August 2025
What impact does therapy selection have on the course of clinical outcomes for recurrent gliomas?
Oğuzcan Özkan, Aslı Geçgel, Fatma Pınar Açar, Burçak Karaca, Ulus Ali Şanlı
Department of Medical Oncology, Ege University Hospital, İzmir, Turkey
DOI: 10.4328/ACAM.22208 Received: 2024-03-31 Accepted: 2024-06-12 Published Online: 2025-02-25 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):535-538
Corresponding Author: Aslı Geçgel, Department of Medical Oncology, Ege University Hospital, İzmir, Turkey. E-mail: dr.asltrgt@gmail.com P: +90 553 239 14 49 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6942-9858
Other Authors ORCID ID: Oğuzcan Özkan, https://orcid.org/0000-0002-4075-7775 . Fatma Pınar Açar, https://orcid.org/0009-0000-2749-8732 . Burçak Karaca, https://orcid.org/0000-0003-2638-1625 . Ulus Ali Şanlı, https://orcid.org/0000-0002-0062-6105
This study was approved by the Ethics Committee of Ege University, Faculty of Medicine (Date: 2024-02-20, No: 2024-2393)
Aim: The aim of this study is to investigate the effectiveness of systemic treatments in patients with recurrent glioblastoma (GBM), and to assess their impact on overall survival (OS) and progression-free survival (PFS). Despite multimodal treatment approaches, GBM remains a challenging malignancy, and this study aims to contribute to understanding the treatment outcomes and factors influencing prognosis.
Materials and Methods: Twenty patients with recurrent gliomas were included in the study out of the 133 patients who had a glioma diagnosis between 2015 and 2021.
Results: Relapses occurred on average after 30.1 (range: 5.7-182.6) months. The average patient age upon diagnosis was 51 (range: 24-68). Males made up 65% of the patients. Systemic treatment was given to 17 individuals (85%). 70.5% of patients preferred the bevacizumab+irinotecan (BEV+IRI) regimen as their first-line treatment. Carmustine (5.5%) and temozolomide rechallenge (23.5%) were the other regimens. Patients who underwent systemic treatment following a relapse had an average overall survival of 8.1 months. 53.8% was the 6-month OS for patients following recurrence.
Discussion: Consequently, these patients have low systemic treatment effectiveness. The influence of the proposed treatment on performance status and quality of life should be taken into account, regardless of the severity of the disease. A less risky regimen or active surveillance may be beneficial for patients with gliomas that do not show targetable pathological alterations, as there was no statistically significant difference seen when progression-free survival lengths were evaluated.
Keywords: Glioma, Recurrence, Systemic Therapy, Overall Survival, Chemotherapy
Introduction
In oncology, gliomas are among the malignancies with the worst prognoses. Even with the current treatments recommended in the guidelines, the average survival for high-grade gliomas is 15 months, and the 2-year survival rate is 26-33% [1]. To optimize the treatment protocol, a deeper comprehension of the cellular, molecular, and intercellular pathophysiology of gliomas is needed. There are several different treatment choices available at the moment of diagnosis, including radiation, chemotherapy, and surgical resection [2]. Despite ongoing research efforts to devise novel therapeutic approaches, aggressive, treatment-resistant recurrences of original glioblastomas are the inevitable outcome. Research has been done to determine whether and how therapies affect the molecular characteristics, growth pattern, and intratumoral heterogeneity of glioblastoma, as well as the degree to which this knowledge can be applied to therapeutic decision-making [3, 4]. We shared the post-recurrence treatments and survival analyses of our clinic’s glioma patients because we wanted to add to the body of knowledge on the management and therapy protocol for these uncommon malignant brain tumors.
Materials and Methods
Patients treated at our hospital who were diagnosed with gliomas were the subjects of a retrospective investigation. Twenty patients with recurrent gliomas were included in the study out of the 133 patients who had a glioma diagnosis between 2015 and 2021. Information was gathered from the patient’s records and documentation. Inclusion criteria: being over 18 years of age and being diagnosed with recurrent glioma. Exclusion criteria: Being a pediatric case under the age of 18 and having accompanying secondary malignancies. Analysis was done on the patient’s age, operation status, date of recurrence, pathological characteristics, status of reoperation and reirridation, and systemic treatments received following recurrence. Progression-free survival (PFS) was determined using the date on which patients made treatment-related progress; overall survival (OS) was computed using the date of the final follow-up, or ex-date. Pathological aspects of the tumor were EGFR, IDH mutation, grade, and histology. After revision, the data were tallied and examined. The data were analyzed with the SPSS 22 software, and a p value below 0.05 was considered significant.
Ethical Approval
This study was approved by the Ethics Committee of Ege University, Faculty of Medicine (Date: 2024-02-20, No: 2024-2393).
Results
The study comprised 20 patients with recurrent gliomas. 65% of the patients were male. Relapses occurred on average after 30.1 (mean±SD (%95 Cl): 45,25±12.78; range: 5.7-182.6) months. The average patient age upon diagnosis was 51 (mean±SD (%95 Cl) 47,38±12,98; range: 24-68). Males made up 13 (65%) of the patients. The local treatments that patients received after recurrence are summarized in Figure 1. Grade 4 histology was present in 11 (55%) of the patients with glioblastoma multiforme. 4 (20%) had grade 3 anaplastic astrocytomas. Among them, IDH mutations made up 8 (40%). 11 patients (55%) underwent additional surgery. Six patients (30%) underwent reirradiation. Three individuals (15%) tested positive for an EGFR mutation; these patients were considered for treatment with nimotuzumab. 2 patients (10%) had a 1p19q deletion. Grade 4 tumors were found in 11 (55%) of patients, grade 3 tumors in 4 (20%), and grade 2 tumors in 3 (15%) of patients. The pathological and clinical characteristics of patients are summarized in Table 1.
Systemic treatment was given to 17 (85%) individuals. 12 (70.5%) patients preferred the bevacizumab+irinotecan (BEV+IRI) regimen as their first-line treatment. 1 patient (5.5%) received carmustine, and 4 patients (23.5%) received temozolomide rechallenge; the rest were other regimens (Figure 2). Patients on BEV+IRI in the first line had an average PFS of 5.82 months. Four patients who received temozolomide challenge as first-line treatment had an average progression-free survival of six months. After receiving carmustine as the initial line of treatment, one patient made progress in 3.1 months. The mean PFS of treatments given in the first line are summarized in Table 2. Carmustine was moved to the second line following BEV+IRI in 2 patients, and the average PFS was determined to be 3.7 months. On the third line, nimotuzumab was started for one patient; nevertheless, the patient’s PFS was only one month. Patients who underwent systemic treatment following a relapse had an average overall survival of 8.1 months. 53.8% was the 6-month OS for patients following recurrence.
Discussion
Treatment selection for recurrent GBM is a clinical problem that requires consideration of multiple aspects. Nearly all GBM patients are predicted to experience tumor recurrence; yet, very few salvage therapies have shown any efficacy thus far [4]. This challenge results from confounding variables in imaging and molecular heterogeneity, which is believed to be treatment-related as well as spontaneous [4, 5]. Certain individuals may just need supportive care or systemic medications, even if locoregional therapies may be the best course of action in certain situations. Reoperation and reirradiation, along with systemic treatments like procarbazine, vinca alkaloids (vincristine), nitrosoureas (carmustine/lomustine/fotemustine), platinums, topoisomerase inhibitors (irinotecan/etoposide), antiangiogenic bevacizumab, and their combinations, are all used to treat recurrent GBM [6]. Regorafenib is a small-molecule tyrosine kinase inhibitor with inhibitory efficacy against numerous targets implicated in tumor angiogenesis and oncogenesis. It can be administered to patients with recurrent glioblastoma as a first-line systemic treatment. Regorafenib significantly improved OS compared to the lomustine group in phase 2 research that was carried out in Italy and examined the efficacy of the drug in patients with recurrent glioblastoma (OS of 7•4 months (95% CI 5•8-12•0) (7). As with non-small cell lung cancer (targeting mutations like ALK and EGFR) and breast cancer (targeting HER2 overexpression), individualized treatment trials are still in progress. NTRK inhibitors when adult gliomas have fusions of the NTRK gene; the guidelines cover the use of entrectinib and larotrectinib [7, 8]. BRAF+Mek inhibitors Vemurafenib/cobimetinib and Dabrafenib/trametinib are utilized when the BRAF V600E mutant is present [9, 10]. There were no patients using targeted agents in our study. Before beginning normal systemic therapy for recurring diseases, it is crucial to assess clinical studies. Survival is still poor even after recurrent GBM is removed, and there isn’t any evidence to support the idea that surgery is any more beneficial than reirradiation and/or salvage chemotherapy. Resection covering more than 80% of the recurrent GBM volume resulted in an OS advantage (19 months), according to a retrospective study [11]. According to prospective research, individuals with recurrent illnesses who underwent several microsurgical resections had a greater overall survival (OS) than patients who started systemic medication without surgery [12].
Reirradiation is now a viable treatment option for patients with brain tumors due to advancements in radiotherapy technology. This is especially true for patients with recurrent GBM. There is insufficient data on the utilization of reirradiation with bevacizumab (BEV), temozolomide (TMZ) rechallenge, or immune checkpoint inhibition (ICI) therapy [13]. When compared to radiation alone, concurrent radiotherapy and/or adjuvant therapy with TMZ produced prolonged OS and PFS durations; however, this was typically restricted to MGMT-methylated tumors [14, 15]. There was no discernible survival advantage in certain investigations [16, 17]. Roughly 90% of WHO grade IV gliomas (GBM) will recur locally within 2 years, despite rigorous management that involves maximally safe surgical resection followed by external beam radiation therapy (60 Gy/30 fractions) with concurrent and adjuvant TMZ. Numerous studies have demonstrated that patients with recurrent GBM who receive stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) with the help of hypofractionated or conventionally fractionated schedules have an increased chance of survival after reirradiation. Nevertheless, questions remain regarding the safety and efficacy of a second radiation course. In one trial, both treatment modalities had a comparable median overall survival and a comparatively low toxicity profile, lasting between six and twelve months [13]. According to international standards, young patients with good performance status who have progressive or recurrent GBM should be considered for reirradiation, particularly if it has been a long time since previous radiation therapy [4]. Patients who got reirradiation in our study ranged in age from 37 to 68 years old, with an average PFS of 4.6 months. Three patients received BEV+IRI following progression, two patients received TMZ rechallenge, and one patient received carmustine.
The possible superiority of concurrent/adjuvant systemic therapy plus reirradiation over systemic therapy alone is another crucial question that needs to be answered. Tsien et al. assessed the safety and effectiveness of bevacizumab alone versus hypofractionated SRT and concurrent bevacizumab in a phase II randomized study involving 182 patients with recurrent GBM. The patients who received combined therapy had an equivalent duration of 10.1 months, while those who received bevacizumab alone had a duration of 9.7 months. observed median survival duration; yet, a superior 6-month progression-free survival was linked to combination treatment [3]. Since 2009, BEV has been the accepted salvage therapy for individuals with recurrent GBM [14]. Because of its generally low toxicity profile and strong blood-brain barrier penetration, temozolomide is widely utilized as rescue therapy. PFS for recurrent GBM is approximately 15.5 months on average [18]. The PFS of patients receiving first-line TMZ in our trial was found to be 6 months, which was less than expected. It’s possible that because this regimen is recommended for patients with grade 3 and lower grades, the PFS of patients undergoing TMZ rechallenge is longer than that of patients receiving BEV + IRI.
The most important limitations of our study were the small number of patients receiving systemic treatment after relapse and the limited number of patients receiving targeted treatment.
Limitation
The low number of recurrent patients is a limitation of our study because the nature of the disease results in short survival.
Conclusion
As a result, systemic treatment effectiveness is poor for these patients. Curative outcomes are rare with treatment. The impact of the proposed treatment on performance status and quality of life ought to be taken into account, regardless of the severity of the disease. Evaluation of progression-free survival durations revealed no statistically significant difference between therapies; hence, individuals with gliomas that do not exhibit targetable pathological changes may benefit from active surveillance or a less hazardous regimen. Individualized treatments need to be created. Large-phase studies investigating genetic mutations are needed to develop targeted therapies.
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. Kosianova А, Pak O, Bryukhovetskiy I. Regulation of cancer stem cells and immunotherapy of glioblastoma (Review). Biomed Rep. 2023;19;20(2):24.
2. Yu MW, Quail DF. Immunotherapy for Glioblastoma: Current Progress and Challenges. Front Immunol. 2021;13;12:676301.
3. McBain C, Lawrie TA, Rogozińska E, Kernohan A, Robinson T, Jefferies S. Treatment options for progression or recurrence of glioblastoma: a network meta-analysis. Cochrane Database Syst Rev. 2021;5(1):CD013579.
4. Horbinski C, Nabors LB, Portnow J, et al. NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022. J Natl Compr Canc Netw. 2023;21(1):12-20.
5. Angom RS, Nakka NMR, Bhattacharya S. Advances in glioblastoma therapy: An update on current approaches. Brain Sci. 2023;31;13(11):1536.
6. Hundsberger T, Reardon DA, Wen PY. Angiogenesis inhibitors in tackling recurrent glioblastoma. Expert Rev Anticancer Ther. 2017;17(6):507-515.
7. Lombardi G, De Salvo GL, Brandes AA, et al. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): A multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2019;20(1):110-119.
8. Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: Integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020;21(2):271-282.
9. Bourque MS, Salek M, Sabin ND, Canale M, Upadhyaya SA. Comment on: Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib. Pediatr Blood Cancer. 2021; 68(4):e28814.
10. Kaley T, Touat M, Subbiah V, et al. BRAF ınhibition in BRAFV600-mutant gliomas: Results from the VE-BASKET study. J Clin Oncol. 2018; 10;36(35): 3477-3484.
11. Oppenlander ME, Wolf AB, Snyder LA, et al. An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. J Neurosurg. 2014; 120(4):846-53.
12. Hong B, Wiese B, Bremer M, et al. Multiple microsurgical resections for repeated recurrence of glioblastoma multiforme. Am J Clin Oncol. 2013; 36(3):261-8.
13. Minniti G, Niyazi M, Alongi F, Navarria P, Belka C. Current status and recent advances in reirradiation of glioblastoma. Radiat Oncol. 2021;18;16(1):36.
14. Friedman HS, Prados MD, Wen PY, et al. bevacizumab alone and in combination with ırinotecan in recurrent glioblastoma. J Clin Oncol. 2023; 10;41(32):4945-4952.
15. Navarria P, Minniti G, Clerici E, et al. Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO). J Neurooncol. 2019; 142(1):59-67.
16. Ali AS, Chen VE, Zurlo C, Taylor JM, Fernandez C, Shi W. Target treatment with stereotactic radiation for recurrent gliomas. Chin Clin Oncol. 2020; 9(6):74.
17. Chapman CH, Hara JH, Molinaro AM, et al. Reirradiation of recurrent high-grade glioma and development of prognostic scores for progression and survival. Neurooncol Pract. 2019; 6(5):364-374.
18. Schaff LR, Mellinghoff IK. Glioblastoma and other primary brain malignancies in adults: A review. JAMA. 2023; 21; 329(7):574-587.
Download attachments: 10.4328.ACAM.22208
Oğuzcan Özkan, Aslı Geçgel, Fatma Pınar Açar, Burçak Karaca, Ulus Ali Şanlı. What impact does therapy selection have on the course of clinical outcomes for recurrent gliomas? Ann Clin Anal Med 2025;16(8):535-538
Citations in Google Scholar: Google Scholar
This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of the license, visit https://creativecommons.org/licenses/by-nc/4.0/
Predictive role of intraoperative variables in neonatal cardiac surgery outcomes
Serife Ozalp 1, Erkut Ozturk 2
1 Department of Anaesthesiology and Reanimation, 2 Department of Pediatric Cardiology, Health Sciences University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.22505 Received: 2024-11-26 Accepted: 2025-02-04 Published Online: 2025-03-03 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):539-543
Corresponding Author: Serife Ozalp, Department of Anaesthesiology and Reanimation, Health Sciences University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey. E-mail: serife.kaplan@hotmail.com P: +90 212 909 60 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6762-895X
Other Authors ORCID ID: Erkut Ozturk, https://orcid.org/0000-0002-1762-3269
This study was approved by the Ethics Committee of Basaksehir Cam and Sakura City Hospital (Date: 2024-01-17, No: 15)
Aim: This study investigates the association of intraoperative variables, including anesthesia and cardiopulmonary bypass (CPB) durations, delta CO2 (ΔCO2), and lactate levels, with postoperative morbidity and mortality in neonates undergoing complex congenital cardiac surgery.
Materials and Methods: A retrospective analysis was conducted on 42 neonates who underwent surgery in a single center. Data on demographic characteristics, genetic anomalies, anesthesia and CPB durations, and blood gas parameters (ΔCO2 and lactate levels at entry [T0], post-CPB [T1], and intensive care unit admission [T2]) were collected. Associations between these variables and major adverse events (MAEs) or mortality were statistically analyzed.
Results: A total of 42 neonatal patients were included in the study. The median age of the patients was calculated as 0.4 ± 0.3 months. The mean weight of the sample was 3.3 ± 0.6 kg, and the median total anesthesia and CPB durations were 378.45 ± 103.67 and 116.86 ± 55.03 minutes, respectively. ΔCO2 levels at T0 were significantly associated with MAEs (p < 0.05), while elevated ΔCO2 at T0 and T1 was observed in patients who died. Total anesthesia duration was a significant predictor of both MAEs and mortality (p = 0.014). Lactate levels, however, showed no significant correlation with either MAEs or mortality at any time point.
Discussion: Prolonged anesthesia and CPB durations, along with elevated ΔCO2 levels, are key predictors of adverse outcomes in neonates undergoing cardiac surgery. Delta CO2 may serve as an additional marker for early postoperative risk stratification. Larger prospective studies are warranted to confirm these findings and improve clinical management strategies.
Keywords: Neonatal Cardiac Surgery, Delta CO2, Anesthesia Duration, Cardiopulmonary Bypass, Morbidity, Mortality
Introduction
Pediatric cardiac surgery is a high-risk and complex process in all aspects. Numerous factors, from the preoperative period to the intensive care phase, influence morbidity and mortality. During pediatric cardiac surgery, particularly in neonates, tissue hypoxia and postoperative organ failure are among the leading causes of mortality. Advanced monitoring techniques and rapid therapeutic interventions based on the results of arterial and venous blood gas analyses are critical in the follow-up process. Various parameters indicating impaired tissue perfusion/oxygenation have been investigated to identify patients at high risk of mortality and morbidity following surgery.
Hemodynamic strategies and treatments aimed at maintaining or improving tissue oxygenation and/or perfusion during and after surgery have been shown to positively affect postoperative outcomes. Early detection and correction of tissue oxygenation/perfusion deficiencies, particularly in patients with diminished physiological reserves, are crucial to preventing adverse outcomes. The delta carbon dioxide (ΔCO2) value reflects whether CO2 produced in peripheral tissues is adequately cleared through venous blood flow. It is not influenced by pulmonary venous desaturation, intracardiac shunting, anemia, or insufficient inspiratory oxygen, which can impair oxygen delivery. Studies have explored the association between ΔCO2 values and reduced tissue perfusion in cardiac surgeries. While ΔCO2 has been shown to be a useful parameter for assessing tissue perfusion in adult patients, studies investigating its prognostic significance in neonates undergoing pediatric cardiac surgery are limited [1, 2] Given the increased susceptibility of pediatric patients undergoing open-heart surgery to early postoperative complications, developing and assessing advanced diagnostic methods for these patients is essential.
In this study, we aimed to investigate the effectiveness of perioperative anesthesia and cardiopulmonary bypass (CPB) durations, central venous-to-arterial partial carbon dioxide pressure differences (ΔCO2), and lactate levels in predicting postoperative mortality and morbidity in neonates undergoing cardiac surgery. By analyzing the findings, we also aim to propose new clinical routines and contribute to the literature.
Materials and Methods
This retrospective observational study was designed to evaluate the impact of intraoperative variables on postoperative mortality and morbidity in patients operated on in our pediatric cardiac surgery unit. We planned to retrospectively review all neonates aged 0–1 month, regardless of sex, who underwent congenital heart surgery with cardiopulmonary bypass (CPB) between January 1, 2023, and January 1, 2024. Of the 87 patients during this period, those with incomplete blood gas data (n = 45) were excluded, resulting in a total of 42 cases included in the study.
Upon admission to the operating room, patients routinely undergo electrocardiography (ECG), non-invasive blood pressure, and pulse oximetry monitoring, followed by induction with midazolam (0.1 mg/kg), fentanyl (1 μg/kg), ketamine (1 mg/kg), and rocuronium bromide (0.6 mg/kg). Subsequently, cefazolin (30 mg/kg IV) and methylprednisolone (3 mg/kg IV) are administered as standard protocol. After intubation, central venous catheters (CVCs) and arterial cannulas are placed by experienced anesthesiologists specializing in pediatric cardiac anesthesia.
Routine arterial and central venous blood gases are collected simultaneously via these cannulas at three time points: entry (T0), after cardiopulmonary bypass (T1), and upon admission to the pediatric cardiac intensive care unit (T2). All patients are transferred to the pediatric cardiac intensive care unit postoperatively as part of standard care.
This retrospective observational study recorded central venous-to-arterial partial carbon dioxide pressure differences (ΔCO2) and lactate levels at these three time points for neonates. Postoperative follow-up included evaluating major adverse events (e.g., acute kidney injury, seizures, arrhythmia), the need for extracorporeal membrane oxygenation (ECMO), length of hospital and intensive care unit (ICU) stays, and mortality.
The data collected aimed to compare total anesthesia and CPB durations, perioperative ΔCO2 values, and lactate levels, assessing their association with postoperative mortality and morbidity in neonates undergoing cardiac surgery.
Statistical Analysis
Descriptive statistics summarized the sample, with means and standard deviations (SD) for parametric data, medians, minimum (MIN), and maximum (MAX) values for non-parametric data, and frequencies (n) and percentages (%) for categorical variables. The Shapiro-Wilk test assessed numerical data normality.
Inferential statistics analyzed group differences and relationships. For normally distributed data, independent t-tests were used for two-group comparisons, and ANOVA for more than two groups. For non-normal data, the Wilcoxon rank-sum test and Kruskal-Wallis test were applied. Categorical data were analyzed using chi-square tests or Fisher’s exact test for small sample sizes.
Correlations were evaluated with Pearson’s coefficient for normal distributions or Spearman’s rank/Kendall’s tau for non-normal or non-linear data, with Kendall’s tau preferred for small samples (n < 30).
Ethical Approval
This study was approved by the Ethics Committee of University of Health Sciences Türkiye, Basaksehir Cam and Sakura City Hospital (Date: 2024-01-17, No: 15).
Results
A total of 42 neonatal patients were included in the study. Of these, 28 (66.67%) were male, and 14 (33.33%) were female. The median age of the patients was calculated as 0.4 ± 0.3 months. The mean height and weight of the sample were 50.52 ± 3.09 cm and 3.3 ± 0.6 kg, respectively. Genetic anomalies were absent in 38 (90.48%) patients and present in 4 (9.52%). The median total anesthesia duration was 378.45 ± 103.67 minutes, and the median CPB duration was 116.86 ± 55.03 minutes.
The median lactate level at admission (T0) was 1.86 ± 1.6 mmol/L, and the mean ΔCO2 value at T0 was 8.31 ± 4.99 mmHg. At the point of CPB cessation (T1), the median lactate level increased to 3.8 ± 1.79 mmol/L, while the mean ΔCO2 value was 7.04 ± 4.13 mmHg. Upon ICU admission (T2), the median lactate level further increased to 4.5 ± 2.84 mmol/L, and the mean ΔCO2 value was 10.87 ± 5.15 mmHg. The demographic and perioperative descriptive characteristics of the patients are summarized in Table 1.
Statistical analyses revealed significant associations between anesthesia duration, CPB duration, T0 ΔCO2 values, and the occurrence of major adverse events (p < 0.05, Table 2). A significant relationship was also found between total anesthesia duration and mortality (p = 0.014). However, no significant associations were observed between mortality and variables other than anesthesia duration (p > 0.05). Interestingly, ΔCO2 values at T0 and T1 were higher in patients who experienced mortality, although the results did not reach statistical significance. The detailed analysis of these findings is presented in Table 3.
Discussion
Our study is one of the rare contributions in the literature focusing on morbidity and mortality prediction in neonates undergoing complex congenital cardiac surgery. The high average total anesthesia duration, CPB time, and overall mortality rate in our study highlight the complexity of the patients’ pathologies.
We identified prolonged anesthesia duration as a predictive parameter for major adverse events and mortality. This may be attributed to the unique vulnerability of this sensitive population, consisting of neonates under 5 kg, where extended intraoperative times may lead to temperature fluctuations, heightened inflammatory responses, intravascular volume changes, and tissue perfusion disorders. Similar associations between CPB duration and morbidity or mortality have been demonstrated in studies on adult patients [3, 4]. Likewise, studies on pediatric populations have reported correlations between CPB duration and mechanical ventilation, ICU stay length, and postoperative complications (5, 6).
One of the strengths of our study lies in utilizing simple but effective parameters, such as lactate and ΔCO2, to provide valuable insights into the recovery process of neonates post-surgery. Additionally, by focusing on specific time intervals (T0, T1, T2), we could track changes in these parameters, offering a novel perspective on early detection of tissue oxygenation and perfusion impairments.
In our study, ΔCO2 values at T0 were associated with major adverse events, and elevated ΔCO2 values at T0 and T1 were more pronounced in patients who died, suggesting that ΔCO2 may serve as an important indicator of impaired tissue oxygenation. However, no significant relationship was observed between ΔCO2 values at T2 and adverse outcomes. This may reflect the effect of intraoperative corrective interventions on tissue oxygenation and the repair of congenital cardiac defects.
In the adult cardiac surgery literature, some studies have failed to demonstrate ΔCO2’s utility in predicting major adverse events or mortality (7-9). Negative findings have been reported by Morel et al. and Huette et al., who noted that various parameters influencing tissue perfusion can complicate the interpretation of ΔCO2 [10, 11]. Factors such as CPB itself, endothelial dysfunction, and microcirculation alterations may directly or indirectly contribute to complications, complicating the interpretation of outcomes. However, other studies have yielded positive results; for example, Mukai et al. reported that ΔCO2 measured at the end of cardiac surgery was a moderate predictor of postoperative major adverse events and mortality [12].
Similar to our findings, studies on neonates and infants have shown that elevated ΔCO2 values at admission are strongly associated with poor prognosis [1, 2]. Gong et al. also demonstrated a negative correlation between ΔCO2 and cardiac index (CI) in infants undergoing CPB for complex congenital heart surgery [13]. Based on these findings, we believe that ΔCO2 can serve as an additional measure for early postoperative risk stratification in neonates undergoing cardiac surgery. Nevertheless, further studies with larger cohorts are needed to validate this hypothesis.
Regarding lactate, no significant relationship was observed between lactate levels and tissue perfusion in our study. The association between lactate levels at all time points and major adverse events or mortality was insignificant. Although earlier studies linked lactate levels and clearance to outcomes in pediatric cardiac surgery [14-16], more recent research has indicated that elevated lactate levels in CPB patients may not necessarily reflect tissue hypoxia [17, 18]. For instance, Hakim et al. found an association between lactate levels and morbidity but not mortality [19].
We also believe that lactate alone is not a sufficient parameter for predicting postoperative mortality and morbidity in neonates undergoing cardiac surgery. It may be influenced by factors beyond tissue hypoxia, warranting further investigation.
Limitation
One of the major limitations of our study is its retrospective design, which inherently limits the ability to establish causal relationships. Additionally, the exclusion of patients with incomplete blood gas data reduced the sample size, potentially impacting the robustness of our findings. The small sample size (42 patients) further restricts the generalizability of the results.
Another limitation is the single-center nature of the cohort, comprising neonates younger than 30 days. This specificity limits the applicability of our findings to other cardiac disease populations or similar cohorts in different institutions.
Future large-scale, multicenter, prospective studies are needed to validate these findings in broader populations and improve their generalizability. Such research would provide a more comprehensive foundation for integrating these parameters into routine clinical practice.
Conclusion
Our study highlights the roles of anesthesia duration, CPB duration, and ΔCO2 in predicting postoperative complications following neonatal cardiac surgery. These findings provide valuable insights into the integration of these parameters into clinical monitoring and suggest new approaches to managing neonates undergoing cardiopulmonary bypass.
ΔCO2, in particular, may serve as a potential component in postoperative complication scoring systems for this population, offering a basis for future research. However, validating these findings in larger studies and improving their generalizability is essential. This underscores the need for prospective, multicenter research to establish the reliability of these parameters in broader clinical settings.
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. Rhodes LA, Erwin WC, Borasino S, Cleveland DC, Alten JA. Central Venous to Arterial CO2 Difference After Cardiac Surgery in Infants and Neonates. Pediatr Crit Care Med. 2017;18(3):228-33.
2. Singh G, Pujara J, Trivedi V, et al. Correlation of venous to arterial carbon dioxide partial pressure difference with other cardiac output indices in patients undergoing intracardiac repair for tetralogy of fallot. Ann Card Anaesth. 2023;26(2):171-176.
3. Shultz B, Timek T, Davis AT, et al. Outcomes in patients undergoing complex cardiac repairs with cross clamp times over 300 minutes. J Cardiothorac Surg 2016;11(1):105.
4. Moh’d AF, Al-Odwan HT, Altarabsheh S, Makahleh ZM, Khasawneh MA. Predictors of aortic clamp time duration and intensive care unit length of stay in elective adult cardiac surgery. Egypt Heart J. 2021;73(1):92.
5. Mehmood A, Nadeem RN, Kabbani MS, et al. Impact of Cardiopulmonary Bypass and Aorta Cross Clamp Time on the Length of Mechanical Ventilation after Cardiac Surgery among Children: A Saudi Arabian Experience. Cureus. 2019;11(8):e5333.
6. Agarwal HS, Wolfram KB, Saville BR, Donahue BS, Bichell DP. Postoperative complications and association with outcomes in pediatric cardiac surgery. J Thorac Cardiovasc Surg. 2014;148(2):609-16.e1.
7. Zhang S, Zheng D, Chu XQ, et al. ΔPCO2 and ΔPCO2/C(a-cv)O2 Are Not Predictive of Organ Dysfunction After Cardiopulmonary Bypass. Front Cardiovasc Med. 2021;8:759826.
8. Guinot PG, Badoux L, Bernard E, Abou-Arab O, Lorne E, Dupont H. Central Venous-to-Arterial Carbon Dioxide Partial Pressure Difference in Patients Undergoing Cardiac Surgery is Not Related to Postoperative Outcomes. J Cardiothorac Vasc Anesth. 2017;31(4):1190-6.
9. Huette P, Ellouze O, Abou-Arab O, Guinot PG. Venous-to-arterial pCO2 difference in high-risk surgical patients. J Thorac Dis. 2019;11(Suppl 11):1551-7.
10. Morel J, Grand N, Axiotis G, Bouchet JB, Faure M, Auboyer C, et al. High veno-arterial carbon dioxide gradient sis not predictive of worst outcome after an elective cardiac surgery: A retrospective cohort study. J Clin Monit Comput. 2016;30(6):783-9.
11. Huette P, Beyls C, Mallat J, et al. Central venous-to-arterial CO2 difference is a poor tool to predict adverse outcomes after cardiac surgery: A retrospective study. Can J Anaesth. 202;68(4):467-76.
12. Mukai A, Suehiro K, Kimura A, et al. Comparison of the venous-arterial CO2 to arterial-venous O2 content difference ratio with the venous-arterial CO2 gradient for the predictability of adverse outcomes after cardiac surgery. J Clin Monit Comput. 2020;34(1):41-53.
13. Gong X, Zhu L, Liu Y, et al. Elevated arterial-central venous carbon dioxide partial pressure difference indicates poor prognosis in the early postoperative period of open heart surgery in infants with congenital heart disease. Pediatr Cardiol. 2021;42(7):1601–6.
14. Ranucci M, Isgrò G, Carlucci C, De La Torre T, Enginoli S, Frigiola A. Surgical and Clinical Outcome REsearch Group. Central venous oxygen saturation and blood lactate levels during cardiopulmonary bypass are associated with outcome after pediatric cardiac surgery. Crit Care. 2010;14(4):R149.
15. Laine GA, Hu BY, Wang S, Thomas Solis R, Reul GJ Jr. Isolated high lactate or low central venous oxygen saturation after cardiac surgery and association with outcome. J Cardiothorac Vasc Anesth. 2013;27(6):1271-6.
16. Ladha S, Kapoor PM, Singh SP, Kiran U, Chowdhury UK. The role of blood lactate clearance as a predictor of mortality in children undergoing surgery for tetralogy of Fallot. Ann Card Anaesth. 2016;19(2):217-24.
17. Bar S, Nguyen M, de Broca B, Bernard E, Dupont H, Guinot PG. Risk factors and determinants of intraoperative hyperlactatemia in major non-cardiac surgery. J Clin Anesth. 2021;74:110359.
18. Zante B, Reichenspurner H, Kubik M, Kluge S, Schefold JC, Pfortmueller CA. Base excess is superior to lactate-levels in prediction of ICU mortality after cardiac surgery. PLoS One. 2018;13(10):e0205309.
19. Hakim MZ, Tewarson V, Kumar S, Rahul K, Prabha R, Singh SK. Early Mortality in Cardiac Surgery- Is Lactate Significant? Braz J Cardiovasc Surg. 2024;39(5):e20230245.
Download attachments: 10.4328.ACAM.22505
Serife Ozalp, Erkut Ozturk. Predictive role of intraoperative variables in neonatal cardiac surgery outcomes. Ann Clin Anal Med 2025;16(8):539-543
Citations in Google Scholar: Google Scholar
Analysis of the frequency and etiology of traumatic lumbar punctures in a neonatal intensive care unit in Turkiye and documentation of microorganisms
Ayşenur Engin Erdal 1, Ayşegül Zenciroğlu 2
1 Department of Pediatric Metabolism, Ankara Bilkent City Hospital, 2 Department of Neonatology, Dr. Sami Ulus Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkiye
DOI: 10.4328/ACAM.22520 Received: 2025-01-01 Accepted: 2025-02-11 Published Online: 2025-02-22 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):544-548
Corresponding Author: Ayşenur Engin Erdal, Department of Pediatric Metabolism, Ankara Bilkent City Hospital, Ankara, Turkiye. E-mail: erdalaysenur88@gmail.com P: +90 536 278 68 87 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6139-6027
Other Authors ORCID ID: Ayşegül Zenciroğlu, https://orcid.org/0000-0002-3488-4962
This study was approved by the Ethics Committee of Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital (Date: 2018-11-12, No: 2018-180)
Aim: In neonatal clinics and intensive care units, lumbar puncture (LP) is often used to diagnose neurological, infectious, and metabolic disorders. The aim of our study was to determine the rate of LP traumatization and associated anthropometric variables, as well as to compare concurrent microbiological outcomes for traumatic and non-traumatic LP procedures.
Materials and Methods: We performed a retrospective analysis of electronic records of neonates who underwent LP over eight years in the level three neonatal intensive care unit (NICU) of a teaching hospital in Turkey. We classified a CSF material as traumatizing lumbar puncture (TLP) when the red blood cell (RBC) count exceeded 500 cells/mm3 and classified the rest as non-traumatizing lumbar puncture (nTLP).
Results: During the study period, 854 newborn infants underwent LP procedures and 325 (38.06%) had TLP. There was no significant difference between the TLP and nTLP groups in terms of birth weight, birth weight percentile, gestational week, and year of procedure. As postnatal age increased, the TLP rate decreased in both term and preterm patients (p = 0.001). When the rates of laboratory evaluation of CSF samples were compared, the rate of sending the sample to the laboratory was significantly lower in the TLP group compared to the nTLP group (p<0.05).
Discussion: The TLP rate in our center is consistent with the rates found in the literature. Our findings suggest that the likelihood of TLP decreases with increasing age of the newborn. Further studies with ancillary methods such as superficial ultrasonographic imaging are needed to decrease the rate of TLP.
Keywords: Traumatic Lumbar Puncture, Neonatal Meningitis, Neonatal Sepsis
Introduction
Lumbar puncture (LP) is a frequently used diagnostic and sometimes therapeutic procedure. This allows for the examination of the CSF using biochemical, cytological, and microbiological analyses of the CSF. Neonatal can undergo LP to diagnose a variety of conditions, including meningitis, subarachnoid hemorrhage, sepsis, convulsions, and neurometabolic disease [1]. The evaluation of CSF for the diagnosis of meningitis, a major cause of illness and mortality, remains the most reliable technique currently available [2]. If blood cultures of patients suspected of early sepsis reveal microorganisms, we recommend performing an LP and treating the condition as confirmed sepsis. The LP procedure’s success rates have not yet reached optimal levels. The literature indicates that the prevalence of TLP in neonates ranges from 40% to 50% [3]. During the procedure, there is a possibility of blood and CSF mixing due to the LP needle puncturing the radicular artery or vein. In the literature, TLP is typically defined as an RBC count that is higher than 400 cells/mm3 or 1000 cells/mm3 in the CSF [4]. These values indicate the point at which the visual characteristics of the CSF experience noticeable alterations on a significant level.
We aimed to determine the failure rate of the LP procedure in neonates, as well as assess the laboratory methods for bloody CSF samples and concurrent microbiological results. We noted the gender, gestational and postnatal age, birth weight, and microbiological results of the patients.
Materials and Methods
We performed a retrospective analysis of electronic medical records of newborns who received LP and CSF collection at Health Sciences University’s Dr. Sami Ulus Gynecology and Pediatrics Training and Research Hospital’s NICU from 2010 to 2018. We classified newborns delivered before 37 weeks of gestation as preterm, and those born after 37 weeks as term. We assessed the rate of traumatization by analyzing the results of the initial LP on the study group. We classified specimens as TLP if their RBC count exceeded 500 cells/mm3. The study examined the year of the procedure, the patient’s gender, the gestational week of the procedure, the patients’ birthweight, the birthweight percentile, and the age of the LP in both the TLP and nTLP patient groups. The analysis focused on the microorganisms that developed in the CSF culture, the results of the CSF polymerase chain reaction (PCR), and the simultaneous growth in the blood culture. We analyzed the frequency of performing a control LP in the groups, following the guideline to perform the procedure within 72 hours after the initial LP. According to the clinic’s protocol, the LP procedure must be performed with the patient in positions of lower extremity flexion and lateral decubitus. Due to a lack of recorded needle thickness in the file data, comparison was not possible. We obtain three vials containing CSF samples, each containing 1-2 ml of fluid. We perform Gram staining and bacterial culture on the CSF samples from the first tube and analyze biochemistry parameters from the sample in the second tube. We ascertain the cell count from the third tube sample and conduct other tests on samples in additional tubes.
Statistical analysis
The statistical data was defined using numerical values such as number, percentage, mean, standard deviation, median, maximum, and minimum. We used the Kruskal-Wallis test to compare two groups that displayed a Gaussian distribution. We used the Mann-Whitney U test to compare two groups that displayed a non-normal distribution. We used the Student T test to compare two groups of quantitative variables. We employed the chi-square test to compare categorical variables among independent groups. We used the Spearman correlation test to determine the relationships between the variables and to assess the test’s assumptions. We used Cochran’s Q test to compare variables within the same group. IBM Corp. in Armonk, NY, USA developed the Statistical Package for the Social Sciences (SPSS) 25 software to analyze the data. We determined significance based on p-values below 0.05.
Ethical Approval
This study was approved by the Ethics Committee of Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital (Date: 2018-11-12, No: 2018-180).
Results
A total of 854 infants underwent the LP procedure, with 339 (39.69%) being female and 515 (60.31%) being male. The patients’ file notes and self-reports classified 272 (31.85%) as preterm and 582 (68.15%) as term newborns. The newborns with recorded weights ranged from 650 to 5133 grams, with an average birthweight of 2751 grams. 325 out of 854 newborns experienced TLP procedures, which accounts for 38.06% of the total. We found no significant relationship between the year of the procedure and TLP (p = 0.571). In 2010, the highest annual traumatization rate was 42.60%. We found no statistically significant relationship between gender (p = 0.775), gestational week (p = 0.198), birthweight (p = 0.564), birthweight percentile (p = 0.914), and TLP. We could access delivery method data for 831 (97.30%) patients. We detected 173 (43.68%) TLP and 223 (56.32%) nTLP in patients born vaginally, and 144 (33.10%) TLP and 291 (66.90%) nTLP in patients born by cesarean section. When compared to those born via cesarean section, the TLP rate was significantly lower (p = 0.002). We determined the mean age of LP in the term patient group to be 12.8 (1-39) days, while it was 27.6 (1-101) days in the preterm group. We observed a decline in the TLP rate as postnatal age increased in both the term and preterm patient groups (p = 0.001). We analyzed the biochemical parameters, cell count, and Gram staining rates of the CSF samples obtained from 325 TLP. The rates of laboratory evaluation of CSF samples of the patients are summarised in Table 1.
We compared the cell count and biochemical parameters of the CSF samples from the TLP and nTLP groups. The statistical analysis revealed that there was no significant difference in the WBC count between the two groups (p = 0.832). The RBC count showed a significant increase in the TLP group (TLP: average 436 cells/mm3, nTLP: average 11 cells/mm3) (p = 0.001). We conducted an RBC count in 11% of the total TLP CSF samples. The abundance of erythrocytes observed in the cell count report of most samples made it impossible to assess the accuracy of the data. The TLP group significantly increased the CSF protein level (p = 0.001) among the biochemical parameters, while the levels of glucose, chloride, and lactate did not show a significant increase (p = 0.759, p = 0.38, and p = 0.315, respectively).
Growth of microorganisms was found in CSF cultures of 19 (2.22%) of the patients. We found that 8 (2.4%) of 325 patients with TLP and 11 (2.07%) of 529 patients with nTLP had growth in CSF cultures. The microorganisms detected in CSF cultures are summarised in Table 2. No growth was observed in 82.54% of the patients whose blood cultures were sent simultaneously. Control LP was performed in 45 (5.3%) of 854 patients. There was no significant difference between the rates of control LP (24 patients (4.5%) in the nTLP group and 21 patients (6.4%) in the TLP group).
Discussion
Our study revealed that the prevalence of TLP was 38.06% in our center. This rate is within the average range reported in the literature (30-50.7%) [3,4,5]. In our study, no significant correlation was found between gestational week, gender, birth weight, birth weight percentile, and TLP; however, a negative correlation was found between postnatal age at LP and TLP prevalence in both term and preterm infants. In studies on the frequency of TLP in newborns in the literature, TLP was found to be higher in preterm and low birth weight newborns [4,5,6]. We found that babies born by cesarean section had a lower rate of TLP compared to babies born vaginally. We did not find any study associating TLP with the type of delivery. Based on the age at LP, we hypothesized that the mode of delivery may trigger TLP. Studies have shown that cesarean section may prevent early neonatal sepsis [7]. Matettore et al. made a comparison between TLP and several factors such as the age at which LP was performed, gender, the department where the procedure was performed (emergency department or NICU), and the timing of the procedure [4]. They reported that the rate of TLP decreased as the age at LP application increased. In the study, they found that LP procedures performed in the emergency department had a lower TLP rate compared to the NICU. The authors attributed this increase to the fact that emergency physicians were more experienced and the patients in the emergency department were relatively healthy, whereas the infants in the NICU were low birth weight, preterm, or had other congenital disorders. In our study, we found a significant difference in RBC count and protein level in the TLP group compared to the nTLP group. We attributed the lack of a significant difference in WBC count to the very low rate of sending CSF obtained after TLP for cell counting. A recent study has shown that the presence of any number of CSF RBCs (including <500 cells/µL) affects CSF WBC count and protein content [8].
The literature has shown that the subarachnoid space plays an important role in obtaining CSF during the LP procedure and in causing the TLP procedure in neonates. Öncel et al. showed that being in a sitting position with hip flexion may increase the likelihood of a successful LP by widening the external interspinous space [9]. Oulego-Erroz et al. conducted a prospective study and found that sitting in a position with hip flexion increased both the external and internal subarachnoid distance [10]. However, head flexion did not cause a significant increase in interspinous distance. According to Oulego-Erroz et al., sitting with hip flexion increases both the distance between the layers of the spinal cord and the distance within the spinal cord, while head flexion does not cause a significant increase in the space between the spinous processes. This suggests that the head flexion position is a position which sick newborns and preterm infants have low tolerance and does not provide any anatomical benefit in preventing TLP. In a study conducted by Lo et al. in 2013, subarachnoid space distances of infants in different positions (straight lateral decubitus, 45-degree tilt, and sitting) were measured and no significant difference was found between the three positions [11]. Factors such as elevated CSF pressure, enlarged interspinous space, or improved landmark identification may contribute to the higher success rate of LP in the sitting or tilting position. A recent and comprehensive study found that a successful and simple LP procedure was more likely to occur when performed in the sitting position and also showed no correlation between the time taken to remove the stylet and TLP [12]. Due to the retrospective nature of our study and the use of a chart review, it was not possible to evaluate patient positioning. In our center, the lateral decubitus position with hip flexion and neutral head position is commonly used.
On the other hand, the size of the LP needle is thought to be one of the most important factors that may increase the risk of TLP. In 2020, Flett et al. published a study examining the relationship between TLP and dry tap LP and the LP needle used. They found that TLP was less common when a 25G needle was used. However, the 25G group showed a higher probability of dry tap. The study found no association between gestational week, birth week percentile, practitioner experience, clinical status of the newborn, and TLP [13]. Orman et al. examined the TLP rates of two neonatal patient groups who underwent LP in the lateral decubitus position using 22G and 25G spinal needles. The study data supported that 25 G-tipped spinal needles caused less TLP in neonates compared to 22 G-tipped spinal needles [14].
Many studies in the literature show that the use of ultrasound during the LP procedure provides higher success rates compared to the conventional method [15, 16, 17, 18]. Olowoyeye et al. showed a significant increase in the incidence of nTLP in ultrasound procedures in neonates and infants [19]. Gupta et al. measured the L3-L4 vertebral space of newborns using bedside ultrasound and developed a formula related to the gestational week and body weight of the infant [20]. The study, which aimed to find a mathematical formula specific to gestational age and weight to predict the optimal depth of spinal needle insertion, found that spinal canal dimensions showed an increasing trend as the weight and postnatal age of infants increased.
CSF culture positivity rate was 2% in our study. The microorganisms causing early and late-onset meningitis detected in CSF cultures were similar to the literature [21, 22, 23].
Limitations
Our study’s significant limitation lies in the inability to compare crucial factors like position, LP needle size, and practitioner experience due to the retrospective acquisition of information through electronic file data scanning. Furthermore, the analysis of CSF specimens precluded the inclusion of dry-tap LPs in the evaluation.
Conclusion
Although it is a frequently needed interventional procedure in neonatal intensive care clinics, both clinicians and patients’ families continue to avoid LP due to its high failure rate. After a difficult persuasion process, a failed LP procedure does not help the diagnostic process and causes stress for both the clinician and the family. Prolonged hospitalization and the use of broad-spectrum antibiotics are inevitable due to unreliable CSF cell counts after TLP. It is noteworthy that our study included a significant number of patients who underwent LP over 8 years. We confirmed that the success rate of the LP procedure increased with postnatal age. We also found that the cell count rate in the CSF sample obtained by TLP was low, which hindered the diagnostic process. It seems likely that performing LP using bedside ultrasonographic imaging in neonatal intensive care units should be a common and routine procedure, which may reduce the failure rate in the future.
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. Srinivasan L, Harris MC, Shah SS. Lumbar puncture in the neonate: Challenges in decision making and interpretation. Semin Perinatol. 2012;36(6):445-53.
2. Aleem S, Greenberg RG. When to Include a Lumbar Puncture in the Evaluation for Neonatal Sepsis. Neoreviews. 2019;20(3):e124-e34.
3. Glatstein MM, Zucker-Toledano M, Arik A, Scolnik D, Oren A, Reif S. Incidence of traumatic lumbar puncture: Experience of a large, tertiary care pediatric hospital. Clin Pediatr (Phila). 2011;50(11):1005-9.
4. Matettore A, Kollmann TR. Traumatic Neonatal Lumbar Punctures: Experience at a Large Pediatric Tertiary Care Center in Canada. Am J Perinatol. 2018;35(8):764-8.
5. Sievänen H, Kari J, Eskola V, Huurre A, Soukka H, Palmu S. Incidence of traumatic lumbar punctures in adults: The impact of a patient’s first procedure. Clin Med (Lond). 2023;23(1):31-7.
6. García-De la Rosa G, De Las Heras-Flórez S, Rodríguez-Afonso J, Carretero-Pérez M. Interpretation of white blood cell counts in the cerebrospinal fluid of neonates with traumatic lumbar puncture: A retrospective cohort study. BMC Pediatr. 2022;16;22(1):488.
7. Traoré FB, Sidibé CS, Diallo EHM, et al. Prevalence and factors associated with maternal and neonatal sepsis in sub-Saharan Africa: A systematic review and meta-analysis. Front Public Health. 2024;12:1272193.
8. Gunti S, Nair V, Kannan Loganathan P. Reference range for cerebrospinal fluid values in neonates: 5-year retrospective study. J Matern Fetal Neonatal Med. 2022;35(26):10584-90.
9. Öncel S, Günlemez A, Anik Y, Alvur M. Positioning of infants in the neonatal intensive care unit for lumbar puncture as determined by bedside ultrasonography. Arch Dis Child Fetal Neonatal Ed. 2013;98(2):F133-5.
10. Oulego-Erroz I, Mora-Matilla M, Alonso-Quintela P, Rodríguez-Blanco S, Mata-Zubillaga D, de Armentia SL. Ultrasound evaluation of lumbar spine anatomy in newborn infants: Implications for optimal performance of lumbar puncture. J Pediatr. 2014;165(4):862-5.e1.
11. Lo MD, Parisi MT, Brown JC, Klein EJ. Sitting or tilting position for infant lumbar puncture does not increase ultrasound measurements of lumbar subarachnoid space width. Pediatr Emerg Care. 2013;29(5):588-91.
12. Marshall ASJ, Scrivens A, Bell JL, Linsell L, Hardy P, Yong J, et al. Assessment of infant position and timing of stylet removal to improve lumbar puncture success in neonates. Lancet Child Adolesc Health. 2023;7(2):91-100.
13. Flett T, Athalye-Jape G, Nathan E, Patole S. Spinal needle size and traumatic neonatal lumbar puncture: An observational study (neo-LP). Eur J Pediatr. 2020;179(6):939-45.
14. Orman A, Aydın H. Do Spinal Needle Sizes Affect the Development of Traumatic CSF in Neonatal LP Procedures? Children (Basel). 2023;10(3):509.
15. Gorn M, Kunkov S, Crain EF. Prospective Investigation of a Novel Ultrasound-assisted Lumbar Puncture Technique on Infants in the Pediatric Emergency Department. Acad Emerg Med. 2017;24(1):6-12.
16. Özdamar E, Özkaya AK, Güler E, et al. Ultrasound-Assisted Lumbar Puncture in Pediatric Emergency Department. Pediatr Emerg Care. 2017;33(8):e21-e3.
17. Gottlieb M, Holladay D, Peksa GD. Ultrasound-assisted Lumbar Punctures: A Systematic Review and Meta-Analysis. Acad Emerg Med. 2019;26(1):85-96.
18. Kuitunen I, Renko M. Ultrasound-Assisted Lumbar Puncture in Children: A Meta-Analysis. Pediatrics. 2023;152(1):e2023061488.
19. Olowoyeye A, Fadahunsi O, Okudo J, Opaneye O, Okwundu C. Ultrasound imaging versus palpation method for diagnostic lumbar puncture in neonates and infants: A systematic review and meta-analysis. BMJ Paediatr Open. 2019;3(1):e000412.
20. Gupta N, Venkatesh HA, Pejaver R, Garg C, Nagesh K. Determining the Spinal Canal Depth in Neonates Using Bedside Ultrasonography. Indian Pediatr. 2023;60(11):927-30.
21. Leazer R, Erickson N, Paulson J, et al. Epidemiology of Cerebrospinal Fluid Cultures and Time to Detection in Term Infants. Pediatrics. 2017;139(5):e20163268.
22. Xu M, Hu L, Huang H, et al. Etiology and Clinical Features of Full-Term Neonatal Bacterial Meningitis: A Multicenter Retrospective Cohort Study. Front Pediatr. 2019;7:31.
23. El-Naggar W, Afifi J, McMillan D, et al. Epidemiology of Meningitis in Canadian Neonatal Intensive Care Units. Pediatr Infect Dis J. 2019;38(5):476-80.
24. Zinganell A, Berek K, Bsteh G, et al. Subarachnoid hemorrhage or traumatic lumbar puncture. Differentiation by cerebrospinal fluid parameters in a multivariable approach. Sci Rep. 2023;13(1):2231.
Download attachments: 10.4328.ACAM.22520
Ayşenur Engin Erdal, Ayşegül Zenciroğlu. Analysis of the frequency and etiology of traumatic lumbar punctures in a neonatal intensive care unit in Turkiye and documentation of microorganisms. Ann Clin Anal Med 2025;16(8):544-548
Citations in Google Scholar: Google Scholar
Effect of oral appliances on cephalometric measurements and sleep apnea severity: A clinical study
Oral Sokucu 1, Dler Mourad 1, Haluk Goren 2, Deniz Tuncel 3
1 Department of Orthodontics, Private Clinics, Gaziantep, 2 Department of Orthodontics, School of Dentistry, Sutcu Imam University, Kahramanmaras, 3 Department of Neurology, School of Medicine, Sutcu Imam University, Kahramanmaras, Turkey
DOI: 10.4328/ACAM.22523 Received: 2024-12-17 Accepted: 2025-02-19 Published Online: 2025-03-02 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):549-553
Corresponding Author: Oral Sokucu, Department of Orthodontics, Private Clinics, Gaziantep, Turkey. E-mail: oralorto@gmail.com P: +90 543 543 09 74 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8206-6227
Other Authors ORCID ID: Dler Mourad, https://orcid.org/0000-0002-4745-7556 . Haluk Goren, https://orcid.org/0000-0001-7552-3322 . Deniz Tuncel, https://orcid.org/0000-0003-2347-472X
This study was approved by the Ethics Committee of Elazığ University, Faculty of Medicine (Date: 2024-11-14, No: 2024 /301)
Aim: This study aimed to evaluate the effects of oral appliances (OA) in OSA cases by using cephalometric measurements that rejected the use of CPAP therapy. The research question focused on whether oral appliances could significantly alter craniofacial structure and reduce sleep apnea severity.
Materials and Methods: Ten participants (8 males and 2 females) from the sleep clinic were included in this study. The medical instructor advised them to use the CPAP device, but the participants confirmed to use OA. The patients underwent the same polysomnography laboratory with a sleep oral appliance continuously one month after using it all night. Cephalometric radiographs were taken before and after using the OA. The Apnea-Hypopnea Index (AHI) and other sleep apnea parameters were measured through polysomnography. Statistical analysis was performed using the Mann-Whitney U test.
Results: The median AHI significantly decreased from 26.2 events/hour to 11.3 events/hour (p=0.008) after using the oral appliance. The SNB angle increased from 75.6 to 78.8 degrees (p=0.003), and the ANB angle decreased from 5.6 to 2.8 degrees (p=0.01), indicating improved mandibular positioning. The Sn-GoGn angle also increased significantly from 37.0 to 43.1 degrees (p=0.001), suggesting changes in mandibular plane orientation.
Discussion: The study demonstrated that oral appliances significantly reduce the severity of sleep apnea and induce favorable cephalometric changes. These appliances are effective alternatives for patients who are unable to tolerate CPAP, potentially improving airway patency by repositioning the jaw.
Keywords: Oral Apnea Appliances, Sleep Apnea, Polysomnography (PSG), Mandibular Advancement Devices (MAD)
Introduction
The word apnea originates from the Greek Word apnoia and means without breathing. Obstructive Sleep Apnea Syndrome (OSAS) is characterized by episodes of obstruction of the upper airway during sleep, resulting in a reduction in oxygen saturation [1]. These situations lead the patients to a reduction in oxygen saturation. Untreated OSAS may carry a high risk of comorbid diseases, such as systemic hypertension, depression, stroke, and cardiac dysrhythmias [2, 3]. Excessive daytime sleepiness is a significant symptom, and due to this problem, patients have an increased risk for motor vehicle accidents [4].
OSAS affects 3.9% of men and 1.2% of women, and this prevalence increases with age, to approximately 20-54% for elderly women and 28-67% for elderly men [5].
Continuous positive airway pressure (CPAP) is accepted as a gold standard treatment for OSA by most authorities [6]. It is effective in reducing breathing disturbances during sleep. CPAP has been shown to improve daytime sleepiness, cognitive function, blood pressure, and quality of life [7]. Contrary to these positive outcomes, only half of the patients with OSA adhere to the CPAP therapy [8]. Patients complain that CPAP is difficult to tolerate due to high pressure and wearing a mask during the night. This reduces the clinical effectiveness of CPAP [9]. In recent years, it has been observed that Oral sleep appliances are an alternative treatment option for snoring and mild to moderate OSA in patients who refuse CPAP or can not tolerate it. Recently, studies have shown that oral appliance may be an alternative option for patients who refuse to use CPAP [10].
Cephalometric analysis, which uses standardized lateral skull radiographs, has become an essential tool for studying the craniofacial structures associated with OSAS. Through cephalometric measurements, clinicians and researchers can identify skeletal and dental characteristics that contribute to the pathophysiology of OSAS [11].
The purpose of the present study is to observe the effects of Oral appliance in patients who refused to use CPAP by using Cephalometric landmarks.
Materials and Methods
In the present study, a significance level of 0.05 (α = 0.05) was chosen for the power analysis to control the probability of errors. A desired power level of 0.90 (1 – β = 0.90) was selected to ensure adequate sensitivity to detect the specified effect size. An effect size of 1.2 (Cohen’s d = 1.2) was estimated based on the observed differences in the AHI score. Using these parameters by GPower 3.1.9.7 software, a sample size of 10 participants per group was determined to be enough to achieve the desired level of statistical power.
The study group consisted of ten subjects. The subjects were enrolled into the study from the sleep clinic belonging to the department of Neurology, University of Sütçü İmam, Kahramanmaraş, Turkey.
Untreated and CPAP noncompliant participants were included in the study. This study was approved by the local ethical committee. All participants were recommended for oral sleep appliance therapy by a neurologist supervising the sleep clinic.
Participants were excluded by study dentist if sleep oral appliance therapy was contraindicated in these participants. These exclusion criteria were periodontal disease and insufficient teeth for device retention.
Patients were excluded by the sleep clinic director if they had central sleep apnea or were taking medications affecting sleep or breathing. Patients with mental conditions preventing the use of an oral sleep appliance or the ability to provide informed consent were also excluded.
Oral Sleep Apnea Appliance Protocol
The patients referred from Polysomnographic laboratories (PSG) and agreed to use an oral sleep appliance were referred to the dental clinic. The referred participants underwent dental intervention in the dental clinic. An experienced dentist took dental impressions from the participants. The material of the oral sleep appliance was polyvinyl siloxane (PVS). The thickness of this material was 1.0mm (.040”).In the second appointment, the mandibular advancement was applied following the trademark OSP sleep appliance patent under the PCT/TR2020/050697-PCT05 (Figure 1).
After completing the oral sleep appliance, detailed information was given to the participants. They confirmed that they use it during sleep. All the participants were called after 3 days by phone to provide feedback about their comfort with the oral sleep appliance. If there were no problems, they were accepted as participants in this study.
The second PSG was conducted 1 month after using the oral sleep appliance at night. The second PSG record was taken with the oral sleep appliance in the same polysomnographic laboratory.
Cephalometric Records
All the cephalometric radiographs were obtained from all participants under standardized conditions with their teeth in centric occlusion. The radiographs were taken by the participants with and without oral sleep appliances. The second cephalometric with appliance was taken before going to the second PSG. All the cephalometric radiographs were traced by the same investigator (HB).
Cephalometric parameters that were used in this study included:
SNAo: Angle formed by the intersection of sella-nasion and nasion-A-lines.
SNBo: Angle formed by the intersection of sella-nasion and nasion-B- B lines.
ANBo: Angle formed by the intersection of nasion- A and nasion- B lines.
These angles describe the relative positions of the maxilla and mandible.
Sn-GoGn Angle: SN-GoGno is the angle between the SN planes and the mandibular plane (GoGn). This angle elucidates the behavior of the mandibular base with the cranium base, indicating the facial growth type, whether horizontal, vertical, or balanced. This angle indicates the mandibular plane angle (Figure 2).
Statistical analysis
Statistical analysis was performed using SPSS software, version 27.0 (SPSS Inc., Chicago, IL, USA). Quantitative data were described as medians (Min-Max), and categorical data were presented as frequencies and percentages. Shapiro Wilk test was used to control the conformity of continuous variables to normal distribution. Wilcoxon Test was applied to assess the difference between the parameters before and after using an oral sleep appliance. Relationships between categorical variables were tested with Chi-square analysis. Statistical significance was set at p < 0.05.
Ethical Approval
This study was approved by the Ethics Committee of Elazığ University, Faculty of Medicine (Date: 2024-11-14, No: 2024 /301).
Results
The demographic characteristics of the cases are shown in Table 1. A total of 10 participants were included in the study, with a median age of 53 years (range: 40-72 years). The majority of participants were male (80.0%, 8/10), with females comprising 20.0% (2/10) of the study group (Table 1). The effect of Oral Appliance on Sleep Apnea Severity was shown in Table 2. The Apnea-Hypopnea Index (AHI) showed a significant reduction following treatment with the oral appliance. The median AHI decreased from 26.2 events per hour (range: 11.9-60.3) without the appliance to 11.3 events per hour (range: 2.9-35.5) with the appliance, representing a statistically significant change (p=0.007).
Hypopnea events per hour also demonstrate a slight decrease, from a median of 9.0 (range: 2.2-44.5) without the appliance to 7.6 (range: 2.5-14.0) with the appliance (p=0.023), which was statistically significant.
Regarding apnea events per hour, there was a decrease from a median of 11.0 (range: 3.6-26.5) to 4.2 (range: 0.4-24.9) with the appliance (p=0.042). However, this reduction was statistically significant.
Significant changes were observed in certain cephalometric measurements. In terms of skeletal changes, the SNA angle remained stable (P = 0.833), suggesting no significant maxillary movement. However, a notable increase in the SNB angle from 75.6 (72.0–78.1) to 78.8 (74.8–80.4) (P = 0.002) indicates a forward shift of the mandible, which can enhance airway patency. Although the ANB angle showed a downward trend from 5.6 (2.9–7.8) to 2.8 (0.7–50.9), this change was not statistically significant (P = 0.082). Additionally, the Sn-GoGn angle increased significantly from 37.0 (33.7–43.0) to 43.1 (39.2–48.3) (P = 0.002), reflecting vertical mandibular movement that may further contribute to reduced airway obstruction (Table 2).
Discussion
The results of this study demonstrate that the use of OA can significantly reduce the severity of sleep apnea, as indicated by the decrease in the Apnea-Hypopnea Index (AHI). The results revealed that OA has a clinically meaningful effect on reducing apnea and hypopnea events during sleep. Many studies support our findings. Serra-Torres et al. found these appliances to be an effective alternative solution for snoring and in mild to moderate OSA patients [12]. In another study, researchers mentioned that using an OA reduces snoring and obstructive breathing events and shows positive effects on daytime sleepiness [13]. In this recent study, the mean AHI score was 26.2, close to the severe level (AHI=30). After using OA, the decrease was significant, with a score of 11.3.
The other parameters, apnea/hour and hypopnea/hour values, showed a decrease after the use of the OA. The results did not show a significant decrease in AHI scores. The changes in apnea per hour and the saturation of oxygen are limited by the number of participants in this study. The limited number of participants may prevent a significant reduction. Only 1 month after using the oral sleep appliance may not be enough time to show improvement in these parameters in OSA patients. Studies on the effects of using an OA in many other studies focused on blood pressure, heart rate, and the cardiovascular system waited from 3 months to 1 year [14-16].
The cephalometric data indicate that the appliance affects mandibular positioning, as evidenced by the significant increase in the SNB angle and the decrease in the ANB angle. SNB means the forward position of the chin, and ANB is the relationship with the position of the maxilla. These changes in mandibular alignment likely contribute to a more open airway, thereby reducing the frequency of apnea and hypopnea events. These findings support the notion that oral appliances work by repositioning the jaw to improve airway patency during sleep. Previous studies have shown that people with sleep apnea may have a small retruded mandible, a narrow posterior airway space, an enlarged tongue and soft palate, an inferiorly positioned hyoid bone, and a retroposition of the maxilla [17].
Our study used another landmark that is widely used in orthodontics: SN-GoGn. This showed the relationship between mandible and craniofacial structure. Our results showed that using OA has significantly positively affected the OSA scores. A larger Sn-GoGn angle suggests a more downwardly tilted mandible, potentially reducing airway space and increasing the risk of airway obstruction [18]. It is known that holding the lower jaw in a more anterior position enlarges the upper airway space and provides expansion in the lateral dimension of the velopharyngeal region [19]. Contrary to this, it has been shown that the patients with OSA have smaller Sn-GoGn angles than the control group [17].
Our study supports that there is a negative relationship between AHI scores and the mandible downward retruded position. The position of the mandible did not affect only the AHI scores but also the posture of the head. According to this topic many years ago, Solow and Kreiborg termed ‘the soft tissue stretching hypothesis’ that means upper airway obstruction causes a change in posture via extension of the skeletal structures such as cervical angle [20]. From childhood till adult age, subjects spontaneously put their head in more extension positions to eliminate the obstruction of the airway. This leads the subjects on skeletal structures and causes a decrease in the forward growth of the maxilla and mandible. Unfortunately, this is a severe sign in the future to be a a patient with apnea and declared in year 1977.
In 2019, researchers estimated that nearly 1 billion adults aged 30-69 years worldwide could have OSA [21]. Nearly half of them are classified as moderate to severe sleep apnea patients and need any intervention to treat. Under the light of this result, we need a new approach to OSA in the early stage. Dental and medical specialists who have experience with OSA cases have to come together. Potential OSA cases in childhood may have to be treated orthodontically to eliminate apnea. The solution is upgrading the Medicine and Dental Program, including OSA cases. Prevention from apnea needs severe steps to do with all disciplines, otherwise, it could not be solved by traditional methods.
Limitation
This study has several limitations that should be acknowledged. First, the sample size was small, with only ten participants included, which may limit the generalizability of the findings. A larger cohort would provide more robust statistical power and better represent the broader population of OSA patients. Second, the follow-up period was relatively short, with outcomes assessed after just one month of oral appliance use. Long-term studies are needed to evaluate the sustained efficacy of oral appliances and their impact on clinical parameters over time. Third, the study did not include a control group, which limits the ability to directly compare the effects of oral appliance therapy to alternative treatments such as continuous positive airway pressure (CPAP) or no intervention. Additionally, self-reported compliance and subjective feedback from participants may introduce bias in assessing the device’s acceptability and effectiveness. Future research should aim to address these limitations by incorporating larger sample sizes, longer follow-up durations, and controlled study designs.
Conclusion
Our findings showed that OA is an effective alternative treatment for sleep apnea, especially in patients who may not tolerate continuous positive airway pressure (CPAP) therapy.
The observed reduction in AHI is consistently reinforcing the role of OA in managing sleep apnea. All the participants have a good tolerance to use this OA, and subjectively, the patients have positive moods, and voluntarily they want to use it in furthermore.
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. Vezina K, Mariasine J, Young R, et al. Cardiorespiratory Monitoring Data during Sleep in Healthy Canadian Infants. Ann Am Thorac Soc. 2020;17(10):1238-46.
2. Henning RJ, Anderson WM. Sleep apnea is a common and dangerous cardiovascular risk factor. Curr Probl Cardiol. 2025;50(1):102838-48.
3. DiCaro MV, Lei K, Yee B, Tak T. The Effects of Obstructive Sleep Apnea on the Cardiovascular System: A Comprehensive Review. J Clin Med. 2024;13(11):1-7.
4. Lee JJ, Sundar KM. Evaluation and Management of Adults with Obstructive Sleep Apnea Syndrome. Lung. 2021;199(2):87-101.
5. Okşayan R, Sökücü O, Uyar M, Topçuoğlu T. Effects of edentulism in obstructive sleep apnea syndrome. Nigerian Journal of Clinical Practice. 2015;18(4):502-5.
6. Kim HY, Jo JH, Chung JW, Park JW. The multisystemic effects of oral appliance therapy for obstructive sleep apnea: A narrative review. Medicine (Baltimore). 2022;101(29):1-9.
7. Tong BK, Tran C, Ricciardiello A, et al. Efficacy of a novel oral appliance and the role of posture on nasal resistance in obstructive sleep apnea. J Clin Sleep Med. 2020;16(4):483-92.
8. Oliver C, Li H, Biswas B, Woodstoke D, Blackman J, Butters A, et al. A systematic review on adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) in individuals with mild cognitive impairment and Alzheimer’s disease dementia. Sleep Med Rev. 2024;73(11):1-12.
9. Rubanenko AO, Dyachkov VA, Miroshnichenko AI. Factors affecting adherence to CPAP therapy in patients with obstructive sleep apnea syndrome. Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(5):58-65.
10. Tsai MS, Chen HC, Liu SY, et al. Holistic care for obstructive sleep apnea (OSA) with an emphasis on restoring nasal breathing: A review and perspective. J Chin Med Assoc. 2022;85(6):672-8.
11. Nomura T, Sasaki A, Fujimoto M, Mano M, Suda N, Kondo K. Effects of jaw movement in bimaxillary orthognathic surgery on the upper airway: Computational fluid dynamics analysis. Orthod Craniofac Res. 2023;26(3):311-9.
12. Serra-Torres S, Bellot-Arcis C, Montiel-Company JM, Marco-Algarra J, Almerich-Silla JM. Effectiveness of mandibular advancement appliances in treating obstructive sleep apnea syndrome: A systematic review. Laryngoscope. 2016;126(2):507-14.
13. Sutherland K, Vanderveken OM, Tsuda H, et al. Oral appliance treatment for obstructive sleep apnea: an update. J Clin Sleep Med. 2014;10(2):215-27.
14. Langaliya A, Alam MK, Hegde U, Panakaje MS, Cervino G, Minervini G. Occurrence of Temporomandibular Disorders among patients undergoing treatment for Obstructive Sleep Apnoea Syndrome (OSAS) using Mandibular Advancement Device (MAD): A Systematic Review conducted according to PRISMA guidelines and the Cochrane handbook for systematic reviews of interventions. J Oral Rehabil. 2023;50(12):1554-63.
15. Cohen-Levy J. The influence of obstructive sleep apnea syndrome on the orthodontic treatment decision in children and adolescents. Part 2: Which orthodontic treatments for children with apnea? Orthod Fr. 2023;94(1):173-85.
16. Segu M, Cosi A, Santagostini A, Scribante A. Efficacy of a Trial Oral Appliance in OSAS Management: A New Protocol to Recognize Responder/Nonresponder Patients. Int J Dent. 2021;20211-10.
17. Sokucu O, Oksayan R, Uyar M, Ademci KE, Usumez S. Relationship between head posture and the severity of obstructive sleep apnea. Am J Orthod Dentofacial Orthop. 2016;150(6):945-9.
18. Sfondrini MF, Gallo S, Pascadopoli M, Gandini P, Roncoroni C, Scribante A. Upper Airway Dimensions among Different Skeletal Malocclusions: A Retrospective Observational Study by Cephalometric Analysis. Dent J (Basel). 2024;12(1):1-8.
19. Brown EC, Cheng S, McKenzie DK, Butler JE, Gandevia SC, Bilston LE. Tongue and lateral upper airway movement with mandibular advancement. Sleep. 2013;36(3):397-404.
20. Solow B, Kreiborg S. Soft-tissue stretching: A possible control factor in craniofacial morphogenesis. Scand J Dent Research. 1977;85:505-7.
21. Benjafield AV, Ayas NT, Eastwood RP, Heinze R. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019;8(1):687–98.
Download attachments: 10.4328/ACAM.22523
Oral Sokucu, Dler Mourad, Haluk Goren, Deniz Tuncel. Effect of oral appliances on cephalometric measurements and sleep apnea severity: A clinical study. Ann Clin Anal Med 2025;16(8):549-553
Citations in Google Scholar: Google Scholar
Comparison of the effects of three methods used in the treatment of tubal ectopic pregnancy on tubal patency
Fatma Kılıç Hamzaoğlu 1, Emine Türen Demir 1, Adeviye Elçi Atılgan 2, Fedi Ercan 3, Ali Acar 1
1 Department of Gynecology and Obstetrics, Faculty of Medicine, Necmettin Erbakan University, Konya, 2 Department of Gynecology and Obstetrics, Private Ordu Umut Hospital, Ordu, 3 Department of Gynecology and Obstetrics, Dr. Fedi Ercan Women’s Health Clinic, Aydın, Turkey
DOI: 10.4328/ACAM.22537 Received: 2024-12-25 Accepted: 2025-02-04 Published Online: 2025-02-23 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):554-558
Corresponding Author: Fatma Kılıç Hamzaoğlu, Department of Gynecology and Obstetrics, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkiye. E-mail: dr.fatmakilich@gmail.com P: +90 505 568 70 35 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9735-3552
Other Authors ORCID ID: Emine Türen Demir, https://orcid.org/0000-0001-5510-4411 . Adeviye Elçi Atılgan, https://orcid.org/0000-0003-4833-8979 . Fedi Ercan, https://orcid.org/0000-0003-2175-5405 . Ali Acar, https://orcid.org/0009-0006-1474-3958
This study was approved by the Ethics Committee of Necmettin Erbakan University, Meram Faculty of Medicine (Date: 2015-03-15, No: 2015/223)
Aim: We aimed to compare the three methods used in the treatment of tubal ectopic pregnancy to the effects of tubal patency with hysterosalpingography. This study aims to evaluate the use of methotrexate therapy, surgery, and expectant supervision in the assessment of risks and benefits of the characteristics of individual patients.
Materials and Methods: In our clinic between January 2009- May 2015, 60 patients who were diagnosed with tubal ectopic pregnancy and had treatment and also have no history of previous ectopic pregnancy and tubal surgery enrolled in our study. The first group received treatment with methotrexate, the second group received laparoscopic salpingostomy and the third group received laparotomy which is made tubo-tubal anastomosis with a catheter after the resection of the ectopic pregnancy. The patients without an ipsilateral tubal passage were treated with diagnostic laparoscopy. Data were analyzed using descriptive statistical methods (mean, standard deviation, frequency) quantitative data, and the Mann-Whitney U test. Fisher’s Exact Chi-square test was used to compare the qualitative data. The significance was evaluated as a <0.05 level.
Results: Tubal patency cannot be observed for 5 out of 20 (25%) patients in the MTX group, 4 out of 20 (20%) patients in the salpingostomy group, 1 out of 20 patients (5%)in the anastomosis group.
Discussion: When tubal patency was evaluated for all 3 groups no statistically significant difference was seen (p> 0.05) between the MTX group and salpingotomy groups in terms of tubal patency. But after treatment of anastomosis group tubal patency was monitored statistically significant (p <0.05).
Keywords: Tubal Ectopic Pregnancy, Laparoscopic Salpingostomy, Methotrexate, Tubo-Tubal Anastomosis, Tubal Patency
Introduction
Ectopic pregnancy is described as an instance in which the ovum is fertilized but fails to implant in the cavity of the uterus, rather the fallopian tubes are the most common site for such an occurrence. It may also occur at the tubal, interstitial, ovarian, cervical, abdominal, intraligamentary, or heterotopic sites. Nevertheless, it occurs more often in the ampullar part of the fallopian tubes. The incidence of ectopic pregnancy is roughly estimated to be around 2% of all pregnancies. In the last few decades, an increasing trend in the instances of ectopic pregnancies has been noted. This upsurge is mainly due to the increased rates of pelvic infections, the increase in the number of intrauterine device users, and the increase in the use of surgical procedures for the treatment of infertility [1, 2].
Ectopic pregnancy is diagnosed through integrating obstetric history, gynecological and physical history, ultrasound examination, determination of the beta-hCG levels in serum, culdocentesis, D&C, and laparoscopy. Methotrexate (MTX) therapy is commonly used in the treatment of ectopic pregnancy, but it needs proper characterization of the clinical features as well as the rate of success [3, 4]. Medical, surgical, and expectant management can all be employed in the management of ectopic pregnancy, and all methods appear to be effective. Effective treatment options are guided by the clinical conditions, the site of the ectopic pregnancy, and the actual resources available. Both ectopic pregnancy and the treatment utilized have the potential of causing damage to the fallopian tubes which is a major risk factor in women who wish to conceive in the future [5, 6].
The objective of preparing this study is to evaluate and compare the effectiveness of three different methods of performing surgery for ectopic pregnancy on the patency of the fallopian tubes. This assessment will enable the evaluation of treatment options and their effect on the patency of fallopian tubes and subsequently, fertility available to the woman while minimizing chances of ectopic pregnancy. This study aims to evaluate the use of methotrexate therapy, surgery, and expectant supervision in the assessment of risks and benefits concerning the characteristics of individual patients.
Materials and Methods
The purpose of this study was to evaluate the tubal patency rates following the treatment of tubal ectopic pregnancies with methotrexate (MTX) laparoscopic salpingostomy or the catheter-assisted tubo-tubal anastomosis methods. The research was conducted retrospectively by reviewing the medical records of patients hospitalized with a diagnosis of tubal ectopic pregnancy between January 2009 and March 2015 at Necmettin Erbakan University, Meram Faculty of Medicine, Department of Obstetrics and Gynecology. Before the study commenced, clearance was obtained from the Necmettin Erbakan University Meram Faculty of Medicine Ethics Committee.
The inclusion criteria of the study were 60 patients aged between 20 and 44 years who never had contact with ectopic pregnancy or tubal surgery and who were recruited in this study. These women were subjected to hysterosalpingography(HSG) 6 months after treatment and if no ipsilateral tubal patency was observed, diagnostic laparoscopy was performed. For treatment of ectopic pregnancy patients were categorized into three groups of twenty each according to the management technique used: those who received strawberry Texas sisters; the salpingostomy group, including patients who ended up having laparoscopic salpingostomy; and the anastomosis group which included patients who had laparotomy and underwent catheter assisted tubo-tubal anastomosis. Women who had had salpingectomy, salpingotomy, or had heterotopic pregnancy were not included in the trial. These treatment approaches have been followed based on specific criteria (Table 4).
Women were chosen by looking backward at their records of gynecological history and examinations; β-hCG check-ups, transvaginal ultrasound, and D & C to verify tubal ectopic pregnancy. For those who were surgically operated on, the diagnosis of the disease was confirmed by histopathological examinations of the operated parts. For instance, in women who were administered MTX, the diagnosis was based on the absence of the chorionic villi in the D & C specimen, while there was a clear mass of ectopic pregnancy observable in the ultrasound outside the corpus luteum.
The age of the patients, the pre-treatment serum β-hCG levels, hemogram and liver and kidney function tests (LFT and KFT), the results of the TVUSG examination, the site of ectopic pregnancy, the size of the ectopic pregnancy if present, and the presence of fetal heart sounds were all documented for every patient.
The patients who received MTX treatment in a single-dose MTX protocol were included in this group. On Day 1, women received MTX at a dosage of 50mg/m². Only one patient was given MTX on Day 7 through an unplanned policy due to having a serum β-hCG decrease of less than 15%.
Laparoscopic salpingostomy is performed on hemodynamically stable women who have not yet ruptured tubal ectopic pregnancy. A linear cautery incision of a length of 2 cm was done on the antimesenteric border of the mass of ectopic pregnancy to permit the excision of the ectopic tissue. Hemostasis was achieved and the procedure was completed.
A combination of catheter-assisted and tubo-tubal anastomosis techniques was used in women with ruptured, hemodynamically unstable tubal ectopic pregnancies. The excised tube was a 20G epidural catheter at one of its ends through the medial portions of the upper Gonadal tubal and then towards its fundus end. The advancing lateral end of the upper Gonadal tubal pointed anteriorly and was fimbrial. The aligned sides of the upper Gonadal tubal were sutured with six zero Vicryl over the tip of the catheter insertion tube. The cut lateral end of the catheter that pointed anteriorly and fimbrial was guided through the abdominal wall and removed after forty-eight hours following the surgery.
In each of the 3 treatment groups, women who responded and benefited from the treatment were called after six months to have HSGs done after normalization of serum β-hCG levels. Women with the loss of opposite-sided tubal patency previously confirmed by HSG proceeded to diagnostic laparoscopy to confirm the passage of the methylene blue dye out of the cervical by looking at the tubes.
The clinical and demographic variables including the treatment outcomes were assessed for the females who had the HSG and the diagnostic laparoscopes aimed at patency of the tubes.
Statistical Analysis
The verification of the findings of this study makes use of SPSS 16 Statistical Software as well as statistical analyses. For the analysis of the data, several descriptive statistical methods such as mean, standard deviation, and frequency were utilized. A Mann-Whitney U test was used for the comparison of quantitative variables. In the case of the comparison of qualitative variables, a Fisher’s Exact Chi-Square test was used. Statistical significance was set at the p<0.05 level.
Ethical Approval
This study was approved by the Ethics Committee of Necmettin Erbakan University, Meram Faculty of Medicine (Date: 2015-03-15, No: 2015/223).
Results
Patients aged between 20 and 44 years with sixty patients in the study are the focal point. Three groups were formed based on the treatment applied to the twenty patients: MTX, L/S, and L/P. In particular, the study spanned from January 2009 until March 2015.
The average age of the MTX group was 30.90 years, the salpingostomy group aged 28.75 years and below, and the anastomosis group had an average age of 30.90. Across the three treatments, the average age difference was insignificant.
The participants enrolled in the MTX group had pre-treatment levels of β-hCG levels that varied in value between 244 to 7542 mIU/mL with a mean of 2287±1735 mIU/mL. Except for a single participant who received a second dose, all participants in the MTX group were treated with a single MTX dose. β- hCG of the salpingostomy group had endpoints of 360 to 15,810, with 7611.395±4615.53 as their average. For the anastomosis group minimum and maximum levels of β-hCG were 244 and 19,435 mIU/mL respectively while the mean value was 6468.25±5069.82 mIU/mL. Between the salpingostomy and anastomosis groups, they had pre-treatment β-hCG levels within the same range, however when compared to β-hCG levels in the MTX group, the levels were significantly lower as was statistically established with (p<0.05).
In terms of measurement using transvaginal ultrasonography (TVUSG), the ectopic pregnancy that was measured weighed within a range of 16.20±5.80 mm for the MTX group, 26.25±11.36 mm for the salpingostomy group and 28.89±4.84 mm for the anastomosis group. The range of sizes of the ectopic pregnancies as measured by ultrasonography differed across the three groups as the p-value was greater than 0.05.
The TTG obtained results for six patients who were confirmed to have prima-facie tubal patency, this was for the MTX group who showed HSG results of absence of ipsilateral tubal patency. During the procedures one of these six patients was revealed to have tubal patency and the other five did not hence, there were no tubal patency for the five patients (25%) identified in the MTX group.
Ninety-five % of the merged tubular group achieved a surgical conception. A thirty-eight-year-old woman with bilateral salpingostomy went on to achieve pregnancy even with transection of the conjoined tubes.
Fifty-eight percent of patients in the tubal implantation and reconstruction group achieved conception through assisted reproductive techniques. These specific patients with reached an average age of thirty-eight years were able to carry the child to term, a fallback surgical conception taking effect due to well-nourished tubal implantation.
With the results of the subgroups completed, an impression of conclusive relevance with thirty-seven percent of pregnancies resulting in a live birth rate with six–seven average tubal tone through the mechanochemistry transposition technology. Though the targets have been achieved, patient well-being should be prioritized when operating.
Discussion
Ectopic pregnancy is a serious condition that compromises women’s future fertility and, in cases of delayed diagnosis, can pose a life-threatening risk. Recent advances in ectopic pregnancy treatment and early diagnosis have significantly reduced postoperative morbidity and preserved fertility potential [7].
While recurrence rates of ectopic pregnancy are similar after radical and conservative treatments, intrauterine pregnancy rates are higher following conservative tubal surgery [8-10]. Management in diagnosed cases is planned based on factors such as gestational age, implantation site, vital signs, the presence of comorbidities, and patient cooperation. Historically, radical surgical methods were commonly used for treating ectopic pregnancy; However, conservative treatment approaches have gained popularity to enhance fertility chances. For patients desiring fertility, systemic methotrexate (MTX) therapy has been proposed as an alternative to laparoscopic salpingostomy. Although hysterosalpingography (HSG) is subject to interpretation challenges, it remains a reliable method for assessing tubal patency.
Elito et al. [11] evaluated tubal patency in 115 cases of ectopic pregnancy treated with medical and surgical methods. They reported ipsilateral tubal patency rates of 84% in MTX-treated cases and 78% in cases managed expectantly. Contralateral tubal patency rates were reported as 97%, 92%, and 83% for MTX, expectant management, and salpingectomy groups, respectively, with no significant differences among the groups. In our study, the ipsilateral tubal patency rate was 25% in the MTX group, compared to 20% and 5% in the salpingostomy and anastomosis groups, respectively.
Hajenius PJ et al. [12] evaluated tubal patency three months after treatment in patients receiving laparoscopic salpingostomy and 1 mg/kg IM MTX + 0.1 mg/kg folinic acid. No significant difference in ipsilateral tubal patency was observed between the two treatment types. Similarly, Sowter et al. [13] found no difference in ipsilateral tubal patency between patients treated with a single dose of 50 mg/m² methotrexate and those undergoing laparoscopic salpingostomy. A study comparing the outcomes of multiple fixed-dose MTX therapy and laparoscopic salpingostomy revealed better tubal patency with salpingostomy but without a statistically significant difference. A meta-analysis evaluating multiple-variable dose MTX therapy and laparoscopic salpingostomy in 115 women also found no significant difference between the groups [14]. Consistent with these findings, our study also demonstrated no statistically significant difference in tubal patency between MTX therapy and laparoscopic salpingostomy.
Lundorff et al. [15] assessed tubal patency in patients undergoing laparoscopic salpingostomy and laparotubal anastomosis for ectopic pregnancy, reporting higher patency rates in the anastomosis group. Vermesh et al. [16] found similar results in a smaller patient population. In one study evaluating tubal patency after tubal pregnancy, the success of salpingostomy with and without suturing was compared. Tubal patency was evaluated three months postoperatively using HSG or second-look laparoscopy. Ipsilateral tubal patency rates were 94% in the sutured group and 90% in the non-sutured group, while pregnancy rates were 92% in the non-sutured group and 79% in the sutured group. No significant difference in cumulative pregnancy rates was found between the two groups [17]. In our study, tubal patency was significantly higher in the group treated with catheter-assisted tubal-tubal anastomosis compared to laparoscopic salpingostomy. Additionally, a 20G epidural catheter was placed in the laparotubal anastomosis group and removed 48 hours postoperatively to minimize postoperative adhesion formation and promote healthy tubal healing. Although catheter use in reconstructive tubal surgeries has been reported, no studies have specifically addressed catheter use in tubal ectopic pregnancies.
Colacurci et al. [18] evaluated tubal patency based on initial β-hCG levels in patients undergoing laparoscopic salpingostomy. They assessed patients with β-hCG levels above and below 10,000 IU/ml three months postoperatively and concluded that β-hCG levels did not significantly affect tubal patency in this retrospective study. Conversely, another study suggested a correlation between increasing β-hCG levels and the development of tubal obstruction [19].
The outcomes of this research and the benchmark with other previous research emphasize the need for individualized management strategies based on β-hCG status, the size of the ectopic pregnancy, and the hemodynamic state of the patient. On the one hand, MTX represents an option that is less invasive for selected patients, and on the other hand, surgical procedures result in better results in tubal surgery especially among women with increased β-hCG titer or larger size of the ectopic pregnancy. In addition, the considerably higher tubal patency rate among the anastomosis group suggests that more advanced surgical techniques may be effective in limiting the loss of fertility in women who have ruptured ectopic pregnancies.
Limitation
Several constraints in this study need consideration while interpreting the results. First of all, the number of the sample, which was only 60 patients divided into three groups, was rather low, which might affect the ability to generalize the findings. Second, the retrospective design of the study might have introduced some selection bias and lacked the power to adjust for confounding factors. Third, the timeframe of the follow-up was restricted to six months following treatment which may not adequately reflect the late reproductive outcomes and tubal patency rates. Further, the study was undertaken in a single tertiary center which does not necessarily mean that similar healthcare outcomes would be obtainable in healthcare centers with different levels of expertise and resources.
Conclusion
This study sheds light on the real-world effectiveness of methotrexate (MTX), laparoscopic salpingostomy, and catheter-assisted tubo-tubal anastomosis in the treatment of tubal ectopic pregnancies. It emphasizes the need for treatment plans to be customized based on the patient’s conditions including β-hCG levels, the size of the ectopic sac, and the hemodynamic state of the patient. MTX is applicable for those stable patients who have certain clinical parameters, but surgical approaches, in particular, tubo-tubal anastomosis provide more clinical tubal function and low uterine pregnancy rates. The drastically higher pregnancy success rates in the group that underwent anastomosing are a clear indication of the advancement of reproductive techniques in complex situations. More effective ways of managing tubal ectopic pregnancy can be developed along this line and conclusively confirmed through larger studies with longitudinal follow-up of the cohort. Further studies with greater sample sizes, prospective designs, and longer duration of follow-up are necessary to validate these results and build on the management plans for tubal ectopic pregnancies.
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. Baggio S, Garzon S, Russo A, et al. Fertility and reproductive outcome after tubal ectopic pregnancy: Comparison among methotrexate, surgery, and expectant management. Arch Gynecol Obstet. 2021;303(1):259-68.
2. Grigoriu C, Bohiltea RE, Mihai BM, et al. Success rate of methotrexate in the conservative treatment of tubal ectopic pregnancies. Exp Ther Med. 2022;23(2):150.
3. Zhang J, Zhang Y, Gan L, Liu XY, Du SP. Predictors and clinical features of methotrexate (MTX) therapy for ectopic pregnancy. BMC Pregnancy Childbirth. 2020;20(1):1-9.
4. Ozyuncu O, Tanacan A, Duru SA, Beksac MS. Methotrexate therapy for ectopic pregnancies: A tertiary center experience. Rev Bras Ginecol Obstet. 2018;40(11):680-5.
5. Gervaise A, Masson L, de Tayrac R, Frydman R, Fernandez H. Reproductive outcome after methotrexate treatment of tubal pregnancies. Fertil Steril. 2004;82(2):304-8.
6. Solangon SA, Van Wely M, Van Mello N, Mol BW, Ross JA, Jurkovic D. Methotrexate vs expectant management for treatment of tubal ectopic pregnancy: An individual participant data meta-analysis. Acta Obstet Gynecol Scand. 2023;102(9):1159-75.
7. Jiménez-Oliver KD, Ortiz MI, Barragán-Ramírez G. Ectopic pregnancy: Incidence associated with fertility treatment. Clin Exp Obstet Gynecol. 2023;50(11):233-42.
8. Miao H. Comparative analysis of laparoscopy versus laparotomy approaches in treating ectopic pregnancy. Adv Obstet Gynecol Res.2023;1(3):33-7.
9. De Cherney AH, Maheaux R, Naftolin F. Salpingostomy for ectopic pregnancy in the sole patent oviduct: reproductive outcome. Fertil Steril. 1982;37(5):69.
10. Selvaraj Y. Conservative management of unruptured ectopic pregnancy: A retrospective study. Surg Sci. 2024;15(10):536-46.
11. Elito J, Han KK, Camano L. Tubal patency after clinical treatment of unruptured ectopic pregnancy. Int J Gynaecol Obstet. 2005;88(3):309-13.
12. Hajenius PJ, Engelsbel S, Mol BW, et al. Randomized trial of systemic methotrexate versus laparoscopic salpingostomy in tubal pregnancy. Lancet. 1997;350(9080):774-9.
13. Sowter MC, Farquhar CM, Petrie KJ, Gudex G. A randomized trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy. BJOG. 2001;108(2):192-203.
14. El-Sherbiny MT, El-Gharieb IH, Mera IM. Methotrexate versus laparoscopic surgery for the management of unruptured tubal pregnancy. Middle East Fertil Soc J. 2003;8(3):256-62.
15. Lundorff P, Thorburn J, Hahlin M, Kallfelt B, Lindblom B. Laparoscopic surgery in ectopic pregnancy: A randomized trial versus laparotomy. Acta Obstet Gynecol Scand. 1991;70(4-5):343-8.
16. Vermesh M, Silva PD, Rosen GF, Stein AL, Fossum GT, Sauer MV. Management of unruptured ectopic gestation by linear salpingostomy: A prospective, randomized clinical trial of laparoscopy versus laparotomy. Obstet Gynecol. 1989;73(3):400-4.
17. Fujishita A, Masuzaki H, Khan KN, Kitajima M, Hiraki K, Ishimaru T. Laparoscopic salpingotomy for tubal pregnancy: Comparison of linear salpingotomy with and without suturing. Hum Reprod. 2004;19(5):1195-200.
18. Colacurci N, Zarcone R, de Franciscis P, Mele D, Mollo A, de Placido G. Tubal patency after laparoscopic treatment of ectopic pregnancy. Panminerva Med. 1998;40(1):45-7.
19. Elito J, Han KK, Camano L. Values of beta-human chorionic gonadotropin as a risk factor for tubal obstruction after tubal pregnancy. Acta Obstet Gynecol Scand. 2005;84(9):864-7.
Download attachments: 10.4328.ACAM.22537
Fatma Kılıç Hamzaoğlu, Emine Türen Demir, Adeviye Elçi Atılgan, Fedi Ercan, Ali Acar. Comparison of the effects of three methods used in the treatment of tubal ectopic pregnancy on tubal patency. Ann Clin Anal Med 2025;16(8):554-558
Citations in Google Scholar: Google Scholar
Evaluation of laboratory parameters in patients with acute gastroenteritis caused by salmonella enteritidis
Gökhan Eyüpoğlu 1, Ertuğrul Altuğ 1, Adem Çakır 2, Kemal Şener 3, Halil Ölmez 1, Selda Kömeç 4, Ramazan Güven 1
1 Department of Emergency Medicine, Başakşehir Cam and Sakura City Hospital, Istanbul, 2 Department of Emergency Medicine, Canakkale Mehmet Akif Ersoy State Hospital, Canakkale, 3 Department of Emergency Medicine, Mersin City Hospital, Mersin, 4 Microbiology and Clinical Microbiology, Başakşehir Cam and Sakura City Hospital, Istanbul, Türkiye
DOI: 10.4328/ACAM.22575 Received: 2025-01-20 Accepted: 2025-02-24 Published Online: 2025-03-06 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):559-563
Corresponding Author: Gökhan Eyüpoğlu, Department of Emergency Medicine, Başakşehir Cam and Sakura City Hospital, Istanbul, Türkiye. E-mail: gokhanbey982@gmail.com P: +90 555 422 34 83 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8583-3690
Other Authors ORCID ID: Ertuğrul Altuğ, https://orcid.org/0000-0001-6807-643X . Adem Çakir, https://orcid.org/0000-0002-4966-4882 . Kemal Şener, https://orcid.org/0000-0002-8579-6663 . Halil Ölmez, https://orcid.org/0000-0001-7191-8167 . Selda Kömeç, https://orcid.org/0000-0002-6726-0048 . Ramazan Güven, https://orcid.org/0000-0003-4129-8985
This study was approved by the Ethics Committee of Basaksehir Cam and Sakura City Hospital (Date: 2023-06-22, No: 281)
Aim: Gastroenteritis, an inflammation of the stomach and small intestine, presents with symptoms such as diarrhea, abdominal pain, nausea, and vomiting. Salmonella Enteritidis, a significant bacterial pathogen commonly transmitted via poultry and eggs, can cause severe complications, particularly in immunocompromised individuals. Rapid diagnosis is crucial in emergency settings, highlighting the need for effective diagnostic tools. This study investigates the utility of the Systemic Immune-Inflammation Index in diagnosing SE infections.
Materials and Methods: This retrospective study, conducted in the emergency department of an urban hospital from May 1 to June 1, 2024, included 29 adult patients with acute gastroenteritis. Data on demographics, clinical parameters, and laboratory test results were analyzed. SE-positive and SE-negative patients were compared regarding systemic inflammation markers and clinical features. Statistical analyses using SPSS version 26.0 assessed the diagnostic value of SIII and other parameters through ROC curve analysis.
Results: SE was identified in 12 of the 29 patients. SE-positive individuals showed significantly higher levels of platelets, C-reactive protein, creatinine, and SIII compared to SE-negative patients (p<0.05). Specifically, SIII with a cutoff of 1209.17 had 100% sensitivity and 41.2% specificity (p=0.042). CRP with a cutoff of 27.50 showed 83.3% sensitivity and 64.7% specificity (p=0.010). NLR analysis was not statistically significant. Additionally, creatinine levels were notably higher in SE-positive patients.
Discussion: SIII appears to be a valuable diagnostic parameter for SE in emergency department gastroenteritis cases. It may aid in rapid decision-making for suspected SE infections. Further multicenter studies are necessary to confirm and generalize these findings.
Keywords: Gastroenteritis, Salmonellosis, Systemic Immune-Inflammation Index, Emergency Department
Introduction
Gastroenteritis is a common condition characterized by inflammation of the gastrointestinal tract, affecting the stomach and small intestine. It typically presents with sudden onset of diarrhea, abdominal pain, nausea, and vomiting. It is often triggered by viral infections (e.g., rotavirus, norovirus), bacterial pathogens (e.g., Escherichia coli, Salmonella spp.), or parasites (Giardia lamblia, Cryptosporidium spp.). Gastroenteritis is a widespread cause of morbidity and mortality among children and adults globally, and can lead to serious health issues, particularly in developing countries [1, 2].
While gastroenteritis cases in developed countries are generally self-limiting and mild, they can have severe consequences in individuals with weakened immune systems or in communities with limited access to healthcare. The treatment of gastroenteritis is usually symptomatic, focusing on maintaining fluid and electrolyte balance. However, severe cases may require antibiotic or antiviral therapy [3, 4].
Salmonella Enteritidis (SE) is one of the most common bacterial species causing acute gastroenteritis worldwide. A Gram-negative bacterium, SE is primarily found in poultry and eggs and is transmitted to humans typically through the consumption of these foods. The bacterium colonizes the intestinal mucosa, leading to infection and gastroenteritis symptoms such as diarrhea, abdominal pain, fever, and nausea [5, 6].
SE infections constitute a significant public health concern in both developed and developing countries. The spread of infection has become a major issue, particularly in areas with poor hygiene standards. Furthermore, inadequate controls in food production and processing can lead to outbreaks. The development of antibiotic resistance also complicates treatment, potentially leading to more severe outcomes [5-7]. Enhancing food safety measures plays a crucial role in preventing the spread of SE [7, 8].
The Systemic Immune-Inflammation Index (SIII) is a novel systemic inflammation prognostic marker associated with the outcomes of many chronic/acute inflammatory diseases, as well as malignancies [9, 10]. The ease of calculation, low cost, and reliance solely on a complete blood count, without subjective findings, suggest that SIII may also be useful in the diagnosis of gastroenteritis caused by SE.
In our study, we investigated the utility of the systemic immune-inflammatory index in detecting SE in patients presenting with acute gastroenteritis to the emergency department.
Materials and Methods
Study Design
Our study was conducted in the emergency department of a city hospital that serves as a training and research hospital. Necessary permissions were obtained before starting the study, and the study commenced thereafter. This study is a single-center, retrospective, observational study. The study was carried out between May 1, 2024, and June 1, 2024.
Study Setting and Population
Patients presenting to our hospital’s emergency department with symptoms of nausea, vomiting, abdominal pain, and diarrhea, and meeting the inclusion criteria, were included in the study. The ICD-10 diagnosis code A09 (acute infectious diarrhea and gastroenteritis) was used in the hospital automation system to identify the patients.
The participants in the study were adult patients diagnosed with acute gastroenteritis. The cause of infection was confirmed through stool cultures. Patients were excluded from the study if they had other pathologies causing abdominal pain, incomplete treatments, stool cultures showing mixed or contaminated microbial agents, or missing data.
Demographic data (age and gender), clinical data, and laboratory test results (leukocytes (WBC), neutrophils, lymphocytes, platelets, urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), stool direct microscopy, and stool culture) for the included patients were obtained from the hospital automation system and patient files. Using these laboratory parameters, the NLR and SIII values were calculated.
Microbiologic Examination
Stool samples from patients were inoculated on Hecto Enteric (HE) agar and Salmonella Shigella (SS) agar media. After incubation at 37°C for 16-24 hours, suspicious colonies were identified using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) (EXS 2600, Zybio, China). Upon identifying Salmonella spp. at the genus level, Salmonella antiserum (Difco, BD, USA) was used to identify the species level.
Statistical Analysis
Data were analyzed using SPSS Statistics Software version 26.0. Descriptive statistics including frequency, percentage, mean, standard deviation, median, minimum, and maximum were used to present the data. The normality of the data distribution was assessed using the Kolmogorov-Smirnov Test. In univariate analysis, continuous variables showing normal distribution were expressed as Mean ± SD and compared using the T-Test. The Pearson Chi-Square Test was employed for the analysis of categorical variables. Fisher’s Exact Test was used when the number of categorical variables was less than five. The T-Test was utilized for comparing two independent numerical data sets. Diagnostic accuracy was evaluated using Receiver Operating Characteristic (ROC) curve analysis. Optimal cutoff values were determined, and sensitivity and specificity values were calculated for parameters with an Area Under the Curve (AUC) greater than 0.600.
A significance level of p <0.05 was considered.
Ethical Approval
This study was approved by the Ethics Committee of Basaksehir Cam and Sakura City Hospital (Date: 2023-06-22, No: 281).
Results
A total of 29 enteritis cases were included in our study. These patients were evaluated, and symptomatic treatments were initiated. Stool cultures were obtained from all cases before starting treatment. Of these, 12 cases tested positive for SE, while the remaining 17 cases tested negative for SE.
Among the 29 patients included in the study, 2 (6.9%) were female and 27 (93.1%) were male. The average age of the patients was 31.00 ± 12.57 years. The vital signs upon admission showed an average systolic blood pressure of 115.10 ± 17.48 mmHg, average diastolic blood pressure of 69.48 ± 14.76 mmHg, average pulse rate of 97.97 ± 18.90 beats per minute, average oxygen saturation of 98.31 ± 1.07%, and an average body temperature of 36.73 ± 0.70°C.
When grouped by SE positivity, the average age was similar between the SE-positive and SE-negative groups (29.17 ± 12.71 vs. 32.29 ± 12.69; p = 0.519). No significant relationship was found between SE positivity and gender. Comparison of vital signs by SE positivity revealed no significant differences in any of the parameters between the two groups.
Laboratory test results of SE-positive and SE-negative groups were compared, showing that the mean values of Platelet Count (PLT), C-Reactive Protein (CRP), creatinine, and SIII were significantly higher in the SE-positive group compared to the SE-negative group (p=0.004, p=0.034, p<0.001, and p=0.033, respectively). However, no statistically significant differences were found in the mean values of White Blood Cell Count (WBC), neutrophils, lymphocytes, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Neutrophil-to-Lymphocyte Ratio (NLR) (Table 1).
ROC curve analysis to determine the diagnostic value of SIII, NLR, and CRP showed that a cutoff value of 1209.17 for SIII had a sensitivity of 100% and a specificity of 41.2% (AUC: 0.725; 95% CI: 0.541-0.910; p=0.042). Similarly, a cutoff value of 27.50 for CRP had a sensitivity of 83.3% and a specificity of 64.7% (AUC: 0.784; 95% CI: 0.618-0.950; p=0.010). ROC analysis for NLR did not show statistical significance (Table 2 and Figure 1).
Discussion
SE is a significant gastrointestinal pathogen that presents diagnostic challenges in emergency departments. Patients typically present with non-specific symptoms, including abdominal pain, diarrhea, fever, and vomiting, which complicates clinical differentiation from other gastrointestinal infections. Diagnosis of Salmonella infection is usually confirmed through stool cultures; however, the results of these tests can take several days, which conflicts with the need for rapid decision-making in an emergency setting. Rapid and accurate diagnosis is particularly important in risk groups such as immunocompromised patients, the elderly, and young children, as infections in these groups can lead to more severe complications. Additionally, with increasing concerns about antibiotic resistance, sensitivity testing is crucial for selecting appropriate treatment. Therefore, emergency physicians need to be aware of existing diagnostic methods and their limitations to expedite diagnostic processes and initiate appropriate treatment when SE infection is suspected [11, 12]. Considering that some diagnostic tests in emergency departments may requrie extended time to yield results, emergency physicians may use supportive parameters to strengthen preliminary diagnoses and initiate early treatment if necessary. In our study, we found that SIII and CRP levels were significantly elevated in patients who presented to the emergency department and were diagnosed with SE. Furthermore, ROC Curve analysis showed that a cutoff value of 1209.17 for SIII had a sensitivity of 100% and a specificity of 41.2% (AUC: 0.725; 95% CI: 0.541-0.910; p = 0.042). In this context, we determined SIII to be a significant parameter in supporting the diagnosis of SE.
Treatment of Salmonella infections is typically symptomatic. These infections often resolve spontaneously, and therapeutic treatment may not be required. However, in immunocompromised or elderly patients, Salmonella infections can lead to a wide range of outcomes, including severe complications and even mortality. In a case report by Sundbom et al., myocarditis was identified in a patient with gastroenteritis despite symptomatic treatment, and SE positivity was subsequently detected [13]. Katsenos et al. reported a case of meningitis following Salmonella infection in an immunosuppressed patient with AIDS, who unfortunately died on the 8th day of the illness despite treatment [14]. Similarly, Vidal et al. presented a case of liver abscess following SE infection in a patient with HIV [15]. Arda et al. reported a case of prosthetic infection associated with SE [16]. Tsugawa et al. described infective endocarditis following SE infection in a patient undergoing hemodialysis for chronic kidney disease [17]. Gönen et al. reported prosthetic valve endocarditis following SE infection [18]. These literature reports indicate that while SE infections can resolve with symptomatic treatment, they can also lead to life-threatening infectious complications across various systems. Therefore, especially in emergency departments, where gastroenteritis cases frequently present, SE should be considered or identified, and initiating treatment in immunosuppressed or patients with a history of chronic illness can be life-saving.
SE is frequently transmitted through food and is known to cause outbreaks, particularly in settings with poor hygiene. A study by Pijnacker et al. reported SE positivity among individuals eating at food establishments using eggs from Poland, leading to outbreaks in European countries [19]. Rounds et al. found SE in cases associated with frozen chicken products in Minnesota, which resulted in an outbreak [20]. Hedican et al. reported a cluster of gastroenteritis cases following sandwich consumption at a restaurant in the United States, with SE positivity detected [21]. As demonstrated in the literature, SE-related infections can range from simple gastroenteritis to outbreaks and even serious infections leading to mortality in immunosuppressed individuals.
In our study, we also observed that creatinine levels were significantly higher in cases with SE infection compared to SE-negative cases. This suggests that in cases of gastroenteritis, elevated creatinine levels may indicate the need for proper fluid replacement therapy and that identifying the etiological agent could be beneficial. Besides elevated SIII and CRP, elevated creatinine might also be considered a supportive finding for SE diagnosis in our study.
Limitation
Our study has several limitations. The primary limitation of our study is its single-center design and small sample size. We attribute the small sample size to the fact that diagnosis codes given to patients presenting to the emergency department depend on the physician’s preliminary diagnosis, which may vary and affect the number of patients included. Another limitation is the retrospective nature of the study. However, we believe that these limitations did not significantly impact our results.
Conclusion
In patients presenting with gastroenteritis in the emergency department, outcomes can range from mild symptoms to mortality, depending on the clinical condition and medical history (such as chronic illnesses, immunosuppression, comorbid infections, etc.). Identifying the causative agent is essential, but this process is often delayed in emergency settings. Therefore, we believe that SIII is an important parameter for supporting diagnosis in these patients in the emergency department. However, to generalize our results, multi-center studies are needed.
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. Black RE, Cousens S, Johnson HL, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375(9730):1969-87.
2. Walker CLF, Rudan I, Liu L, et al. Global burden of childhood pneumonia and diarrhoea. Lancet. 2013;381(9875):1405-16.
3. Kosek M, Bern C, Guerrant RL. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ. 2003;81(3):197-204.
4. GBD 2016 Lower Respiratory Infections Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18(11):1191-210.
5. European Food Safety Authority; European Centre for Disease Prevention and Control. The European Union One Health 2019 Zoonoses Report. EFSA J. 2021;19(2):e06406.
6. Eng SK, Pusparajah P, Ab Mutalib NS, Ser HL, Chan KG, Lee LH. Salmonella: A review on pathogenesis, epidemiology and antibiotic resistance. Front. Life Sci. 2015;8(3):284–93.
7. Scallan E, Hoekstra RM, Angulo FJ, et al. Foodborne illness acquired in the United Statesmajor pathogens. Emerg Infect Dis. 2011;17(1):7-15.
8. Kirk MD, Pires SM, Black RE, et al. World Health Organization Estimates of the Global and Regional Disease Burden of 22 Foodborne Bacterial, Protozoal, and Viral Diseases, 2010: A Data Synthesis. PLoS Med. 2015;12(12):e1001921.
9. Altuğ E, Kılavuz H, Çakir A, Şener K, Güven R, Korkut S. Diagnostic value of systemic immune inflammation index in acute appendicitis and complicated appendicitis in pregnant patients. Langenbecks Arch Surg. 2024;409:222.
10. Telafarlı MA, Yeni M. The diagnostic value of the systemic immune-inflammatory index in acute appendicitis cases in the emergency department. Langenbecks Arch Surg. 2023;408(1):136.
11. Ao TT, Feasey NA, Gordon MA, Keddy KH, Angulo FJ, Crump JA. Global burden of invasive nontyphoidal Salmonella disease, 2010(1). Emerg Infect Dis. 2015;21(6):941-9.
12. Chiu CH, Su LH, Chu C. Salmonella enterica serotype Choleraesuis: epidemiology, pathogenesis, clinical disease, and treatment. Clin Microbiol Rev. 2004;17(2):311-22.
13. Sundbom P, Suutari AM, Abdulhadi K, Broda W, Csegedi M. Salmonella enteritidis causing myocarditis in a previously healthy 22-year-old male. Oxf Med Case Rep. 2018;2018(12):106.
14. Katsenos C, Anastasopoulos N, Patrani M, Mandragos C. Salmonella enteritidis meningitis in a first-time diagnosed AIDS patient: case report. Cases J. 2008;1(1):5.
15. Vidal JE, da Silva PR, Schiavon Nogueira R, Bonasser Filho F, Hernandez AV. Liver abscess due to Salmonella enteritidis in a returned traveler with HIV infection: case report and review of the literature. Rev Inst Med Trop Sao Paulo. 2003;45(2):115-7.
16. Arda B, Sipahi OR, Yamazhan T, Emircan I, Aksu K, Ulusoy S. Salmonella enteritidis related prosthetic joint infection. West Indian Med J. 2006;55(6):454-55.
17. Tsugawa Y, Futatsuyama M, Furukawa K, Taki F, Nishizaki Y, Tamagaki K, et al. Infective endocarditis caused by Salmonella enteritidis in a dialysis patient: a case report and literature review. BMC Infect Dis. 2009;9:161.
18. Gönen C, Topeli A, Cetinkaya YS. Prosthetic valve endocarditis caused by Salmonella enteritidis. Scand J Infect Dis. 2004;36(1):72-5.
19. Pijnacker R, Dallman TJ, Tijsma ASL, et al. An international outbreak of Salmonella enterica serotype Enteritidis linked to eggs from Poland: a microbiological and epidemiological study. Lancet Infect Dis. 2019;19(7):778-86.
20. Rounds JM, Taylor AJ, Eikmeier D, et al. Prospective Salmonella Enteritidis surveillance and outbreak detection using whole genome sequencing, Minnesota 2015-2017. Epidemiol Infect. 2020;148:e254.
21. Hedican E, Hooker C, Jenkins T, et al. Restaurant Salmonella Enteritidis outbreak associated with an asymptomatic infected food worker. J Food Prot. 2009;72(11):2332-6.
Download attachments: 10.4328.ACAM.22575
Gökhan Eyüpoğlu, Ertuğrul Altuğ, Adem Çakır, Kemal Şener, Halil Ölmez, Selda Kömeç, Ramazan Güven. Evaluation of laboratory parameters in patients with acute gastroenteritis caused by salmonella enteritidis. Ann Clin Anal Med 2025;16(8):559-563
Citations in Google Scholar: Google Scholar
Efficacy of microwave therapy in the treatment of viral warts: A cross-sectional study from Saudi arabia
Dhaifallah Alenizi
Department of Medicine, Faculty of Medicine, Norther Border University, Arar, Saudi Arabia
DOI: 10.4328/ACAM.22576 Received: 2025-01-20 Accepted: 2025-02-24 Published Online: 2025-03-07 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):564-567
Corresponding Author: Dhaifallah Alenizi, Department of Dermatology, Faculty of Medicine, Norther Border University, Arar, Saudi Arabia. E-mail: Daalenizi@nbu.edu.sa P: +966 55 691 5555 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8571-2231
This study was approved by the Ethics Committee of Northern Border University (Date: 2024-6-25, No: 89/24/H)
Aim: Microwave therapy has emerged as a promising treatment modality for viral warts, showing potential in improving treatment outcomes. Therefore, this study evaluated the safety and efficacy of microwave therapy in the treatment of viral warts.
Materials and Methods: A cross-sectional study was conducted at Alkhibrah Medical Complex in Arar, Saudi Arabia. The study enrolled patients presenting with viral warts and treated with microwave therapy. Data was collected using a standardized data collection form, including age, gender, wart characteristics (size, location, number), treatment response, and recurrence.
Results: A total of 30 patients were included in the study. The participants’ ages ranged from 6 months to 45 years. Female participants were 16 (53.3%), while 14 (46.7%) were male. The most common anatomical locations of warts were the hands (40.0%). Microwave therapy led to complete wart eradication of 22 patients (73.3%). The number of sessions received by the enrolled cases till successful eradication varied between 2 and 5 sessions. Follow-up data revealed recurrence among only 4 patients (18.2%). There was no effect of the demographic and clinical characteristics on the outcomes and recurrence data.
Discussion: Microwave therapy represents a highly effective and convenient option for wart management, particularly for single warts. However, higher recurrence rates in multiple warts underscore the need for further optimization of treatment protocols. Future research should focus on addressing the limitations identified in this study, including the development of standardized protocols and comparative trials.
Keywords: Warts, Microwave Therapy, Human Papillomavirus, Warts Recurrence.
Introduction
Viral warts, caused by human papillomavirus (HPV) infection, are a common dermatological condition affecting individuals of all ages. Despite the availability of various treatment modalities, achieving complete and long-lasting clearance of warts remains a challenge [1]. Current treatment modalities include topical salicylic acid, cryotherapy, topical immunotherapy, and cantharidin [2]. Microwave therapy has emerged as a promising treatment modality for viral warts, showing potential in improving treatment outcomes [2].
Recent studies have provided valuable insights into the efficacy and safety of microwave therapy in the management of viral warts. However, there is a lack of data specifically evaluating its use in the Saudi Arabian population. Therefore, this proposal aims to conduct a cross-sectional study at Alkhibrah Medical Complex in Arar, Saudi Arabia, to evaluate the safety and efficacy of microwave therapy in the treatment of viral warts.
Microwave therapy, which utilizes high-frequency electromagnetic waves to heat and destroy abnormal tissue, has shown promise in the treatment of HPV-related conditions. The mechanism of action of microwave therapy in the context of HPV-related conditions is believed to be the generation of thermal energy, which induces cell death and tissue destruction, ultimately eliminating the HPV-infected cells [3]. This approach has been explored as a treatment for various HPV-related conditions, including genital warts, cervical dysplasia, and certain types of HPV-associated cancers.
Several studies have investigated the efficacy and safety of microwave therapy for the management of HPV-related conditions. A systematic review and meta-analysis conducted by Zhang et al. [4] aimed to evaluate the effectiveness of microwave therapy for the treatment of genital warts. The authors reviewed 17 studies involving a total of 1,362 patients and found that microwave therapy had a high overall effective rate, with a pooled clearance rate of 89.1%. The review also indicated that microwave therapy was associated with a relatively low recurrence rate and a good safety profile, with few reported adverse events.
Another study by Zhao et al. [5] focused on the use of microwave therapy for the treatment of cervical intraepithelial neoplasia (CIN), a precancerous condition of the cervix often associated with HPV infection. The study reported that microwave therapy was effective in treating CIN, with a complete response rate of 92.1% and a low recurrence rate of 8.2% during the follow-up period.
In a study conducted by Peng et al. [6], researchers investigated the efficacy of microwave therapy for the treatment of HPV-associated anal intraepithelial neoplasia (AIN). The study demonstrated that microwave therapy was an effective and safe treatment option, with a complete response rate of 86.7% and a low recurrence rate of 13.3% over the follow-up period.
Furthermore, a review by Xu et al. [7] examined the use of microwave therapy for the treatment of HPV-associated head and neck cancers. The review reported promising results, suggesting that microwave therapy holds potential as a minimally invasive and effective treatment option for these types of cancers.
In conclusion, the existing literature suggests that microwave therapy is a promising treatment modality for various HPV-related conditions, including genital warts, cervical dysplasia, and HPV-associated cancers. The available evidence indicates that microwave therapy is generally effective, with relatively low recurrence rates and a good safety profile. However, further research is still needed to fully understand the long-term efficacy and safety of this approach, as well as to optimize treatment protocols and identify the most suitable patient populations for microwave therapy. Hence, the current study was conducted to assess the efficacy of microwave therapy in achieving complete clearance of viral warts with an evaluation of the safety profile of microwave therapy in the Saudi population. In addition, the potential factors that may affect the therapy outcomes will be studied.
Materials and Methods
Study Design
This project was conducted as a cross-sectional study at Alkhibrah Medical Complex in Arar, Saudi Arabia. The study will span from July 2024 to December 2024. The study included all patients from different age groups presenting with viral warts at the dermatology clinic of the Medical Complex. The sample size was determined based on the prevalence of viral warts and the expected response rate to microwave therapy. A power analysis was conducted to ensure an adequate sample size to achieve statistically significant results.
Data were collected using a standardized data collection form. The following variables will be recorded: age, gender, wart characteristics (size, location, number), previous treatments, treatment response, adverse events, and follow-up duration. Patients underwent microwave therapy for the treatment of viral warts. The microwave therapy protocol was standardized and administered by trained healthcare professionals following established guidelines.
Statistical Analysis
Descriptive statistics were used to summarize patient demographics and wart characteristics. The treatment response rate was calculated as the proportion of patients achieving complete clearance of warts. Factors associated with treatment response and adverse events were analyzed using Exact Fisher tests, which help get exact p-values with small-sized study groups.
Ethical Approval
This study was approved by the Local committee of bioethics, Northern Border University (Date: 2024-6-25, No: 89/24/H).
Results
After informed consenting, 30 patients were enrolled in the study with varying ages, genders, wart locations, and numbers. The demographic data and wart characteristics of the participants are shown in Table 1. The participants’ ages ranged from 6 months to 45 years (15.8±9.5 years). Females were 16 (53.3%), while 14 (46.7%) were male. The anatomical locations of warts in the enrolled patients were variable. The commonest location was the hands (40.0%), followed by the feet (23.3%). Multiple warts were more common and observed in 20 cases (66.7%) (Table 1).
Microwave therapy was applied in all cases through the standardized approach. Complete wart eradication was shown in 22 patients (73.3%), while in 8 patients (26.7%), there was no observed significant eradication. The number of sessions received by the enrolled cases till successful eradication varied between 2 and 5 sessions. Follow-up data revealed recurrence among only 4 patients (18.2%) (Table 2). There was no effect of the demographic and clinical characteristics on the outcomes and recurrence data (Tables 3 and 4).
Discussion
The current study was conducted to assess the efficacy of microwave therapy in achieving complete clearance of viral warts with an evaluation of the safety profile of microwave therapy in the Saudi population. In addition, the potential factors that may affect the therapy outcomes were studied. The study outcomes show that microwave therapy is an effective modality for treating warts. The enrolled cases showed a high eradication rate with relatively low recurrence among successfully treated cases. These outcomes agree with earlier published data, which recommended the application of microwave therapy for the localized immune lesions of dermatological diseases [1, 8, 9]. This recommendation was based on the capability of the thermal effect of microwave therapy to enhance immune surveillance as well as targeting the infected tissues, which is expected to be efficient in the management of HPV induced warts. Patients with single warts demonstrated a notably better eradication rate than patients with multiple warts, which is consistent with previously published data, which highlight multiple warts as a real challenge with the different effective treatment modalities with lower eradication rates and higher levels of recurrence [10, 11].
In cases of single wart lesion, recurrence was also observed in lower rates, which highlights the complexity of the treatment outcomes as multiple variables may contribute to immune status, viral load, and wart depth [12]. In addition, wart locations such as genital and subungual wart microwave therapy outcomes highlight the importance of tailored therapeutic strategies for these challenging locations [13].
There was no statistically significant effect of the participant’s age or gender, and the others studied clinical features of warts on the treatment outcomes and eradication rates. This finding suggests that microwave therapy can be broadly recommended across diverse demographic groups. However, higher recurrence rates were shown in multiple warts cases, which signifies the importance of adjunctive treatments with modalities, such as cryotherapy and immunotherapy, for cases with multiple warts with the need for longer durations of follow-up [14-17].
Limitation
The study provides clinical evidence about the efficacy of microwave therapy in the management of warts; however, this study has its limitations. Small-sized sample, with two months short follow-up duration, absence of other groups with the conventional modalities for comparison with microwave therapy data, in addition to being a single center study can limit the findings generalizability. Also, the variations in patient adherence and personal characteristics of the immune responses could bias the results. Hence, Further studies are recommended to address these limitations for a more comprehensive assessment for microwave therapy in wart management.
Conclusion
In conclusion, based on the current results, microwave therapy can be considered a highly effective modality for wart management, especially for cases with single warts in hands and other accessible locations. Cases with multiple warts mostly require combined treatment with other modalities such as cryotherapy and immunotherapy with further optimization of treatment protocols. Further studies are recommended to address the studied limitations considered for a more comprehensive assessment for microwave therapy in wart management to improve patient outcomes.
Acknowledgment
The deanship of Scientific Research at Northern Border University, Arar, KSA, funded this research work through the project number “NBU-FFR-2025–124-02.
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. Zhu P, Qi RQ, Yang Y, et al. Clinical guideline for the diagnosis and treatment of cutaneous warts (2022). J Evid Based Med. 2022;15(3):284-301.
2. Sterling JC, Gibbs S, Haque Hussain S, Mustapa MF, Handfield-Jones S, British Association of Dermatologists. British Association of Dermatologists guidelines for the management of cutaneous warts 2014. Br J Dermatol. 2019;171(4):696–712.
3. Scheinfeld N. The use of targeted microwave therapy in dermatology. Dermatol Online J. 2013;19(5):18609.
4. Zhang T, Xi L, Wang Y, Hu J. Efficacy and safety of microwave therapy for external genital warts: a systematic review and meta-analysis. Int J Dermatol. 2015;54(12):1484–9.
5. Zhao Y, Chen X, Zhou L, Jiang Y, Zhong Z. Efficacy and safety of microwave therapy for cervical intraepithelial neoplasia: A retrospective study. Oncotarget. 2019;10(41):4151–7.
6. Peng J, Wang Y, Peng Y, Chen Y, Zhang H, Zeng X. Microwave therapy for anal intraepithelial neoplasia associated with human papillomavirus infection. J Dermatol Treat. 2020;31(4):396–9.
7. Xu L, Kang Y, Hu K, Zhang H. Microwave ablation for human papillomavirus-associated head and neck cancer: A systematic review. Oncotarget. 2018;9(20):15172–82.
8. Sterling JC, Handfield-Jones S, Hudson PM. Guidelines for the management of cutaneous warts. Br J Dermatol. 2001;144(1):4–11.
9. Chaudhary D, Sun Y, Gao X. Comparison of Cryotherapy and Topical Salicylic Acid in Common Warts: A Systematic Review and Meta-Analysis. Dermatol Ther. 2023;2023(1):4283918.
10. Truong K, Joseph J, Manago B, Wain T. Destructive therapies for cutaneous warts: A review of the evidence. Aust J Gen Pract. 2022;51(10):799-803.
11. Kwan Z, Loo S, Smith MK. Microwave therapy in dermatology. Dermatol Ther. 2018;31(4):e12607.
12. Bencini PL, Guida S, Cazzaniga S, Pellacani G, Galimberti MG, Naldi L. Risk factors for recurrence after successful treatment of warts: The role of smoking habits. J Eur Acad Dermatol Venereol. 2017;31(4):712–6.
13. Ockenfels HM. Therapeutic management of cutaneous and genital warts. JDDG J Dtsch Dermatol Ges. 2016;14(9):892–9.
14. Shimizu T, Nakagawa H, Kanekura T, Nishikawa T, Kawana S. Immunotherapy for cutaneous warts: A review. J Dermatol. 2017;44(8):816–21.
15. Cha S, Lee GW, Shin JO, et al. Predictive dermoscopic features of cryotherapy treatment response in cutaneous warts. Sci Rep. 2024;14(1):29363.
16. Friedman PC. Management of difficult-to-treat warts: Traditional and new approaches. Am J CliniDermatol. 2021;22(3):379-94.
17. Nasr Hassan AG, Nofal A, Abdelshafy AS. Immunotherapy agents are used for treatment of warts. J Pharm Negat. 2023;14(3): 399-405.
Download attachments: 10.4328.ACAM.22576
Dhaifallah Alenizi. Efficacy of microwave therapy in the treatment of viral warts: A cross-sectional study from Saudi arabia. Ann Clin Anal Med 2025;16(8):564-567
Citations in Google Scholar: Google Scholar
Factors increasing the risk of atrial fibrillation and hyperuricemia in geriatric normotensive patients
Musa İlker Durak 1, Beyza Algül Durak 2, Naim Ata 3, Mustafa Mahir Ülgü 3, Şuayip Birinci 3
1 Department of Cardiology, Ankara Etlik City Hospital, 2 Department of Nephrology, Ankara Bilkent City Hospital, 3 Department of Health Information Systems, Turkish Ministry of Health, Ankara, Turkiye
DOI: 10.4328/ACAM.22664 Received: 2025-03-20 Accepted: 2025-05-05 Published Online: 2025-05-19 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):568-572
Corresponding Author: Musa İlker Durak, Department of Cardiology, Ankara Etlik City Hospital, Ankara, Turkiye. E-mail: ilkerdurak@gmail.com P: +90 533 710 67 67 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2232-4316
Other Authors ORCID ID: Beyza Algül Durak, https://orcid.org/0000-0002-3182-4382 . Naim Ata, https://orcid.org/0000-0001-6947-2821 . Mustafa Mahir Ülgü, https://orcid.org/0000-0003-0825-1851 . Şuayip Birinci, https://orcid.org/0000-0001-8104-6198
This study was approved by the Ethics Committee of Ministry of Health (Date: 2023-08-10, No: 953413442-020)
Aim: Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by uncontrolled atrial electrical activity. Hyperuricemia is a metabolic disease caused by an imbalance in purine metabolism and the production and excretion of uric acid. Although some studies report a significant association between hyperuricemia and AF, few studies have examined this relationship in the elderly population. This study aimed to investigate the relationship between hyperuricemia and atrial fibrillation in elderly individuals and to compare the other risk factors and mortality status in people of the same age group without AF.
Materials and Methods: The study included patients over the age of 65 who had not been previously diagnosed with hypertension, non-alcoholic fatty liver disease, clinical/subclinical hyperthyroidism, or heart failure and had not used antihypertensive medications, along with a control group of the same number of individuals without these conditions.
Results: Patients with AF had higher uric acid levels. Unlike previous studies, this study conducted in an elderly population found that women had a higher prevalence of AF compared to men. It was also identified that predisposition to inflammation is an independent risk factor for the development of AF. In the very elderly group (over 85 years), the mortality rate was higher, and GFR was lower in patients with AF.
Discussion: In the normotensive elderly population, individuals with hyperuricemia had a significantly higher risk of AF. Hyperuricemia may be a marker of AF in normotensive elderly individuals. Moreover, closer monitoring for AF is recommended in elderly women, during infections, or in cases of renal failure.
Keywords: Atrial Fibrillation, Hyperuricemia, Older Patients
Introduction
Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by uncontrolled atrial electrical activity. Its average global prevalence is 2–4% [1]. AF is the most common arrhythmia among patients with various cardiovascular comorbidities and becomes more frequent with age [2]. By 2050, the number of people aged 65 and older is expected to double to 1.5 billion, while the number of individuals aged 80 and older is projected to triple to 0.4 billion. [3]. In the European Union, the number of elderly AF patients aged 65 and older is expected to increase by 89% by 2060. Very elderly AF patients aged 80 and older represented 51.2% of the total AF population in 2016, expected to rise to 65.2% by 2060 [4].
Known risk factors for AF include advanced age, male sex, smoking, hypertension, heart failure, diabetes, obesity, valvular heart disease, myocardial infarction, and cardiac surgery [5].
Hyperuricemia (HUA) is a metabolic disease caused by an imbalance in purine metabolism and the production and excretion of uric acid. Several studies have reported a significant association between hyperuricemia and AF [6-7].
However, limited research has explored the association between elevated uric acid levels (hyperuricemia) and AF in older adults, where AF is known to be more prevalent.
In this context, the purpose of this research was to examine the relationship between HUA and AF in elderly individuals and compare other risk factors and mortality status in individuals of the same age group without AF.
Materials and Methods
Patient Selection
Patients registered in the Turkish Ministry of Health data screening system between 2022 and 2023 were retrospectively reviewed. The study included patients over 65 years of age who had not been previously diagnosed with hypertension or heart failure and had not used antihypertensive medications. Research has previously established an association between non-alcoholic fatty liver disease (NAFLD) and both a higher occurrence of AF and elevated uric acid levels [8]. Therefore, patients diagnosed with NAFLD or hyperthyroidism from one year before four years after the diagnosis date were excluded based on ICD codes. The age of individuals when they were first diagnosed with AF and their blood test results at that time were recorded. Of these patients, the ones who died within the following 4 years were recorded to determine the mortality rates. A total of 500 patients who received a first-time diagnosis of AF were included in the study. A comparison group consisting of 500 participants of the same age group without a chronic disease diagnosis was also recorded. Blood test results and mortality data for the control group over the same four-year period were analysed.
Determination of Hyperuricemia
Uric acid levels higher than 7.0 mg/dL in men and 6.0 mg/dL in women were considered indicative of hyperuricemia [9].
Detection of Atrial Fibrillation
Patients with an ICD code of AF in the database of the Turkish Ministry of Health’s national database and in whom this diagnosis was made for the first time were identified. The date of first diagnosis was reviewed. Patients with this diagnosis at least 3 episodes since this date were included in the study.
Clinical and Laboratory Characteristics of Patients
Laboratory data obtained at the time of diagnosis in patients with AF and the control group were recorded from the system. Age, gender, uric acid, glucose, creatinine, total cholesterol, low-density lipoprotein cholesterol (LDL), c-reactive protein (CRP), estimated glomerular filtration rate (eGFR), and mortality status were analysed at the time of diagnosis in both AF patients and the healthy group.
Statistical Analysis
The data were determined using IBM SPSS 26 (IBM Corp., Released 2019). The Kolmogorov-Smirnov test was used to assess the normality of the distribution. The Mann-Whitney U test was employed for comparing quantitative variables that did not follow a normal distribution between groups. Pearson’s chi-square test was used to compare categorical variables between groups, and multiple comparisons were evaluated with the Bonferroni-corrected Z test. Factors affecting AF within age groups were analysed with multivariate logistic regression analysis. Factors influencing AF were examined using logistic regression analysis. The results of the analyses were presented as median (minimum-maximum) for quantitative variables and as frequency (percentage) for categorical variables. The significance level was set at “p < 0.05”.
Ethical Approval
This study was approved by the Ethics Committee of Turkish Ministry of Health (Date: 2023-08-10, No: 953413442-020).
Results
Our study included 500 elderly participants with AF and 500 with normal sinus rhythm (NSR). Among the elderly participants, the mean age of those with AF was 75.35, while the mean age of those with NSR was 73.14. Women constituted 35.2% of the AF group, whereas 53% of the NSR group were women. When elderly participants in the AF group were further divided based on the presence of hyperuricemia, 179 patients (35.8%) were found to have hyperuricemia. While 47% of the participants with NSR were male, 64.8% of the AF group were male.
Comparison of Patients with and without Atrial Fibrillation
There is a statistically relevant difference between the uric acid values of the patients according to the groups (p < 0.001). The median uric acid value of patients in normal sinus rhythm is 5, while AF patients had a higher median uric acid value of 6.
Our study results showed that in individuals with AF, as opposed to those with normal sinus rhythm (NSR), AF increased with advancing age (p < 0.001). A significant difference was observed in the diagnosis age distributions between the groups (p < 0.001). The median age at diagnosis was 72 for the NSR group and 74 for the AF group. A significant difference was observed between the age at diagnosis distributions of the patients between the groups (p < 0.001). This difference was determined between the proportions of patients aged 65-74 years and patients aged 85 years and over. While 66% of patients with normal sinus rhythm were between 65-74 years of age, this rate was 55.2% in AF patients. While 5.6% of patients in normal sinus rhythm were 85 years and older, this rate was 15.2% in AF patients. Statistically significant variations were also observed in gender distribution between the two groups (p < 0.001). While 47% of patients with normal sinus rhythm were male, 64.8% of AF patients were male. Furthermore, uric acid, CRP, and mortality rates were higher, and GFR was lower in the AF group (Table 1).
Comparison of Hyperuricemia Presence in Patients with Atrial Fibrillation
No differences were detected in the ages of patients with and without hyperuricemia. A statistically significant relationship was found between gender and hyperuricemia status (p < 0.001). The ratio of women with hyperuricemia was 46%, compared to 30.2% in men. In the hyperuricemia group, creatinine and CRP levels were statistically higher, while eGFR levels were statistically decreased. No differences in mortality were observed between normal and elevated uric acid levels in patients with AF (Table 2)
Factors Affecting Atrial Fibrillation
Factors affecting AF were examined using univariate and multivariate logistic regression models.
In the univariate analysis, patients aged 85 and above were at a higher risk of AF compared to those aged 65–74 (OR: 3.245, p < 0.001). Women had a higher risk of AF compared to men (OR: 0.482, p < 0.001). As UA and CRP levels increased, the risk of AF also increased (OR: 1.855, p < 0.001; OR: 1.004, p = 0.037). Conversely, as GFR, LDL, and total cholesterol levels increased, the risk of developing AF decreased (OR: 0.865, p < 0.001; OR: 0.996, p = 0.018; OR: 0.993, p < 0.001). In the multivariate logistic regression analysis, patients aged 85 and above had a significantly higher risk of AF (OR: 2.753, p = 0.018). As GFR and total cholesterol levels increased, the risk of AF decreased (OR: 0.889, p < 0.001; OR: 0.991, p = 0.002). However, as CRP levels increased, the risk of AF increased (OR: 1.007, p = 0.048). The model generated from the multivariate analysis correctly classified 70% of cases (Table 3).
Discussion
Main Findings
Our study revealed several key findings. Uric acid levels were higher in patients with AF. Unlike previous studies, this study conducted in an elderly population found that women had a higher prevalence of AF compared to men. It was also identified that predisposition to Inflammation acts as an independent contributor to AF development. In the very elderly group (over 85 years), the mortality rate was higher, and GFR was lower in patients with AF. Finally, our study demonstrated an inverse relationship between high cholesterol levels and the development of AF.
Hyperuricemia and AF
Similar studies have indicated that hyperuricemia increases risk due to its association with inflammation, fibrosis progression, apoptosis activation, calcium homeostasis impairment, and immune regulation [10]. A key mechanism underlying the detrimental cellular effects of uric acid is the heightened activity of xanthine oxidoreductase (XOR), a critical enzyme in UA metabolism. XOR contributes to the generation of reactive oxygen species (ROS), a process further amplified by elevated nicotinamide adenine dinucleotide phosphate oxidase (NADPH) activity [11]. Taufiq et al. found that uric acid triggers electrical remodelling by altering action potential repolarization and reducing action potential duration. This effect is mediated by the upregulation of Kv1.5 protein, a key player in the electrophysiological function of atrial myocytes [12].
In our study, hyperuricemia was markedly significantly higher in AF patients than in individuals with normal uric acid levels. Cross-sectional studies conducted have reported a positive association between hyperuricemia and AF prevalence. Furthermore, population-based prospective cohort studies have shown that hyperuricemia is associated with a higher risk of AF [13].
Age and Atrial Fibrillation
According to the 50-year follow-up of the Framingham Heart Study, advancing age is the most significant risk factor for the development of AF [14]. Large-scale European studies also report a significant increase in AF incidence in men after age 50 and in women after age
60 [15]. The “Consensus of the French Society of Geriatrics and Gerontology and the French Society of Cardiology,” which analysed AF prevalence classified by age and gender across studies published between 1991 and 2011, indicates that 70% of AF patients are over 75 years old, suggesting that this arrhythmia predominantly affects the elderly. Aging is associated with the continuously increasing prevalence and incidence of AF [16]. Similarly, in our study, individuals in the NSR group were younger compared to those with AF, and advancing age was identified as an independent risk factor for AF.
Gender and Atrial Fibrillation
In a study of 1,544 patients (821 men and 723 women) with newly diagnosed AF, Schnabel et al. found that women with AF were older, had a higher rate of hypertension medication
prescriptions, and exhibited a poorer blood pressure profile [16]. European Observational Research Program on Atrial Fibrillation (EORP-AF) corroborated recent reports stating that Women tended to be older, exhibited more symptoms, and were more frequently affected by non-ischemic heart failure. EORP-AF also noted that women were prescribed fewer antiarrhythmic treatments, primarily involving rate-controlling medications, although they were more symptomatic than men. Furthermore, women had a higher overall risk of stroke and had a higher rate of oral anticoagulation use (95.3% vs. 76.2%) [17].
Although the incidence of AF is typically lower in women, studies indicate that in populations over 75, the gender distribution of AF becomes similar due to women’s longer life expectancy. Benjamin et al. reported that 55% of AF patients are women. Although SUA is higher in men than in women before menopause, it also increases in women after menopause. Considering that the incidence of AF increases with age in both groups, the fact that SUA increases with age in women can be attributed to the higher incidence of AF in older women compared to men [18].
In our study, which included elderly patients, the percentage of women with AF was higher.
Inflammation and Atrial Fibrillation
Studies found that CRP significantly enhances inward L-type calcium (Ca²⁺) currents in atrial myocard cells. This suggests that the primary mechanism by which CRP promotes AF is through increased calcium currents, rather than affecting pro-collagen gene expression in atrial fibroblasts or altering other ionic currents. Highlighted the crucial role of inflammation in AF development and progression [19]. CRP can act as an indicator of inflammatory states that potentially promote the ongoing persistence of AF through structural and/or electrical changes in the atrial tissue. Inflammatory pathways could form the basis for AF treatments, highlighting the necessity for randomized trials involving anti-inflammatory drugs and/or other medications that reduce CRP levels [20].
Similarly, in our study, CRP levels were found to be higher in patients with AF, consistent with the studies. Both univariate and multivariate analyses revealed that as CRP levels increased, the risk of AF also rose.
Renal Function and Atrial Fibrillation
The presence of cardiovascular disease, as well as traditional cardiovascular risk factors such as smoking, hypertension, dyslipidaemia, and diabetes, is more prevalent in individuals with impaired kidney function. Other factors linked to kidney dysfunction, such as elevated inflammatory signalling molecules, elevated oxidative stress, and impaired endothelial function, disturbances in calcium-phosphate balance, proteinuria, and high uric acid levels, also contribute to accelerated atherosclerosis and cardiovascular risk [21]. Both renal dysfunction and AF are associated with elevated levels of asymmetric dimethylarginine (ADMA), a potent endogenous nitric oxide synthase inhibitor. ADMA is a recognized risk factor for oxidative stress, impaired vascular function, and heart failure, as well as a strong predictor of poor cardiovascular prognosis and increased mortality. Moreover, AF has been demonstrated to impact renal function through various mechanisms, such as the downregulation of renal neutral endopeptidase expression and the activation of pro-fibrotic cascade. These factors may explain the observed changes in renal function [22]. In our study, patients with AF had lower GFR levels compared to the NSR group, and regression analysis identified reduced GFR as an independent risk factor for AF.
Mortality and Atrial Fibrillation
AF is a major contributor to mortality due to stroke and cardiovascular disorders, and it is independently associated with a 1.5- to 2-fold increase in the risk of all-cause mortality, stroke, and heart failure-related morbidity.
In our study, the mortality rate was significantly greater in AF patients compared to individuals in the NSR group.
Conclusion
Studies have confirmed that hyperuricemia is independently related to the incidence of AF. A key factor in uric acid elevation is the heightened activity of xanthine oxidoreductase (XOR), a critical enzyme in uric acid metabolism. XOR drives the production of reactive oxygen species (ROS), a process further amplified by increased nicotinamide adenine dinucleotide phosphate oxidase (NADPH) activity. Reduction of oxidative stress through inhibition of xanthine oxidase using allopurinol or another similar drug, of NADPH-oxidase using apocynin, or the use of N-acetylcysteine, might be beneficial. Hyperuricemia may be a marker of AF in normotensive elderly individuals. The mortality rate was significantly greater in AF patients compared to individuals in the NSR group. We would like to emphasize the importance of rhythm control and medication use in elderly patients with AF.
Limitation
Among the limitations of our study, there were limitations in the physical examination and evaluation of additional diseases of the patients because our study was a cross-sectional study.
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 lines, 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 comparable ethical standards.
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. Lippi G, Sanchis-Gomar F, Cervellin G. Global epidemiology of atrial fibrillation: an increasing epidemic and public health challenge. Int J Stroke. 2021;16(2):217-21.
2. Sagris M, Vardas EP, Theofilis P, Antonopoulos AS, Oikonomou E, Tousoulis D. Atrial fibrillation: pathogenesis, predisposing factors, and genetics. Int J Mol Sci. 2021;23(1):6.
3. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110(9):1042-6.
4. Di CarloA, Bellino L, Consoli D, et al. National Research Program: Progetto FAI. La Fibrillazione Atriale in Italia. Prevalence of atrial fibrillation in the Italian from 2020 to 2060 for Italy and the European Union: the FAI Project. Europace 2019;21(10):1468–75.
5. Bizhanov KA, Аbzaliyev KB, Baimbetov AK, Sarsenbayeva AB, Lyan E. Atrial fibrillation: epidemiology, pathophysiology, and clinical complications (literature review). J Cardiovasc Electrophysiol. 2023;34(1):153-65.
6. Gao Z, Shi H, Xu W, et al. Hyperuricemia increases the risk of atrial fibrillation: a systematic review and meta-analysis. Int J Endocrinol. 2022; 2022(1):8172639.
7. Deng Y, Li Q, Zhou F, et al. Hyperuricemia and gout are associated with the risk of atrial fibrillation: an updated meta-analysis. Rev Cardiovasc Med. 2022;23(5):178.
8. Targher G, Valbusa F, Bonapace S, et al. Non-alcoholic fatty liver disease is associated with an increased incidence of atrial fibrillation in patients with type 2 diabetes. PLoS One. 2013;8(2):e57183.
9. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-41.
10. Deng Y, Liu F, Yang X, Xia Y. The key role of uric acid in oxidative stress, inflammation, fibrosis, apoptosis, and immunity in the pathogenesis of atrial fibrillation. Front Cardiovasc Med. 2021;8(1):641136.
11. Liu N, Xu H, Sun Q, et al. The role of oxidative stress in hyperuricemia and xanthine oxidoreductase (XOR) inhibitors. Oxid Med Cell Longev. 2021;2021(1):1470380.
12. Taufiq F, Maharani N, Li P, et al. Uric acid-induced enhancements of Kv1.5 protein expression and channel activity via the Akt-HSF1-Hsp70 pathway in HL-1 atrial myocytes. Circ J. 2019;83(4):718-26.
13. Nyrnes A, Toft I, Njølstad I, et al. Uric acid is associated with future atrial fibrillation: an 11-year follow-up of 6308 men and women–the Tromso Study. Europace. 2014;16(3):320-6.
14. Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD, et al. 50-year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet. 2015;386(9989):154-62.
15. Magnussen C, Niiranen TJ, Ojeda FM, et al. BiomarCaRE Consortium. Sex differences and similarities in atrial fibrillation epidemiology, risk factors, and mortality in community cohorts: results from the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe). Circulation. 2017;136(17):1588-97.
16. Kodani E, Kaneko T, Fujii H, et al. Prevalence and incidence of atrial fibrillation in the general population based on National Health Insurance Special Health Checkups – TAMA MED Project-AF. Circ J. 2019;83(3):524-31.
17. Lip GY, Laroche C, Boriani G, et al. Sex-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe: a report from the Euro Observational Research Programme Pilot survey on atrial fibrillation. Europace. 2015;17(1):24-31.
18. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67-e492.
19. Meyre PB, Sticherling C, Spies F, et al. C-reactive protein for prediction of atrial fibrillation recurrence after catheter ablation. BMC Cardiovasc Disord. 2020;20(1):427.
20. Rafaqat S, Rafaqat S, Ijaz H. The role of biochemical cardiac markers in atrial fibrillation. J Innov Card Rhythm Manag. 2023;14(10):5611-21.
21. Wang Y, Yang Y, He F. Insights into concomitant atrial fibrillation and chronic kidney disease. Rev Cardiovasc Med. 2022;23(3):105.
22. Bukowska A, Lendeckel U, Krohn A, et al. Atrial fibrillation down-regulates renal neutral endopeptidase expression and induces profibrotic pathways in the kidney. Europace. 2008;10(10):1212-7.
Download attachments: 10.4328.ACAM.22664
Musa İlker Durak, Beyza Algül Durak, Naim Ata, Mustafa Mahir Ülgü, Şuayip Birinci. Factors increasing the risk of atrial fibrillation and hyperuricemia in geriatric normotensive patients. Ann Clin Anal Med 2025;16(8):568-572
Citations in Google Scholar: Google Scholar
Acute respiratory disease as a fulcrum point to quit smoking: Evaluation of an ED-based intervention
Neslihan Ergun Süzer 1 , Nazmiye Koyuncu 2 , Lütfü Şenel 3 , Özgür Karcıoğlu 4 , Seda Oğuz 1 , Kenan Kart 5
1 Department of Emergency Medicine, Darica Farabi Education and Research Hospital, Kocaeli, 2 Department of Emergency Medicine, Private Clinic, Konya, 3 Department of Otolaryngology (ENT), Medipol University, Istanbul, 4 Department of Emergency Medicine, Istanbul Training and Research Hospital, Istanbul, 5 Department of Anesthesiology, Karabük University, Karabük, Turkey
DOI: 10.4328/ACAM.22731 Received: 2025-05-06 Accepted: 2025-07-08 Published Online: 2025-07-24 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):573-577
Corresponding Author: Neslihan Ergun Süzer, Department of Emergency Medicine, Darica Farabi Education and Research Hospital, Kocaeli, Turkey. E-mail: dr.ergunsuzer@gmail.com P: +90 506 481 0683 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4839-8110
Other Authors ORCID ID: Nazmiye Koyuncu, https://orcid.org/0000-0001-7108-692X . Lütfü Şenel, https://orcid.org/0000-0003-1744-1710 . Özgür Karcıoğlu, https://orcid.org/0000-0002-8814-6164 . Seda Oğuz, https://orcid.org/0000-0001-9244-8125 . Kenan Kart, https://orcid.org/0000-0001-7112-8878
This study was approved by the Ethics Committee of Haydarpaşa Numune Training and Research Hospital (Date: 2016-10-10, No: 2016-KK-104).
Aim: This study evaluated the effectiveness of a structured smoking cessation intervention and its relationship with nicotine dependence in smokers presenting to the emergency department (ED) with acute respiratory infections (ARI).
Materials and Methods: A single-center, prospective, randomized controlled trial was conducted. Participants (adults with ARI) were randomized to a control group (standard medical care) and an intervention group (standard care + structured smoking cessation counseling). Nicotine dependence was measured by the Fagerström Test of Nicotine Dependence (FTND). Smoking cessation rates were analyzed after one week and one month.
Results: The mean age of the 288 participants was 45 years (± 19.09 SD), and 72.6% (n = 209) were male. The smoking cessation rate was 45.7% (n = 21) in the intervention group and 7.3% in the control group (at one-month follow-up, p < 0.001). While high FTND scores negatively affected smoking cessation rates (p < 0.001), cessation rates were significantly higher in individuals with low FTND scores in comparison to those with high scores. 21.2% (n = 61)of the participants stated that they decided to quit smoking on the same day.
Discussion: Structured smoking cessation interventions may prove effective in increasing smoking cessation rates in these adult patients with ARI in the emergency setting. However, more comprehensive support programs are needed for individuals with high addiction levels.
Keywords: Smoking Cessation, Emergency Department, Fagerström Test, Intervention Programs, Nicotine Dependence
Introduction
Smoking is one of the leading preventable causes of death worldwide and an important risk factor in the emergence of many chronic diseases, especially respiratory diseases [1]. Tobacco use remains one of the leading causes of preventable deaths worldwide, with global smoking prevalence showing only a modest decline in recent decades despite various control measures [2]. Smoking affects not only the health of individuals but also public health and the economic burden on healthcare systems.
The Centers for Disease Control and Prevention (CDC) defines “current smokers” as those who have smoked 100 or more cigarettes in their lifetime and continue to smoke. The CDC further defined smoking cessation from 1991 onwards as not using cigarettes for one day or more, although earlier definitions were based on attempts to quit [3]. In 2024, a study classified those who had quit smoking as individuals who had not smoked for at least 12 months [1].
Emergency departments (EDs) are critical referral centers for individuals with smoking-related health problems. These individuals are often motivated to change their smoking habits, particularly during acute respiratory infections (ARI). The American College of Emergency Physicians (ACEP) recommends smoking cessation counseling for smokers treated for ARI in EDs, though many emergency physicians consider smoking cessation outside their professional responsibilities [4–6].
Nicotine dependence (ND) severity plays a significant role in smoking cessation success. The Fagerström Test for Nicotine Dependence (FTND) is widely used to measure ND levels [7]. In Turkey, the reliability and validity of the test were studied by Uysal et al. [8]. Personalized interventions based on ND levels are crucial in increasing cessation success. Higher addiction levels may require nicotine replacement therapy and regular follow-up, while moderate addiction might benefit from behavioral therapies.
The 5A model (Ask, Advise, Assess, Assist, and Arrange), widely recommended for smoking cessation in clinical practice, has demonstrated effectiveness even in high-paced healthcare settings [9]. This study aims to evaluate the effectiveness of structured interventions on smoking cessation in ARI patients in EDs and follow up for one month.
Materials and Methods
This study has a single-center, prospective, randomized controlled design and was conducted over four weeks between November 10, 2016, and December 8, 2016.
A total of 20,928 patients presented to the ED during the specified period, and 2,018 of these patients were evaluated with acute respiratory complaints and diagnosed with ARI. Of the patients admitted with ARI, 541 reported active smoking. Exclusion criteria included individuals under 18 years of age, ASA class III-IV, pregnancy or breastfeeding, communication difficulties such as language barrier or cognitive impairment, psychotic behaviors or history of psychiatric treatment, and initiation of smoking cessation treatment. A total of 253 individuals meeting the exclusion criteria were excluded, and the final analysis was performed on 288 patients (Figure 1).
Demographic characteristics (age, gender, education level, income) and smoking-related data (age at initiation, number of cigarettes smoked per day, longest smoking cessation period) were recorded in detail. The level of smoking dependence was measured using the FTND. The randomization process of the patients was conducted using a computer-generated random allocation method, ensuring that all patients were assigned to either the intervention or control group with an equal probability. Blinding and allocation concealment were not performed because of the interventions included in the study procedure. Group A, which included standard care and diagnostic procedures, and Group B, which received structured interviewing and smoking cessation support. The structured support in Group B followed the World Health Organization (WHO) 5A model (Ask, Advise, Assess, Assist, Arrange). All participants were followed up by telephone at one week and one month to collect information about their smoking status, quit attempts, and general health status.
Statistical Analysis
The collected data were analyzed using SPSS 16.0 software. Descriptive statistics were used to describe continuous variables. Comparisons of more than two independent and normally distributed continuous variables were made with the Kruskal-Wallis test, and the comparison of two independent and non-normally distributed variables was made with the Mann-Whitney U test. Independent sample t-test was used for continuous variables, and the Chi-Square or Fisher’s exact test was used for categorical variables. P < 0.05 was accepted as the level of statistical significance.
Ethical Approval
This study was approved by the Ethics Committee of Haydarpaşa Numune Training and Research Hospital (Date: 2016-10-10, No: 2016-KK-104).
Results
A total of 288 patients were evaluated in the study. The mean age of the included patients with ARI was 45 ± 14 years, and the age range was between 18 and 90 years. The female population constituted 27.4% (n = 79) of the participants. The mean age of women was 44 ± 19.09 years, as opposed to 45 ± 19.09 years in men. A history of chronic systemic disease was present in 27.1% (n = 78) of the participants. The majority of the patients, 66.7% (n = 192), were individuals with an active working life. Among active smokers, 77.8% (n = 224) had a family history of active smoking.
Regarding daily cigarette consumption, 11.1% (n = 32) smoked 1-10 cigarettes every day, while 54.9% (n = 158) of the patients who participated in the study smoked 11-20 cigarettes. In addition, 20.8% (n = 60) of the patients consumed 20-30 cigarettes, while 13.2% (n = 38) smoked 30 or more cigarettes daily (Table 1).
A majority (70.8%, n = 204) of the participants stated that they had thought about quitting smoking at some point in their lives. Additionally, 21.2% (n = 61) stated that they decided to quit smoking on the day they participated in the study. Of those who decided to quit smoking on the day of participation, 50.7% (n = 31) attempted to quit smoking.
At the follow-up one week later, 16% (n = 46) had completely quit smoking, 18.4% (n = 53) had reduced their cigarette consumption, 7.3% (n = 21) had quit for at least one day but relapsed, and 56.9% (n = 164) continued smoking.
At the follow-up one month later, 7.3% (n = 21) had completely quit smoking, while 9.4% (n = 27) initially quit but resumed smoking after two weeks.
The mean score received from the FTND was determined as 5.5 ± 3.8. According to the FTND score, 27.8% (n = 80) of the participants were found to have low dependence, while 18.4% (n = 53) were classified as highly dependent. These findings indicate that the smoking cessation process varies according to ND levels.
The rate of pathologic findings on physical examination was found to be statistically significantly higher in individuals who smoked 30 or more cigarettes per day compared to individuals who smoked fewer cigarettes (n = 18, 47.4%; p < 0.001). This rate was 15.2% (n = 24) in those who smoked 11-20 cigarettes daily.
When the intention of individuals with high ND according to the FTND score to quit smoking after admission due to ARI was analyzed, the rate of those who said ‘I think I will quit sometime but not this time’ was found to be significantly different when compared according to the level of ND. This rate was 47.2% (n = 25) in individuals with an FTND score of 8-10, 75% (n = 54) in individuals with an FTND score of 6-7, 80% (n = 64) in individuals with an FTND score of 3-4, and 64.9% (n = 24) in individuals with a FTND score of 0-2, and a statistically significant difference was found between the groups (p < 0.001).
In the evaluation one week after admission, the proportion of individuals who continued to smoke was found to be significantly higher in individuals with high FTND scores compared to other individuals (p < 0.001). It was determined that individuals with high dependence (n = 60, 20.8%) had lower smoking cessation rates than individuals with low dependence (n = 129, 45.1%).
The rate of participants who quit smoking was 45.7% (n = 132) in the intervention group and 7.3% (n = 21) in the control group. Smoking cessation rates were significantly higher in the intervention group (p < 0.001) (Table 2).
Discussion
This study investigates the efficacy of smoking cessation interventions for smokers presenting with ARI in EDs. The findings revealed multiple factors influencing cessation behavior, showing significant differences between groups.
Globally, smoking is more prevalent among men, with the highest prevalence in the 45-54 age group for men and 55-64 for women [2]. In this study, the mean age of participants was 45 years, with men comprising 72.6%. The age of smoking initiation was found to be lower in Turkey than in many developed countries, a factor that contributes to higher addiction levels later in life. The significant relationship between early smoking initiation and addiction severity underlines the importance of preventive measures for younger populations.
Family and social environments play a role in smoking behavior. The study found that 77.8% of participants had active smokers in their families, consistent with literature suggesting that individuals with smoking family members or friends are more likely to smoke themselves [10, 11].
The intention to quit smoking is influenced by age, gender, ethnicity, and education. In this study, 70.8% of participants expressed a desire to quit smoking at some point in their lives, while 21.2% decided to quit on the day of participation. Studies have shown that individuals with a higher intention to quit have lower rates of delay discounting, indicating a greater likelihood of quitting smoking [12]. The intention to quit was shown to have a significant effect on smoking cessation rates (p < 0.001).
In the first month, smoking cessation rates were highest (50.7%), but these rates declined over time, with only 21.2% maintaining cessation at the one-week follow-up. This highlights the importance of sustained support and awareness during the cessation process. The high addiction levels and limited support were key factors contributing to lower long-term success rates.
In communities, health concerns and increasing cigarette costs motivate people to quit smoking [13]. A study by Im et al. showed that individual and interpersonal triggers play a crucial role in cessation, supporting the effectiveness of motivation-driven interventions in healthcare settings [13].
ND, as measured by the FTND, was a significant predictor of cessation success. Those with high FTND scores had significantly lower cessation rates compared to individuals with lower scores (p < 0.001). This finding is consistent with the literature indicating that individuals with higher ND levels are less likely to quit smoking successfully [14].
Additionally, gender and age differences were noted. Women and younger individuals had lower FTND scores and higher quit rates. In contrast, older individuals and men had higher FTND scores and more difficulty quitting, emphasizing the need for tailored cessation strategies [14].
The study also examined the relationship between daily cigarette consumption and ED readmissions. A higher rate of readmission was observed among those who smoked more (16.7% for 30+ cigarettes/day). This suggests that increased cigarette consumption significantly raises the likelihood of ED visits due to health problems, confirming previous studies on chronic obstructive pulmonary disease (COPD) patients [15].
The smoking cessation rates in the intervention group were significantly higher compared to the control group (p < 0.001), with the intervention group showing 45.7% cessation at one month. This confirms the potential of ED-based smoking cessation interventions, especially during acute admissions due to ARI. However, the long-term sustainability of these interventions needs further investigation.
Limitations
This study is limited by its single-center design and relatively small sample size. Future multi-center studies with larger cohorts are recommended.
This study has several limitations that should be acknowledged:
1. Single-center design and limited sample size: The study was conducted in a single emergency department over a short period and with a relatively small sample size. This may limit the generalizability of the findings to other populations or healthcare settings. Multi-center studies involving larger and more diverse cohorts are needed to confirm the external validity of the results.
2. Short follow-up duration: The follow-up period was limited to one month, which may not adequately reflect the long-term sustainability of smoking cessation. Smoking relapse frequently occurs beyond the first month. Therefore, longer follow-up durations (e.g., 6 or 12 months) would provide more comprehensive insights into cessation behavior and outcomes.
3. Lack of blinding: Although randomization was performed, neither the participants nor the researchers were blinded to group allocation due to the nature of the intervention. This could have introduced performance or reporting bias that may have influenced the results. Future prospective studies can incorporate blinding and allocation concealment to prevent bias.
4. Absence of pharmacologic support: No pharmacologic treatment (e.g., nicotine replacement therapy, varenicline, or bupropion) was offered as part of the intervention. Considering that high levels of nicotine dependence negatively impact cessation success, future studies should incorporate pharmacologic support, especially for individuals with high Fagerström scores. Future research can involve comparisons including nicotine replacement therapy or certain medications plus usual therapy in comparison with counseling or interviews as a SC intervention.
5. Self-reported outcomes without biochemical verification: Smoking status during follow-up was based on self-report, without biochemical validation methods such as carbon monoxide breath testing or cotinine level analysis. This limitation may lead to reporting bias and an overestimation of smoking cessation rates.
Conclusion
In conclusion, the study underscores that smoking cessation behavior is influenced by multiple factors, including ND levels, daily consumption, and intention to quit. High ND levels are associated with lower cessation rates, while interventions in ED settings may be more effective for individuals with lower addiction levels.
Future studies should focus on long-term follow-up and larger, multi-center studies to assess the sustainability of smoking cessation interventions. Multidisciplinary approaches are essential for enhancing smoking cessation rates. Healthcare professionals must emphasize increasing the intention to quit and managing ND effectively.
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. Notley C, Belderson P, Ward E, et al. The context of the ED as a location for a smoking cessation intervention: Process evaluation findings from the cessation of smoking trial in the ED trial. Nicotine Tob Res. 2024;26(2):123–31.
2. Bilano V, Gilmour S, Moffiet T, et al. Global trends and projections for tobacco use, 1990–2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control. Lancet. 2015;385(9972):966–76.
3. Ryan H, Trosclair A, Gfroerer J. Adult current smoking: Differences in definitions and prevalence estimates – NHIS and NSDUH, 2008. J Environ Public Health. 2012;2012:1–6.
4. Scott RR, Lamparski D. Variables related to long-term smoking status following cardiac events. Addict Behav. 1985;10(3):257–64.
5. Leventhal H, Nerenz DR, Steele DJ. Illness representations and coping with health threats. In: Baum A, Taylor SE, Singer JE, editors. Handbook of Psychology and Health. Vol IV. Hillsdale (NJ): Erlbaum; 1984.p.219–52.
6. Weinstein ND. Perceived probability, perceived severity, and health-protective behavior. Health Psychol. 2000;19(1):65–74.
7. Boudreaux ED, Moon S, Baumann BM, Camargo CA, O’Hea E, Ziedonis DM. Intentions to quit smoking: Causal attribution, perceived illness severity, and event-related fear during an acute health event. Ann Behav Med. 2010;40(3):350–5.
8. Uysal MA, Kadakal F, Karşidağ Ç, Bayram NG, Uysal Ö, Yılmaz V. Fagerström test for nicotine dependence: Reliability in a Turkish sample and factor analysis. Tuberk Toraks. 2004;52(2):115–21.
9. Fiore MC, Jaén CR, Baker TB, et al. Treating tobacco use and dependence: 2008 update—clinical practice guideline. JAMA. 2008;300(22):2635–45.
10. Nugent KL, Million-Mrkva A, Backman J, et al. Familial aggregation of tobacco use behaviors among Amish men. Nicotine Tob Res. 2014;16(7):923–30.
11. Hébert ET, Vandewater EA, Businelle MS, Harrell MB, Kelder SH, Perry CL. Tobacco advertising exposure and product use among young adults: An ecological momentary assessment approach. Addict Behav. 2023;139:107623.
12. Athamneh LN, Stein JS, Bickel WK. Will delay discounting predict intention to quit smoking? Exp Clin Psychopharmacol. 2017;25(4):273–80.
13. Im PK, McNeill A, Thompson ME, et al. Individual and interpersonal triggers to quit smoking in China: A cross-sectional analysis. Tob Control. 2015;24(Suppl 4):iv40–7.
14. Kim SW, Lee JM, Ban WH, Park CK, Yoon HK, Lee SH. Smoking habits and nicotine dependence of North Korean male defectors. Korean J Intern Med. 2016;31(4):685–93.
15. Kee YS, Wong CK, Aziz MAA, et al. 30-day readmission rate of patients with COPD and its associated factors: A retrospective cohort study from a tertiary care hospital. Int J Chron Obstruct Pulmon Dis. 2023;18:2623–31.
Download attachments: 10.4328.ACAM.22731
Neslihan Ergun Süzer, Nazmiye Koyuncu, Lütfü Şenel, Özgür Karcıoğlu, Seda Oğuz, Kenan Kart, Acute respiratory disease as a fulcrum point to quit smoking: Evaluation of an ED-based intervention. Ann Clin Anal Med 2025;16(8):573-577
Citations in Google Scholar: Google Scholar
A comparative analysis of the performance of large language models in the basic life support exam: Comprehensive evaluation of ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1
Bensu Bulut 1, Medine Akkan Öz 1, Murat Genç 2, Ayşenur Gür 3, Mehmet Yortanlı 4, Betül Çiğdem Yortanlı 5, Ramiz Yazıcı 6, Hüseyin Mutlu 7, Mustafa Sirri Kotanoglu 8, Eray Cinar 9, Ramazan Kocaaslan 10
1 Department of Emergency Medicine, Health Science University, Ankara Gulhane Training and Research Hospital, Ankara, 2 Department of Emergency Medicine, Ankara Training and Research Hospital, Ankara, 3 Department of Emergency Medicine, Etimesgut Şehit Sait Ertürk State Hospital, Ankara, 4 Department of Emergency Medicine, Konya Numune Hospital, Konya, 5 Department of Internal Medicine, University of Health Sciences, Konya City Hospital, Konya, 6 Department of Emergency Medicine, Health Science University, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, 7 Department of Emergency Medicine, Aksaray University, Aksaray Training and Research Hospital, Aksaray, 8 Department of Anesthesiology And Reanimation, Ankara Training and Research Hospital, Ankara, 9 Department of Thoracic Surgery, University of Health Sciences, Bilkent City Hospital, Ankara, 10 Depatment of Urology, Kafkas University, Kars, Turkey
DOI: 10.4328/ACAM.22758 Received: 2025-05-28 Accepted: 2025-07-29 Published Online: 2025-07-30 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):578-581
Corresponding Author: Bensu Bulut, Department of Emergency Medicine, Health Science University, Ankara Gulhane Training and Research Hospital, Ankara, Turkey. E-mail: bensu.bulut@gmail.com P: +90 553 181 93 62 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5629-3143
Other Authors ORCID ID: Medine Akkan, https://orcid.org/0000-0002-6320-9667 . Murat Genç, https://orcid.org/0000-0003-3407-1942 . Ayşenur Gür, https://orcid.org/0000-0002-9521-1120 . Mehmet Yortanlı, https://orcid.org/0000-0002-6744-2423 . Betül Çiğdem Yortanlı, https://orcid.org/0000-0003-2698-3159 . Ramiz Yazıcı, https://orcid.org/0000-0001-9210-914X . Hüseyin Mutlu, https://orcid.org/0000-0002-1930-3293 . Mustafa Sirri Kotanoglu, https://orcid.org/0000-0002-6906-573X . Eray Cinar, https://orcid.org/0000-0002-4564-6097 . Ramazan Kocaaslan, https://orcid.org/0000-0003-1944-7059
Aim: Considering the growing role artificial intelligence technologies play in medical education, this study aims to provide a comparative evaluation of the performances of large language models ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1 in the Basic Life Support (BLS) Exam.
Materials and Methods: In this observational study, we presented four large language models with 25 multiple-choice questions based on the American Heart Association (AHA) guidelines. Questions were divided into two categories as knowledge-based (n = 14, 56%) and case-based (n = 11, 44%). Response consistency was ensured by presenting each question on three separate days to all models. Models’ accuracy rates were assessed using overall accuracy, strict accuracy, and ideal accuracy criteria.
Results: In the overall accuracy assessment, ChatGPT-4o and DeepSeek R1 models showed 100% success, and Gemini 2.0 and Claude 3.5 models achieved 96% success rate. All models performed perfectly on the case-based questions. On the knowledge-based questions, ChatGPT-4o and DeepSeek R1 scored full points, while Gemini 2.0 and Claude 3.5 achieved 90.9% success. Statistical analysis showed no significant difference between results (p = 0.368).
Discussion: Large language models show high accuracy rates in BLS training. These technologies can be used in supportive roles in medical education, but human supervision is critical in clinical decision-making.
Keywords: Artificial Intelligence, Large Language Models, Basic Life Support, Medical Education, ChatGPT, Resuscitation
Introduction
Basic Life Support (BLS) is a critical procedure that includes timely initiation of life-saving interventions in life-threatening situations such as cardiac or respiratory arrest. Timely and appropriate resuscitation significantly improves survival rates and neurological outcomes of patients [1]. Organisations such as the American Heart Association (AHA) organise and deliver courses around the world to improve accessibility of cardiopulmonary resuscitation (CPR) and automatic external defibrillators (AED) training [2]. Similarly, the Resuscitation Council UK (RCUK) organizes Basic Life Support (BLS) and Advanced Life Support (ALS) courses that are mandatory for all healthcare providers, and these courses are updated every five years [3]. In all these courses, pre-course tests are performed to facilitate participant learning, and post-course tests are performed to provide certification for participants.
The rapid development of artificial intelligence (AI) technologies is leading to important transformations in medical education. Nowadays, large language models (LLMs) are playing ever-increasing roles in the training of healthcare professionals through platforms such as ChatGPT, Bard, and Claude [4]. Studies focusing on the performance of large language models in medical exams have increased remarkably in recent years [4,5,6]. King et al.’s study, where GPT-4V achieved success rates of 96% in BLS and 90% in ACLS exams, shows the potential of these technologies in medical education [7]. In their study where they performed a comparative analysis of the performances of ChatGPT and Bard in resuscitation-based medical questions, Patel et al. found similar results where these models achieved success rates between 75-96% [4]. These successful performances suggest that AI models can be used effectively as supportive tools in medical education [8]. It has been reported that AI-supported tools can provide high-quality and empathetic health recommendations, and in some cases, can even surpass physicians’ answers [9].
However, despite the successful performances of specifically engineered software, the question of whether widely used general-purpose chatbots such as GPT-3.5, GPT-4, Bard, and Bing have the same competence in emergencies is still unanswered. The study by Aqavil-Jahromi et al. revealed that there are significant differences in the accuracy and reliability of different AI models in BLS scenarios [10]. Meanwhile, Birkun’s study showed that AI-based chatbots do not generate content in accordance with resuscitation guidelines and can give potentially harmful recommendations [11].
The aim of this study is to analyse the performances of four large language models, such as ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1 in standard questions based on the American Heart Association’s (AHA) BLS protocols and the reliability of these chatbots in emergencies. In our study, all models were asked the same BLS questions on three separate days, and the answers were assessed using the overall accuracy, strict accuracy, and ideal accuracy criteria. The findings of this study have critical importance for understanding the potentials and limitations of large language models in emergencies, parallel to technological advancements.
Materials and Methods
In this observational study, response accuracy and consistency of ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1 models’ performances in answering Basic Life Support (BLS) module questions were examined. Models’ comparative performances were analysed in overall accuracy, strict accuracy, and ideal accuracy levels. BLS training has been a routine training provided to all healthcare workers and even students for many years, and is updated every five years [1,2]. The BLS exam consists of 25 multiple-choice questions with five options. BLS courses are the highest level courses based on the American Heart Association (AHA) BLS guidelines [3].
We used four large language models (LLMs) in our study. First is ChatGPT-4o; ChatGPT 4 Omni (ChatGPT-4o) version of ChatGPT, which is currently known to have the highest level of medical knowledge among its peers, was used [4]. This model is trained on extensive data, including medical texts and journals published up to and including September 2024 [7,9]. Second is Gemini 2.0, representing Google’s evolving family of large language models (including Bard and earlier Gemini versions), known for producing medically relevant, accurate, and referenced outputs in scientific contexts [10,12]; third is Claude 3.5, used for its accuracy and quality levels similar to that of physicians in the medical field [13]; fourth is DeepSeek R1, used because it is reported as a promising AI tool in facilitating the diagnosis of diseases and conditions [14,15].
25 multiple choice BLS questions were assessed by authors R.Y. and H.M. separately and divided into two groups as knowledge-based questions and case-based questions. Where the assessment of these authors differed, questions were assessed by author B.B. for a final decision. Out of all BLS questions, 11 (44%) were case-based and 14 (56%) were knowledge-based. BLS questions were presented to ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1 models once each on three separate days between 1-30 January, and three answers were generated for each question. This approach is similar to other studies where LLMs are presented with a question three times in order to provide LLM consistency and response stability [4,14]. Models’ accuracy rates were evaluated using overall accuracy, strict accuracy, and ideal accuracy criteria.
Overall accuracy: Considered correct when all three responses are correct.
Strict accuracy: Considered correct when two out of three responses are correct.
Ideal accuracy: Considered correct when one out of three responses is correct.
AHA’s BLS questions and answers and responses of ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1 models were recorded in a separate Microsoft Excel 2023 file (Version 16.73, Microsoft Corporation, Redmond, WA). Because only artificial intelligence models were used in this study, and there were no human or animal test subjects, it did not require ethics committee approval.
Statistical Method
Statistical analysis was performed using SPSS 27.0 (IBM Corp, Armonk, NY, USA). Categorical variables were expressed as numbers and percentages (%). Categorical variables were analysed by the Chi-square and Fisher’s exact test. Models’ performances were compared using the Cochran Q test. Statistical differences between the models were evaluated using the McNemar test for pairwise comparisons. Fleiss’ Kappa test was applied to measure the consistency between the responses of models in three separate sessions.
Results
BLS exam questions were presented to four large language models (LLMs): ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1. All models showed complete success in case-based questions. On knowledge-based questions, ChatGPT-4o and DeepSeek R1 achieved 100% accuracy, while Gemini 2.0 and Claude 3.5 models achieved 90.9% accuracy rates. According to strict accuracy criteria, ChatGPT-4o, Gemini 2.0, and DeepSeek R1 achieved %100 success, while Claude 3.5 was inconsistent on one question and achieved only %96 accuracy. On the ideal accuracy level, only Claude 3.5 lagged behind other models with an accuracy rate of 96%. There was no significant difference between models in the statistical analysis (p = 0.368) (Table 1, Figure 1, Figure 2).
Discussion
In this study, we compared the performances of ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1 models in Basic Life Support (BLS) questions. Our study is the first study that evaluates the performances of ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1 in the BLS exam. Our findings demonstrate the increasing role AI models play in medical education, while also highlighting the current limitations. While ChatGPT-4o and DeepSeek R1 perform with %100 accuracy on the overall accuracy measure reflects these models’ perfect progress in medical knowledge, the 96% accuracy rate of Gemini 2.0 and Claude 3.5 is also satisfactory. Similarly, in their study comparing the performances of ChatGPT and Bard in BLS exams, Patel et al. reported that Bard achieved 96% accuracy rates, and ChatGPT’s performance was 75% [4]. These findings show that large language models can be utilised effectively as medical training tools.
In the study of Fijačko et al., ChatGPT’s performance in AHA exams differed between 68% and 92.1% according to the model used [16]. Patel et al. reported that ChatGPT showed success rates ranging between 75-96% for medical questions [4]. Kokulu et al. reported that ChatGPT achieved 94% success in the Pediatric Advanced Life Support (PALS) exam [17]. Similarly, in their study evaluating the performance of GPT-4 in BLS and ACLS exams, King et al. showed a success rate of 96% in the BLS exam [7]. In our study, we found that ChatGPT-4o and DeepSeek R1 achieved % 100% accuracy rates in knowledge-based questions. The high success rates achieved in our study demonstrate the perfect progress of integrating AI models into medical education and highlight the potential of these technologies.
The complete success shown by our models in case-based questions reflects their potential in analysing clinical scenarios. The fact that all models achieved 100% accuracy rates in case-based questions demonstrates that these tools can be used in practical resuscitation training. Beck et al. also obtained similar findings and concluded that AI models could be useful in clinical case analysis [18]. However, this success needs to be interpreted with caution as there are more complex variables in real clinical practice.
One of the remarkable findings of our study was that Claude 3.5 lagged behind other models in case-based questions. Claude 3.5 performing with an accuracy rate of 90.9% in case-based questions demonstrates that different models perform differently in complex clinical scenarios. Beck et al. also obtained similar findings in their study, where they evaluated the European Council (ERC) guidelines with different ChatGPT versions. In this study, ChatGPT-3.5 was reported to be only 77% compliant with the guidelines, whereas ChatGPT-4 was 84% compliant [18]. These findings indicate that while AI models are competent in the transfer of medical knowledge, there are still areas open for improvement when analysing complex clinical scenarios.
Providing a comprehensive assessment of four different large language models and being one of the first comprehensive studies to include different question types (case and knowledge-based) are the strengths of our study. Also, presenting each question three times in order to assess response consistency improves the reliability of our findings. However, our study also has weaknesses. Firstly, we evaluated only 25 BLS questions, and 14 of these were knowledge-based and 11 were case-based. A larger question pool could better evaluate the models’ performances with questions of different difficulty levels. Secondly, our study was limited to four large language models, and other available AI models were not included. Finally, due to the constant updating of language models, our findings are valid only for a specific version, and performance may change with future updates.
Conclusion
This study comprehensively evaluated the performances of large language models in Basic Life Support training and provided important findings. The performances of ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1 in BLS questions were overall satisfactory. In particular, ChatGPT-4o and DeepSeek R1 achieve 100% accuracy rates in knowledge-based questions, indicates that these models can be used as reliable sources of information in medical education. However, their current technological levels are not mature enough to provide services as independent advisors in clinical settings. At this time, when human supervision and oversight are necessary, the use of these technologies as training and supporting tools should be considered, but they should not be relied upon to make vital decisions. Future studies should evaluate the adaptive capacity of these models to updated guidelines and their performance in multi-language education.
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. Blewer AL, Ibrahim SA, Leary M, et al. Cardiopulmonary resuscitation training disparities in the United States. J Am Heart Assoc. 2017;6(5):e006124.
2. Bray JE, Smith K, Case R, Cartledge S, Straney L, Finn J. Public cardiopulmonary resuscitation training rates and awareness of hands-only cardiopulmonary resuscitation: a cross-sectional survey of Victorians. Emerg Med Australas. 2017;29(2):158-64.
3. Soar J, Böttiger BW, Carli P, et al. European Resuscitation Council Guidelines 2021: Adult advanced life support. Resuscitation. 2021;161:115–51.
4. Patel S, Patel R. Embracing Large language models for adult life support learning. Cureus. 2024;16(12):e75961.
5. Clusmann J, Kolbinger FR, Muti HS,et al. The future landscape of large language models in medicine. Commun Med. 2023;3(1):141.
6. Mutlu H, Kokulu K, Sert ET, Topuz MA. Evaluation of ChatGPT’s performance in Türkiye’s first emergency medicine sub-specialization exam. Eur J Emerg Med. 2025;24(1):17–26.
7. King RC, Bharani V, Shah K, Yeo YH, Samaan JS. GPT-4V passes the BLS and ACLS examinations: An analysis of GPT-4V’s image recognition capabilities. Resuscitation. 2024;195:110106.
8. Onan A, Simsek N, Elcin M, Turan S, Erbil B, Deniz KZ. A review of simulation-enhanced, team based cardiopulmonary resuscitation training for undergraduate students. Nurse Educ Pract. 2017;27:134 43.
9. Ayers JW, Poliak A, Dredze M, et al. Comparing physician and artificial intelligence chatbot responses to patient questions posted to a public social media forum. JAMA Intern Med. 2023;183(6):589–96.
10. Aqavil Jahromi S, Eftekhari M, Akbari H, Aligholi Zahraie M. Evaluation of correctness and reliability of GPT, Bard, and Bing chatbots’ responses in basic life support scenarios. Sci Rep. 2025;15(1):11429.
11. Birkun AA, Gautam A. Large language model–powered chatbots fail to generate guideline-consistent content on resuscitation and may provide potentially harmful advice. Prehosp Disaster Med. 2023;38(6):757–63.
12. Omar M, Nassar S, Hijazi K, Glicksberg BS, Nadkarni GN, Klang E. Generating credible referenced medical research: A comparative study of OpenAI’s GPT 4 and Google’s Gemini. Comput Biol Med. 2025;185:109545.
13. Jin H, Guo J, Lin Q, Wu S, Hu W, Li X. Comparative study of Claude 3.5 Sonnet and human physicians in generating discharge summaries for patients with renal insufficiency: assessment of efficiency, accuracy, and quality. Front Digit Health. 2024;6:1456911.
14. Curtin LB, Finn LA, Czosnowski QA, Whitman CB, Cawley MJ. Computer-based simulation training to improve learning outcomes in mannequin-based simulation exercises. Am J Pharm Educ. 2011;75(6):113.
15. Faray de Paiva L, Luijten G, Puladi B, Egger J. DeepSeek-R1 and GPT-4 are comparable in a complex diagnostic challenge: A historical control study. Int J Surg. 2025;110(6):123456.
16. Fijačko N, Gosak L, Štiglic G, Picard CT, Douma MJ. Can ChatGPT pass the life support exams without entering the American Heart Association course? Resuscitation. 2023;185:109732.
17. Kokulu K, Demirtaş MS, Sert ET, Mutlu H. ChatGPT and pediatric advanced life support: A performance evaluation. Resuscitation. 2024;205:110451.
18. Beck S, Kühner M, Haar M, Daubmann A, Semmann M, Kluge S. Evaluating the accuracy and reliability of AI chatbots in disseminating the content of current resuscitation guidelines: A comparative analysis between the ERC 2021 guidelines and both ChatGPT 3.5 and 4. Scand J Trauma Resusc Emerg Med. 2024;32(1):95.
Download attachments: 10.4328.ACAM.22758
Bensu Bulut, Medine Akkan Öz, Murat Genç, Ayşenur Gür, Mehmet Yortanlı, Betül Çiğdem Yortanlı, Ramiz Yazıcı, Hüseyin Mutlu, Mustafa Sirri Kotanoglu, Eray Cinar, Ramazan Kocaaslan. A comparative analysis of the performance of large language models in the basic life support exam: Comprehensive evaluation of ChatGPT-4o, Gemini 2.0, Claude 3.5, and DeepSeek R1. Ann Clin Anal Med 2025;16(8):578-581
Citations in Google Scholar: Google Scholar
Analysis of one-year endoscopy data: A single center retrospective study
Abdulkadir Çelik 1, Arslan Hasan Kocamaz 2, Ömer Kişi 3, Berkan Acar 4, Elif Yılmaz 5
1 Department of General Surgery, Gaziantep Dr.Ersin Arslan Training and Research Hospital, Gaziantep, 2 Department of General Surgery, Kayseri State Hospital, Kayseri, 3 Department of General Surgery, School of Medicine, Necmettin Erbakan University, Konya, 4 Department of General Surgery, School of Medicine, Giresun University, Giresun, 5 Department of General Surgery, Gümüşhane Kelkit State Hospital, Gümüşhane, Turkey
DOI: 10.4328/ACAM.22760 Received: 2025-05-30 Accepted: 2025-07-04 Published Online: 2025-07-08 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):582-585
Corresponding Author: Abdulkadir Çelik, Department of General Surgery, Gaziantep Dr.Ersin Arslan Training and Research Hospital, Gaziantep, Turkey. E-mail: c.abdulkadir@hotmail.com P: +90 506 662 78 31 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5537-7791
Other Authors ORCID ID: Arslan Hasan Kocamaz, https://orcid.org/0000-0002-5257-9611 . Ömer Kişi, https://orcid.org/0000-0001-8606-2453
Berkan Acar, https://orcid.org/0000-0001-9798-295X . Elif Yılmaz, https://orcid.org/0009-0000-6782-8820
This study was approved by the Ethics Committee of Necmettin Erbakan University (Date: 2025-06-13, No: 2025/5825)
Aim: Endoscopy plays a crucial role in the diagnosis and treatment of gastrointestinal diseases. The prevalence and findings of endoscopic procedures vary across regions, making local data analysis essential for optimizing clinical approaches. This study retrospectively analyzes one year of endoscopic procedures performed in a single-center endoscopy unit, evaluating patient demographics, indications, findings, and complication rates.
Materials and Methods: We examined the records of upper and lower gastrointestinal endoscopies performed between January 1 and December 31, 2024, at Necmettin Erbakan University Meram Faculty of Medicine Hospital. Patient characteristics, procedure findings, pathology results, and complications were assessed.
Results: A total of 2,824 cases were included, with 1,965 undergoing upper gastrointestinal endoscopy and 859 undergoing colonoscopy. The most common findings in upper gastrointestinal endoscopy were gastritis (40.8%), hiatal hernia (13.4%), and esophagitis (10.6%), while the malignancy rate was 1.8%. Among colonoscopy cases, the malignancy rate was 4.7%, with polyps (17.9%) and hemorrhoidal disease (14.6%) being the most frequent non-malignant findings. Complications were minimal, with only one case of colonic perforation reported, and there was no mortality.
Discussion: Our findings underscore the importance of endoscopy in gastrointestinal disease diagnosis, highlighting common pathologies and the low incidence of major complications. Future prospective multicenter studies are warranted to validate our results and further explore the diagnostic and therapeutic potential of endoscopy.
Keywords: Endoscopy, Colonoscopy, Gastrointestinal System
Introduction
Endoscopic examinations are crucial in diagnosing gastrointestinal system pathologies [1, 2]. Upper gastrointestinal (upper GI) endoscopy involves advancing an endoscope via the oral route to examine the esophagus, stomach, and duodenum. Colonoscopy involves inserting a colonoscope through the anal canal to evaluate the rectum, all colon segments, and the terminal ileum. These endoscopic methods, which allow for the examination of the luminal surfaces of these organs, are essential for the comprehensive evaluation of gastrointestinal diseases [3].
Endoscopy is currently widely used for the early diagnosis, treatment, and follow-up of both benign and malignant gastrointestinal disorders [4]. It is also employed in numerous therapeutic interventions, such as controlling gastrointestinal bleeding, dilating strictures, removing foreign bodies, and placing stents in cases of advanced tumors [3].
Colonoscopy is considered the gold standard for evaluating the lower gastrointestinal system. This technique allows for the assessment of all segments of the colon, the collection of biopsies, and the performance of polypectomy on polyps detected during the procedure [5]. Furthermore, for therapeutic purposes, colonoscopy can be used to manage lower gastrointestinal bleeding, extract foreign bodies, and perform detorsion in cases of sigmoid colon volvulus [3]. However, it is important to note that these procedures can be associated with complications, such as perforation and bleeding, that may require surgical intervention [6].
Upper gastrointestinal malignancies are among the leading causes of mortality worldwide [7]. Endoscopy enables the early detection and diagnosis of these malignancies. Upper GI endoscopies are performed for indications including dyspeptic complaints, dysphagia, retrosternal burning or pain, epigastric burning or pain, bloating, belching, nausea, vomiting, unexplained iron deficiency anemia, hematemesis, positive fecal occult blood tests, and suspected malignancy on imaging studies [8]. Consequently, the luminal and mucosal structures of the upper GI organs are directly examined, with biopsies obtained when necessary for further evaluation.
According to the latest data, colorectal cancers are one of the most common types of cancer among both sexes worldwide [9]. Current guidelines recommend that individuals at elevated risk undergo at least one colonoscopy screening beginning at the age of 45. Colonoscopy screenings are critical for the early diagnosis and treatment of colorectal diseases. Additional indications for colonoscopy include hematochezia, tenesmus, positive fecal occult blood test results, weight loss, changes in bowel habits, and a family history of colorectal cancer in first-degree relatives. Colonoscopy not only enables the detection of both benign and malignant colonic pathologies but also allows for concurrent diagnostic and therapeutic interventions [10].
The prevalence of gastrointestinal diseases exhibits regional variability worldwide. Therefore, we believe that analyzing the local outcomes of endoscopy centers may contribute to the more effective use of these procedures.
Materials and Methods
In our study, the results of upper and lower gastrointestinal endoscopic examinations performed at the General Surgery Endoscopy Unit of Necmettin Erbakan University Meram Faculty of Medicine Hospital between January 1 and December 31, 2024, were retrospectively evaluated. This study was conducted in accordance with the principles of the Declaration of Helsinki.
Patients with a history of major gastrointestinal surgery were excluded from the study. For the included patients, data such as age, gender, findings from the procedures, pathology results, and procedure-related complications were extracted from the hospital information management system. All data were recorded and analyzed anonymously.
Ethical Approval
This study was approved by the Ethics Committee of Necmettin Erbakan University (Date: 2025-06-13, No: 2025/5825).
Results
Out of the 2,824 patients included in the study, 1,965 underwent upper gastrointestinal endoscopy and 859 underwent colonoscopic examination.
Among the patients who underwent upper GI endoscopy, 54.9% were female and 45.1% were male. The youngest patient was 17 years old, and the oldest was 93 years old. The mean age was 52.4 years for men and 47.4 years for women. Normal findings were observed in 19.2% of the cases. Gastritis was detected in 40.8% of the cases, hiatal hernia in 13.4%, esophagitis in 10.6%, duodenal ulcer in 5.6%, and gastric ulcer in 5.1%. The overall malignancy rate was calculated as 1.8% (Table 1). Among the patients diagnosed with malignancy, 4 (0.2%) had esophageal cancer and 31 (1.6%) had gastric cancer.
Among the patients who underwent colonoscopy, 52.7% were male and 47.3% were female. The youngest patient was 18 years old, and the oldest was 87. The mean age was 52.7 years for males and 47.3 years for females. In the lower GI examinations, no pathology was detected in 427 patients. Malignancy was identified in 4.7% of the patients undergoing colonoscopy. Polyps were found in 17.9% of cases, hemorrhoidal disease in 14.6%, diverticula in 7.8%, and inflammatory bowel disease in 2.9% (Table 2). There were no complications or mortalities during or after upper gastrointestinal endoscopic procedures. In the colonoscopy group, only one patient experienced colonic perforation during the procedure; however, no mortality was observed.
Discussion
Endoscopy is fundamentally important due to its capacity to facilitate a wide range of diagnostic and therapeutic interventions for gastrointestinal lesions. In recent years, endoscopic procedures have evolved to be safer and more effective. However, as an interventional technique, it requires the use of anesthesia and carries the inherent risk of potential complications.[3]
Currently, there is no dedicated endoscopic screening program for upper gastrointestinal malignancies.[7] Instead, diagnostic endoscopy is performed in patients exhibiting alarm symptoms or possessing relevant risk factors. The findings from endoscopic examinations guide the selection of appropriate treatment modalities, and follow-up endoscopic assessments are planned when necessary.[4], [8]
The prevalence of upper gastrointestinal (GI) pathologies varies regionally in the literature [11,12]. In upper GI endoscopies performed for indications such as dyspepsia, dysphagia, and epigastric pain, benign pathologies are predominantly encountered, while malignant conditions of the stomach and esophagus are relatively rare [13,14]. In our study, the most frequently observed pathologies were gastritis (40.8%), hiatal hernia (13.4%), and esophagitis (10.6%). Previous studies have reported that the incidence of gastric cancer ranges from 0.5% to 4%, and that of esophageal cancer from 0.2% to 0.4% [14, 15]. In our series, the overall malignancy rate was determined to be 1.8%, with esophageal cancer accounting for 0.2% and gastric cancer for 1.6% of the cases.
The rate of major complications in diagnostic upper GI endoscopies is notably low. For instance, Yücel et al. reported no complications or mortalities in a series of 7,703 upper GI endoscopies, and Tamer et al. similarly observed no complications in their series of 5,551 cases [14, 15]. In our study, no major complications or mortalities were identified in the upper GI endoscopy records.
Colorectal cancer, one of the most common malignancies and a significant cause of mortality worldwide, is detected in our country using the fecal occult blood test as a noninvasive screening tool [16]. In patients with a positive test result, colonoscopy is subsequently performed for screening based on risk assessment. Current guidelines recommend initiating colonoscopy screening at the age of 45 according to the individual’s risk profile [10]. In our study, the mean age for male patients undergoing colonoscopy was 52.7 years, while that for female patients was 47.3 years. The overall malignancy detection rate was calculated at 4.7%. For comparison, Köker et al. reported a rate of 6.1%, Yaşar et al. reported a rate of 4%, and Yılmaz et al. detected adenocarcinoma in 18 out of 322 patients [16,17,18]. These findings indicate that our malignancy detection rate is consistent with the literature.
Normal colonoscopic findings were observed in 49.7% of the cases in our study. Similar studies have reported normal findings in a wide range of percentages, which may be attributed to the variability in the indications for colonoscopy [18,19,20,21].
In our study, hemorrhoids were the second most frequently observed pathology, with a prevalence of 14.6%. The considerable variability in hemorrhoid rates reported across similar studies may be partly due to incomplete documentation, differences in patient populations, diagnostic criteria, and endoscopic techniques [5,17,21].
Limitation
Although our findings provide valuable insights into gastrointestinal pathologies, the study’s retrospective, single-center design may limit the generalizability of its results and introduce inherent selection and documentation biases. Furthermore, when compared with international data, our findings both align with and diverge from previously reported rates, highlighting regional variations in the prevalence of gastrointestinal disorders.
Conclusion
In light of these observations, future prospective multicenter studies are warranted to validate our results and further explore the diagnostic and therapeutic potential of endoscopy.
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. Vennes JA. Gastrointestinal endoscopy. In: Wyngaarden JB, Lloyd SH Jr, Bennett JC, eds. Cecil textbook of medicine. 19th ed. Philadelphia: W.B. Saunders Company; 1992:630-4.
2. Kuipers EJ, Haringsma J. Diagnostic and therapeutic endoscopy. J Surg Oncol. 2005;92(3):203-9.
3. Valdastri P, Simi M, Webster RJ 3rd. Advanced technologies for gastrointestinal endoscopy. Annu Rev Biomed Eng. 2012;14:397-429.
4. Evans JA, Chandrasekhara V, Chathadi KV, et al. The role of endoscopy in the management of premalignant and malignant conditions of the stomach. Gastrointest Endosc. 2015;82(1):1-8.
5. Karaca A. Genel Cerrahi Endoskopi Ünitemizdeki Rektal Kanamalarda Kolonoskopi Deneyimlerimiz. [Our Colonoscopy Experiences for Rectal Hemorrhages in our Endoscopy Department of General Surgery]. Ankara Med J. 2014;14(4):151-5.
6. Rex DK, Bond JH, Winawer S, et al. Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2002;97(6):1296-308.
7. Gupta N, Bansal A, Wani SB, Gaddam S, Rastogi A, Sharma P. Endoscopy for upper GI cancer screening in the general population: a cost-utility analysis. Gastrointest Endosc. 2011;74(3):610-624.e2.
8. Shaukat A, Wang A, Acosta RD, et al. The role of endoscopy in dyspepsia. Gastrointest Endosc. 2015;82(2):227-32.
9. Patel SG, May FP, Anderson JC, et al. Updates on age to start and stop colorectal cancer screening: recommendations from the U.S. multi-society task force on colorectal cancer [published correction appears in Gastroenterology. 2022;163(1):339]. Gastroenterology. 2022;162(1):285-99.
10. Davila RE, Rajan E, Adler D, Hirota WK, Jacobson BC, Leighton JA, et al. ASGE guideline: the role of endoscopy in the diagnosis, staging, and management of colorectal cancer. Gastrointest Endosc. 2005;61(1):1-7.
11. Crew KD, Neugut AI. Epidemiology of upper gastrointestinal malignancies. Semin Oncol. 2004;31(4):450-64.
12. Fatih A, Yasin O, Hakan D, Yavuz A. Should every region use the same gastric cancer scanning and treatment approaches? Let’s reconsider: a northeastern Turkey example. BMC Gastroenterol. 2016;16(1):120.
13. Ateş M, Köşüş A, Köşüş N, Güler A. Results of upper gastrointestinal system endoscopy in women with dyspeptic symptoms. Eurasian J Med. 2009;41(2):80-3.
14. Yücel Y, Aktümen A, Aydoğan T, et al. Üst gastrointestinal sistem endoskopisi: 7703 olgunun retrospektif analizi. [Upper gastrointestinal endoscopy: A retrospective analysis of 7703 cases]. Endoskopi Gastrointestinal. 2016;24(1):1-3.
15. Tamer A, Korkut E, Korkmaz U, Akcan Y. Üst Gastrointestinal Endoskopi Sonuçları: Düzce Bölgesi. [The Upper Gastrointestinal Endoscopy Results: Region of Duzce] KTD. 2005;6(2):31-4.
16. Köker G, Kocabıyık AB, Eren Durmuş M, et al. Evaluation of colonoscopy and histopathology results in patients undergoing colonoscopy for occult blood positivity in stool. Akademik Gastroenterol Derg. 2025;24(1):9-14.
Download attachments: 10.4328.ACAM.22760
Abdulkadir Çelik, Arslan Hasan Kocamaz, Ömer Kişi, Berkan Acar, Elif Yılmaz. AAnalysis of one-year endoscopy data: A single center retrospective study. Ann Clin Anal Med 2025;16(8):582-585
Citations in Google Scholar: Google Scholar
Evaluation of ocular biometric changes and disease activity in patients with acromegaly
Pınar Alarslan 1, Sinan Emre 2, Bilgin Özmen 3, Zeliha Hekimsoy 3
1 Department of Endocrine and Metabolic Diseases, Faculty of Medicine, University of Health Sciences, Izmir Tepecik Training and Research Hospital, Izmir, 2 Department of Ophthalmology, Faculty of Medicine, Batıgöz Eye Hospital, İzmir, 3 Department of Endocrinology and Metabolism, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey
DOI: 10.4328/ACAM.22765 Received: 2025-06-03 Accepted: 2025-07-08 Published Online: 2025-07-31 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):586-591
Corresponding Author: Pınar Alarslan, Department of Endocrine and Metabolic Diseases, Faculty of Medicine, University of Health Sciences, Izmir Tepecik Training and Research Hospital, Izmir, Turkey. E-mail: drpinaralarslan2024@gmail.com P: +90 505 271 46 05 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1790-0796
Other Authors ORCID ID: Sinan Emre, https://orcid.org/0000-0002-9788-3895 . Zeliha Hekimsoy, https://orcid.org/0000-0002-6003-0485
This study was approved by the Clinical Research Ethics Committee of Celal Bayar University (Date: 2009-03-15, No: 2009/003)
Aim: Acromegaly is a chronic systemic disorder due to the excessive secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), having well-known repercussions on many organ systems. Its consequences on the eyes and ocular structures have been less investigated. Thus, this study aims to assess ocular biometric changes of patients with acromegaly and evaluate the association of these changes with disease activity markers.
Materials and Methods: This is a retrospective study of 35 patients with acromegaly along with 25 age and sex-matched controls. Thorough ophthalmologic evaluation was performed, including measurements of CCT, IOP, CH, CRF, retinal thickness (OCT), and SE. Also, biochemical parameters, along with disease activity (GH and IGF-1 levels), were analyzed.
Results: Patients with acromegaly reported higher IOP, CCT, and retinal thickness values than controls which were significantly retarded in CH and CRF. Increased prevalence of visual field defects and lower SE values were also noted in the acromegaly group. These results imply that chronic exposure to elevated levels of GH and IGF-1 may influence ocular structures, both anterior and posterior.
Discussion: The research shows that there are important differences in ocular biometric measurements in acromegaly patients that may indicate active phases of the disease. Implementing regular ophthalmologic evaluation as part of the comprehensive treatment approach can aid in identifying complications in patients, thereby optimizing their health outcomes.
Keywords: Acromegaly, Growth Hormone, Insulin-Like Growth Factor-1, Intraocular Pressure, Corneal Hysteresis
Introduction
Acromegaly is a chronic endocrine disorder with systemic effects, characterized by elevated levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), typically caused by somatotroph adenomas originating from the anterior pituitary. Excess GH and IGF-1 lead to soft tissue overgrowth, visceromegaly, metabolic alterations, and cardiovascular complications, thereby increasing disease-related morbidity and mortality [1-3]. These effects are not limited to internal organs but may also cause structural and functional alterations in ocular structures, particularly the retina and cornea [4-7]. GH has endocrine, autocrine, and paracrine effects, playing a role in eye development and homeostasis, and influencing parameters such as ocular size, corneal thickness, and intraocular pressure [4, 5, 8].
There are a limited number of studies in the literature examining the relationship between GH/IGF-1 levels and ophthalmologic parameters. In some animal models, GH mRNA expression and GH immunoreactivity have been detected in the retinal layer, suggesting a direct involvement of these hormones in ocular development [9]. Studies in patients with acromegaly have reported increased IGF-1 levels in subretinal fluid [10], increased central corneal thickness [7], and elevated intraocular pressure [6]. Moreover, there is evidence indicating a predisposition to glaucoma in the context of GH excess [11, 12]. Conversely, increased average ocular dimensions have been observed after treatment in patients with GH deficiency [12]. However, existing studies generally have small sample sizes and limited variables, and comprehensive analyses of ocular biometric data in relation to the GH–IGF–1 axis remain insufficient [7].
This study aimed to evaluate various ophthalmological parameters (such as central corneal thickness, axial length, intraocular pressure, and visual field) in individuals diagnosed with acromegaly and to investigate the relationship of these parameters with disease activity indicators, including GH and IGF-1 levels. These parameters were selected due to their known sensitivity to hormonal influences and their potential to reflect early subclinical changes in ocular structure. The goal was to elucidate in more detail the effects of systemic disease activity on ocular structures in acromegaly.
Given its systemic nature, acromegaly requires a multidisciplinary approach, and ocular findings may provide important contributions to diagnosis, follow-up, and early detection of complications. However, the insufficient investigation of associations between changes in ocular biometric structures and GH/IGF-1 levels in the existing literature results in a knowledge gap in this area. To the best of our knowledge, few studies have evaluated a comprehensive set of ocular biometric and functional parameters in relation to biochemical disease activity. This study seeks to demonstrate the diagnostic and prognostic value of ocular changes in acromegaly and provide new perspectives for the early diagnosis and management of eye diseases. By integrating corneal biomechanics, pachymetry, IOP, and retinal structure analyses, this research offers a more holistic evaluation compared to previous studies and aims to support the inclusion of ophthalmologic screening in routine endocrine assessment. Additionally, it is expected to offer original data that will contribute to the field of endocrine ophthalmology.
Materials and Methods
This retrospective study reviewed the medical records of 35 patients diagnosed with acromegaly who were followed in the Department of Endocrinology and Metabolism at Celal Bayar University Faculty of Medicine, evaluating the association between their ophthalmologic findings and disease activity.
Findings from acromegaly patients were compared with those of a control group formed from control cases included in the Celal Bayar University Scientific Research Project No. 2009-003. Of the acromegaly patients, 21 were female and 14 were male, with a mean age of 47.26±12.59 years (range: 20 to 70 years). Six patients were in postoperative remission without medical treatment, 25 were receiving long-acting somatostatin analogs after surgery, and four patients had not yet received any treatment.
Inclusion Criteria
– Individuals aged 18 years and older diagnosed with acromegaly.
– Patients were followed in the Department of Endocrinology and Metabolism at Celal Bayar University.
– Patients with complete medical records related to ocular biometric measurements and GH/IGF-1 levels.
– Patients who underwent a full ophthalmologic examination and measurements during the study period.
– For the control group: age- and sex-matched individuals without systemic diseases and with complete ophthalmologic data.
Exclusion Criteria
– Individuals under the age of 18.
– Individuals with a history of ocular trauma, eye surgery, or corneal pathology.
– Patients with glaucoma, retinal diseases, or other serious ocular conditions.
– Patients with missing GH and IGF-1 levels or other incomplete biochemical data.
– Cases with incomplete or inaccurate ophthalmologic examination findings.
– Individuals with pituitary disorders other than acromegaly.
Patients were considered in remission if IGF-1 levels were within age- and gender-appropriate reference ranges, random GH levels were below 2.5 ng/mL, and GH levels in the oral glucose tolerance test were suppressed below 1 ng/mL. Based on these remission criteria, 26 patients were found not to be in remission.
Biochemical Analysis
In our hospital, serum GH levels were measured using a chemiluminescent immunometric assay with the IMMULITE 2000 system (SIEMENS) and GRH kit (Gwynedd, UK), while serum IGF-1 levels were determined using an enzyme-labeled chemiluminescent immunometric assay with the same system and an IGF-1 kit (Gwynedd, UK). Serum glucose was measured using the hexokinase end-point method, total and HDL cholesterol by the cholesterol esterase method with the Beckman Coulter DXC analyzer and commercial kits (California, USA). LDL cholesterol levels were calculated using the Friedewald formula.
Ophthalmological Evaluation
All ophthalmological evaluations of acromegaly and control group patients were performed by the same specialist. Autorefractometry was measured, and visual acuity was assessed using the Snellen chart and decimal system. Intraocular pressure was measured using a Goldmann applanation tonometer. Corneal hysteresis (CH) and corneal resistance factor (CRF) were evaluated with ORA. Retinal thickness was analyzed quantitatively using the OCT scan protocol. Central corneal thickness was measured with ultra-high frequency ultrasound pachymetry after the application of a local anesthetic, and the axial length and corneal thickness were evaluated using a non-contact optical biometry device.
Statistical Analysis
Statistical analyses were conducted using NCSS (Number Cruncher Statistical System) 2007 and PASS (Power Analysis and Sample Size) 2008 software (Utah, USA). While evaluating the study data, descriptive statistical methods (mean, standard deviation, median, frequency, and ratio) were used.
For intergroup comparisons, the Student’s t-test was used for normally distributed parameters, and the Mann-Whitney U test was used for non-normally distributed ones. Pearson and Spearman’s correlation analysis was used to assess relationships between parameters. For categorical variables, Chi-square, Yates corrected Chi-square, and Fisher’s exact tests were applied. A p-value of <0.05 or <0.01 was considered statistically significant.
Ethical Approval
This study was approved by the Clinical Research Ethics Committee of Celal Bayar University (Date: 2009-03-15, No: 2009/003).
Results
In the current study, records of 35 patients diagnosed with acromegaly were evaluated, and these findings were analyzed concomitantly with a control group. The demographic features of the subjects in both groups are detailed in Table 1.
No statistically significant difference was found between the groups regarding gender, age, systolic and diastolic blood pressure (p > 0.05). Nevertheless, body mass index (BMI) was markedly greater in the acromegaly group (p < 0.025) (Table 1).
The proportion of patients with hypertension, average total cholesterol, and HDL cholesterol did not change significantly between the patient and control groups. However, the portion of patients with diabetes mellitus (DM), average levels of LDL cholesterol, and fasting blood glucose were markedly elevated in the acromegaly group (p < 0.05) (Table 2).
Table 3 illustrates the ophthalmological data of acromegaly patients and controls. Right eye and mean SE values for both eyes were significantly lower in acromegaly patients as compared to controls (p = 0.048 and p = 0.032, respectively). However, the left eye values remained similar. No statistically significant differences were observed in the visual acuity of the eyes between the groups (p > 0.05).
Significant differences were found between the acetabulum patients and the controls for the right eye, left eye, and averages of both eyes for intraocular pressure (IOP) measurements, as the values were significantly higher for the acetabulum patients (p = 0.001) (Figure 1).
Pachymetric measurements obtained by contact and non-contact ultrasonic and optical devices showed a marked increase in average readings among eyes of acetabulum patients compared to the control group (p > 0.01). Octopus visual field testing revealed scotoma (tangential defect) in 12 of the 35 acetabulum subjects (34.3%), which was not present in the control group (p = 0.003).
CH for the right eye, left eye, and both averaged for the acromegaly group were significantly lower than expected, which explains the value difference of (p = 0.001) (Figure 2). The same applies for corneal resistance factor (CRF) measurements, with marked differences between patients and controls (p = 0.001 and p = 0.002, respectively).
According to optic coherent tomography (OCT) results, the averages for the right eye, left eye, and both were significantly higher for the acromegaly group compared to the control group (p < 0.01) (Figure 3).
Significant differences were found between acetabulum patients and the controls for right eye, left eye, and averages of both eyes for intraocular pressure (IOP) measurements, as the values were significantly higher for chancre patients (p = 0.001).
Discussion
This study analyzed the ocular biometric parameters of patients suffering from acromegaly and evaluated their relationship with markers of disease activity such as GH and IGF-1. Significant differences between patients and healthy controls were noted with respect to central corneal thickness (CCT), intraocular pressure (IOP), corneal biomechanical properties (CH and CRF), and retinal thickness (OCT measurements).
Central to our observations are the elevated IOP values noted in acromegaly patients, which are greater than those of the controls. This is in agreement with earlier reports, which indicate that the excess production of GH and IGF-1 may augment the production of aqueous humor or diminish its outflow [13,14]. High IOP is said to be associated with heightened chances of glaucomatous optic neuropathy and has been noted in some studies as a predisposition risk factor for glaucoma in this population [2].
CCT values were higher in the acromegaly group compared to other groups. This aligns with earlier research by Batur et al., who also noted increased CCT in these patients [15]. Increased CCT may be a result of the profound remodeling that occurs due to IGF-1 proliferative actions on keratocyte stroma stromal which are known to express IGF-1 receptors [16].
This study also showed reduced corneal hysteresis (CH) and corneal resistance factor (CRF) in patients with acromegaly, indicating changing corneal biomechanical properties. The literature describes reduced CH and CRF in patients with ocular hypertension and considers these characteristics indicators of corneal integrity and viscoelasticity. This may contribute to the evaluation of glaucoma risk in acromegalic patients and underlines the need for thorough ocular assessment [17].
In acromegaly patients, we noted higher retinal thickness values on OCT, indicating increased retinal volume. Recently, Erol et al. reported changes in the choroidal microvasculature of acromegaly patients using OCT angiography, suggesting that hormonal dysregulation may alter the retinal and choroidal architecture and their blood supply [14]. These results appear to support the impact of the GH/IGF-1 axis on the structures of the posterior segment, although more work with OCT angiography and dynamic imaging, such as ERG, is needed to understand the pathophysiology.
Despite refractive errors not being a primary outcome, SE values were lower in the acromegaly group, particularly in the right eye. Some studies have proposed increased axial length in acromegaly, presumably from GH-related somatic growth [18]. However, this parameter was not measured in the current study, which was not included in the present study, and deserves further attention.
Visual field testing showed scotomas in 34.3% of acromegaly patients, a finding that was absent in the control group. These data may indicate some degree of optic nerve or chiasmal compression even in treated patients, or long-standing microvascular compromise due to chronic disease.
Compared with recent literature, our study features a relatively comprehensive ophthalmologic evaluation, supporting recent claims like those of Batur et al. [13], Erol et al.[14] and their growing emphasis on the potential relationships between ocular alterations and biochemical activity of the disease, and attempts to fill this research gap. Most studies provided isolated parameters assessing acromegaly-related changes to the eyes; our study integrates corneal biomechanics and other parameters such as pachymetry, IOP measurements, and retinal scrutiny, advancing the understanding of eye involvement in acromegaly.
Limitation
The study has a few limitations regarding its design, including being retrospective and having a smaller sample size. As well, the omission of axial length measurements, along with hormone levels not correlating with imaging parameters in a quantitative model, remains a shortcoming. Regardless, the results validate the need for comprehensive eye examinations in acromegaly patients as part of multidisciplinary care, which is often overlooked. To confirm the findings and better understand the underlying mechanisms relating to the GH/IGF-1 axis and eye structures, more longitudinal prospective studies with larger patient groups should be conducted.
Conclusion
The research shows that patients with acromegaly have remarkable changes to certain eye measurement parameters, characterized by greater intraocular pressure, central corneal thickness, and retinal thickness, while also exhibiting diminished hysteresis and corneal resistance. These results indicate that enduring GH and IGF-1 elevation impacts ocular structures both in front of and at the back of the eye. Systematic eye checks in acromegaly patients can aid in the early identification of complications that pose a risk to vision and, therefore, should be considered in the holistic management of the condition.
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. Ben-Shlomo A, Melmed S. Acromegaly. Endocrinol Metab Clin North Am. 2008;37(1):101–22.
2. Fleseriu M, Langlois F, Lim DST, Varlamov EV, Melmed S. Acromegaly: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol. 2022;10(11):804-26.
3. Melmed S, Colao A, Barkan M, et al. Guidelines for acromegaly management: An update. J Clin Endocrinol Metab. 2009;94(5):1509–17.
4 . Harvey S, Baudet ML, Sanders EJ. Growth hormone and developmental ocular function: clinical and basic studies. Pediatr Endocrinol Rev. 2007;5(1):510–5.
5. Harvey S, Kakebeeke M, Murphy AE, Sanders EJ. Growth hormone in the nervous system: autocrine or paracrine roles in retinal function? Can J Physiol Pharmacol. 2003;81(4):371–84.
6. Kober AM, Sobol M. Intraocular pressure (IOP) in patients with acromegaly versus healthy controls: a systematic review and meta-analysis. Vision (Basel). 2024;8(3):54.
7. Ciresi A, Amato MC, Morreale D, Lodato G, Galluzzo A, Giordano C. Cornea in acromegalic patients as a possible target of growth hormone action. J Endocrinol Invest. 2011;34(2):30–5.
8. Skrzypiec I, Wierzbowska J, Sobol M, Zieliński G. Corneal tonometric and morphological changes in patients with acromegaly. J Clin Med. 2022;11(22):6750.
9. Bourla DH, Laron Z, Snir M, Lilos P, Weinberger D, Axer-Siegel R. Insulinlike growth factor I affects ocular development: a study of untreated and treated patients with Laron syndrome. Ophthalmology. 2006;113(7):1197.e1–5.
10. Zhang X, Ma J, Li L, et al. Elevated IGF-1 and GH levels are correlated with a thicker iris and wider anterior chamber angle in treatment-naïve acromegaly patients. Invest Ophthalmol Vis Sci. 2022;63(11):27.
11. Congdon NG, Broman AT, Bandeen-Roche K, Grover D, Quigley HA. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol. 2006;141(5):868–75.
12.. Shirke S, Faber SC, Hallem E, et al. Misexpression of IGF-I in the mouse lens expands the transitional zone and perturbs lens polarization. Mech Dev. 2001;101(1):167–74.
13. Batur M, Özer MD, Üçler R, Seven E, Tekin S, Ünal F. Corneal parameters, ocular biometers, and retinal and choroidal thickness in acromegaly patients. Photodiagnosis Photodyn Ther. 2023;44(1):103773.
14. Erol RS, Tiryaki S, Şen EÇ, et al. Alteration in choroidal microvasculature determined by optical coherence tomography angiography in patients with acromegaly. Photodiagnosis Photodyn Ther. 2021;36(1):102590.
15. Ross A, Banerjee S, Chowdhury A. Deducing health cues from biometric data. Comput Vis Image Underst. 2022;221(1):103438.
16. Wang W, Yang T, Huang Q. Quality of life in patients with acromegaly: a scoping review. Orphanet J Rare Dis. 2024;19(1):251.
17. Demarchis L, Chiloiro S, Giampietro A, et al. Cancer screening in patients with acromegaly: a plea for a personalized approach and international registries. Rev Endocr Metab Disord. 2025:1-14.(open Access)
18. Badawi NES, Fawzy A, Osman MH, Mohamed MI. Possible effects of growth hormone therapy on the eye. Med J Cairo Univ. 2019;87(1):2963-66.
Download attachments: 10.4328.ACAM.22765
Pınar Alarslan, Sinan Emre, Zeliha Hekimsoy. Evaluation of ocular biometric changes and disease activity in patients with acromegaly. Ann Clin Anal Med 2025;16(8):586-591
Citations in Google Scholar: Google Scholar
The Power of the pitt bacteremia score in bloodstream infections in older adults
Onur Ozalp, Ebru Muderrisoğlu, Fatih Tune, Fatma Yildiz, Meryem Sahin Ozdemir, Alper Gunduz
Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Basaksehir Cam and Sakura Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.22781 Received: 2025-06-19 Accepted: 2025-07-30 Published Online: 2025-07-31 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):592-597
Corresponding Author: Onur Ozalp, Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Basaksehir Cam and Sakura Hospital, Istanbul, Turkey. E-mail: onur.ozalp@yahoo.com P: +90 212 909 60 00 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4284-2225
Other Authors ORCID ID: Ebru Muderrisoglu, https://orcid.org/0009-0005-4446-6392 . Fatih Tune, https://orcid.org/0009-0000-2482-9671 . Fatma Yildiz, https://orcid.org/0009-0001-0368-2911 . Meryem Sahin Ozdemir, https://orcid.org/0000-0002-3928-3840 . Alper Gunduz, https://orcid.org/0000-0001-9154-844X
This study was approved by the Ethics Committee of Basaksehir Cam and Sakura City Hospital (Date: 2024.03.13, No:181)
Aim: High morbidity and mortality rates, particularly among older adults, are associated with bloodstream infections (BSIs). This study evaluates clinical characteristics, microbiological profile, and predictive factors of 30-day mortality in BSI patients.
Materials and Methods: A retrospective study was conducted on 1,147 BSI patients from a tertiary hospital. Patients were classified based on pathogen type-Gram-positive bacteria (GPB), Gram-negative bacteria (GNB), and others—and mortality outcomes were assessed.
Results: A 64.9% rate of BSIs was attributed to GNB in the study. GNB infections had a significantly higher 30-day mortality rate (70.4%, n=380) than GPB (28.7%, n=155), resulting in an overall mortality rate of 47.1% (n=540). Increased intensive care unit (ICU) lengths of stay, higher Pitt Bacteremia Scores (PBS), and more frequent use of mechanical ventilation and vasopressors were observed in non-survivors. PBS was identified as the strongest predictor of mortality, with each one-unit increase in PBS being associated with a 61% higher risk of death (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.53–1.69, p < 0.001).
Discussion: This research shows the substantial burden of BSIs in older adults, thus emphasizing the need for early risk assessment through PBS and implementing targeted antimicrobial therapies for better outcomes.
Keywords: Bloodstream Infections, Gram-Negative Bacteria, Gram-Positive Bacteria, Mortality, Pitt Bacteremia Score
Introduction
Aging, an unavoidable physiological process, is accompanied by immunosenescence [1]. The aging process affects both the cell-mediated and humoral immune responses, and many innate immune functions are also impaired. Within this context, a rise in the percentage of deaths among older adults attributable to certain infectious diseases is anticipated [2]. Studies show age is an independent risk factor for death caused by infection [2-4]. The global population of people aged 60 years and over is expected to be 22% by 2030 [5], making infections and deaths within this age group increasingly significant for the entire world.
The high morbidity and mortality rates associated with bloodstream infections (BSIs) worldwide place a considerable burden on healthcare systems [6]. BSI by pathogenic microorganisms results in these infections, characterized by systemic inflammatory responses; severe cases may cause septic shock and multi-organ failure. Patient demographics, healthcare practices, and developing antimicrobial resistance significantly affect the complex epidemiology of BSIs [6]. Their impact on healthcare is substantial, especially within hospitals and among patients with compromised immunity. Gram-positive bacteria (GPB), gram-negative bacteria (GNB), and fungal agents are among the various pathogens that may lead to BSIs [7]. Recent decades have seen an increase in BSIs, driven by factors including an aging population, the growing use of immunosuppressive treatments, and the increased use of invasive medical devices (like central venous catheters and ventilators) [7].
BSIs result in higher healthcare spending, longer hospitalizations, and increased intensive care unit (ICU) demand [8]. Research indicates that patients with BSIs, especially those caused by multidrug-resistant (MDR) pathogens, experience substantially longer hospital stays and increased ICU admission rates than those with infections from susceptible strains [8,9]. Analysis of deceased patients at two hospitals showed a 15.1% (280 patients) rate of BSI in the two weeks before death, emphasizing BSIs’ considerable impact on mortality [10]. Disease severity and clinical outcome prediction in patients with BSIs frequently involve the use of the Pitt bacteremia score (PBS) [10].
Patient factors, pathogen traits, and healthcare factors all contribute to the risk of death in BSI patients [11]. Depending on the pathogen, resistance, and comorbidities, 30-day mortality rates have been reported between 20% and 50% in recent studies [9,12,13]. Al-Hasan et al. found that in patients with GNB BSI, underlying conditions, non-urinary BSI sources, central venous catheter infections, and high PBS independently predicted 28-day mortality [14]. To understand the effect of BSIs on patients and healthcare, this study aimed to examine clinical characteristics, microbiological distribution, and predictors of 30-day mortality in patients with BSIs. Identifying key mortality risk factors allows us to optimize treatment and develop targeted interventions, thus contributing to improved patient prognosis.
Materials and Methods
This study retrospectively analyzed data from BSI patients treated at a tertiary care hospital from January 2020–January 2024.
Study population
This study’s participants comprised 1,141 patients with confirmed BSIs. The inclusion criteria for the study were: (1) blood culture-confirmed bacteremia, (2) age 65 or older, and (3) complete clinical and laboratory data. The study excluded patients whose BSI stemmed from fungi or viruses, those lacking complete data, and those without consent (patient or relative). Based on the causative pathogen, patients were divided into three groups: GPB (390 patients), GNB (751 patients), and other bacteria (16 patients). Survival outcomes were determined by a 30-day mortality comparison of 601 survivors and 540 non-survivors.
Data collection and variables
Demographic, clinical, and microbiological data were obtained from the hospital information management system and patient files. Data collected included demographics (age, sex) and clinical variables (ICU admission, mechanical ventilation, vasopressors, mental status, hospital/ICU length of stay). Diabetes, cardiovascular diseases, malignancies, chronic pulmonary diseases, and neurological conditions (e.g., cerebrovascular accidents [CVA], epilepsy) were recorded. Microbiological data, including pathogen identification and antibiotic susceptibility, enabled infection classification. Bacteremia sources were categorized into primary, pneumonia-related, intraabdominal, hepatobiliary, urinary, and soft tissue/bone infections. The use of antibiotics, such as carbapenems, cephalosporins, and penicillins, was documented, both as monotherapy and combination therapy. Each patient had their PBS [9], a severity indicator, calculated. Thirty-day mortality, defined as death within 30 days of a positive blood culture, was the primary outcome. From patient blood cultures, microbiological analysis identified GPB (n=390) and GNB (n=751) microorganisms. Blood cultures underwent automated processing (e.g., BD BACTEC™, bioMérieux VITEK®), with bacterial identification via standard biochemical tests and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). The Clinical and Laboratory Standards Institute (CLSI) or the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines direct the interpretation of antibiotic susceptibility tests.
Statistical analysis
R version 4.4.2, along with several packages, performed the statistical analysis, managed data, created visualizations, and generated reports. All variables underwent descriptive statistical analysis. The Shapiro-Wilk test determined whether the numerical data were normally distributed. Means and standard deviations (SD) described the parametric data. Medians, minimum, and maximum summarize the non-parametric data. Number and percentage (%) frequencies showed the categorical data.
T-tests analyzed normally distributed numerical data for two independent groups, while ANOVA handled comparisons of three or more. The Wilcoxon rank test was used for two groups and the Kruskal-Wallis test for multiple groups when data were non-normally distributed. Categorical data analysis employed Chi-square tests (sufficient cell counts >5) or Fisher’s exact test (small samples). The independent variables were checked for multicollinearity. To identify independent mortality risk factors, a multivariate binary logistic regression model included significant variables from univariate analysis. Results are shown as 95% confidence intervals (CIs) and odds ratios (OR). A P value below 0.05 was considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of Basaksehir Cam and Sakura City Hospital (Date: 2024.03.13, No:181).
Results
Characteristics of participants
The study included 1,141 patients, mean age of 76.2 ± 8.0 years; 47.7% (n=544) were female. Table 1 shows participant clinical, microbiological data, and outcomes related to BSI.
The most frequently isolated pathogens were Klebsiella pneumoniae (n=211), Staphylococcus aureus (n=194), and Escherichia coli (n=182). Table 2 lists the most frequently isolated pathogens in blood cultures. These findings highlight the distribution of clinically significant pathogens, particularly in nosocomial infections and antimicrobial resistance development. GNB (64.9%, n=751) was seen more than GPB (33.7%, n=390). Bacteremia most commonly stemmed from primary infections (48.6%, n=558), followed by pneumonia (27.8%, n=317) and urinary tract infections (9.2%, n=105).
Median hospital stays and ICU stays were 28 days (0–249), and 13 days (0–249), respectively. ICU admission occurred in 68.0% (n=780) of patients. PBS scores ranged from 0 to 14, with a median of 5 of 540 patients, 47.1% had the 30-day mortality.
Comparison between gram-positive and gram-negative bacteremia
A significant difference was observed between patients with GNB and GPB BSIs, with the former group showing significantly longer ICU (p=0.002) and hospital stays (p<0.001) and higher PBS levels (p=0.009). Pneumonia, hepatobiliary infections, and urinary tract infections occurred significantly more often with GNB (p<0.001). Mechanical ventilation, vasopressor support, and central venous catheters were significantly more needed in cases of GNB infections (p<0.001, p=0.030, and p=0.023, respectively). Patients with GNB had a substantially greater 30-day mortality rate than those with GPB (28.7% vs. 70.4%, p<0.001).
Comparison between survivors and non-survivors
The 30-day mortality rate was 47.1% (n=540). Non-survivors were significantly older (75 vs. 77 years old, p<0.001), had more GNB BSI (p<0.001), and were more likely to have ICU admission (p<0.001). Significantly increased ICU lengths of stay (6 vs. 21 days, p<0.001), PBS scores (2 vs. 10, p<0.001), and mechanical ventilation needs (21% vs 78.9%, p<0.001) were observed in non-survivors. Non-survivors showed significantly higher rates of comorbidities, including lung disease (p=0.008), neurological conditions (p=0.014), and acute renal failure (p<0.001). Patients with pneumonia-related bacteremia had the greatest mortality (p<0.001). Mortality was significantly higher with a combination of antibiotic therapy (p<0.001).
Predictors of 30-day mortality
As shown in Table 3, multivariate logistic regression analysis revealed PBS to be the strongest predictor of 30-day mortality. The 30-day mortality rate increases by 61% with a one-unit increase in PBS (OR=1.61, 95% CI: 1.53-1.69, p<0.001). An association was found between GNB infections and an increased risk of 30-day mortality (OR=1.44, 95% CI: 1.01-2.06, p=0.046). Surprisingly, steroids have a protective effect against mortality (OR=0.34, 95% CI: 0.14-0.85, p=0.020).
Discussion
The high morbidity and mortality associated with BSIs make them a significant concern in healthcare. Key insights into the clinical features, microbial spread, and 30-day mortality prediction in older BSI patients emerged from our study. This study showed that higher PBS levels predicted 30-day death rates among older adults. In addition, a relationship existed between GNB infections and 30-day mortality. The results support prior studies, emphasizing the significant impact of BSIs, especially among older adults, critically ill individuals, and immunocompromised patients [6, 7].
Mortality was observed in almost half of the participants in the current study. Mortality rates in our cohort demonstrate the seriousness of BSIs. Previous studies [6, 10, 15-19] also reported high mortality rates associated with nosocomial BSIs. A retrospective propensity-matched cohort study, for example, revealed a considerable mortality burden linked to nosocomial BSIs, thus emphasizing the importance of effective preventive and management measures [20]. Our study’s death rate mirrored that of Gutiérrez-Gutiérrez and Tuncer [18,19], while others reported lower mortality among BSI patients [3,20,21]. Differences in mortality rates across studies might be due to variations in participant number, age, and the types of microorganisms involved.
Our study prominently revealed GNB as the leading causative pathogen, responsible for 64.9% of the cases. This aligns with prior epidemiological research showing a trend towards GNB predominance in nosocomial infections [15]. The most frequently occurring pathogens in this group were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Limited treatment and increased mortality associated with MDR GNB are cause for alarm due to their increasing prevalence [8,13]. The worldwide surge in antimicrobial resistance is alarming; projections predict millions of annual deaths from drug-resistant infections by 2050 without intervention [21]. According to a study, antimicrobial resistance may cause over 39 million deaths by 2050, with older people disproportionately affected [21]. These points highlight the importance of early detection and timely antibiotic treatment for infections in older patients.
Existing research supports the identification of advanced age as a major risk factor for infection-related mortality [9,10,11,16]. The vulnerability of older patients to negative health consequences stems from their decreased physiological reserves and co-existing conditions [1]. Age is a universal risk factor for mortality in BSIs, as identified by a study emphasizing its significance in patient assessment [16]. The risk of death is substantially greater for older BSI patients with co-existing conditions [9,11]. Univariate analysis linked advanced age to mortality, but multivariate analysis, adjusting for age, sex, microorganism, and immunosuppressant use, identified high PBS as the strongest mortality predictor within 30 days in the present study.
Our study revealed that higher PBS scores strongly predicted mortality, indicating a correlation with poorer patient outcomes. Our findings agree with prior research [19] indicating the PBS is a useful tool for risk stratification and early identification of high-risk patients such as older adults. To improve early risk assessment in older adults with BSI, the PBS, due to its prognostic value, should be integrated into standard clinical practice. A study on older adults with MRSA bacteremia showed a significant link between a PBS score of 3 or higher and 30-day mortality [2]. High PBS was a significant mortality predictor across GPB, GNB, and fungal BSIs in numerous studies [2,19,22]. Given these results, we propose that PBS is a valuable parameter for predicting BSI mortality risk in older adults.
Our study unexpectedly revealed a link between steroid use and reduced 30-day mortality among patients with BSI. This discovery supports earlier research indicating corticosteroids could lessen excessive inflammation during sepsis, possibly leading to better results [23]. Low-dose corticosteroids have been shown to lessen vasopressor dependence and improve hemodynamic stability among critically ill patients in studies [24]. Conversely, other research points to a potential link between long-term steroid use and increased secondary infections and mortality [25]. Further research is required to elucidate the effect of corticosteroids on BSI treatment.
This study has several strengths, including a large sample size (1,141 patients) and a specific focus on BSI in older adults, a vulnerable yet understudied population. The findings underscore the PBS as a strong predictor of 30-day mortality, reinforcing its clinical utility. Detailed microbiological and clinical analyses provide valuable insights into pathogen distribution and patient outcomes. The use of rigorous statistical methods, including multivariate logistic regression, enhances the study’s reliability. Our study yields valuable insights into BSI risk factors and outcomes; however, it is not without limitations. Selection bias is a potential consequence of the retrospective design, limiting the generalizability of findings to diverse healthcare settings. The study’s single-center design may limit the generalizability of its findings to other settings. Furthermore, the absence of geriatric syndrome data in this study precluded assessing how frailty, malnutrition, and sarcopenia impact mortality in BSI cases. To validate these findings and explore other factors affecting BSI outcomes, future multicenter prospective studies are needed.
Limitation
This study has several limitations that warrant consideration. First, its retrospective and single-center design may introduce selection bias and limit the generalizability of the findings to other healthcare settings or populations. Second, although the Pitt Bacteremia Score (PBS) was identified as a strong predictor of mortality, other potentially relevant prognostic tools, such as the Charlson Comorbidity Index or SOFA score, were not assessed for comparison. Future multicenter prospective studies incorporating functional assessments and broader pathogen profiles are needed to validate and extend these findings.
Conclusion
Findings highlight the substantial burden of BSIs and pinpoint key indicators for 30-day mortality. This study demonstrated the Pitt bacteremia score’s ability to predict mortality in older patients. High mortality rates associated with BSIs continue to pose a serious threat to patient health. Demonstrating the effectiveness of short, rapid, and useful parameters, such as PBS, in predicting mortality is vital for developing improved prevention and management strategies in clinical settings. Combating BSIs requires strong infection control, proper antimicrobial treatment, and close monitoring of drug resistance.
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. Ajoolabady A, Praticò D, Tang D, et al. Immunosenescence and inflammaging: mechanisms and role in diseases. Ageing Res Rev. 2024;101:102540.
2. Cuervo G, Gasch O, Shaw E, et al. Clinical characteristics, treatment and outcomes of MRSA bacteraemia in the elderly. J Infect. 2016;72(3):309 16.
3. Hasmukharay K, Ngoi ST, Saedon NI, et al. Evaluation of methicillin-resistant Staphylococcus aureus bacteremia: epidemiology, clinical characteristics, and outcomes in the older patients in a tertiary teaching hospital in Malaysia. BMC Infect Dis. 2023;23(1):241.
4. Tuon FF, Telles JP, Cieslinski J, et al. Development and validation of a risk score for predicting positivity of blood cultures and mortality in patients with bacteremia and fungemia. Braz J Microbiol. 2021;52(4):1865-71.
5. Bloom DE, Chatterji S, Kowal P, et al. Macroeconomic implications of population ageing and selected policy responses. Lancet. 2015;385(9968):649-57.
6. Bassetti M, Righi E, Carnelutti A. Bloodstream infections in the intensive care unit. Virulence. 2016;7(3):267-79.
7. Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis. 2003;36(9):1103-10.
8. Kollef MH, Shorr AF, Tabak YP, et al. Epidemiology, microbiology and outcomes of healthcare associated and community acquired bacteremia: a multicenter cohort study. J Infect. 2011;62(2):130-5.
9. Paterson DL, Ko WC, Von Gottberg A, et al. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial infections. Ann Intern Med. 2004;140(1):26-32.
10. Kang CI, Kim SH, Park SW, et al. Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia. J Infect. 2011;62(1):26-33.
11. Gudiol C, Albasanz Puig A, Cuervo G, et al. Understanding and managing sepsis in patients with cancer in the era of antimicrobial resistance. Front Med (Lausanne). 2021;8:636547.
12. Lee H, Yoon EJ, Kim D, et al. Antimicrobial resistance of major clinical pathogens in South Korea, May 2016 to April 2017: first one year report from Kor GLASS. Euro Surveill. 2018;23(42):1800047.
13. Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318-27.
14. Al Hasan MN, Lahr BD, Eckel Passow JE, Baddour LM. Predictive scoring model of mortality in Gram negative bloodstream infection. Clin Microbiol Infect. 2013;19(10):948-54.
15. de Kraker MEA, Davey PG, Grundmann H, BURDEN Study Group. Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe. PLoS Med. 2011;8(10):e1001104.
16. Jin L, Zhao C, Li H, et al. Clinical profile, prognostic factors, and outcome prediction in hospitalized patients with bloodstream infection: results from a 10 year prospective multicenter study. Front Med (Lausanne). 2021;8:629671.
17. Sit PS, Tan TY, Khoo KL, et al. Methicillin resistant Staphylococcus aureus bacteremia: correlations between clinical, phenotypic, genotypic characteristics and mortality in a tertiary teaching hospital in Malaysia. Infect Genet Evol. 2018;59:132–41.
18. Tuncer G, Geyiktepe-Guclu C, Surme S, et al. Determination of associated factors with death in Staphylococcus aureus bacteremia in hospitalized patients during the COVID-19 pandemic: a single-center, retrospective study. Rev Med Chil. 2023;151(10):1319-31.
19. Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, et al. A predictive model of mortality in patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae. Mayo Clin Proc. 2016;91(10):1362-71.
20. Battle SE, Augustine MR, Watson CM, et al. Derivation of a quick Pitt bacteremia score to predict mortality in patients with Gram-negative bloodstream infection. Infection. 2019;47(4):571-8.
21. GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. Lancet. 2024;404(10459):1199-226.
22. Sasaki T, Harada S, Yamamoto S, et al. Clinical characteristics of peripheral venous catheter-associated gram-negative bloodstream infection among patients with malignancy. PLoS One. 2020;15(1):e0228396
23. Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids for treating sepsis in children and adults. Cochrane Database Syst Rev. 2019;12(12):CD002243.
24. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378(9):797-808.
25. Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019;179(2):213-23.
Download attachments: 10.4328.ACAM.22781
Onur Ozalp, Ebru Muderrisoğlu, Fatih Tune, Fatma Yildiz, Meryem Sahin Ozdemir, Alper Gunduz. The Power of the pitt bacteremia score in bloodstream infections in older adults. Ann Clin Anal Med 2025;16(8):592-597
Citations in Google Scholar: Google Scholar
Is there a relationship between kisspeptin, oxidative stress, and polycystic ovary syndrome?
Onur Türkmen 1, Ilyas Turan 2, İbrahim Veysel Fenkçi 3, Erhan Okuyan 4
1 Department of Obstetrics and Gynecology, Manisa City Hospital, Manisa, 2 Department of Gynecologic Oncology, Batman Training and Research Hospital, Batman, 3 Department of Obstetrics and Gynecology, Pamukkale University Hospital, Denizli, 4 Department of Obstetrics and Gynecology, Private Zilan Hospital, Batman, Turkey
DOI: 10.4328/ACAM.22783 Received: 2025-06-22 Accepted: 2025-07-28 Published Online: 2025-07-31 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):598-602
Corresponding Author: İlyas Turan, Department of Gynecologic Oncology, Batman Training and Research Hospital, Batman, Turkey. E-mail: ilyasturan04@gmail.com P: +90 530 871 32 14 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3611-9428
Other Authors ORCID ID: Onur Türkmen, https://orcid.org/0000-0002-1552-8241 . İbrahim Veysel Fenkçi, https://orcid.org/0000-0003-4929-5252 . Erhan Okuyan, https://orcid.org/0000-0001-9636-9539
This study was approved by the Ethics Committee of Pamukkale University (Date: 2016-09-27, No: 17)
Aim: The etiology of PCOS is primarily accepted as an ovarian disorder, and many mechanisms and theories have been proposed regarding the causes of this disease picture. It is thought that the relationship between kisspeptin and the hypothalamic-pituitary-gonadal axis may be related to changes in GnRH secretion in patients with PCOS.
Materials and Methods: In our study, 37 patients with newly diagnosed Polycystic Ovary Syndrome and 38 healthy control groups were analyzed.
Result: No significant difference was found between kisspeptin, glutathione peroxidase, and superoxide dismutase levels in the patient and control groups. However, the mean catalase level was found to be significantly lower in the PCOS group compared to the control group (285.73 ± 26.10 vs. 382.30 ± 39.76, p<0.05). No significant correlation was observed between kisspeptin and HOMA, free testosterone, and DHEA-S levels in our PCOS group. However, catalase levels were observed to be statistically significantly correlated with kisspeptin (r=0.340, p<0.05).
Discussion: It is obvious that new studies are needed to evaluate PCOS phenotypes and subgroups in a larger series in order to understand the real role of kisspeptin in PCOS pathophysiology and to analyze its metabolic relationships.
Keywords: Glutathione Peroxidase, Catalase, Kisspeptin, Insulin Resistance, Polycystic Ovary Syndrome, Superoxide Dismutase
Introduction
PCOS is a syndrome with many clinical findings in the short term, such as anovulation, amenorrhea, oligomenorrhea, menstrual irregularities, dysfunctional uterine bleeding, and hirsutism. More serious long-term risks include infertility, endometrial thickening, endometrial cancer, lipid metabolism disorder, cardiovascular disease, and breast cancer development risk. PCOS is an endocrine-metabolic disease that is well-known to be associated with long-term health problems such as diabetes mellitus and coronary artery disease [1]. The increased cardiovascular risk in polycystic ovary syndrome is thought to be due to insulin resistance, hyperandrogenemia, and dyslipidemia [2]. Kisspeptin is a protein consisting of 54 amino acids and was first obtained from human placenta in 2001. It is encoded by the kiss-1 gene. Problems in kiss-1 gene expression have been shown to be associated with hypogonadotrophic hypogonadism. Therefore, it is thought that kisspeptin is effective on pulsatile GnRH secretion [3-4].
Kisspeptins are a family of neuropeptides with an RF-Amid structure encoded by the Kiss-1 gene (1q32) (neuropeptides containing C-terminal dearginine-phenylalanine (Arg-Phe) are called RF-Amids). It has been suggested that kisspeptin, synthesized locally in the ovaries, may play a role in ovulation. Kisspeptins in the peripheral circulation show their functions by crossing the blood-brain barrier and/or by acting directly on GnRH neurons. The signals formed as a result of the binding of kisspeptins to GPR54 receptors on GnRH neurons in the hypothalamus ensure the release of GnRH from the median eminence to the portal hypophyseal circulation. GnRH binds to GnRH receptors in the pituitary gland and causes the release of gonadotropins (FSH, LH) from the pituitary gland. It is thought that the only receptor of kisspeptins on GnRH neurons is GPR54, and its primary function is to support GnRH secretion [5].
Oxidative stress occurs as a result of the imbalance between free radical formation and the antioxidant system that fights against oxidative damage. Recent studies and publications have shown that oxidative stress plays a role in many important pathological processes. The damage caused by oxidative stress also plays an important role in the pathogenesis of criteria that constitute metabolic syndrome, such as hyperglycemia, hypertriglyceridemia, obesity, and hypertension. Therefore, this study also aimed to compare the levels of oxidative stress parameters in PCOS, which has a multifactorial etiology.
Materials and Methods
The study group consisted of women of reproductive age (18-39 years old) who applied to Pamukkale University, gynecology and obstetrics clinic, and who met Rotterdam PCOS diagnostic criteria (chronic oligo/anovulation, clinical/biochemical hyperandrogenism, transvaginal ultrasonographically subcapsular follicles in their ovaries (more than 12)). Patients with diabetes mellitus, Cushing syndrome, androgen-secreting tumors, and late-onset 21-hydroxylase deficiency, including endocrinopathy, infectious diseases, hypertension, thyroid dysfunction, hyperprolactinemia, chronic liver disease, those using drugs that affect or change insulin secretion and function, sex hormones, and lipid profile, and alcohol and cigarette users were not included in the study.
Healthy women of reproductive age (18-39 years old) who did not have the diseases mentioned above and had regular menstrual cycles (25-34 days of menstruation lasting 2-7 days) were included in the study as a control group.
This study aimed to make an evaluation using parametric statistical methods. For this purpose, the minimum number of cases that would be sufficient to obtain a normal Gaussian distribution in the studied parameters was calculated with the “power analysis” method.. Of all the cases included in the study, spontaneous or progesterone-induced cycles were 3-5. On the 12th day, venous blood samples were taken between 09:00-10:00 in the morning after 12 hours of fasting. Serum fasting glucose (FBG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), insulin, dehydroepiandrosterone sulphate (DHEAS), free testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Total testosterone, Kisspeptin, Glutathione Peroxidase, Catalase and Superoxide dismutase levels were studied from the samples taken. On the day the serum samples were taken, waist circumference, hip circumference, height, and weight of the subjects were measured, and waist-hip ratio and body mass index (BMI) (kg/m2) were calculated.
In the determination of insulin resistance, the “homeostasis model assessment (HOMA-IR)” score [fasting insulin concentration (mIU/L) x glucose (mmol/L)/22.5] was used. For the measurement of kisspeptin levels in serum, HumanKisspeptin1ElisaKit (Cat. NO EA3122Hu) was used. The kits were taken out of +4 oC one hour before and allowed to reach room temperature. Standards were prepared at 6 different concentrations specified in the kit protocol, and 6 different wells were determined as blanks. The study was planned as duplicate standards and samples (50 uL). After 50uL of biotinylated antigen was added to the wells containing standards and samples, they were incubated at 37 oC for 1 hour. At the end of incubation, 96 wells were washed 5 times with 1X wash buffer. Afterwards, 50 μLavidin-HRP was added and incubated for one hour at 37 degrees. The washing was repeated 5 times by pouring with a wrist movement. After preparing Substrate A and B solutions, 50 μL were added one after another and incubated for 10 minutes at 37 oC in a dark environment. At the end of incubation, absorbances were measured at 450 nm wavelength in a Promega device. Results were given as ng/L. Human SOD Elisa Kit (Cat. NO EA0918Hu) was used for measuring SOD activity in serum.
Human Catalase Elisa Kit (Cat. NO EA3053Hu) was used for measuring catalase activity in serum. At the end of the incubation, absorbances were measured at 450nm wavelength in a Promega device. Results were given as KU/L. Human GPX Elisa Kit (Cat. NO EA3696Hu) was used for measuring Glutathione Peroxidase activity in serum.
Statistical Analysis
SPSS (Statistical Package for the Social Sciences, version 17.0) program was used for statistical analysis. Data were expressed as mean ± standard error (X ± SE). Since normal “Gaussian” distribution was observed in many of the studied parameters, the “T-test” method, which is a parametric method, was used in the evaluation of the data. Correlation analysis between the parameters was calculated with “Pearson’s Correlation Coefficient”. The significance limit for all statistical analyses was accepted as p< 0.05.
Ethical Approval
The study was conducted in accordance with the ethical standards set forth in the Declaration of Helsinki and approved by the Ethics Committee of Pamukkale University (Date: 2016-09-27, No: 17). Before participation, informed consent was obtained from participants.
Results
The basic demographic and basic anthropometric characteristics of the patient and control groups are summarized in Table 1. A significant difference was observed only for body weight between the patient and control groups. (p<0.05). No significant difference was found for age, BMI (Body Mass Index), Gravide, Parity, and Waist/Hip ratio. [p>0.05]
Acne, hair loss, seborrhea, and acanthosis nigricans findings of the cases in the entire study group were also evaluated. The results of this evaluation are summarized in Table 2. In the PCOS patient group, LH levels and LH/FSH ratio were found to be significantly higher than the control group, while FSH levels were found to be lower. In addition, DHEA-S and Free Testosterone were also observed to be statistically higher in the patient group. However, no significant difference was found between the patient and control groups for Fasting Blood Glucose, HOMA-IR, Total Cholesterol, HDL, LDL, Triglyceride levels (Table 3).
According to the results obtained, no significant difference was found between kisspeptin, glutathione peroxidase, and superoxide dismutase levels in the patient and control groups. However, the mean catalase level was found to be significantly lower in the PCOS group compared to the control group. The results of these analyses are shown in Table 3. In addition, PCOS patients were examined in 2 subgroups according to AMH (below or above 6 ng/dl). In this comparison, kisspeptin levels were found to be significantly lower in the group with low AMH compared to the other group, between these two groups separated according to AMH levels (45.20 ng/l and 120.19 ng/l, respectively, p=0.038).
The relationship between kisspeptin levels and insulin resistance and hyperandrogenism was analyzed within the PCOS group. For this purpose, a correlation analysis was performed between kisspeptin levels and HOMA-IR results, and no significant correlation was observed between the two parameters (r=-0.032, p>0.05). Similarly, a correlation analysis was performed between kisspeptin levels and free testosterone and DHEA-S levels, and the correlation coefficients were found to be 0.17 and -0.55, respectively (p>0.05). Only catalase was observed to be significantly different in oxidative stress parameters between the PCOS and control groups, and catalase levels were observed to be statistically significantly correlated
with kisspeptin within the PCOS group (r=0.340, p<0.05).
Discussion
The most striking result of our study is that only catalase was significantly different among oxidative stress parameters between the PCOS and control groups, and catalase levels were statistically significantly correlated with kisspeptin in the PCOS group. In our study, no statistical difference was found between the patient group and the control group in terms of age, body weight, BMI, height, gravity, parity, waist circumference, hip circumference, and waist/hip ratio. This situation shows that homogenization was achieved in demographic and anthropometric measurements between the patient and control groups. We also think that this situation makes the data in our study more reliable. Acne and hair loss were significantly more common in the PCOS group. As expected, LH levels and LH/FSH ratio were significantly higher in the patient group compared to the control group, while FSH levels were lower. In addition, DHEA-S and Free Testosterone were also statistically significantly higher in the patient group. In addition, no significant difference was found between the levels of kisspeptin, glutathione peroxidase, and superoxide dismutase in the patient and control groups. PCOS is defined as oligo-anovulation, clinical and/or biochemical hyperandrogenism findings, and polycystic ovary appearance on ultrasound [6]. In our study, the PCOS group also had oligomenorrhea-amenorrhea, hirsutism, increased serum free testosterone and DHEA-S levels, high modified Ferriman-Gallway Score, and significantly elevated polycystic ovary appearance on ultrasound when compared to the control group.
Hirsutism is the most common clinical finding of hyperandrogenism in patients with PCOS and is mostly evaluated with the modified Ferriman Gallwey (mFG) method. Before scoring, the patient should not have had laser or electrolysis for three months, their hair should not have been removed for 4 weeks, and their hair should not have been shaved for 5 days. In this method, the hair density in a total of 9 body regions, including the upper lip, chin, chest area, lower and upper back, lower and upper abdominal areas, upper arms and legs, is scored between 1 and 4, and when the total mFG score is ≥8 points, it is evaluated as hirsutism [7]. In our study, it was observed that the mFG score was significantly higher in patients with PCOS. The main hormones that provide ovulation and menstruation are FSH and LH. The release of these hormones is impaired in PCOS [8,9]. Pulsatile release of gonadotropin-releasing hormone (GnRH) causes the release of LH and FSH. LH stimulates theca cells in the ovaries and causes androgen production (especially androstenedione). FSH stimulates granulosa cells and converts androgen to estrone. Normally, FSH is secreted more than LH, but in PCOS, LH is secreted in higher amounts than FSH, and thus, androgen production, especially androstenedione production, increases. Thus, more androstenedione is converted to testosterone in peripheral tissues, and hyperandrogenism occurs [10,11]. In our study, LH and LH/FSH levels were found to be significantly higher in the PCOS patient group, in direct proportion to literature data. Again, in our study, laboratory findings of hyperandrogenism, free testosterone, and DHEA-S levels were found to be significantly higher in the PCOS study group. As a result of these data, clinical and laboratory findings of hyperandrogenism were significantly higher in the patient group, which shows the accuracy of patient selection. It has been shown that insulin resistance and hyperinsulinemia are more common in women with PCOS compared to normal women of similar age and weight [12].
In our study, FBG and fasting insulin levels were examined in the PCOS patient and control groups, and HOMA-IR values were calculated. In the results we obtained, FBG, fasting insulin, and HOMA-IR values were found to be higher in the patient groups, but no statistically significant difference was shown between the patient and control groups. Kisspeptin levels and insulin resistance were also analyzed in our PCOS patient group. For this purpose, a correlation analysis was performed between kisspeptin levels and HOMA results, and no significant correlation was observed between the two parameters. Problems in kiss-1 gene expression are associated with hypogonadotrophy-hypogonadism. Therefore, it is thought that kisspeptin is effective on pulsatile GnRH secretion. It is thought that the relationship between kisspeptin and the hypothalamo-pituitary-gonadal axis may be related to changes in GnRH secretion in PCOS patients. A recent study reported by Ozay et al. from Türkiye found that kisspeptin levels were higher in PCOS patients than in controls, but it did not reach statistical significance [13]. This may be due to the fact that the PCOS group is not homogeneous enough. Similarly, no significant difference in kisspeptin levels was observed between the two groups in our study. However, it may be possible to encounter different results in future studies where the PCOS group will be classified more precisely within itself. According to our oxidative stress markers in our study, serum catalase levels were found to be significantly lower in the patient group compared to the control group, but no significant difference was found for glutathione peroxidase and superoxide dismutase. Ozer et al. found glutathione peroxidase and catalase levels to be lower in PCOS cases in a similar study design [14]. However, they also did not find a significant difference for SOD in their study. This different result in our study may be related to the sample size, as well as to differences in the diagnosis of PCOS. Therefore, we think that in order to obtain comparable results, other studies with larger series are needed in which more objective parameters will be considered in addition to standard diagnostic criteria [15]. In the PCOS patient group, a correlation analysis was performed between kisspeptin levels and serum glutathione peroxidase, catalase, and superoxide dismutase levels, and only catalase was observed to be significantly different, and it was observed that catalase levels were statistically significantly correlated with kisspeptin in the PCOS group.
In our study, as a general perspective, in the analysis conducted within the PCOS group, it is understood that kisspeptin levels show a positive correlation with catalase values. A similar relationship is not observed for glutathione peroxidase and superoxide dismutase. Again, no significant relationship was observed between kisspeptin levels and insulin resistance and hyperandrogenism in PCOS patients. However, when examined in detail, it is striking that kisspeptin levels are not distributed homogeneously in PCOS cases and vary among different subgroups. Therefore, without a more detailed comparison of PCOS subgroups, it is not possible to reach a definitive conclusion about the nature of the real relationship between kisspeptin and the aforementioned parameters.
Conclusion
It is obvious that new studies are needed to evaluate PCOS phenotypes and subgroups in a larger series in order to understand the real role of kisspeptin in PCOS pathophysiology and to analyze its metabolic relationships.
Limitation
We tried to prevent differences between the groups by trying to keep our groups as homogeneous as possible. Blood samples were taken under the same conditions for each patient. The gynecologist who performed the ultrasonographic examination was the same person. These points are the strengths of our study. In addition to the small sample size, while kisspeptin, glutathione peroxidase, and superoxide dismutase levels were found to be similar in our PCOS and control groups, catalase levels were observed to be significantly lower in PCOS patients.
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. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab.. 2004;89(6):2745-9.
2. Witchel SF, Tena-Sempere M. The Kiss1 system and polycystic ovary syndrome: lessons from physiology and putative pathophysiologic implications. Fertil Steril. 2013;100(1):12-22.
3. Goodarzi MO, Quinones MJ, Azziz R, Rotter JI, Hsueh WA, Yang H. Polycystic ovary syndrome in Mexican-Americans; prevalence and association with the severity of insulin resistance. Fertil Steril. 2005;84(3):766-9.
4. Goodarzi MO, Azziz R. Diagnosis, epidemiology, and genetics of the polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab. 2006;20(2):193-205.
5. Ruohonen ST, Poutanen M, Tena-Sempere M. (2020). Role of kisspeptins in the control of the hypothalamic-pituitary-ovarian axis: old dogmas and new challenges. Fertil Steril. 2020;114(3):465-74.
6. Daneshmand S, Weitsman SR, Navab A, Jakimiuk AJ, Magoffin DA. Overexpression of theca-cell messenger RNA in polycystic ovary syndrome does not correlate with polymorphisms in the cholesterol side-chain cleavage and 17 alpha-hydroxylase/C(17-20) lyase promoters. Fertil Steril. 2002;77(2):274-80.
7. Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol. 1981;140(7):815-30.
8. Siddiqui S, Mateen S, Ahmad R, Moin S. (2022). A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS). J Assist Reprod Genet. 2022;39(11):2439-73.
9. Yildiz BO. Oral contraceptives in polycystic ovary syndrome: risk-benefit assessment. Semin Reprod Med. 2008;26(1):111-120.
10. Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2004;60(1):1-17.
11. González Centeno A, Hernández Marín I, Mendoza R, Tovar Rodríguez JM, Ayala AR. Ovarios poliquísticos: expresión clínica y bioquímica [Polycystic ovarian disease: clinical and biochemical expression]. Ginecol Obstet Mex. 2003;71:253-258.
12. Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes. 1992;41(10):1257-66.
Download attachments: 10.4328.ACAM.22783
Onur Türkmen, Ilyas Turan, İbrahim Veysel Fenkçi, Erhan Okuyan. Is there a relationship between kisspeptin, oxidative stress, and polycystic ovary syndrome? Ann Clin Anal Med 2025;16(8):598-602
Citations in Google Scholar: Google Scholar
The effects of minimally invasive surgery in liver hydatid cysts
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.22789 Received: 2025-06-29 Accepted: 2025-07-29 Published Online: 2025-07-31 Printed: 2025-08-01 Ann Clin Anal Med 2025;16(8):603-607
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: +90 332 221 00 00 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-2025/09/12)
Aim: This study aims to compare laparoscopic and open surgical techniques in hepatic hydatid cysts.
Materials and Methods: This retrospective study was conducted at the Department of General Surgery, Faculty of Medicine, Kocaeli University. Patients who underwent surgery for hydatid liver cysts between January 1, 2020, and January 1, 2025, were included in the study. Cases were divided into two groups: the laparoscopic and open groups. The demographic and clinical characteristics of the patients were obtained through a review of their medical records.
Results: A total of 39 patients, 20 male and 19 female, were included in the study. The mean age of the patients was 43.3 (± 17.2). Laparoscopic surgery was performed on 8 patients and open surgery on 31 patients. Although the length of hospital stay was longer in the open group, no significant difference was found. (p=0.08) The most common type of cyst in all groups was a single cyst. The largest cyst diameters were 8.2 cm in the laparoscopic group and 9.1 cm in the open group. (p=0.58) Although bile duct-related cysts were more common in the open group, no significant difference was detected. (p=0.82) According to the Gharby classification, types 1, 2, and 3 cysts were more common in the laparoscopic group, while types 4 and 5 cysts were more common in the open group. (p<0.001) The most commonly performed procedure was cystotomy and external drainage.
Discussion: In the treatment of hydatid cysts, laparoscopic treatment is as effective as open surgery, with shorter hospital stays and similar recurrence rates.
Keywords: Hydatid Cyst, Laparoscopic, Liver, Open Surgery
Introduction
Liver hydatid cyst, also known as echinococcosis, is a disease caused by the Echinococcus granulosus tapeworm. It is more common in rural areas where animal husbandry is widespread than in urban centers. It is more prevalent in certain countries in Asia, such as the Middle East, Africa, South America, India, Pakistan, and China [1].
The main approaches to treating hydatid cysts are surgical or percutaneous drainage treatments. In addition, antiparasitic treatments are also used. Percutaneous treatment (PAIR) can only be used on certain selected patients. These are generally type 2-3 hydatid cysts. Surgical treatments must be used on patients who cannot undergo PAIR treatment [2,3].
Surgical treatment is commonly performed as an open procedure. Although open surgery appears to be more effective in controlling cysts, it has disadvantages such as a large incision, more postoperative pain, and slower recovery. For this reason, minimally invasive treatment methods have also come to the fore in the treatment of these cysts. These methods are known to have advantages such as smaller incisions, less postoperative pain, and faster recovery and return to work [4].
This study aims to compare laparoscopic and open surgical techniques used in the treatment of hydatid cysts.
Materials 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 for suspected hydatid liver cysts between January 1, 2020, and January 1, 2025, were included in the study.
Inclusion criteria were as follows: patients over the age of 18 and patients who underwent surgery due to hepatic hydatid cyst.
Exclusion criteria were as follows: patients under the age of 18, patients who underwent other treatment methods (PAIR) due to hepatic hydatid cyst.
Outcomes
The medical records of the included patients were reviewed to collect clinical data such as demographic characteristics (age, gender), presenting complaints, medical history, previous treatments, preoperative imaging methods and laboratory results, characteristics of the cysts, and surgical procedures performed. Patients were divided into two groups based on the surgical procedures performed: laparoscopic and open groups, and demographic and clinical data were compared between these groups.
The primary outcome was the recurrence rate, while the secondary outcomes included the surgical procedures performed and other clinical data.
Statistical Analysis
Normality was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. If normality was violated in any group, non-parametric tests were applied. The Mann-Whitney U test compared continuous variables, while chi-square and Fisher’s exact tests analyzed categorical variables. 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-2025/09/12).
Results
A total of 39 patients were included in the study. Eight of these patients underwent laparoscopic surgery, while 31 underwent open surgery. The average age of the patients was 43.3 (± 17.2). The average age in the laparoscopic group was 35.6 (±13.2), while in the open group it was 45.3 (± 17.7). (p=0.16) Twenty patients were male and 19 were female. No difference was found between the groups in terms of gender (p=0.38) (Table 1).
When the patients’ presenting complaints were examined, the most common complaint in both groups was abdominal pain. Additionally, the proportion of patients without active complaints was also high. No significant difference was found between the groups in terms of presenting complaints (p=0.84) (Table 1).
When the patients’ medical histories and family histories were examined, only one patient had a family history (2.6%), and PAIR or surgical treatment had been administered to five patients previously (12.8%). Although no statistical difference was found in terms of hospital stay duration, the hospital stay duration of patients in the open group was longer (11.1–6.4) (p=0.08). Recurrence rates were lower in the laparoscopic group compared to the open group, but this difference was not statistically significant. (12.5-12.9%) (p=0.97) The need for postoperative ERCP occurred in a total of 8 patients, all of whom were in the open surgery group (p=0.11) (Table 1).
Among the laboratory parameters evaluated in patients, indirect hemagglutination was positive in 28 patients. Four of these were in the laparoscopic group and 24 were in the open surgery group (p=0.058). The immunoglobulin G value was 20.5 (± 9.8) µl on average in all patients. When this value was examined in terms of subgroups, it was 14.5 (± 10.1) µl in the laparoscopic group and 22.1 (± 9.3) µl in the open group (p=0.048) (Table 2).
Ultrasonography was used in 56.4% of patients, CT in 66.7%, and MRI in 46.2% during the diagnostic phase. A single cyst was most commonly detected in patients in all groups; all patients with multiple cysts were in the open group (p=0.23). The average size of the largest cyst was 8.2 cm in the laparoscopy group and 9.1 cm in the open group. (p=0.58) Eleven cysts were bile duct-related. Although bile duct-related cysts were more numerous in the open group, no statistically significant difference was found. (p=0.82) According to the Gharbi classification, type 1 and 2 cysts were significantly more common in the laparoscopy group, while type 3, 4, and 5 cysts were significantly more common in the open surgery group (p<0.001) (Table 2).
When the surgical procedures performed were evaluated, it was determined that the most frequently performed procedure in all groups was cystotomy and drainage (p=0.55) (Table 3) (Figure 1-3).
Discussion
Liver hydatid cyst is one of the most common parasitic diseases. Although the use of the PAIR method in its treatment has become widespread, surgical treatment still retains its primary role. In particular, the use of minimally invasive methods such as laparoscopic and robotic surgery, which have become widely used in recent years, is increasing. In this study, laparoscopic and open techniques were compared.
In our study, the mean age of patients was 43.3, which is consistent with the literature [5,6]. Nearly half of the patients who underwent surgery were male, and the other half were female. A similar distribution was observed in many studies [7,8]. The most common reason for referral was abdominal pain. Similar studies in the literature have shown that patients most commonly present with complaints of abdominal pain [9,10]. Family history is detected at a low rate in studies [11] (5.6%). Similarly, in our study, there was one patient (2.6%) with a family history.
A hydatid cyst is a disease that can often recur. For this reason, in some patients who have previously undergone surgery, the disease may recur due to certain reasons related to the patient and the surgical procedure. In studies, the rate of patients who have previously undergone interventional procedures due to hydatid cyst among patients who have undergone surgery has been reported as 11.2% [11]. In our study, the percentage of patients who had previously undergone interventional treatment methods was found to be 12.8%. Open surgery was preferred in the majority of these patients (80%). It is likely that these recurrence cases were considered more complex and, due to previous surgical and interventional procedures, laparoscopic methods were less preferred in these patients.
The average length of stay in hospital was found to be 10.1 days, which was longer than in the laparoscopic group (11.1 days), although this difference was not statistically significant. This supports the finding reported in many previous studies that laparoscopic surgery results in shorter hospital stays [5,12].
When patients were evaluated in terms of recurrence, it was found that 4 of the 5 patients (12.8%) with recurrence were in the open group, and 1 patient was in the laparoscopic group. Shabani also reported that recurrence developed in 3 patients in the open group and 1 patient in the laparoscopic group [12]. In another study, the recurrence rate was reported to be 2.83% in laparoscopic surgery and 4.7% in open surgery [13]. Based on the information in the literature and the results of our study, it can be said that recurrence is more common in open surgery.
In our study, a total of 8 patients required ERCP in the postoperative period, and all of these patients were in the open surgery group. In addition, the number of bile-related cysts was numerically higher in the open surgery group. Previous studies have reported that the number of postoperative bile fistulas and the need for ERCP are higher in patients undergoing open surgery [14-17].
Most of the patients included in the study had a single cyst. However, although open surgery was more frequently preferred in patients with multiple cysts, no statistically significant difference was found. In studies similar to ours, the proportion of patients with a single cyst was generally found to be higher [9,12]. When the largest cyst diameters were examined, this value was found to be 9.1 cm in the open group and 8.2 cm in the laparoscopic group, and no significant difference was detected between the two groups. Similar studies in the literature have indicated that there is no significant relationship between the treatment method and cyst diameter [14,18].
When cysts were classified according to the Gharby classification, it was found that type 1 and 2 cysts were more common in the laparoscopy group, while type 3, 4, and 5 cysts were more common in the open surgery group. Kaya and colleagues also reported in their study that laparoscopy is more advantageous in type 1-3 cysts [19]. In our study, surgeons may have preferred laparoscopy more often in patients with these cysts.
Surgical treatment for hydatid cysts is divided into two categories: radical and conservative treatment. Radical surgery involves procedures such as pericystectomy and liver resection, while conservative surgery involves opening the cyst, removing its contents, and partially resecting the cyst. The most commonly used surgical procedure, whether laparoscopic or open, is cystotomy, which is a conservative treatment method involving the controlled opening of the cyst and the removal of its contents with the aid of scolosidal agents, followed by external drainage [7,9]. In our study, this method was the most frequently preferred in both the open and laparoscopic groups.
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, our study suggests that laparoscopic surgery is comparable to open surgery in terms of treatment efficacy. We believe that laparoscopy may also offer advantages in terms of hospital stay and recurrence rate. Further prospective studies with larger sample sizes are needed to clarify this issue.
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. Wen H, Vuitton L, Tuxun T, et al. Echinococcosis: Advances in the 21st Century. Clin Microbiol Rev. 2019;32(2):e00075-18.
2. Brunetti E, Kern P, Vuitton DA, Writing Panel for the WHO-IWGE. Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop. 2010;114(1):1-16.
3. Brunetti E, White AC Jr. Cestode infestations: hydatid disease and cysticercosis. Infect Dis Clin North Am. 2012;26(2):421-35.
4. Chopra N, Gupta V, Rahul, et al. Liver hydatid cyst with cystobiliary communication: laparoscopic surgery remains an effective option. J Minim Access Surg. 2018;14(3):230-5.
5. Zaharie F, Bartos D, Mocan L, Zaharie R, Iancu C, Tomus C. Open or laparoscopic treatment for hydatid disease of the liver? A 10-year single-institution experience. Surg Endosc. 2013;27(6):2110-6.
6. Jabbari Nooghabi A, Mehrabi Bahar M, Asadi M, Jabbari Nooghabi M, Jangjoo A. Evaluation and comparison of the early outcomes of open and laparoscopic surgery of liver hydatid cyst. Surg Laparosc Endosc Percutan Tech. 2015;25(5):403-7.
7. Bostanci O, Kartal K, Yazici P, Karabay O, Battal M, Mihmanli M. Laparoscopic versus open surgery for hydatid disease of the liver. A single center experience. Ann Ital Chir. 2016;87(1):237-41.
8. Polat FR. Hydatid cyst: open or laparoscopic approach? A retrospective analysis. Surg Laparosc Endosc Percutan Tech. 2012;22(3):264-6.
9. Elmoghazy W, Alqahtani J, Kim SW, Sulieman I, Elaffandi A, Khalaf H. Comparative analysis of surgical management approaches for hydatid liver cysts: conventional vs. minimally invasive techniques. Langenbecks Arch Surg. 2023;408(1):320.
10. Duta C, Pantea S, Lazar C, Salim A, Barjica D. Minimally invasive treatment of liver hydatidosis. JSLS. 2016;20(1):e2016.00002.
11. Cantay H, Anuk T. Factors affecting the choice of treatment in hepatic hydatid cyst surgery. J Invest Surg. 2022;35(4):731-6.
12. Shabani M, Behnam F, Akbari H, Eidy M. Comparison of the frequency of complications resulting from open and laparoscopic surgery for hydatid cyst. Asian J Endosc Surg. 2025;18(1):e13391.
13. Daradkeh S, El-Muhtaseb H, Farah G, Sroujieh AS, Abu-Khalaf M. Predictors of morbidity and mortality in the surgical management of hydatid cyst of the liver. Langenbecks Arch Surg. 2007;392(1):35-9.
14. Kunal BD, Rahul K, Govinda T, Hemanth K, Ganga RV, Harjeet S. Surgical management of hepatic hydatid cysts–conservative versus radical surgery. HPB.2020;22(10):1457–62.
15. Chen X, Chen X, Shao Y, Zhao J, Li H, Wen H. Clinical outcome and immune follow-up of different surgical approaches for human cyst hydatid disease in liver. Am J Trop Med Hyg. 2014;91(4):801–5.
16. Chen KF, Tang YY, Wang R, et al. The choose of different surgical therapies of hepatic alveolar echinococcosis: A single-center retrospective case-control study. Medicine (Baltimore). 2018;97(8):e0033.
17. Gupta N, Javed A, Puri S, Jain S, Singh S, Agarwal AK. Hepatic hydatid: PAIR, drain or resect? J Gastrointest Surg. 2011;15(10):1829–36.
18. Muhammedoğlu B, Pircanoğlu EM, Pişkin E, et al. Treatment of hepatic hydatid disease: role of surgery, ERCP, and percutaneous drainage: a retrospective study. Surg Laparosc Endosc Percutan Tech. 2020;31(3):313-20.
19. Kaya S, Altuntas YE, Kaptanoglu L, et al. Laparoscopic treatment of hepatic hydatid cysts. Our approach. Ann Ital Chir. 2019;90(1):560-4.
Download attachments: 10.4328.ACAM.22789
Enes Şahin, Mehmet Eşref Ulutaş. The effects of minimally invasive surgery in liver hydatid cysts. Ann Clin Anal Med 2025;16(8):603-607
Citations in Google Scholar: Google Scholar