analysis. The rapid progression of ALS, its heterogeneous clinical course, and uncertainties in treatment response are considered limiting factors for TMS-related research in this population (Figure 3A).
These findings indicate that TMS is widely addressed in the context of motor and cognitive rehabilitation processes. The keyword co-occurrence network also reflects these clinical themes and their associated concepts in detail. Concept mapping analyses reveal dense conceptual clusters formed around key themes such as PD, spinal cord injury, rehabilitation, and the subthalamic nucleus. These themes are examined in conjunction with functional recovery, motor improvement, brain plasticity, and technological applications (e.g., brain-machine interface).
According to the citation analysis, the journals with the highest number of citations were Movement Disorders (n=4,370), Neurology (n=4,163), and Brain (n=3,952). The highly cited studies published in these journals indicate that the role of TMS in motor dysfunction and neurodegenerative diseases has been extensively investigated. Among the journals publishing the greatest number of articles, Neuromodulation (n=78), Frontiers in Neurology (n=72), and IEEE Transactions on Neural Systems and Rehabilitation (n=55) were the most prominent.
The international collaboration map generated using VOSviewer visualizes country-based scientific interactions. Türkiye holds a moderate position through its connections with countries such as Spain, Germany, and France. In the institutional collaboration map (Figure 3B), institutions such as Northwestern University, UCLA, the University of Toronto, and the University of Oxford were found to have high network connectivity. In terms of the author collaboration network (Figure 3B), clusters were observed around researchers such as Edgerton, Fregni, Pascual-Leone, and Field-Fote.
The analyses of collaboration at both the institutional and authorship levels (Figure 3B) indicate that scientific output in the field of TMS is largely clustered around institutions based in North America (particularly the United States and Canada) and Western Europe (the United Kingdom, Germany, and Italy). The central positioning of institutions like Northwestern University, UCLA, the University of Toronto, and the University of Oxford within the network highlights their key roles not only in productivity but also in collaborative influence. Similarly, the co-authorship network reflects international connections through clusters shaped around authors such as Fregni, Edgerton, and Pascual-Leone.
Although Turkiye is present within these networks, it is primarily represented through secondary connections and demonstrates a mid-level regional interaction profile. This suggests that while Turkiye contributes to the TMS-related neurorehabilitation literature, it does not yet occupy a central leadership role at the global level. Therefore, it is important for researchers to establish stronger institutional collaborations to enhance international visibility and contribute more significantly to the advancement of the field.
Discussion
This bibliometric analysis reveals a significant growth and evolution in the literature on the use of TMS in neurorehabilitation between 1991 and 2025. When examining publication trends by year, a notable acceleration is observed beginning in the mid-2000s. While TMS-related studies were almost nonexistent in the early 1990s, a slow upward trend began in the 2000s and gained marked momentum from the 2010s onward. Indeed, Zheng et al. [19] reported that the number of annual publications increased from approximately 200 in 2009 to 375 in 2018, indicating a steady and positive trend in publication growth during that period. Similarly, Juhi et al. [20], emphasized that stroke rehabilitation-focused studies remained limited until 2011, but experienced a sharp increase after 2014, reaching record levels between 2022 and 2024.
Our analysis confirms that over a broad time span, interest in TMS within the field of neurorehabilitation has grown exponentially, with annual publication numbers peaking in the 2020s compared to previous decades. This upward trend likely stems from increasing recognition of TMS’s therapeutic potential.
Analyses focusing on stroke rehabilitation have shown that the left dorsolateral prefrontal cortex and the primary motor cortex are among the most frequently targeted regions; low-frequency TMS has been associated with inhibition, while high-frequency TMS has been linked to excitation. Juhi et al. [20] noted that the most highly cited studies in this area are generally controlled trials that support improvements in motor function. Similarly, our analysis also demonstrated that publications related to stroke are high in number and have gained increasing momentum over the years.
In a bibliometric analysis specifically focused on PD, it was reported that, in recent years, there has been an increase in studies investigating the effects of TMS on both motor and non-motor symptoms [20]. The same study emphasized that protocols targeting the primary motor cortex and dorsolateral prefrontal cortex were particularly prominent, and that high-frequency TMS could produce significant effects on gait and motor scores. In our study, the volume of publications related to PD and the increasing trend in this area are consistent with the existing literature.
In the broader analysis conducted by Zheng et al. [21], publications in the field of TMS demonstrated a consistent annual increase between 2009 and 2018, with a particular concentration in developed countries such as the United States, Canada, and Germany. In our analysis, while these countries remained prominent, a noticeable rise in the number of publications from China and South Korea has also been observed in recent years, suggesting that these countries may be considered emerging contributors in terms of research output. This finding aligns with the study by Juhi et al., which identified China as the country with the highest number of publications in the stroke-TMS literature.
The decrease observed in the average number of citations after 2020 may largely be due to the fact that studies published during these years have not yet had sufficient time to accumulate citations. Citation delays are typical in recent publications. Therefore, the relatively low citation counts of articles published in or after 2020 reflect a natural delay effect that may be compensated over time. This situation stems from the time-dependent nature of bibliometric analyses, and the long-term impact of recent studies will become clearer in the future.
Most previous bibliometric analyses have focused on specific neurological conditions such as stroke or PD. This study provides one of the first thematic analyses across multiple neurological conditions involving TMS. In this respect, it is a pioneering study that offers a holistic assessment of TMS’s role in neurological rehabilitation. While the literature includes separate bibliometric studies addressing either clinical or disease-specific aspects of TMS in neurorehabilitation, the uniqueness of our study lies in its integration of both dimensions into a unified, comprehensive evaluation.
Limitation
Our study has several limitations. It includes only publications indexed in the WoSCC database; other data sources such as Scopus, PubMed, and Embase were excluded from the analysis. Bibliometric analyses rely on quantitative metrics and do not assess qualitative aspects such as methodological rigor, clinical efficacy, or outcome validity. Only English-language publications were included in the analysis, which may have excluded important studies published in other languages. Articles published after 2023 may not yet have had enough time to accumulate citations. Keyword and thematic analyses are based on automated indexing systems defined by journal databases, which may lead to limited representation of term diversity and semantic overlap. Clinical effectiveness, patient response, or functional outcomes of TMS applications were not directly addressed within the scope of this analysis.
Conclusion
This bibliometric analysis has revealed the scientific development of TMS in the field of neurorehabilitation in a multidimensional manner. It is important that future studies evaluate the effects of TMS in underrepresented clinical areas indicated by bibliometric findings with multicenter and long-term designs.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Atçeken H, Duray M. [Transcranial magnetic stimulation and its use in neurorehabilitation.] Celal Bayar Univ Sag Bilim Enst Derg. 2023;10(4):420–6.
2. Li XY, Hu R, Lou TX, Liu Y, Ding L. Global research trends in transcranial magnetic stimulation for stroke [1994–2023]: promising, yet requiring further practice. Front Neurol. 2024;15:1424545.
3. Kesikburun S. Non-invasive brain stimulation in rehabilitation. Turk J Phys Med Rehabil. 2022;68(1):1–8.
4. Liew SL, Santarnecchi E, Buch ER, Cohen LG. Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery. Front Hum Neurosci. 2014;8:378.
5. Nollet H, Van Ham L, Deprez P, Vanderstraeten G. Transcranial magnetic stimulation: review of the technique, basic principles and applications. Vet J. 2003;166(1):28–42.
6. Wang M, Zhang W, Zang W. Repetitive transcranial magnetic stimulation improves cognition, depression, and walking ability in patients with Parkinson’s disease: a meta-analysis. BMC Neurol. 2024;24(1):490.
7. Xie G, Wang T, Deng L, Zhang Z, Huang H, Liu B, et al. Repetitive transcranial magnetic stimulation for motor function in stroke: a systematic review and meta-analysis of randomized controlled studies. Syst Rev. 2025;14(1):47.
8. Zheng W, Zhang X, Chen J, Wang M, Liu Y, Tang Y, et al. The effect of repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex on the amyotrophic lateral sclerosis patients with cognitive impairment: a double-blinded, randomized, and sham control trial. CNS Neurosci Ther. 2025;31(3):e70316.
9. Mori F, Ljoka C, Magni E, Kusayanagi H, Monteleone F, Buttari F, et al. Transcranial magnetic stimulation primes the effects of exercise therapy in multiple sclerosis. J Neurol. 2011;258(7):1281–7.
10. Şan AU, Yılmaz B, Kesikburun S. The effect of repetitive transcranial magnetic stimulation on spasticity in patients with multiple sclerosis. J Clin Neurol. 2019;15(4):461–7.
11. Chen CL. Unlocking the potential of repetitive transcranial magnetic stimulation to enhance motor function in pediatric cerebral palsy: a comprehensive review. Biomed J. 2025;48:100835.
12. Gupta M, Lal Rajak B, Bhatia D, Mukherjee A. effect of r-TMS over standard therapy in muscle tone of spastic cerebral palsy patients. J Med Eng Technol. 2016;40(4):210–6.
13. Pink AE, Williams C, Alderman N, Stoffels M. The use of repetitive transcranial magnetic stimulation (rTMS) following traumatic brain injury (TBI): a scoping review. Neuropsychol Rehabil. 2021;31(3):479–505.
14. Awad BI, Carmody MA, Zhang X, Lin VW, Steinmetz MP. Transcranial magnetic stimulation after spinal cord injury. World Neurosurg. 2015;83(2):232–5.
15. Hassan W, Duarte AE. Bibliometric analysis: a few suggestions. Curr Probl Cardiol. 2024;49(8):102640.
16. Tang S, Hao R, Liu X, Zhang Y, Wang L, Zhou Y, et al. global trends in Cryptococcus and its interactions with the host immune system: a bibliometric analysis. Front Immunol. 2024;15:1397338.
17. Aria M, Cuccurullo C. Bibliometrix: an R-tool for comprehensive science mapping analysis. J Informetrics. 2017;11(4):959–75.
18. Huang Y, Hu R, Wu L, He K, Ma R. Immunoregulation of glia after spinal cord injury: a bibliometric analysis. Front Immunol. 2024;15:1402349.
19. Zheng KY, Dai GY, Lan Y, Wang XQ. Trends of repetitive transcranial magnetic stimulation from 2009 to 2018: a bibliometric analysis. Front Neurosci. 2020;14:106.
20. Juhi A, Gayen RK, Sharma S, Choudhary PK, Mondal H. Repetitive transcranial magnetic stimulation in stroke rehabilitation: a bibliometric review. Cureus. 2025;17(2):e79509.
21. Wei YX, Tu LD, He L, Zhang J, Zhao Y, Wang R, et al.. research hotspots and trends of transcranial magnetic stimulation in Parkinson’s disease: a bibliometric analysis. Front Neurosci. 2023;17:1280180.
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Lütfiye Parlak, Transcranial Magnetic Stimulation in Neurological Rehabilitation: A Bibliometric Mapping of 34 Years of Literature. Ann Clin Anal Med 2025;16(7):516-520
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Surgical management and outcomes of rare adult ıntussusception: A single tertiary center experience
Enes Şahin 1, Mehmet Eşref Ulutaş 2
1 Department of General Surgery, Faculty of Medicine, Kocaeli University, Kocaeli, 2 Department of General Surgery, University of Health Sciences, Gaziantep City Hospital, Gaziantep, Turkey
DOI: 10.4328/ACAM.22748 Received: 2025-05-19 Accepted: 2025-06-30 Published Online: 2025-06-30 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):521-524
Corresponding Author: Mehmet Eşref Ulutaş, Department of General Surgery, University of Health Sciences, Gaziantep City Hospital, Gaziantep, Turkey. E-mail: esref_ulutas@hotmail.com P: +90 507 476 90 36 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9206-4348
Other Authors ORCID ID: Enes Şahin, https://orcid.org/0000-0003-3777-8468
This study was approved by the Ethics Committee of Kocaeli University, Faculty of Medicine (Date: 2025-04-24, No: KÜ GOKAEK-2025/09/11)
Aim: Intussusception in adults is a rare condition. Since it is usually associated with an underlying intestinal pathology, surgical treatment is typically required. This study aims to evaluate cases of intussusception managed at a tertiary care center.
Material and Methods: This retrospective study was conducted in the Department of General Surgery at Kocaeli University Faculty of Medicine. Patients who underwent surgery for intussusception between January 1, 2015, and January 1, 2025, were included in the study. The cases were categorized into enteroenteric, ileocolic, and colocolic subgroups and compared in terms of clinical and pathological data. Demographic and clinical characteristics of the patients were obtained through a review of medical records.
Results: A total of 12 patients underwent surgery for intussusception. The mean age of the patients was 45.4 years. Of these, 9 were classified as having enteroenteric, 2 ileocolic, and 1 colocolic intussusception. The most common presenting symptom was abdominal pain (73.3%). The most frequent etiology was small bowel tumors (33.3%). Segmental small bowel resection was the most commonly performed surgical procedure (41.7%). Histopathological evaluation revealed submucosal lipoma as the most common finding (22.2%). Among the ileocolic cases, one patient was diagnosed with adenocarcinoma.
Discussion: Surgical resection of the affected bowel segment is the mainstay of treatment for intussusception in adults. Although benign etiologies are more commonly observed in small bowel cases, it is important to note that malignancies may be present, particularly in ileocolic and colocolic types. Therefore, surgical procedures should be performed with careful consideration of this possibility.
Keywords: Adult, Intussusception, Emergency, Surgical Treatment, Bowel Resection
Introduction
Intussusception in adults is a rare condition. It accounts for 1–5% of mechanical bowel obstructions [1-5]. Unlike in children, adult intussusceptions are generally caused by an underlying pathology within the intestinal lumen.
Intussusception has been reported to occur more frequently in patients with acquired immunodeficiency syndrome (AIDS). This is attributed to the higher incidence of infectious and neoplastic conditions in the intestines of these patients, such as lymphoid hyperplasia, Kaposi’s sarcoma, and non-Hodgkin lymphoma [3].
There are various classifications of intussusception. One classification is based on etiology: benign, malignant causes, and idiopathic. Another classification is based on localization. Intussusceptions confined to the small intestine are termed enteroenteric; those involving prolapse of the terminal ileum into the colon are ileocolic intussusceptions; and intussusceptions confined to the large intestine are referred to as colocolic intussusceptions [3-7].
Intermittent abdominal pain is the most common presenting symptom in adults; however, patients may also present with symptoms of intermittent partial bowel obstruction, such as nausea, vomiting, melena, weight loss, fever, and constipation. While diagnosis is often made by ultrasonography in children, it is usually established by abdominal computed tomography (CT) in adults. The ‘target sign’ observed on CT is the most characteristic finding of intussusception [3, 4].
Causes of intussusception in adults generally require surgical treatment. Therefore, reduction and/or various resection procedures are frequently performed [8-10].
The aim of this study is to evaluate the etiology, clinical presentation, surgical management, and pathological outcomes of this rare condition in adults. For this purpose, data from a tertiary care hospital were analyzed.
Material and Methods
Trial Design
This retrospective study was conducted in the Department of General Surgery at Kocaeli University Faculty of Medicine. Written informed consent was obtained from all individual participants included in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Participants and Eligibility Criteria
Adult patients who underwent surgery with a preliminary diagnosis of intussusception between January 1, 2015, and January 1, 2025, were included in the study.
Inclusion criteria were: patients over 18 years of age and those operated on due to intussusception.
Exclusion criteria were: patients under 18 years of age, patients treated medically for intussusception, and patients operated on for causes other than intussusception.
Outcomes
The medical records of the included patients were reviewed to collect clinical data such as demographic characteristics (age, gender), presenting symptoms, preoperative imaging methods, etiology, surgical procedures performed, and pathological results. Patients were categorized into subgroups based on the type of intussusception: enteroenteric, ileocolic, and colocolic, and demographic and clinical data were compared among these groups.
The primary outcome was the underlying causes of intussusception, while secondary outcomes included clinical data such as the surgical procedures performed and pathological findings.
Statistical Analysis
Data were presented as means and medians (min–max) for quantitative variables and percentages for qualitative variables. Statistical analysis was performed with SPSS version 22.0, and p < 0.05 was considered significant.
Ethical Approval
This study was approved by the Ethics Committee of Kocaeli University, Faculty of Medicine (Date: 2025-04-24, No: KÜ GOKAEK-2025/09/11).
Results
Twelve patients who underwent surgery for intussusception between January 1, 2015, and January 1, 2025, were included in the study. The mean age of the patients was 45.4 years. Half of the patients were male (n = 6) and half were female (n = 6) (Table 1). Intussusception types were enteroenteric (EE) in 9 patients (75%), ileocolic (IC) in 2 patients (16.7%), and colocolic (CC) in 1 patient (8.3%). The mean ages were 45.4 years. The male-to-female ratios were 6:6 (Table 1).
Abdominal pain was the most common presenting symptom across all patients (73.3%). Diagnosis was established by CT scan in 11 patients (91.7%), while only one patient (8.3%) in the EE group was diagnosed by ultrasonography (Table 1) (Figure 1).
Small bowel tumors were the most frequent etiology across all patient groups (33.4%) (Figure 2). In the EE group, small bowel tumors were the leading cause (44.4%), whereas in the IC and CC groups, colonic tumors accounted for 100% of cases. Segmental small bowel resection was the most commonly performed surgical procedure in all patients (41.7%) (Table 1). Pathological examination revealed submucosal lipoma and Meckel’s diverticulum as the most common findings in all patients (22.2% each) (Table 1).
Discussion
Intussusception is a rare condition in adults; however, it should be considered in the differential diagnosis of patients presenting with symptoms such as abdominal pain, nausea, and vomiting. Previous studies in the literature have reported a higher incidence in middle-aged patients, typically around 45 to 52 years of age [11, 12]. Similarly, the mean age of patients in our study was approximately 45 years.
Kim reported in a study including 28 patients that the most common presenting symptom was abdominal pain [11]. A systematic review published in 2024 also identified abdominal pain as the most frequent presenting complaint, occurring in 86% of cases [12]. Consistent with the literature, abdominal pain was the most common presenting symptom in our study as well (73.3%).
Diagnosis of intussusception in patients is predominantly established by computed tomography (CT). A systematic review reported a CT diagnosis rate of 88.5% [12], while Neymark et al. reported a 100% CT diagnosis rate [13]. In our study, this rate was also notably high at 91.7%.
In the study conducted by Neymark et al., enteroenteric (EE) intussusceptions were reported as the most common type, accounting for 73% of cases [13]. Conversely, Kim reported ileocolic (IC) intussusceptions as the most frequent, with a rate of 36% [11]. A systematic review including approximately 1900 patients indicated colocolic (CC) intussusceptions as the most prevalent type, occurring in 16.8% of cases [12]. As observed, there is no clear consensus in the literature regarding the most common type of intussusception. In our study, EE intussusceptions were the most frequently detected type (75%).
In Kim’s study, idiopathic causes were most commonly identified in both small bowel and colonic intussusceptions [11]. In contrast, Su et al. reported that malignancies were the most frequent causes in colonic intussusceptions, whereas benign small bowel tumors were predominant in small bowel intussusceptions [14]. Meera and colleagues found that malignancies were the leading causes of intussusceptions in their study [15]. In our study, small bowel tumors were identified as the most common cause.
Kim reported that lipomas were the most frequently observed lesions in the pathological evaluation of resections [11]. Similarly, Neymark et al. also identified lipomas as the most common finding [13]. In contrast, Su et al. reported that adenomas were the predominant pathology in small bowel intussusceptions, whereas adenocarcinomas were most frequently observed in colonic cases [14]. In our study, the most common pathological findings were lipomas and Meckel’s diverticula. Among small bowel cases, Meckel’s diverticulum was the most frequently detected pathology, while adenocarcinoma incidence was higher in colonic intussusceptions.
Limitation
The major limitation of this study is its retrospective design and small case series, which may be attributed to the rarity of intussusception in adults.
Conclusion
In conclusion, although intussusception is rare, it does occur in adults. It is mostly associated with underlying benign small bowel tumors. However, especially in colonic intussusception cases, the likelihood of an underlying malignancy is increased, and surgical procedures should be performed following oncological principles.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Marinis A, Yiallourou A, Samanides L, Dafnios N, Anastasopoulos G, Vassiliou I, et al. Intussusception of the bowel in adults: a review. World J Gastroenterol. 2009;15(4):407-11.
2. Zubaidi A, Al-Saif F, Silverman R. Adult intussusception: a retrospective review. Dis Colon Rectum. 2006;49(10):1546-51.
3. Gayer G, Zissin R, Apter S, Papa M, Hertz M. Pictorial review: adult intussusception-a CT diagnosis. Br J Radiol. 2002;75(890):185-90.
4. Lvoff N, Breiman RS, Coakley FV, Lu Y, Warren RS. Distinguishing features of self-limiting adult small-bowel intussusception identified at CT. Radiology. 2003;227(1):68-72.
5. Ulutaş ME, Şimşek G, Şahin A. Yetişkinlerde nadir bir ileus nedeni: invajinasyon. Bozok Tip Derg. 2019;9(4):168–71.
6. Panzera F, Di Venere B, Rizzi M, Biscaglia A, Praticò CA, Nasti G, et al. Bowel intussusception in adult: prevalence, diagnostic tools and therapy. World J Methodol. 2021;11(3):81-7.
7. Hadid T, Elazzamy H, Kafri Z. Bowel intussusception in adults: think cancer! Case Rep Gastroenterol. 2020;14(1):27-33.
8. Aghahowa ME, Alu FE, Emuze O, Atinko SI, Alada MA, Olofin KE, et al. Adult intussusception: a 10-year institutional review. West Afr J Med. 2024;41(11):1137-42.
9. González-Carreró Sixto C, Baleato-González S, García Palacios JD, Sánchez Bernal S, Junquera Olay S, Bravo González M, et al. Intestinal intussusception in adults: location, causes, symptoms, and therapeutic management. Radiologia. 2023;65(3):213-21.
10. Hong KD, Kim J, Ji W, Wexner SD. Adult intussusception: a systematic review and meta-analysis. Tech Coloproctol. 2019;23(4):315-24.
11. Kim KH. Intussusception in adults: a retrospective review from a single institution. Open Access Emerg Med. 2021;13:233-7.
12. T Chand J, R R, Ganesh MS. Adult intussusception: a systematic review of current literature. Langenbecks Arch Surg. 2024;409(1):235.
13. Neymark M, Abramov R, Dronov M, Gilshtein H. Management of adult intussusception-a case series experience from a tertiary center. World J Surg. 2021;45(12):3584-91.
14. Su T, He L, Zhou T, Wu M, Guo Y, Wang Q, et al. Most adult intussusceptions are caused by tumors: a single-centre analysis. Cancer Manag Res. 2020;12:10011-5.
15. Sainaba SM, Ganapath AS, Sivakumar A, Gayathri AV, Yadev IP. Adult intussusception at a tertiary care center: a retrospective study. Niger J Surg. 2020;26(1):63-5.
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Enes Şahin, Mehmet Eşref Ulutaş. Surgical management and outcomes of rare adult ıntussusception: A single tertiary center experience. Ann Clin Anal Med 2025;16(7):521-524
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Trend analysis of family-centered care in the neonatal intensive care unit (NICU): A bibliometric study
Mustafa Törehan Aslan 1, Mehmet Semih Demirtas 2
1 Department of Pediatrics, Division of Neonatology, Koç University Hospital, Istanbul, 2 Department of Pediatrics, Faculty of Medicine, Aksaray University, Aksaray, Turkey
DOI: 10.4328/ACAM.22755 Received: 2025-05-26 Accepted: 2025-06-30 Published Online: 2025-06-30 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):525-529
Corresponding Author: Mustafa Törehan Aslan, Department of Pediatrics, Division of Neonatology, Koç University Hospital, Istanbul, Turkey. E-mail: torehanaslan@yahoo.com P: +90 532 132 21 39 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3966-4635
Other Authors ORCID ID: Mehmet Semih Demirtas, https://orcid.org/0000-0003-2965-1811
Aim: The study focuses on the analysed trends in FCC practices in NICUs and their effects on neonatal and family outcomes.
Material and Methods: This study conducted a bibliometric analysis of 1,198 peer-reviewed articles from the Scopus database (2000–2025). Publication, citation, H index, and keyword analysis were used to track research developments. Research themes were identified using co-citation analysis and bibliometric mapping (VOSViewer) tools to identify intellectual connections and institutional contributions.
Results: The number of publications by FCC in NICUs (2000–2025) was analysed, and 1,198 publications were found, with the U.S. (2,208), Canada (555), and the UK (250) in corresponding order. With 28 articles, Axelín A is the leading author, and the University of Turku is the leading affiliation (Affiliation with 64 publications). Female (1,163) and infant (799) are the most frequent keywords. From 95 articles, Advances in Neonatal Care emerges as the leading source of information.
Discussion: The results of this study reiterate the growing importance of Family Centered Care (FCC) in NICUs, key contributors, institutions, and journals. FCC improves neonatal outcomes and family well-being while recognizing the need for global collaboration.
Keywords: Bibliometric Analysis, Family-Centered Care (FCC), Neonatal Intensive Care Unit (NICU), Neonatal Outcomes, Co-citation Analysis, Parental Involvement
Introduction
Family-centered care (FCC) is the healthcare approach that acknowledges the family’s role in a patient’s normal well-being and recovery, particularly in the neonatal intensive care unit (NICU) [1]. FCC principles respect families’ unique needs and culture, empower them to participate in care decisions, and promote open communication [2]. FCC units in NICUs achieve priority rank and focus predominantly on creating a healing environment, which is accomplished by offering private spaces and educating parents [3]. Before the FCC, medical care of children was largely limited to clinical interventions with less consideration of the child’s psychological and emotional needs or the child’s family. The care process often excluded families, leaving families feeling helpless and disconnected from the child’s well-being. FCC grew to include skin-to-skin contact (kangaroo care), shared rounding, and family-led care plans [4].
The Neonatal Intensive Care Unit (NICU) is a specialized hospital unit in which premature newborns, low birth weight, or critically ill newborns are cared for and closely monitored by intensive care [5]. These are units of a controlled environment with life-sustaining technology, stabilizing fragile infants in their most critical weeks or months of life. NICU cares for different conditions, including respiratory distress syndrome, congenital anomalies, infection, and complications of prematurity [6].
Family-centered care (FCC) significantly improves infant outcomes by promoting a nurturing environment that enhances infants’ physical and emotional well-being [7]. Strong parent-infant bonding early and sustained helps parents regulate emotions and helps with cognitive growth [8]. Implementation of family-centered care (FCC) in NICUs is a very challenging process. One of the main obstacles is time constraints since NICU staff often work with highly critical sick newborns at a fast pace [9]. Another barrier is staff resistance, which is based on the staff’s fear that doing something with families might prevent the family from fully engaging with the clinical workflows or delay critical procedures [10]. The objectives of the study are to identify key developments in the implementation of FCC, evaluate the benefits of FCC to infants and families, identify barriers to the adoption of FCC, and explore institutional and cultural factors that influence the use of FCC to improve FCC practices and inform public policy relating to NICU care.
Material and Methods
Data Resource and Search Strategy
The study was performed using data gathered in the Scopus database, a leading database renowned for its wide and high-quality academic content. The study covers the timespan from 2000 to 2025, a 25-year period covered to track the evolution of FCC practices and get a long-term view of research developments in the field. The articles in the dataset are 1,198 all peer-reviewed journal publications, making these articles credible and relevant. Analysis of this subject revealed a total of 326 unique sources, including journals and books, of which only 232 were published. Most relevant studies were extracted using search terms “family-centered care”, “neonatal intensive care”, “parental involvement”, and “neonatal outcomes”. The depth of the research was provided by the advanced bibliometric data from Scopus, such as Keywords Plus (3,445) and Author’s Keywords (2,197), allowing us to analyze recurring concepts and emerging trends of this research.
This research strategy directs the choice of articles based on the systematic selection of some of the most influential and thematically relevant publications to obtain a comprehensive and insightful view of FCC trends in the NICU. The number of publications, authors, citations, and publication years had been extracted as key metrics to show research trends and growth. Contributions’ impact and academic influence, and their associated institutions, were evaluated using author affiliations and H-index. In addition, the study included references to other countries and regions that contributed their research to evaluate the FCC research globally. To identify leading publications in this field, journals were categorized, and research focus areas were identified through the analysis of keywords, including Keywords Plus and the Author’s Keywords.
Bibliometric Analysis
Bibliometric indicators are major in quantifying research trends and academic impact [11]. The volume and influence of research from 2000 to 2025 are assessed using metrics such as the number of publications (NP) and citations (NC). The sample consists of 1,198 articles with an average citation rate, which indicates intensive academic attention. The study is mapped with the help of co-citation analysis, which studies the frequency at which two articles are cited together to study intellectual connections and foundational literature. Further, keyword co-occurrence analysis identifies core themes and research hotspots based on data created using Keywords Plus and 2,197 keywords for those created using Author’s Keywords.
Ethical Approval
Since there were no human or animal participants in our study and the study used publicly accessible resources, ethics committee approval was not obtained. There is no personal information provided in this paper.
Results
Overview of Publications on FCC
The study presents an overview on publications related to the FCC in NICU over a 25-year period (2000–2025). 1,198 journal articles were analyzed that showed a strong focus on FCC amongst the academic and clinical research community. There is an obvious trend towards collaborative authorship, where an average of 4.99 co-authors per document indicates interdisciplinary participation. These articles with international co-authorships constitute a global significance of about 15.44% of the articles.
Annual Trends of Publication Quantity
The analysis of the annual trends in the publication quantity on FCC in NICUs shows that there have been steady increases over the years and large increases in the last decade (Figure 1).
Contributions of Countries
FCC research and implementation are dominated by the United States, which also leads with 8992 citations. Other influential contributors include Canada (2,335), followed by Sweden (1,223), which are well cited on average and are ranked in the top 2,000 most cited authors (Figure 1). The global research efforts add Australia (1,059) and the United Kingdom (822). However, countries such as Israel (427) and Portugal (296) have high citation averages based on a smaller number they produce (Figure 1).
Countries’ production over time
The United States shows a strong lead, growing from 24 articles in 2000 to 2,208 in 2025. Canada and the UK also show steady increases, reaching 555 and 250 articles, respectively (Figure 1C). Most corresponding authors are from the U.S., with 412 articles—93.7% being single-country publications (SCP) and 6.3% multi-country (MCP).
Analysis of Affiliations
The results show the importance of leading academic institutions to do research in this sphere, with the University of Turku leading the table with 64 articles, emphasizing its constant contribution to research. The University of Toronto closely follows with 58 publications, confirming its dedication to top-of-the-range academic group effort. The sustained contributions to this area of research are also seen in the University of California (UC) and the University of Calgary, with 56 and 50 articles, respectively (Figure 2).
Performance of Authors
Axelín A leads with 28 articles, indicating significant contributions to the field. Lehtonen L (24 articles), Franck LS (19), and Latour JM (16) are also key contributors (Figure 2). According to Lotka’s Law, scientific productivity is inversely proportional to the square of the number of authors [12]. The H-index reflects a researcher’s impact, representing the number of publications (H) that have each been cited at least H times [13].
Analysis of Journals
With over 95 publications, Advances in Neonatal Care *stands out as a key journal for high-impact research and innovation in neonatal care, especially in the past decade (Figure 3). According to Bradford’s Law, a small core of journals holds most of the field’s literature. Advances in Neonatal Care is identified as a core source in neonatal research (Figure 3) [14].
Research Keywords Analysis
In the analysis, frequently used terms such as “female” (1163), “male” (845), “human” (998), and “humans” (839) reflect a strong focus on gender and human-centered care in neonatal research. By 2024, “female” emerged as the most common term, likely due to its link with maternal roles, followed by “human,” highlighting the emphasis on person-centered approaches.
Between 2001 and 2010, terms like “neonatal intensive care unit,” “infant,” and “newborn” dominated, indicating foundational research. After 2010, focus shifted toward “family nursing,” “parent,” and “child care,” with significant growth by 2015, reflecting the rise of family-centered practices.
In the last decade, themes such as “psychological aspects,” “social support,” and “parent-infant bonding” gained attention, showing an increasing interest in emotional and relational factors. Clinical terms like “oxygen saturation” and “infection control” underline evidence-based care, while the rise of “nursing methodology research” and “adaptive behaviour” since 2015 reflects growing methodological innovation.
By 2023, terms like “infant,” “NICU,” and “family-centered care” were highly frequent, while emerging themes like “social determinants of health” and “health promotion” suggest a shift toward holistic and professional practices in neonatal care.
Discussion
FCC is a critical approach to healthcare for the neonate in which family involvement in neonatal care improves outcomes for infants and families. The research has been conducted using Scopus, a widely recognised academic database, where 1,198 peer-reviewed articles were analysed, focused on key developments during 25 years. Keywords Plus (3,445 terms) and Author’s Keywords (2,197 terms) are used to identify recurring themes in the analysis of 326 unique sources, including 232 published works. Scholarly impact and contributions to global research are shown by global metrics like publication count, citations, and H index. The findings suggest that family-centered care (FCC) is of increasing importance in NICUs as neonatal outcomes and family wellbeing continue to be promoted. Kokorelias et al. (2019) emphasised that the steady rise in publications reflects the global push to incorporate patient and family-centered approaches into healthcare [15]. The rapid increase in publication numbers after 2010 may reflect increased attention to the FCC’s contribution to neonatal survival rates and less parental stress. Interdisciplinary research has been facilitated by the trend of collaborative authorship, whereby medical, psychological, and nursing perspectives of FCC research have become integrated [16]. This recognition of the FCC as a priority is highlighted by its global significance as a component of international co-authorship.
Study findings illustrate the worldwide distribution of FCC research in NICUs with strong contributions from the United States, Canada, and many European countries. The research output and citations are led substantially by the United States, due to its extensive healthcare infrastructure and adoption of evidence-based practices. However, that leadership is evidenced by Franck et al. (2023), which demonstrates the critical role that the FCC plays in improving neonatal outcomes [17]. Examples of countries with consistent growth are Canada, Australia, and the United Kingdom, which positively emphasize core neonatal collaborative endeavours. Although MCP percentages, along with high DMP fulfilment and data sharing rates, are also observed in European countries such as Italy, Finland, and Denmark, which resonate with European Union research frameworks that emphasise international partnerships. China, India, and Iran’s emerging contributions to the FCC happily highlight its global importance. In particular, studies performed by Sigurdson et al. (2020) highlight the critical importance of further expanding the FCC research in a way that can mitigate disparities and ultimately improve neonatal care in underserved areas [18].
The discussion underlines that academic institutions have the central responsibility to guide the development of research efforts in FCC for NICUs. University of Turku publishes 64 papers and can be recognised as the leader in FCC research, while constantly active in this field since 2017. Research like Weber et al. (2022) established an important position in supporting FCC practices that include parents’ engagement as well as neonatal well-being [19]. Likewise, over 58 publications produced since 2013 are indicative of the University of Toronto’s commitment to growth and focus on research. However, McManus’s (2019) study explains the contribution of the FCC in enhancing emotional support [20]. Both the University of California and the University of Calgary maintain a progressive upward trend in output, which is suggestive of a purposive effort towards enhancing FCC research. Research by Vasli (2018) encourages regional and international collaboration, following research based on FCC’s cultural adaptation in various places [21]. They also show that the promotion of FCC mattresses is part of the global academic efforts aimed at the development of FCC knowledge.
Author productivity in FCC research aligns with Lotka’s Law, where a few prolific authors contribute significantly. Axelín A leads with 28 articles, followed by Lehtonen L with 24 and an H-index of 17, indicating both quantity and quality. Most authors have only one publication, while a few, like Feeley N and Latour JM, show high impact with moderate output. This concentrated pattern mirrors other specialized fields, highlighting the value of both prolific and occasional contributors for advancing and diversifying FCC research [22, 23].
The findings also demonstrate that key authors in FCC research are both productive and influential throughout time, a mix of prolific and steady researchers. Axelíń A and Lehtonen L have grown to a great extent publications representing leaders in the field. Contributions by authors Franck LS and Latour JM contribute to keeping steady in spite of time and leave us with the sense that the contributions remain sustained at this commitment level to keep advancing FCC knowledge. However, Chen et al. (2019) study analysed how high-impact and cooperative authors contribute to nurturing innovation and keep up research growth in particular narrow subject areas [24]. The findings emphasize the central role of core journals in the field of family-centered neonatal care research outlined by Bradford’s Law. Their H-index shows high productivity and impact, and the field is driven by leading journals such as Advances in Neonatal Care, which pump out high output and influence. This is consistent with Scher’s (2024) finding, where a small set of key journals dominate in determining the area in which the academics work [25]. The Journal of Neonatal Nursing and Journal of Perinatal and Neonatal Nursing have provided consistently as foundational resources in the care of the neonatal child, advancing clinical and interdisciplinary advancements.
Conclusion
It summarizes the rise of the FCC in NICU over the past 25 years and its results in improving neonatal outcomes and family wellbeing. The result of the bibliometric analysis was a steady increase in the publication of FCC papers, and the United States, Canada, and the United Kingdom being the leading contributors to the global output. Pivotal contributors on the institutional side have been the University of Turku, and on the author side, authors such as Axelín A. Foundational platforms for dissemination of critical FCC research include core journals such as the Advances in Neonatal Care and the Journal of Neonatal Nursing and specialized journals that address niche areas. Keywords that appear most are “female” and “infant,” indicative of research areas in family and neonatal health. The importance of the FCC highlights the global significance of interdisciplinary perspectives and the growing global collaborations. However, research efforts are not equally equitable (i.e., underrepresented regions, disparities in contributions), and so on. This dynamic field is changing, heralding new, innovative, more inclusive ways to provide neonatal care.
Limitation
This study has several limitations. First, relying solely on the Scopus database may have excluded relevant studies from other sources or non-English publications. Second, while the analysis covers 2000–2025, data for recent years may be incomplete, and older records could be underrepresented. Third, the findings likely overrepresent high-income countries and English-language research, limiting global generalizability.
Additionally, fixed search terms like “family-centered care” may have missed studies using alternative terminology. Citation-based metrics also favor established works, potentially overlooking emerging or niche research. While bibliometrics reveal publication trends, they do not assess study quality or clinical applicability. Finally, the focus on prolific authors and institutions may underrepresent smaller contributors.
Despite these constraints, this analysis offers valuable insights into FCC research evolution. Future studies should incorporate multiple databases, broader language inclusion, and qualitative methods to strengthen findings.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Aljawad B, Miraj SA, Alameri F, Alzayer H. Family-centered care in neonatal and pediatric critical care units: a scoping review of interventions, barriers, and facilitators. BMC Pediatr. 2025;25(1):291.
2. Strine S, Karuri S, Fry JT, Bean K, Horner S, Machut KZ. Culture of family-centered care in the NICU. Adv Neonatal Care. 2025;25(3):293-300.
3. Stovall SG, George RG, Lara MT, Gainous KO, Kitchens RF, Hilton CL. Parent perspectives of co-occupations in neonatal intensive care: a thematic review of barriers and supports. OTJR (Thorofare N J). 2025;45(3):378-87.
4. Bellizzi S, Panu Napodano CM, Murgia P. Family-centered care for newborns: a global perspective and review. J Trop Pediatr. 2024;70(5):fmae026.
5. Johnson J, Akinboyo IC, Schaffzin JK. Infection prevention in the neonatal intensive care unit. Clin perinatol. 2021;48(2):413-29.
6. Tapia Illanes JL, Toso Milos P, Kattan Said J. Respiratory diseases in the newborn. Pediatric Respiratory Diseases: A Comprehensive Textbook. 2020:355-371.
7. Lee J. Neonatal family-centered care: evidence and practice models. Clin Exp Pediatr. 2023;67(4):171.
8. Kim AR, Tak YR, Shin YS, Yun EH, Park H-K, Lee HJ. Mothers’ perceptions of quality of family-centered care and environmental stressors in neonatal intensive care units: predictors of and relationships with psycho-emotional outcomes and postpartum attachment. Matern Child Health J. 2020;24:601-11.
9. Zhang Sw, Hua W, Li Ll, Cao Y, Hu Xj. Medical staff’s sentiments on the establishment of quiet time in the NICU. J Nurs Manag. 2022;30(7):3599-607.
10. Kutahyalioglu NS, Scafide KN, Mallinson KR, D’Agata AL. Implementation and Practice Barriers of Family-Centered Care Encountered by Neonatal Nurses. Adv Neonatal Care. 2022;22(5):432-43.
11. Garner RM, Hirsch JA, Albuquerque FC, Fargen KM. Bibliometric indices: defining academic productivity and citation rates of researchers, departments, and journals. J Neurointerv Surg. 2018;10(2):102-6.
12. Hossain R, Ibrahim RB, Hashim HB. Automated brain tumor detection using machine learning: a bibliometric review. World Neurosurg. 2023;175:57-68.
13. Roldan-Valadez E, Salazar-Ruiz SY, Ibarra-Contreras R, Rios C. Current concepts on bibliometrics: a brief review about impact factor, Eigenfactor score, CiteScore, SCImago Journal Rank, Source-Normalised Impact per Paper, H-index, and alternative metrics. Ir J Med Sci. 2019;188(3):939-51.
14. Xue H. Temporal evolution of Bradford curves in academic library contexts. Publications. 2024;12(4):36.
15. Kokorelias KM, Gignac MA, Naglie G, Cameron JI. Towards a universal model of family-centered care: a scoping review. BMC Health Serv Res. 2019;19(1):1-11.
16. Butler AE, Ridgway L, Henderson EM, Hokke S, Edvardsson K, Adams C, et al. Family-centred care research in paediatrics: a scoping review. J Child Health Care. 2025;29:13674935251337492.
17. Franck LS, Axelin A, Van Veenendaal NR, Bacchini F. Improving neonatal intensive care unit quality and safety with family-centered care. Clin Perinatol. 2023;50(2):449-72.
18. Sigurdson K, Profit J, Dhurjati R, Morton C, Scala M, Vernon L, et al. Former NICU families describe gaps in family-centered care. Qual Health Res. 2020;30(12):1861-75.
19. Weber A, Kaplan H, Voos K, Elder M, Close E, Tubbs-Cooley H, et al. Neonatal nurses’ report of family-centered care resources and practices. Adv Neonatal Care. 2022;22(5):473-83.
20. McManus BM, Murphy N, Richardson Z, Khetani MA, Schenkman M, Morrato EH. Family-centered care (FCC) in early intervention (EI): Examining caregiver perceptions of FCC and EI service Use intensity. Child Care Health Dev. 2019;46(1):1.
21. Vasli P. Translation, cross-cultural adaptation, and psychometric testing of perception of family-centered care measurement questionnaires in the hospitalized children in Iran. J Pediatr Nurs. 2018;43:e26-e34.
22. Raman R, Lathabhai H, Pattnaik D, Kumar C, Nedungadi P. Research contribution of bibliometric studies related to sustainable development goals and sustainability. Discover Sustainability. 2024;5(1):7.
23. Hu Y, Xiao Y, Hua Y, Fan Y, Li F. The more realism, the better? How does the realism of AI customer service agents influence customer satisfaction and repeat purchase intention in service recovery. Behav Sci (Basel). 2024;14(12):1182.
24. Chen K, Zhang Y, Fu X. International research collaboration: An emerging domain of innovation studies? Research Policy. 2018;48(1):149-68.
25. Scher MS. Interdisciplinary fetal-neonatal neurology training improves brain health across the lifespan. Front Neurol. 2024;15:1411987.
Download attachments: 10.4328.ACAM.22755
Mustafa Törehan Aslan, Mehmet Semih Demirtas. Trend analysis of family-centered care in the neonatal intensive care unit (NICU): A bibliometric study. Ann Clin Anal Med 2025;16(7):525-529
Citations in Google Scholar: Google Scholar
Evaluation of inflammatory markers and HALP score in childhood intussusceptions
Mustafa Tuşat 1, Sebahattin Memiş 2
1 Department of Pediatric Surgery, 2 Department of Pediatrics, Faculty of Medicine, Aksaray University, Aksaray, Turkey
DOI: 10.4328/ACAM.22763 Received: 2025-05-31 Accepted: 2025-06-30 Published Online: 2025-06-30 Printed: 2025-07-01 Ann Clin Anal Med 2025;16(7):530-534
Corresponding Author: Mustafa Tuşat, Department of Pediatric Surgery, Faculty of Medicine, Aksaray University, Aksaray, Turkey. E-mail: mustafatusat42@hotmail.com P: +90 382 520 10 20 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2327-4250
Other Authors ORCID ID: Sebahattin Memiş, https://orcid.org/0000-0002-3829-9218
This study was approved by the Ethics Committee of Aksaray University Health Sciences Scientific Research (Date: 2024-09-05, No:2024/082)
Aim: Intussusception is the most common abdominal emergency in infancy. This study aims to determine whether HALP score and inflammatory markers scores, such as NLR and PLR, differ between cases requiring surgical reduction and those not requiring surgical reduction in patients diagnosed with intussusception who presented to the pediatric emergency department.
Material and Methods: Our study included 78 children diagnosed with intussusception who presented to the Aksaray Training and Research Hospital Pediatric Emergency Department between January 1, 2018, and September 31, 2024. The cases were divided into two groups based on their treatment method: surgical and non-surgical.
Results: When comparing the groups, a significant difference was found for all three markers (p<0.0001) in terms of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and HALP score. However, no statistically significant difference was detected for C-reactive protein levels (p=0.095).
Discussion: NLR, PLR, and HALP scores can be utilized as useful markers in evaluating the prognosis of childhood intussusception. The effectiveness of these biomarkers should be validated by future studies.
Keywords: Invagination, Neutrophil/lymphocyte Ratio, Platelet/lymphocyte Ratio, HALP Score
Introduction
Intussusception, a significant cause of acute abdominal emergencies in children, is defined as the telescoping of a proximal bowel segment into a distal one [1]. If left untreated, it disrupts the circulation to the bowel wall, leading to intestinal obstruction, venous congestion, and edema. This can further progress to necrosis, perforation, and shock, [2]. While intussusception primarily affects children under three years of age, it is most commonly observed between five and nine months of age, [3].
While most cases of intussusception in children are idiopathic, approximately 5% of cases have a pathological lead point initiating the intussusception, such as a Meckel’s diverticulum, duplication cyst, intestinal polyps, cystic fibrosis, lymphoma, or lymphadenopathy [4].
While asymptomatic transient ileoileal or jejunal intussusceptions often resolve with conservative observation, symptomatic ileocolic intussusceptions in hemodynamically stable patients are primarily managed with pneumatic or hydrostatic reduction. Surgical manual reduction is reserved for cases where intussusception persists after these interventions or when there are signs of generalized peritonitis, perforation, or shock [5].
In recent years, easily measurable markers like the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to indicate the severity of systemic inflammation and correlate with prognosis in various infectious and inflammatory conditions [6-9]. Recent studies have indicated that the HALP score can serve as a prognostic factor in malignancies affected by inflammation and nutrition. This is attributed to anemia occurring in inflammatory processes, weakened immunity, and severe infections, alongside decreased albumin (a negative acute phase reactant), reduced lymphocyte count, and elevated platelet count [9-11].
In our study, we aim to determine if there is a difference in NLR, PLR, and HALP scores between cases of childhood intussusception requiring surgical manual reduction and those not undergoing surgical treatment. By doing so, we intend to evaluate the effectiveness of these inflammatory markers in predicting the need for surgical manual reduction.
Material and Methods
Study design
Our study was conducted as a retrospective descriptive cohort study. We included 78 children under 18 years of age who presented to the Aksaray University Training and Research Hospital pediatric emergency department with a diagnosis of intussusception and were subsequently followed and treated between January 1, 2018, and September 31, 2024. Children who had previously presented with intussusception, those with an unclear radiological type of intussusception, and those with chronic diseases were excluded from the study.
Data collection
Patient data were obtained from files. The included patients were divided into two distinct groups: a non-surgical group, comprising those treated with conservative observation or hydrostatic reduction, and a surgical group, consisting of patients who did not respond to hydrostatic reduction or presented with signs of generalized peritonitis, perforation, or shock, subsequently undergoing surgical manual reduction.
For each case, sex, age, prominent complaint at admission (abdominal pain, vomiting, bloody stools, diarrhea), season of admission, ultrasonographically measured length and type of the intussuscepted segment, and C-reactive protein (CRP) level at admission were recorded.
NLR (Neutrophil/Lymphocyte Ratio), PLR (Platelet/Lymphocyte Ratio), and the HALP score [(Hemoglobin (g/L) x Albumin (g/L) x Lymphocyte count (n/L) / Platelet count (n/L)] were evaluated at admission. Additionally, in the surgical group, these inflammatory markers were re-evaluated on postoperative day 3, [12].
Statistical analysis
IBM SPSS (Statistical Package for the Social Sciences) 23 for Windows was used for the statistical analysis of the research data. The Kolmogorov-Smirnov test and skewness and kurtosis values, which are other assumptions of normal distribution, were used for normality tests of numerical variables. Comparisons between two independent groups were analyzed using the Mann-Whitney U test, and comparisons between two dependent groups were analyzed using the Wilcoxon signed-rank test. For descriptive statistics, the median (25-75 Interquartile Range) was used for non-normally distributed data, and numbers and percentages were used for categorical variables. Chi-square and Fisher’s Exact tests were used to analyze categorical data. Significance was evaluated based on p < 0.05 for each variable.
Ethical approval
This study was approved by the Ethics Committee of Aksaray University Health Sciences Scientific Research (Date: 2024-09-05, No:2024/082).
Results
The study included 78 patients, of whom 37.2% (n=29) were female and 62.8% (n=49) were male, and no significant difference was observed between the groups in terms of gender (p=0.684). The median age (25-75IQR) of the patients at the time of admission was 19.0 (13.0-39.75) months, which was 35.0 (13.75-58.50) in the surgical group and 16.5 (12.25-31.0) in the non-surgical group, and age was found to be significantly higher in the surgical group (p=0.01) (Table 1). While 71.7% of cases with age ≤3 were treated non-surgically, 60.2% of cases with age >3 underwent surgical reduction, and this difference was found to be statistically significant (p=0.012).
It was observed that 33.3% (n=26) of the cases presented to the hospital in winter, 30.8% (n=24) in autumn, 24.4% (n=19) in spring, and 11.5% (n=9) in summer. No significant difference was found when comparing the groups based on season (p=0.349).
When evaluating the prominent complaints of patients upon admission to the emergency department, it was found that 25% (n=6) of cases presenting with abdominal pain, 90% (n=9) of cases presenting with bloody stools, 47.8% (n=11) of cases presenting with vomiting, and 21.1% (n=4) of cases presenting with diarrhea underwent surgical reduction. A statistically significant difference was observed between the groups in this comparison (p=0.001) (Table 1).
When evaluating the groups based on the ultrasound-detected intussusception type, colocolic and jejunojejunal intussusceptions were not observed in the surgical group. However, 10.3% (n=3) of ileoileal intussusceptions and 60% (n=27) of ileocolic intussusceptions required surgical intervention, with a significant difference found when comparing the groups (p<0.001) (Table 1). Regarding the ultrasonographically measured intussuscepted segment length, the median (25-75 IQR) length in the surgical group was 48 (40-61.25) mm, compared to 20 (15-30) mm in the non-surgical group, a statistically significant difference (p<0.001) (Table 1).
The median (25-75 IQR) CRP level was 9.88 (2.41-21.39) in the surgical group and 3.55 (0.60-14.55) in the non-surgical group, with no significant difference observed between the groups (p=0.095). The median (25-75 IQR) NLR was 5.50 (4.33-7) in the surgical group and 2.01 (1.35-2.52) in the non-surgical group. The median (25-75 IQR) PLR was 203.37 (168.75-250.79) in the surgical group and 101.72 (72.95-131.69) in the non-surgical group. The median (25-75 IQR) HALP score was 2.44 (1.85-3.23) in the surgical group and 5.58 (4.28-7.37) in the non-surgical group. A statistically significant difference was found for all three markers (NLR, PLR, and HALP score) when comparing the groups (p<0.001) (Table 1). Furthermore, in the surgical group, the median (25-75 IQR) NLR on postoperative day 3 was 1.79 (1.63-1.89), the PLR was 109.71 (91.53-121.50), and the HALP score was 4.01 (3.34-5.15). Consequently, a statistically significant difference was observed for all three markers when comparing their values at admission and on postoperative day 3 (p<0.001) (Table 2).
Discussion
In our study, we found that children diagnosed with intussusception who underwent surgical manual reduction had significantly lower NLR and PLR values and a significantly higher HALP score at admission (p<0.001). Furthermore, we observed that CRP levels, which are commonly used for monitoring and prognosis in numerous inflammatory, infectious, and tissue damage conditions [13, 14], were ineffective in predicting the need for surgical manual reduction (p=0.095).
It is generally reported that hematological parameter combinations such as NLR and PLR, calculated from a complete blood count, can be used as biomarkers to predict prognosis in many infectious and inflammatory conditions. This is due to the increase in neutrophil count in the blood and the rise in platelets, which are effective in regulating various inflammatory states in the presence of a systemic infection or inflammatory response [6-8, 12]. In a study of 115 patients who underwent surgical operations for intussusception, with 47 of these cases involving resection, a comparison between the resection and non-resection groups revealed significantly higher NLR and PLR values in the group that underwent resection. This difference was found to be statistically significant, [15]. A retrospective study evaluating the accuracy of NLR in predicting the differentiation between complicated and non-complicated appendicitis, which assessed 81 adult appendicitis cases, reported that an NLR > 7 served as a specific and predictive marker for complicated appendicitis [6]. Another study that evaluated 61 mild and 26 moderate pancreatitis cases found that PLR and NLR values were higher in moderate pancreatitis cases. Statistical analysis revealed a significant difference between the two groups for both NLR and PLR, indicating that NLR and PLR have a discriminatory effect in these cases, [7]. In another study that included 291 appendicitis and 101 control pediatric cases, analysis between the appendicitis and control groups revealed that the NLR value was significantly higher in the appendicitis group. Furthermore, it was reported that the NLR value was significantly higher in children with gangrenous appendicitis compared to those with acute appendicitis [16]. In our study, we found that both PLR and NLR values were significantly higher in the surgical group. We attribute this to more intense ischemia in the intussuscepted segment, leading to the release of more inflammatory factors into the bloodstream. Additionally, we observed a significant decrease in PLR and NLR values on postoperative day 3 in the surgical group compared to their preoperative values (p<0.001).
Research indicates that hematological markers such as albumin, hemoglobin, lymphocytes, and platelets are associated with inflammation or nutritional status. These markers can effectively predict prognosis in inflammatory, infectious, and malignant conditions, [9-11, 17]. A study including 684 cases diagnosed with acute appendicitis reported that the incidence of gangrene, perforation, periappendicular abscess, and postoperative complications was significantly increased in the group with a low HALP score compared to the group with a high HALP score. [11]. In a study evaluating 213 cases in the emergency department, although no statistical significance was found when comparing groups based on albumin, hemoglobin, lymphocyte, and platelet levels, it was reported that patients who underwent surgery due to ileus had significantly lower HALP scores. [18]. In another study that evaluated a total of 436 appendicitis cases, comprising 126 complicated and 310 non-complicated instances, it was reported that the HALP score was significantly lower in the complicated appendicitis group and that the preoperative HALP score could be used to predict the diagnosis [9]. In our study, the median (25-75 IQR) HALP score was found to be 2.44 (1.85-3.23) in the surgical group, while it was 5.58 (4.28-7.37) in the non-surgical group, indicating a significantly lower score in the surgical group (p<0.001). This finding suggests its effectiveness in predicting the need for treatment. We believe this difference is a result of the metabolic response to severe inflammation caused by the compression of the intussuscepted segment in cases requiring surgery.
Studies conducted on children diagnosed with intussusception have identified a positive correlation between the increasing age of the cases and the need for surgical treatment, [19, 20]. A study including 153 intussusception cases in children under 12 years of age reported that the probability of a pathological lead point is very high in children over 5 years old, and early surgical intervention should be considered in these children, [21]. In our study, we also found that age was significantly higher in cases in the surgical group compared to the non-surgical group (p=0.01). We observed that 71.7% of cases aged $\le$3 years were treated non-surgically, whereas 60.2% of cases aged $>$3 years underwent surgical reduction (p=0.012). We believe this is related to the increased incidence of pathologies initiating intussusception with advancing age.
It has been reported that the length of the intussusception segment and the presence of currant jelly stools are effective factors that increase the likelihood of surgical reduction in children with intussusception [19, 20, 22]. In a study investigating successful factors for non-surgical reduction in 99 children diagnosed with intussusception, the average length of the intussuscepted segment in cases requiring surgical treatment was found to be 7.9 cm. In contrast, it was 3.5 cm in cases that underwent non-surgical reduction. A significant difference was observed between these two groups, and in univariate analysis, bloody stool was identified as an effective predictor for surgical intervention, [20]. In a study investigating factors associated with surgical treatment in 106 children with ileoileal and ileocolonic intussusception, it was reported that the length of the intussuscepted segment > 3.5 mm (p= 0.042) and strawberry jelly stool were effective in predicting surgery in the surgical treatment group, [19]. In our study, we also found that 9 out of 10 patients presenting with bloody stools required surgical treatment. Furthermore, the median (25-75 IQR) length of the intussuscepted segment was 48 (40-61.25) mm in the surgical group compared to 20 (15-30) mm in the non-surgical group, a statistically significant difference (p<0.001). We attribute this to the more intense ischemia resulting from obstruction within the longer intussuscepted segment in the surgical group.
Limitation
The main limitations of our study are the retrospective study design and the limited number of cases.
Conclusion
In the treatment of intussusception, early diagnosis and appropriate treatment are vitally important in reducing mortality and morbidity. Alongside ultrasonography, a thorough evaluation of physical examination and clinical findings continues to play a significant role in guiding treatment. Furthermore, NLR, PLR, and HALP scores may contribute to clinical and ultrasonography findings in predicting intussusception cases that require surgical intervention.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Guo H, Lei H, Luo J, Yang J, Bian H, Yang H, Guo Q. Clinical manifestation and treatment of intussusception in children aged 3 months and under: a single centre analysis of 38 cases. BMC pediatrics. 2025:26;25(1):233.
2. Shavit I, Levy N, Dreznik Y, Soudack M, Cohen DM, Kuint RC. Practice variation in the management of pediatric intussusception: a narrative review. Eur J Pediatr.2024;183(11):4897-904.
3. Li Y, Zhou Q, Liu C, Sun C, Sun H, Li X et al. Epidemiology, clinical characteristics, and treatment of children with acute intussusception: a case series. BMC pediatr. 2023;23(1):143.
4. Qian Y, Guo W. Development and validation of a deep learning algorithm for prediction of pediatric recurrent intussusception in ultrasound images and radiographs. BMC Med Imaging. 2025;25(1):67.
5. Wang S,Wang Y, Jia L, Wang X. Transient and persistent small-bowel intussusception in children: a decision tree analysis model based on ultrasound and clinical findings.BMC Gastroentero.2025;25(1):294
6. Ali A, Khan GY, Khan MN, Hassan M, Razaq N. Evaluating the diagnostic accuracy of the neutrophil-to-lymphocyte ratio in acute appendicitis: a distinction between complicated and uncomplicated presentations. Thermsr. 2025;3(1):1085-91.
7. Akoglu EU, Ozdemir S, Ak R, Ozturk TC. The discriminative power of inflammatory markers in patients with mild-to-moderate acute pancreatitis: mean platelet volume, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and neutrophil-monocyte product. South Clin Istanb Eurasia. 2021;32(2):159-65.
8. Yin Q, Yin J, Shen L, Zhou Q, Xu W. The early diagnostic value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in neonatal late-onset sepsis. Front Pediatr.2025;13:1483522.
9. Saridas A, Vural N, Duyan M, Guven HC, Ertas E, Cander B. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis. Open Med. 2024;19(1):20241002.
10. Xu H, Zheng X, Ai J, Yang L. Hemoglobin, albumin, lymphocyte, and platelet (HALP) score and cancer prognosis: A systematic review and meta-analysis of 13,110 patients. Int Immunopharmacol.2023;114:109496.
11. Benli S, Tazeoğlu D. The efficacy of hemoglobin, albumin, lymphocytes, and platelets (HALP) score in signifying acute appendicitis severity and postoperative outcomes. Updates Surg. 2023;75(5):1197-202.
12. Demirtas MS, Memis S, Kocagozoglu SG. Evaluation of hemoglobin, albumin, lymphocyte, and platelet score, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in pediatric patients with rotavirus enteritis. J Clin Pract Res. 2025;47(1):28-35.
13. Ural DA, Karakaya AE, Güler AG, Yalçın HS, Tuşat M. Comparative analysis of the acute appendicitis management in children before and during the coronavirus disease-19 pandemic. KSU Med J. 2023;18(1):120-5.
14. Plebani M. Why C-reactive protein is one of the most requested tests in clinical laboratories?. CCLM. 2023;61(9):1540-5.
15. Chen B, Cao J, Yan C, Zheng C, Chen J, Guo C. A promising new predictive factor for detecting bowel resection in childhood intussusception: the lymphocyte-C-reactive protein ratio. BMC pediatr.2021;21(1):577
16. Duran İ, Avci V, Nazik S, Altun E. Neutrophile lymphocyte ratio and platelets lymphocyte ratio in the diagnosis of childhood appendicitis. J Turk Cli Biochem. 2017;15(1):1-7.
17. Tuşat M, Özmen İ, Demirtaş MS, Ateş C, Öztürk AB, Kankılıç NA, et al. Risk factors for mortality and morbidity in Syrian refugee children with penetrating abdominal firearm injuries: an 1-year experience. TJTES.2023;29(9):1051.
18. Çetinkaya HB, Çay F. Usefulness of hemoglobin, albumin, lymphocyte and platelet (HAKP) score in determining the need for surgery in ileus patients in the emergency department: hemoglobin, albumin, lymphocyte and platelet (HALP) score. Chron Precis Med Res. 2023;4(3):414-7.
19. Peyvasteh M, Askarpour S, Ghanavati M, Javaherizadeh H. Factors associated with surgical treatment in pediatric intussusception. Wien Med Wochenschr.2022;172(13):313-6.
20. Issa K, Ali W, AL-Abbas B. Factors associated with success of sonographically guided hydrostatic reduction of ileocolic intussusception in children. SN Compr Clin Med. 2021;3(1):242-6.
21. Banapour P, Sydorak RM, Shaul D. Surgical approach to intussusception in older children: influence of lead points. J Pediatr Surg. 2015;50(4):647-50.
22. Alsinan T, Altokhais T, Alshayeb F, Hajja A, Boukai MA, Alsalameh S, et al. Risk factors for failure of enema reduction of intussusception in children. Sci Rep. 2024;14(1):20786.
Download attachments: 10.4328.ACAM.22763
Mustafa Tuşat, Sebahattin Memiş. Evaluation of inflammatory markers and HALP score in childhood intussusceptions. Ann Clin Anal Med 2025;16(7):530-534
Citations in Google Scholar: Google Scholar