June 2025
Trauma and associated factors in Türkiye national medical rescue team (UMKE) employees after Kahramanmaraş earthquakes: A six-month follow-up study
Erkut Etçioğlu 1, Yavuz Selim Oğur 2, Elif Merve Kurt Tunagür 3, Cengizhan Yener 4, Esra Yazıcı 4
1 Department of Family Medicine, Sakarya Training and Research Hospital, 2 Department of Psychiatry, Serdivan State Hospital, 3 Department of Psychiatry, Sakarya Training and Research Hospital, 4 Department of Psychiatry, Faculty of Medicine, Sakarya University, Sakarya, Türkiye
DOI: 10.4328/ACAM.22281 Received: 2024-05-24 Accepted: 2024-11-04 Published Online: 2025-01-11 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):389-393
Corresponding Author: Erkut Etçioğlu, Department of Family Medicine, Sakarya Training and Research Hospital, Sakarya, Türkiye. E-mail: erkutetcioglu@gmail.com P: +90 553 574 7 37 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8117-7929
Other Authors ORCID ID: Yavuz Selim Oğur, https://orcid.org/0000-0002-5258-8913 . Elif Merve Kurt Tunagür, https://orcid.org/0000-0002-7883-4190 . Cengizhan Yener, https://orcid.org/0009-0000-7597-019X . Esra Yazıcı, https://orcid.org/0000-0002-2575-7398
This study was approved by the Ethics Committee of Sakarya University (Date: 2023-02-10, No: E-220599-58)
Aim: To investigate the trauma and related symptoms experienced by Türkiye National Medical Rescue Team (UMKE) employees following earthquakes in Kahramanmaraş.
Material and Methods: Twenty-five males (78.1%) and five females (21.9%) were included in the study. A sociodemographic form and clinical data form, DSM-5 Acute Stress Symptom Severity Scale, DSM-5 Trauma Symptom Checklist, Beck Anxiety, and Beck Depression Scales were administered to UMKE employees who completed a one-week of duty in the earthquake-affected area. The assessments were conducted online during the first week and the first, third, and sixth months.
Results: Upon examining the psychiatric scale scores of the participants over time, there was a decrease in Acute Stress Symptom Severity Scale scores, DSM-5 Trauma Symptom Checklist, and Beck Depression Scale, but a statistically significant decrease was not observed (p>0.05). Among factors associated with psychiatric conditions, participants with a previous psychiatric diagnosis had higher Beck Anxiety Scale scores (p=0.05), and those who had experienced a traumatic event had higher Acute Stress Symptom Severity Scale scores (p=0.039).
Discussion: The study sheds light on the enduring psychological impact on emergency response teams, emphasizing the importance of long-term mental health support following natural disasters. Increasing awareness, proactive monitoring, and effective treatment strategies are demonstrated as essential in addressing the mental health issues faced by those actively involved in disaster relief efforts.
Keywords: Anxiety, Depression, Earthquake, Emergency Response Teams, Post-Traumatic Stress Disorder
Introduction
Natural disasters are major catastrophes that affect the lives of individuals and societies. Earthquakes are one of the most terrifying, devastating, and uncontrollable disasters. They are often highly destructive and lead to significant loss of life and economic damage [1].
Effective emergency response and coordination of healthcare services are vital for saving lives and treating the injured during and after these disasters. Search and rescue operations, one of the top priorities following an earthquake, are carried out immediately by professional teams [2].
On February 6, 2023, at 04:17 and 13:24 local time, two earthquakes with magnitudes of with magnitude of Mw 7.8 and Mw 7.6, centered in Pazarcık and Ekinözü in Kahramanmaraş, occurred. These earthquakes caused severe damage in Kahramanmaraş and 11 other provinces, significantly losing life [3].
Healthcare workers involved in earthquake response during the early stages of disasters are exposed to horrific scenes, including corpses, severely injured individuals, and people in pain. Therefore, the teams providing this initial response are more vulnerable to professional stress compared to others [4]. The Türkiye National Medical Rescue Team (UMKE) employees also encounter traumatic experiences in the aftermath of earthquake disasters and must cope with the long-term effects of these experiences. Studies have indicated that survivors are often at risk for Post-Traumatic Stress Disorder (PTSD), depression, and other psychological disorders [5]. During this period, various factors that can be protective or predisposing to trauma and stress have been identified [6]. However, the examination of factors associated with acute stress symptoms during the initial moments of an earthquake and the acquisition of long-term follow-up data are limited.
This study aimed to follow UMKE employees who worked during the acute period following the two major earthquakes centered in Kahramanmaraş on February 6 and worked there for one week. They were followed for a period of six months to investigate trauma and related symptoms.
Material and Methods
Type of Study
Cross-sectional and follow-up study.
The Population and Sample Size of the Study
The study sample consisted of individuals aged 18-65 who volunteered to participate in the research, met the inclusion and exclusion criteria, and participated in all follow-ups among those who worked at Sakarya UMKE during the Kahramanmaraş earthquake.
Measures
Socio-demographic form and clinical data form
This scale was determined based on the purpose of the study by reviewing the literature and includes inquiries about individuals’ social support, economic status, and previous psychiatric treatment.
DSM-5 Acute Stress Symptom Severity Scale
Published by the American Psychiatric Association, this scale is used to assess the severity of acute stress disorder symptoms in individuals aged 18 and over. The Turkish validity and reliability study was conducted by Aşçıbaşı et al. The scale consists of 7 items, each evaluating the severity of acute stress disorder experienced over the past seven days. Designed on a 5-point Likert scale, the scale ranges from 0 to 28 points, with higher scores indicating more severe acute stress symptoms. The validity and reliability of the scale were established, with a Cronbach’s Alpha of 0.95 [7].
DSM-5 Trauma Symptom Checklist (PCL-DSM-5)
PTSD Checklist, also known as the Trauma Symptom Checklist, is one of the most commonly used screening tools for assessing PTSD symptomatology. It is rated on a five-point Likert scale (0-4 points) and provides a range of scores from 0 to 80. Comprising 20 items, this self-report scale has been expanded from the previous DSM-IV version. PCL-5 corresponds to the PTSD diagnostic criteria in DSM-5, including re-experiencing (Criterion B), avoidance (Criterion C), negative alterations in cognitions and mood (Criterion D), and hyperarousal (Criterion E) [8]. A Turkish validity and reliability study was conducted, and a cutoff score of ≥47 was recommended for the diagnosis of PTSD, with a sensitivity of .76 and specificity of .69 [9].
Beck Anxiety Scale
This self-assessment scale consists of 21 items and is widely used to determine the frequency and severity of anxiety symptoms [10]. Validity and reliability studies were conducted in Türkiye by Ulusoy et al. [11].
Beck Depression Scale
This scale measures the risk, severity, and depression change in the adult population [12]. Hisli conducted the Turkish validity and reliability study, and the recommended cutoff score for the scale is 17 [13].
Data Processing
In this study, the measurement tools mentioned above were administered online via Google Forms to UMKE employees who completed one week of duty in the earthquake-affected area during the acute phase and in the 1st week, 1st, 3rd, and 6th months following the earthquake. During the measurements, individuals with high psychiatric scores were contacted by phone and informed, and a recommendation was made for them to consult a psychiatric specialist.
Statistical analysis
Statistical analyses were performed using SPSS version 22. Descriptive statistics (frequency and percentage) were applied for socio-demographic variables, and the chi-square test was used for categorical variables. Independent sample t-tests and one-way ANOVA were employed to compare means in groups that showed normal distribution. At the same time, the Mann-Whitney U and Kruskal-Wallis tests were used for groups that did not exhibit normal distribution. If the Mauchly’s Test of Sphericity value was less than 0.05, the Greenhouse-Geisser value was examined. If the Greenhouse-Geisser value is less than 0.750, the evaluation was made with the Greenhouse-Geisser test. A p-value of ≤ 0.05 was considered statistically significant.
Ethical approval
Ethical approval was obtained from the local Ethics Committee of Sakarya University (Date: 2023-02-10, No: E-220599-58).
Results
Sociodemographic data
It was determined that 78.1% of UMKE employees participating in the study were men, 21.9% were women, 56.3% were married, 6.3% were divorced, 34.4% were single, 3.1% were living separately, 9.4% were paramedics, 12.5% were emergency medical technicians, 18.8% were doctors, 12.5% were midwives and nurses, 15.6% were health officers, and 31.3% were technicians, 40.6% worked both in the Field Hospital and the debris field, 34.4% worked in the Field Hospital, 18.8% worked in the debris field, and 6.3% worked in other areas.
Participants’ psychiatric scale scores and their change over time
Participants filled out online forms 2 weeks, 1 month, 3 months, and 6 months after going to the earthquake region, and their scale scores were compared. The graph showing the change in participants’ scale scores over time is given in Figure 1.
According to the scale results, the rates of those who were determined to be in the risk group were compared. No statistically significant difference was found (Table 1). When the Acute Stress Symptom Severity Scale scores of UMKE employees were compared, it was determined that there was a decrease in the scores during the follow-up period. Still, there was no statistically significant difference between the mean scores. (Since the values did not show a normal distribution, the Friedman test was used, X2 = 4.563, p = 0.207)
When the PTSD Checklist Scale scores of UMKE employees were compared, it was determined that there was a decrease in the scores during the follow-up period. Still, there was no statistically significant difference between the mean scores. (The data were examined using the Repeated Measures ANOVA test. Since Mauchly’s Test of Sphericity value was 0.019 < 0.05, the Greenhouse-Geisser value was examined. Since the Greenhouse-Geisser value was 0.671 < 0.750, the evaluation was made with the Greenhouse-Geisser test. (F (2 40) = 2.101, p = 0.135))
When the Beck Anxiety Scale scores of UMKE employees were compared, it was determined that the scores first decreased and then increased during the follow-up period. There was no statistically significant difference between the score averages. (Since the values did not show a normal distribution, the Friedman test was used, X2 = 0.503, p = 0.918)
When the Beck Depression Scale scores of UMKE employees were compared, it was determined that there was no continuous decrease in the scores during the follow-up period, and there was no statistically significant difference between the mean scores. Since the values did not show a normal distribution, the Friedman test was used (X2 = 1.485, p = 0.686).
Factors associated with participants’ psychiatric states
When the participants were divided into subgroups according to their sociodemographic characteristics and compared with the scores they received from the scales in the first evaluation, the Beck Anxiety Scale scores (U = 73.5, p = 0.05) were found to be higher in those with a previous psychiatric diagnosis. Acute Stress Symptom Severity Scale scores were higher in those who experienced a traumatic event (t=-2.1, p=0.039) (Table 2).
Comparing UMKE employees with a monthly income of above and below 20,000 TL showed no statistically significant difference between the groups (p>0.05). When UMKE employees were grouped and compared as those working in the debris field and those not working, no statistically significant difference was detected between the groups (p>0.05).
A statistically significant decrease in the average Acute Stress Symptom Severity Scale scores was observed between the first and third evaluations and between the first and fourth evaluations. No significant difference was detected between the scale score averages in the other evaluations (p>0.05) (Table 3).
Discussion
In this study, we followed UMKE employees who served in the acute period and completed their one-week duty after the two major earthquakes centered in Kahramanmaraş on February 6, 2023, to investigate their trauma and related symptoms for six months. In this study, face-to-face evaluations were not conducted to make a psychiatric diagnosis, but acute stress reaction, PTSD, anxiety, and depression screening scales were used to evaluate the mental states of the participants.
The comparison of UMKE employees in the debris field with those in other fields revealed no statistically significant difference in terms of cutoff values for acute stress response, PTSD, anxiety, and depression. In a study evaluating emergency medical technicians involved in search and rescue efforts in the Taiwan earthquake, it was shown that working hours and the population studied did not create a statistically significant difference in PTSD [14]. In Chang et al.’s study, it was stated that direct rescue was not associated with psychiatric morbidity or post-traumatic morbidity in rescue workers working in the 1999 Taiwan earthquake, but contact with dead bodies was significantly associated with psychiatric and post-traumatic morbidity [15]. It can be said that the fact that the participants in our study encountered similar cases in both the debris field and the field hospital and similar working conditions caused no statistical difference.
It was determined that the rate of participants above the threshold for Acute Stress reaction was 21.9% immediately two weeks after the earthquake; this decreased in subsequent evaluations. However, after six months, 17.2% of the participants still had symptoms above the cut-off value for acute stress reaction symptoms. In a study examining the effects of trauma on disaster workers, it was stated that the rate of acute stress disorder one week after the disaster was 25.6%. This situation led to depression and PTSD, and there were high rates of depression and PTSD in the third month and seventh months [16].
The rate of participants above the threshold in the evaluation made with the PTSD scale was 12.5% immediately two weeks after the earthquake. At the sixth month measurement, 3.4% of the participants had scores above the cut-off value for PTSD symptoms. In a study conducted among actively working people after a major earthquake in Japan, PTSD was found to be 34.2% after three months and 12.6% after 18 months [17]. In another study conducted two months after the 2003 Bingöl earthquake, the rate of PTSD in rescue workers was 25% [18]. In our study, the rate of participants whose PTSD scale score was above the threshold value was lower than in the literature. This difference may be due to the long-term follow-up of employees in rescue efforts.
The rate of those with Beck anxiety scale scores above the threshold was 13.8% at six months. On the Beck depression scale, 27.6% of the participants were above the depression threshold value in the 6th month. In a study conducted two months after the Taiwan earthquake, the anxiety rate of participants was 10.8%, and the depression rate was 14.9% [19]. In a study after the Bam earthquake, they found that the anxiety rate among Red Crescent employees was 7.1%, and the depression rate was 2.3% [20]. In their study, Fullerton et al. identified a depression rate of 16% in the seventh month, which increased to 21.7% in the thirteenth month [16]. This emphasizes the need for long-term follow-up of those involved in rescue efforts.
In the present investigation, individuals surpassing a designated threshold were proffered psychological assistance; however, none of the national medical rescue team personnel availed themselves of such support. Merely 2.3% to 18.3% of healthcare practitioners undergoing mental distress amid and after the pandemic actively pursued professional assistance [21]. Analogously, a mere 6.1% of rescue workers sought psychological intervention after encounters with terrorist attacks [22]. A prevailing rationale elucidated for the reluctance of health professionals contending with mental health challenges stemming from diverse origins to solicit support was articulated as a preference for autonomous problem resolution [23]. This underscores a concerning trend of underutilization of available psychological support services among healthcare and rescue workers.
In this study, a notable limitation is the small number of participants, the lack of online authentication during the study process, and the inability to conduct face-to-face evaluations due to the distance of the earthquake-affected region to the research area. However, on the other hand, the strength of the study lies in the comprehensive examination of volunteers for six months, taking into account both trauma and anxiety and depression dimensions.
Conclusion
This study has revealed elevated rates of psychiatric symptoms not only in the immediate acute phase following the earthquake but also in the follow-up assessments six months later. Factors associated with these symptoms include exposure to trauma, a history of previous depression, and, despite these findings, a low rate of seeking treatment. The findings underscore the need for heightened awareness and the development of action plans for both monitoring the mental well-being of disaster relief volunteers in the aftermath of earthquakes and other natural disasters and facilitating their access to effective treatment. Subsequent research efforts should be directed toward addressing these aspects.
Acknowledgment
We would like to express our sincere thanks to all those who contributed to this study. First and foremost, we would like to thank the members of the Türkiye National Medical Rescue Team (UMKE), whose unwavering dedication and tireless efforts during and after the Kahramanmaraş earthquakes made this research possible. We are also deeply grateful to Prof. Dr. Ahmet Bülent Yazıcı for his expert guidance and invaluable support throughout the study. Our thanks also go to Dr. Halise Yener for her significant contributions to the design and analysis of the research.
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.
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Download attachments: 10.4328.ACAM.22281
Erkut Etçioğlu, Yavuz Selim Oğur, Elif Merve Kurt Tunagür, Cengizhan Yener, Esra Yazıcı. Trauma and associated factors in Türkiye national medical rescue team (UMKE) employees after Kahramanmaraş earthquakes: A six-month follow-up study. Ann Clin Anal Med 2025;16(6):389-393
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Is previous abdominal surgery a challenge for laparoscopic appendectomy?
Deniz Tikici 1, Salim İlksen Başçeken 2
1 Department of Gastroenterological Surgery, 2 Department of Surgical Oncology, Health Sciences University, Gazi Yaşargil Training and Research Hospital, Diyarbakır, Turkey
DOI: 10.4328/ACAM.22350 Received: 2024-08-01 Accepted: 2024-12-02 Published Online: 2025-01-19 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):394-396
Corresponding Author: Deniz Tikici, Department of Gastroenterological Surgery, Health Sciences University, Gazi Yaşargil Training and Research Hospital, Diyarbakır, Turkey. E-mail: deniztikici@hotmail.com P: +90 541 535 57 05 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1759-2973
Other Author ORCID ID: Salim İlksen Başçeken, https://orcid.org/0000-0002-0918-3208
This study was approved by the Ethics Committee of Gazi Yasargil Training and Research Hospital (Date: 2022-12-30, No: 302)
Aim: Appendectomy is one of the most common emergent surgery and is performed open or laparoscopically. Previous abdominal surgery (AS) is a limiting factor in all procedures, including laparoscopic appendectomy. In this study, we aimed to investigate effect of previous abdominal surgery on laparoscopic appendectomy.
Material and Methods: We retrospectively reviewed 164 patients who underwent laparoscopic appendectomy in the General Surgery Department of XXX Hospital between January 2019 and December 2021. Seven were excluded due to missing data, and histopathology was not appendicitis. Patients were divided into two groups, abdominal surgery and non-abdominal surgery, and compared in terms of open conversion, complication rates, operation time, and length of stay. Statistically, significance was accepted as p<0.05.
Results: 88 (56.1%) were female, 69 (43.9%) were male of 157 patients. The mean age was 32.9±14.4 (18-74) years. 14 (8.9%) patients were with previous abdominal surgery. The mean operative time was 30.5±9.9 (17-102) minutes, and the length of hospital stay was 27.2±12.9 (15-163) hours. No mortality or intraoperative complications were observed, and the postoperative complication rate was 10.2%. There were no statistically significant differences between the groups for age (p=0.478), gender (p=0.075), postoperative complication (p=0.28), and length of hospital stay (p=0.075). There were statistically significant differences between the groups for conversion to open appendectomy rate (p=0.016) and operation time (p=0.008).
Discussion: We recommend that laparoscopy should be started in all cases of acute appendicitis since there was no significant difference between the groups in complication rates and length of hospitalization.
Keywords: Appendectomy, Laparoscopic Appendectomy, Laparoscopic Surgery
Introduction
Acute appendicitis (AA) is one of the most common causes of emergency surgery. The lifetime risk of AA is 7-8% [1]. The primary treatment is surgery and performed open or laparoscopically. Laparoscopic appendectomy (LA) is one of the most commonly performed laparoscopic procedures.
Advances in surgical techniques and the development of technology make laparoscopic surgery more effective. In comparative studies on the efficiency of LA and open appendectomy (OA), factors such as postoperative pain, operative time (OT), conversion to open surgery, intraoperative/postoperative complications, length of stay (LOS), and cost-effectiveness are investigated [1, 2].
Previous abdominal surgery (AS) is a limiting factor in any procedure, whether open or laparoscopic. When LA was first introduced, AS was considered a relative contraindication. In our study, we aimed to evaluate whether previous abdominal surgery is a complicating factor.
Material and Methods
Between January 2019 and December 2021, 164 patients underwent laparoscopic appendectomy at the Department of General Surgery of Gazi Yasargil Training and Research Hospital. All patients over 18 years of age who underwent laparoscopic appendectomy for acute appendicitis were retrospectively analyzed. Seven patients were excluded due to missing data, histopathological results of malignancy, and absence of appendicitis. The patients were divided into two groups, AS and NAS, and compared in terms of open conversion, complication rates, OT, and LOS.
Statistical Analysis
Statistical data are presented as mean ± standard deviation. Parametric test assumptions were examined before the difference analysis was performed. Normality was checked by the Shapiro-Wilk test. Differences between groups were evaluated by the unpaired t-test. Qualitative data were evaluated by Fisher’s exact test. Differences were considered statistically significant if p < 0.05.
Ethical Approval
This study was approved by the Ethics Committee of Gazi Yasargil Training and Research Hospital (Date: 2022-12-30, No: 302).
Results
In our clinic, 157 cases of laparoscopic appendectomy were performed in the last three years. 88 (56.1%) were female and 69 (43.9%) were male. The mean age was 32.9 ±14.4 (range, 18-74) years. 14 (8.9%) patients were with previous abdominal surgery. The types and number of previous abdominal surgeries are listed in Table 1. 28 (17.8%) of the cases were perforated. 10 (6.4%) patients were converted to open appendectomy (OA) due to technical difficulty and adhesions. The risk of conversion to OA was found to be approximately 5.3 times higher in patients with previous abdominal surgery (odds ratio; OR=5.29). The mean operative time was 30.5 ± 9.9 (range, 17-102) minutes. The mean length of hospital stay was 27.2 ± 12.9 (range, 15-163) hours. No mortality or intraoperative complications were observed. The postoperative complication rate was 10.2% (n=16). Minor complication (The Clavien-Dindo Classification 1-2) rate was 7.7% (n=12), and major complication (The Clavien-Dindo Classification 3) rate was 2.5% (n=4). One patient had pneumonia, the only non-surgical complication in our series, and was treated with medication. Wound seroma and wound infection (1.3% and 5.7%, respectively) were treated by changing the dressing at the outpatient department. 2 (1.3%) patients were complicated with intra-abdominal abscess and treated with percutaneous drainage and antibiotherapy in the nonoperative setting. 2 (1.3%) patients required surgical intervention following major complications. The postoperative complications and management of cases are listed in Table 2. There were no statistically significant differences between the groups for age (32.4 vs. 36.8 years, p = 0.478), gender ratio (M/F 0.85 vs. 0.27, p = 0.075), postoperative complication (9.8 vs 14.2%, p = 0.28) and length of hospital stay (26.2 vs. 36.1 hours, p = 0.075). There were statistically significant differences between the groups for conversion rate (5.1 vs. 21.4%, p = 0.016) and operation time (29.8 vs. 37.1 min, p = 0.008). The demographic and operative data of the groups are listed in Table 3.
Discussion
Due to advances in surgical techniques, laparoscopic procedures are commonly performed in daily practice. In many studies, the advantages of laparoscopic procedures have been described as lower wound infection rate, less postoperative pain, rapid recovery, and short hospital stay, while the disadvantages have been longer operative time and cost-effectiveness [2]. Laparoscopic appendectomy is an effective and feasible procedure for acute appendicitis. It should be kept in mind that previous abdominal surgery may complicate laparoscopic surgery, as in all surgical procedures.
In the literature, studies evaluating the effect of previous abdominal surgery on laparoscopic surgical procedures are well documented, especially in colorectal and gallbladder surgeries [3-5]. There is only one study that reported previous abdominal surgery on laparoscopic appendectomy. [6] although different groupings have been made in terms of methodology, similar factors were researched in this study.
In our study, we found that there were no statistically significant differences between AS versus NAS groups in demographic data, postoperative complication rate, and length of hospital stay (p-value, respectively; >0.05, 0.28, and 0.075). Wu et al. reported that female gender unfavorably affected the outcomes of laparoscopic appendectomy, especially due to cesarean section. In our study, although approximately one-third of the AS group had a history of cesarean section, there was no significant difference between genders. In our data, the postoperative complication rate of LA was 10.2%, and wound infection rate was 5.7%. The wound infection rate of LA is reported between 2-9% in different publications [7–10]. The complication rate in our data is acceptable, as in the literature. Wu et al. reported that previous abdominal surgery, similar to our study, had no negative effect on complication rate. [6] The hospital stay is one to seven days, 27 hours on average. Also, similar to Wu et al., the length of hospital stay was not statistically significantly different between the groups.
We revealed significant differences between the groups in conversion to OA and operative time (p-value, respectively: 0.016 and 0.008). The effect of previous abdominal surgery on the conversion rate to OA is controversial. The conversion rate was found to be 6.4% in our study and is similar to the literature. Conversion rates to OA ranged between 1-10% in the literature.[6-10] Masoomi et al. reported a conversion rate to open appendectomy of 6.3% according to Nationwide Inpatient Sample (NIS) data12. In our study, the conversion rate was statistically significant between the groups (AS 20.4% vs. NAS 4.9%, p=0.016). Lezama et al. found that previous abdominal surgery is an independent risk factor for conversion to OA [10]. In our study, subgroup analysis showed that all three patients in the AS group with conversion to OA had perforated appendicitis. The reason for the statistically significant conversion rates in the AS group may be the coexistence of perforation. The mean operative time was approximately 30 minutes and significantly different between groups (AS 29.8 vs. 37.1 minutes, p=0.008). Despite our study, Wu et al. did not find significant differences between the groups in operative time. Condition of previous surgery may prolong the duration of surgery. A possible side effect of prolonged operation time is an increased risk of postoperative complications. We think that prolonged operation time can be ruled out because of no significant difference in postoperative complication rates.
Conclusion
Finally, we consider that laparoscopic appendectomy has no negative effect on patients with a history of previous abdominal surgery, and we recommend starting laparoscopically for all patients presenting with acute appendicitis. Due to the limited number of studies on this subject, more studies are needed.
Limitation
The limitations of this study may be the low number of 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
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4. Figueiredo MN, Campos FG, D’Albuquerque LA, Nahas SC, Cecconello I, Panis Y. Short-term outcomes after laparoscopic colorectal surgery in patients with previous abdominal surgery: A systematic review. World J Gastrointest Surg. 2016;8(7):533-540.
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10. Monrabal Lezama M, Casas MA, Angeramo CA, Bras Harriott C, Schlottmann F. Conversion from Laparoscopic to Open Appendectomy: Trends, Risk Factors and Outcomes. A 15-Year Single-Center Analysis of 2193 Adult Patients. World J Surg. 2022;46(11):2642-2647.
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Deniz Tikici, Salim İlksen Başçeken. Is previous abdominal surgery a challenge for laparoscopic appendectomy?. Ann Clin Anal Med 2025;16(6):394-396
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Determination of axillary metastasis by breast MRI after neoadjuvant chemotherapy in breast cancer
Ahmet Akbas 1, Fikret Calikoglu 2, Mehmet Oncü 3, Atilla Celik 4
1 Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, Trabzon, 2 Department of General Surgery, Antalya Serik State Hopital, Antalya, 3 Department of Radiology, Istanbul Bagcilar Training and Research Hospital, Istanbul, 4 Department of General Surgery, Istanbul Bagcilar Training and Research Hospital, Istanbul, Turkiye
DOI: 10.4328/ACAM.22359 Received: 2024-08-07 Accepted: 2024-10-21 Published Online: 2025-01-10 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):397-400
Corresponding Author: Ahmet Akbas, Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkiye. E-mail: ahmetakbas@ktu.edu.tr P: +90 506 534 19 73 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6333-4919
Other Authors ORCID ID: Fikret Calikoglu, https://orcid.org/0000-0003-4695-6828 . Mehmet Oncü, https://orcid.org/0000-0001-9425-4658 . Atilla Celik, https://orcid.org/0000-0002-0732-9007
This study was approved by the Ethics Committee of Bagcilar Training and Research Hospital Clinical Research (Date: 2021-03-02, No: 2021.01.1.04.004)
Aim: As a result of the developments in breast cancer treatment, the life expectancy of patients has been extended. This fact has brought the morbidity of breast cancer surgery to the fore. Axillary dissection is the major factor responsible for morbidity. In the present study, we aimed to determine the safety of sentinel node biopsy in patients without pathological lymph node involvement using breast MRI taken after neoadjuvant chemotherapy.
Material and Methods: The study was carried out in the General Surgery Department of Bagcilar Training and Research Hospital between 15.02.2021 and 15.07.2021 on patients planned to undergo surgery after neoadjuvant chemotherapy. Postoperative axillary pathology findings were compared with patients without pathological axillary lymphadenopathy in breast MRI results after neoadjuvant chemotherapy.
Results: Ninety patients were operated. After the treatment, 57 of them became cN0 on breast MRI. When ≥ 3 negative SLNB was removed in the group of patients who were cN0 after the treatment, no pathological lymph involvement was observed in the axilla.
Discussion: The gold standard for evaluating chemotherapy efficacy is pathologic assessment, the residual cancer burden score (RCB) and the Miller-Payne score are used for this purpose. However, these evaluations are not practical since they need the patient to undergo surgery. For this reason, imaging methods such as mammography, US, MRI and PET-CT are used in the follow-up of NACT treatment response. WHO criteria and RECIST are used to standardize treatment response values with imaging methods.
Keywords: Breast Cancer, Breast Mri, Complete Response, Neoadjuvant Chemotherapy, Sentinel Lymph Node Biopsy
Introduction
Breast cancer is the most common type of cancer which causes the most deaths among women in the world and in Turkey [1]. According to the 2020 data of the World Health Organization (WHO), breast cancer patients accounted for 11.7% of newly diagnosed cancer types in all ages and genders, and this number is 2,261,419 people annually. The widespread use of screening methods in developed countries has allowed breast cancer to be diagnosed at an early stage and potential treatment for the disease. In addition, continuously developing medical treatments reduce mortality due to breast cancer. The prolonged life expectancy has led to the questioning of the morbidities experienced by patients in the postoperative period and the improvement of quality of life has become increasingly prominent. The most important morbidity of breast cancer surgery is associated with surgical intervention on the axilla. In the current surgical approach, in patients who have not received preoperative chemotherapy and whose axilla is clinically and radiologically negative, sentinel lymph node biopsy (SLNB) instead of axillary dissection is unquestionably accepted. In patients undergoing neoadjuvant chemotherapy (NACT), the gold standard is still axillary dissection. Nevertheless, studies on the adaptation of SLNB to patients who have received NACT have been started, and many such studies have been published on how to evaluate the axilla accurately and reliably using various methods and lymph node detection agents.
This study was planned to investigate the answer to the question of whether the SLNB method with breast MRI taken after NACT could fully reflect the surgical staging of the axilla (low false negativity rate and high true positivity rate) in patients with locally advanced breast cancer.
Material and Methods
This study was conducted retrospectively with the participation of 90 patients who were diagnosed with locally advanced breast cancer between 15.02.2021 and 15.07.2021 at the General Surgery Clinic of Bagcilar Training and Research Hospital. The patients had been given neoadjuvant chemotherapy and subjected to re-staging with radiological controls based on breast MRI after the treatment. In all patients diagnosed with locally advanced breast cancer, breast staging is performed with MRI before and after NACT in our clinic in accordance with the guidelines. The age, demographic data, the Tru-cut pathology result of the breast and/or axillary mass before NACT, the number and the size (mm) of masses in the breast in the breast MRI taken after NACT and the status of the axilla (presence/absence of pathological LAP) were recorded by obtaining them from patient files in electronic environment. The cases that responded completely to the treatment based on physical examination and breast MRI performed after NACT were included in the study. Inclusion criteria: 1. Female patients older than 18 years of age who were T0-4, N1-3 and M0 according to the TNM system after clinical and radiological evaluation before NACT and who were diagnosed with primary invasive breast cancer based on Tru-cut biopsy, 2. The patients with a performance status of 0-1 according to Eastern Cooperative Oncology Group (ECOG), 3. Patients who received NACT treatment, 4. The patients with complete axillary response in the physical examination performed after NACT and on control breast MRI and who underwent surgical treatment.
The exclusion criteria for the study: 1. The patients who had previously undergone surgical treatment to the ipsilateral axillary area for any reason, 2. The patients with pathological axillary LAP or metastatic disease were observed in clinical examination and imaging methods after NACT, and 3. The patients with a history of allergy to isosulfan blue and/or indocyanine green.
A dual method (isosulfan blue (ISB) and indocyanine green (ICG)) was applied to determine sentinel lymph node (SLNB) in patients participating in the study. Axillary dissection, which is the standard treatment, was performed in patients who completed SLNB sampling, and the dissection material was sent in a separate container for pathological examination. It was aimed to remove at least two SLNBs with ISB and ICG. Both SLNB and axillary dissection material were sent to permanent pathology and the false negativity, false positivity, true negativity and true positivity rates of SLNB were calculated from the obtained data.
Statistical evaluation
Frequency and percentage values were presented for categorical variables. Mean, standard deviation, median, minimum and maximum values were presented for continuous variables. Chi-square analysis was performed for relationships between categorical variables. When appropriate, a single sample Chi-square was evaluated by Fisher’s exact and Fisher Freeman Halton Test. The normality of the distribution was determined by Kolmogorov Smirnov Test. For variables that did not satisfy the normal distribution assumption, the Mann Whitney U test was used for two independent group comparisons and the Kruskal Wallis H test was used for more than two group comparisons. The Bonferroni-corrected Dunn Multiple Comparison test was used to determine the source of the significant difference in the Kruskal Wallis H test. The analyses were performed with SPSS 23 (Statistical Package for the Social Sciences) software. p < 0.05 was considered significant.
Ethical Approval
This study was approved by the Ethics Committee of Bagcilar Training and Research Hospital Clinical Research Ethics Committee (Date: 2021-03-02, No: 2021.01.1.04.004).
Results
Ninety patients with breast cancer who met the study criteria and received preoperative NACT were operated. SLN was not found in 10 patients. Thus, 80 patients were included in the study. The median age of the patients was 48 years (range: 29-79).
After physical examination and radiological imaging, it was found that the primary tumor was in the upper outer quadrant in 35 patients, in the upper inner quadrant in 15 patients, in the lower outer quadrant in 13 patients, in the lower inner quadrant in 7 patients, and in the retroareolar region in 10 patients. Tumor was single-focused in 58 patients, multicentric in 14 patients and multifocal in 8 patients. The mean size of primary masses on MRI was 21.8±12.05 mm, and the mean size of satellite lesion was 17.45±6.95 mm in 22 patients with satellite lesions. In the pre-NACT Tru-cut biopsy evaluation of the patients, diagnosis was invasive ductal carcinoma in 75 patients, invasive lobular carcinoma in 4 patients, and invasive ductal carcinoma + invasive lobular carcinoma in 1 patient.
There were 57 patients who were evaluated as cN0 and had SLNB in radiological (breast MRI) evaluations after NACT. Dual method (ICG+ISB) was used to determine sentinel lymph nodes. All patients underwent axillary dissection after sentinel lymph node removal. SLNB was positive in 29 patients and negative in 28 patients. In the evaluation of SLNB negative patients, 2 of the 6 patients with one SLNB negative had metastatic nodule in axillary area and 2 of the 11 patients who had two SLNBs removed had additional metastatic lymph node while none of the 11 patients who had three or more SLNBs removed had additional metastatic lymph node. According to the results of this evaluation, when axillary cN0 was taken into account in breast MRI, the presence of ≥ 3 negative SLNB had a positive predictive value of 100% (Table 1).
Based on the evaluations, the sensitivity of the breast MRI taken after NACT for metastatic lymph node determination in the axillary region was 41.67% while the specificity was 95.45% and the accuracy was 71.25%.
Discussion
Breast cancer is the most common cancer with the highest death toll among women throughout the world [1]. Due to the advances in the diagnosis and treatment of breast cancer, its mortality has decreased considerably with a concomitant longer life expectancy [2]. This has brought to the fore the quality of life in patients after breast cancer surgery. The most important cause of morbidity after breast cancer surgery is the interventions made to axilla. Axillary involvement is the most important prognostic factor in determining the prognosis and treatment of breast cancer and recurrences occur most frequently [3]. For this reason, the question of how to evaluate and treat the axilla with the least intervention that would treat the axilla correctly without compromising the principles of oncological surgery has gained importance. In the 1990s, the lymph node in which cancer first metastasized in lymphatic spread was identified and it was shown that if there was no involvement in this lymph node, the tumor had not yet metastasized [4]. The lymph node where the tumor first metastasizes is called the “sentinel lymph node”. Clinically, SLNB has been shown to be equivalent to axillary dissection in patients who are axillary lymph node negative. Thus, morbidities such as lymphedema, seroma, numbness, wound infection, limitation of movement and chronic pain caused by axillary dissection could be minimized [5]. Therefore, NACT regimens were started to be applied to patients who were clinically axillary lymph node positive. As in early stage breast cancers, it was hypothesized that the axilla could be evaluated with SLNB in patients whose axilla became clinically negative, and studies were started on this issue. In the present study, it was aimed to find SLNB with the dual method (ICG+ISB) for the evaluation of the axilla in patients who did not have axillary pathological lymph nodes clinically and radiologically after NACT. According to the results of our study, it was observed that the negative SLNB ≥ 3 lymph node in patients who did not have pathological LAP in the axilla clinically and radiologically determined the absence of metastatic lymph nodes in the axillary area with a 100% accuracy. This is an important consideration for the evaluation of patients receiving NACT using SLNB instead of axillary dissection.
In breast cancer, NACT is preferred to treat nodal involvement in the axilla in order to both reduce and destroy the mass in the breast. If the chemotherapy regimen given is ineffective, the patient would be treated with an ineffective regimen again because the same regimen would be used both in breast cancer treatment and after surgery. Therefore, follow-up of the response after the chemotherapy regimen used has gained importance. The gold standard for evaluating chemotherapy efficacy is pathologic assessment, the residual cancer burden score (RCB) and the Miller-Payne score are used for this purpose [6]. However, these evaluations are not practical since they need the patient to undergo surgery. For this reason, imaging methods such as mammography, US, MRI and PET-CT are used in the follow-up of NACT treatment response. WHO criteria and RECIST are used to standardize treatment response values with imaging methods [7]. In our study, we used the Miller-Payne scoring system to evaluate the pathology response according to the RECIST criteria and to evaluate the radiological response. US is used in the evaluation of treatment response after NACT due to its advantages such as low cost, no radiation exposure, and ability to be performed on point of care basis. Conventional US has difficulty separating fibrotic and tumor tissues. Another disadvantage of the US in assessing the treatment response is that it depends on the experience of the person who performs NACT. Vriens et al. evaluated the response to NACT in 172 breast cancer patients and showed that US measurements of the tumor tissue size were on the average 20% larger than they actually are [8] .Many studies showed that MRI exhibits higher accuracy in predicting the effectiveness of NACT [9].Although conventional US has low sensitivity in assessing the treatment response of NACT, new techniques such as electrography, CEUS (Contrast Enhanced Ultrasound using microbubbles) can improve US prediction accuracy [10]. In our study, we used breast MRI to evaluate the treatment response of NACT because of the low sensitivity of traditional US. Fibrous tissue has no vascularization whereas the tumor tissue has good vascularization. Since MRI is an imaging method that differentiates these two tissues efficiently, it is used to determine the size of fibrous tissue that develops in response to NACT and remaining tumor tissue. The NACT regimen may affect the evaluation of the MRI because drugs containing taxane and anthracycline have a greater antiangiogenic effect, which negatively affects the evaluation of MRI by disrupting vascularization [11]. In the presence of fibrosis and reactive inflammation around the tumor bed, MRI shows the residual disease larger size than it is. The presence of residual DCIS causes false positive diagnosis, while small residual lesion leads to a false negative diagnosis [12]. De Los Santos et al. found the accuracy of MRI to be 74% in predicting pCR (pathological complete response) [13]. Choi et al. found that in the evaluation of NACT treatment response, MRI had a sensitivity of 88.2%, a specificity of 62.5%, an accuracy of 75.7%, a PPV value of %71,4 and an NPV value of 83.3% [14]. In our study, we found that MRI had 47.7% sensitivity, 95.45% specificity, 88.24% PPV value and 66.67% NPV value in determining the axillary response. According to a meta-analysis by Liu et al., the sensitivity of PET/CT was 86% and the specificity of MRI was 88%, and they concluded that the combined use of these two imaging methods could provide better results in evaluating pCR after NACT [15]. In our study, we used MRI in the diagnosis and staging of pre-NACT breast cancer and in the evaluation of response to treatment after NACT. We found that the probability of metastatic lymph node in the axilla is low if ≥ 3 negative SLNB is performed in patients without pathological LAP in the axilla after NACT. We found that the radiological evaluation of the response to NACT, which was carried out in accordance with the literature, was consistent with the pathological assessment by the Miller-Payne system.
Limitation
The small number of patients in our study was the most important limitation.
Conclusıon
The most important cause of morbidity in locally advanced breast cancer patients is axillary dissection. When the axilla is cN0 based on breast MRI after NACT, SLNB can be performed instead of axillary dissection. Prospective randomized trials are needed in this regard.
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
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2. Yang Y, Liu G, Qin L, Ye L, Zhu F, Ying Y. Overexpression of UHRF1 and its potential role in the development of invasive ductal breast cancer validated by integrative bioinformatics and immuno histochemistry analyses. Transl Cancer Res. 2019;8(4):1086-96.
3. de Meric de Bellefon M, Lemanski C, Ducteil A, Fenoglietto P, Azria D, Bourgier C. Management of the Axilla in the Era of Breast Cancer Heterogeneity. Front Oncol. 2018;4:8-84.
4. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, et al. Sentinel lymph node resection compared with conventional axillary lymph node dissection in clinically node negative patients with breast cancer: Overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;11(10):927-33.
5. Peek MCL, Saeki K, Ohashi K, Chikaki S, Baker R, Nakagawa T, et al. Optimization of SPIO Injection for Sentinel Lymph Node Dissection in a Rat Model Cancers. 2021;13(19):5031.
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7. Cappello G, Romano V, Neri E, Fournier L, D’Anastasi M, Laghi A, et al. A European Society of Oncologic Imaging (ESOI) survey on the radiological assessment of response to oncologic treatments in clinical practice. Insights into imaging. 2023;14(1):220.
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9. Kao YS, Hsu Y. A Meta-analysis for using radiomics to predict complete pathological response in esophageal cancer patients receiving neoadjuvant chemoradiation. In Vivo. 2021;35(3):1857-63.
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15. Liu Q, Wang C, Li P, Liu J, Huang G, Song S. The Role of (18)F-FDG PET/CT and MRI in assessing pathological complete response to neoadjuvant chemotherapy in patients with breast cancer: A systematic review and meta-analysis. Biomed Res Int. 2016;2016:3746232.
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Ahmet Akbas, Fikret Calikoglu, Mehmet Oncü, Atilla Celik. Determination of axillary metastasis by breast MRI after neoadjuvant chemotherapy in breast cancer. Ann Clin Anal Med 2025;16(6):397-400
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Evaluation of autoimmune diseases in pediatric patients with type 1 diabetes mellitus
Onur Sivas 1, Damla Geçkalan 2, Veysel Nijat Baş 3
1 Department of Pediatrics, Kütahya Health Sciences University, Kütahya, 2 Department of Pediatrics, Bakırçay University, Çiğli Regional Education Hospital, İzmir, 3 Department of Pediatric Endocrinology, Kütahya Health Sciences University, Kütahya, Turkey
DOI: 10.4328/ACAM.22396 Received: 2024-09-08 Accepted: 2024-10-21 Published Online: 2025-01-03 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):401-405
Corresponding Author: Damla Geçkalan, Department of Pediatrics, Bakircay University Çiğli Regional Education Hospital, İzmir, Turkey. E-mail: drdamlageckalan@gmail.com P: +90 506 284 36 54 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6344-7035
Other Authors ORCID ID: Onur Sivas, https://orcid.org/0000-0003-1549-9089 . Veysel Nijat Baş, https://orcid.org/0000-0002-0137-7630
This study was approved by the Ethics Committee of Kütahya Health Science University, Faculty of Medicine (Date: 2020-06-26, No: 2020/10-22)
Aim: The incidence of other autoimmune diseases is higher in Type 1 Diabetes Mellitus (T1DM). Autoimmune thyroiditis and celiac disease often accompany T1DM.The aim of this study was to determine how frequently autoimmune thyroiditis and celiac disease occur at the time of diagnosis and during follow-up in T1DM pediatric patients.
Material and Methods: Sixty pediatric patients were included in the study. As laboratory parameters, thyroid function tests (fT4, TSH), Anti-thyroid peroxidase antibody (a-TPO), serum thyroglobulin antibody (a-TG), tissue transglutaminase antibodies (TGA), islet cell antibody, anti insulin antibodies and HbA1c levels were evaluated.
Results: The average diabetes duration of the patients was 3.8 ± 3.2 years and the mean HbA1c value was 9.02% ± 2.18. In the T1DM cases, 36 of the 60 patients (60%) tested positive for any of the DM antibodies. TPO antibodies were found to be positive in 18 of the 60 patients (30%). Of these 18 patients, 15 were female (83.3%) and 3 were male (16.7%). TPO antibody positivity was statistically higher in females. All patients with positive TPO antibodies were diagnosed with autoimmune thyroiditis. TG antibodies were found to be positive in 9 of the 60 patients (15%), 8 of whom were female (88.8%) and 1 was male (11.2%). Tissue transglutaminase IgA antibodies were positive in 6 of the 60 patients (10%). Three of these patients (all of whom were female) were diagnosed with celiac disease.
Discussion: Our study suggested that children diagnosed with type 1 diabetes should be followed up in terms of autoimmune thyroiditis and celiac disease.
Keywords: Type 1 Diabetes Mellitus, Autoimmune Diseases, Celiac Disease, Thyroiditis
Introduction
Diabetes mellitus is a chronic endocrine and metabolic syndrome characterized by hyperglycemia. There are two main types of diabetes mellitus. Type 1 Diabetes Mellitus (T1DM), also known as “insulin-dependent Type 1 DM”, is characterized by a lack of insulin hormone secretion from pancreatic beta cells. Type 2 DM is the type that develops insulin resistance in liver, fat and muscle tissue and has beta cell deficiency.
In cases of T1DM, the probability of developing other autoimmune diseases is high at the time of diagnosis or during follow-up. Autoimmune thyroiditis (OT) is the most common autoimmune disease accompanying T1DM, followed by celiac disease (CD) [1]. The prevalence of thyroid autoantibodies in T1DM patients increases with age and the duration of diabetes. Thyroid antibodies usually do not show positivity at the time of T1DM diagnosis but are seen during the course of diabetes mellitus [2]. Therefore, in the diagnosis of T1DM, serological screening and thyroid function tests are recommended. It is also recommended that patients be checked every six months if a-TPO and a-TG antibodies (Ab) are positive or annually if they negative [3].
The prevalence of Celiac disease is higher in children with T1DM and fluctuates between 1% and 16% [4]. Although not a routine clinical practice, it has been recommended that all patients with T1DM should screened for the development of celiac disease [5].
Our aim in this study was to investigate the frequency and duration of autoimmune diseases (Celiac and Thyroiditis) in our pediatric patients with Type 1 DM.
Material and Methods
In this study conducted between March 2019 and July 2020, 60 pediatric patients (0-18 years) who had been diagnosed with T1DM at least 1 year earlier and were followed regularly (≥3 times/year) in the Pediatric Endocrinology Outpatient Clinic of Health Sciences University were retrospectively analysed from hospital automation records. Data regarding height, weight, duration of diabetes, age at diagnosis of diabetes, presence of another autoimmune disease and family history of autoimmune disease were recorded. Thyroid function tests (FT4, TSH), a-TPO antibody, a-TG antibody, tissue transglutaminase antibodies, islet cell antibodies, anti-GAD antibodies, anti-insulin antibodies and HbA1c values were included in the study as laboratory parameters. Patients with missing data were not included in the study.
Statistical analysis
The descriptive statistics of continuous variables are given as mean ± standard deviation (SD), while the statistical values of discrete variables are given as median, frequency and percentage. Patient’s t tests are the mean of two independent groups. The analyses of the cross tables were calculated by Yates Corrected Chi-Square tests. Statistical analyses were performed with the help of SPSS 17.0 for Windows (SPSS Inc., Chicago, IL, USA). A P value below 0.05 was considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee on Clinical Research of Kütahya Health Science University, Faculty of Medicine (Date: 2020-06-26, No: 2020/10-22).
Results
Of the 60 cases, 29 (48.3%) were male and 31 (51.7%) female. All of them were receiving insulin therapy. The mean age of the cases at the time of the study was 12.3 ± 3.4 years (minimum 1.5 years; maximum 17 years). As regards the age distribution of the patients: 17 cases (28.3%) were in the 0-5 age group, 21 cases (35%) in the 6-10 age group and 22 cases (36.6%) in the ≥11 age group. The mean duration of diabetes in the subjects at the time of the study was 3.8 ± 3.2 years (Table 1). The mean age at diagnosis of T1DM in the subjects was 8.5 ± 4.3 years. The mean HbA1c value of the cases was 9.02% ± 2.18%. Evaluation of the cases in relation to autoimmune DM antibodies: 36 of 60 patients were positive for some DM antibodies. In 25 (41.7%) a-GAD, in 19 (31.5%) anti-Islet Ab, and in 9 (15%) anti-insulin Ab positivity were detected. Anti-GAD and anti-Islet Ab were positive in 11 patients, anti-islet Ab and anti-insulin Ab were positive in 2 patients, all three antibodies were positive in 2 patients, and three antibodies were negative in 24 patients. Anti-GAD Ab and anti-insulin positivity were not observed together in any of the patients (Figure 1). As the cases of T1DM were evaluated in terms of the presence of autoimmune disease in the family history; there were 16 (27.7%) cases with thyroid disease in the family, 29 (48.3%) cases with DM in the family and 1 (1.7%) case with CD in the family.
All of the a-GAD positive patients, 14 (56%) were female, while 11 (44%) were male. Of the anti-islet Ab positive patients, 8 (41%) were female, and 11 (59%) male. Of the anti-insulin Ab positive patients, 4 (44.4%) were female and 5 (55.5%) were male. TPO antibodies were positive in 18 patients (30%) above 35 IU/ml. Of these patients, 15 (83.3%) were girls and 3 (16.7%) were boys. Thus, a-TPO was positive in 15 (48.3%) of 31 female patients and 3 (10.3%) of 29 male patients. Autoimmune thyroiditis was diagnosed in 18 (100%) of 18 patients with positive a-TPO antibodies and in 8 (88.8%) of 9 patients with positive a-TG. OT was detected in 18 of the 60 patients included in the study. Accordingly, the prevalence of OT was found to be 30%. Six of these patients were hypothyroid and were using medication. This eighteen OT patients’ mean age was 13.4 years, and their T1DM diagnosis averaged 4.58 years. The mean TSH value of the patients was 4.58 uIU/ml and the mean fT4 value was 0.89 ng/dl. The mean value of HbA1c was found to be 8.89%. In 18 patients with autoimmune thyroiditis, the mean thyroid volume value was found to be 8.86 ml, and the mean thyroid volume SDS value was 2.02 according to thyroid USG (Table 2). There was a family history of DM in 11 patients (61.1%), and a family history of thyroid disease in 13 patients (72.2%). None of the patients had a family history of CD.
As regards the accompanying autoantibodies in patients diagnosed with autoimmune thyroiditis; GAD antibodies were positive in 8 patients, a-TG Ab in 8 patients, a-Islet Ab in 4 patients, a-Insulin Ab in 3 patients and a-TGA Ab positive in 2 patients (Figure 2).
Anti-TG antibodies were found to be positive over 65 Iu/ml in 9 patients (15%). Of these patients, 8 (88.8%) were female and 1 (11.2%) was male. Thus, it was positive in 8 (25.8%) of 31 female patients and 1 (3.4%) of 29 male patients. Anti-TPO was also positive in 8 of the patients. A diagnosis of OT was made in 8 of 9 patients with positive a-TG. 4 patients had hypothyroidism and were using medication. The mean age of 9 patients with a-TG positivity was 13.7; the BMI SDS mean 1.12; the mean diabetes diagnosis was 5.2 years. The TSH mean value was 4.02 uIU/ml, and the fT4 mean value was 0.95 ng/dl. The mean HbA1c value was found to be 8.6%. In patients with positive a-TG, the mean thyroid volume was 10.75 ml, and the mean thyroid volume SDS was 3.08 (Table 2). Anti-TGA IgA antibodies were positive in 6 (10%) of the 60 patients; 4 of these patients were female (66.6%) and 2 were male (33.3%). 3 of 6 patients with a-TGA Ab positivity were diagnosed with CD by a small bowel biopsy by pediatric gastroenterology. All 3 patients were girls. The mean age of these 3 patients diagnosed with CD was 13.3; weight SDS mean -1.03; size SDS -0.11; BMI SDS was found to be -0.87. The mean age at T1DM diagnosis of the patients was found to be 7 years. The mean plasma IgA level was 2,1 mg/dl, and the mean HbA1c level was 9.0% (showed poor glycemic control). Both of the patients diagnosed with CD had hypothyroidism and were using medication. The mean thyroid volume SDS of these two patients was found to be 0.96. When other accompanying autoimmune antibodies of the 6 patients with celiac disease were examined; a-TPO in 2 patients, a-insulin Ab in 2 patients, a-GAD and a-Islet Ab in one patient each were positive.
Discussion
T1DM is the most common chronic endocrine autoimmune disease of childhood in which genetic predisposition, environmental factors and autoimmunity play a role. In this study, we investigated the frequency of OT and CD, which may occur at the time of diagnosis and during follow-up, and the affecting factors in patients with T1DM in our hospital.
In the studies of Redondo and Singh, the gender distribution of the cases was found to be similar (51% male, 49% female), as in our study [6]. In a study conducted at Istanbul University in our country, 27.9% of the cases diagnosed with T1DM were ≤5 years old, 37.2% were 6-10 years old and 34.9% were ≥10 years old [7]. The age distribution of the patients in our study was found to be compatible with the literature.
The prevalence of autoimmune thyroiditis in patients with T1DM is much more common than in the general population. While the prevalence of thyroid antibody positivity in children 2-5%, there are publications 12-25% in children and adolescents with T1DM [8, 9]. OT is the most common autoimmune disease accompanying T1DM, and celiac disease is the second most common [10]. In our study, similar to the literature, the most common autoimmune disease accompanying T1DM cases was OT with a rate of 30%; It was found that CD followed with the second frequency with the rate of 5%.
It has been shown that the most common autoimmune disease accompanying T1DM is OT. Although there are variable rates in studies, it has been reported that 12.5%-18.5% of T1DM patients were diagnosed with chronic autoimmune thyroiditis [11]. There are two reports about autoimmune thyroiditis from Turkey and Italy, where a-TG antibodies have been observed in 7.9% and 7.8% children with autoimmune thyroid disease [12, 13]. Conversely, in patients with celiac disease, a-TPO antibody and autoimmune thyroiditis have been reported to range from 10.5%-14.6% [13, 14]. Also there are publications with positive a-TG antibodies in 6-7.8% of patients with autoimmune thyroiditis and positive a-TPO in 10.5-14.6% of patients with CD, and it has been stated that children with CD have three times the risk of developing thyroid autoimmunity studies are also available in the literature. İn this study a-TG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively [15]. Also studies from Turkey show that frequency of CD is 23.2%, positive anti-TPO and anti-TG antibodies are 6.9% in patients whose diabetes diagnosis age is less than 5 years. Both CD and the presence of thyroid autoantibodies were more common in girls (73.3%, 68%) [16]. In another single-centre study conducted in Turkey, celiac disease (4.9%) and autoimmune thyroid disease (13.7%) were found in children with type 1 diabetes [17]. In our study, similar to the literature, anti-TG antibodies were found to be positive in 15% of the patients. In our study, we found that 30% of the patients with Type 1 DM had accompanying autoimmune thyroiditis. Although this rate was higher than in the literature, Hashimoto’s thyroiditis was more common in our female patients. Also in our study, we demonstrated with the high prevalence of Hashimoto’s thyroiditis (HT) in our female patients. Especially in girls with T1DM, serological screening and thyroid function test in the diagnosis of T1DM, which are the frequencies recommended by the literature, should be screened once a year if negative or every six months if a-TPO and a-TG antibodies are positive.
As expected, an increased incidence of the disease has been reported in siblings or parents of children with HT. Hashimoto’s thyroiditis was commonly found in both the probands and their relatives, especially among women. Among female diabetic probands, HT was diagnosed in 54–75% of cases depending on age, and among female relatives the frequency of HT was 22–44%. Moreover, diabetic probands with HT were significantly more likely to have a family history of thyroid disease [18]. This was evaluated as similar to the literature in terms of the familial predisposition relationship with HT in our study.
The incidence of CD in childhood is known to be between 0.2% and 5.5%. In some diseases and conditions, the risk of developing CD is greater. T1DM is among the high-risk groups for the development of CD among these diseases. This rate is higher in children with T1DM and has been reported in a wide range of 1-16% [4, 19]. The risk of celiac disease is inversely and independently associated with age at diagnosis of diabetes, with the greatest risk in those with diabetes diagnosed before 5 years of age. The prevalence of CD in the general population is estimated to be 20 times higher than in T1DM patients. Anti-TG-IgA antibodies are positive in 4-12% of children with T1DM [20, 21]. When we evaluated all our cases for celiac disease, (similar to the literature) we found that 10% of our patients were diagnosed by serological positivity and 5% by biopsy. Serological screening for CD in children with T1DM is recommended annually, in the first 5 years of diabetes, and then every 2 years after T1DM diagnosis, according to ISPAD guidelines [22].
IgA deficiency is seen with a frequency of 1:500 in the population. It has been reported that it is more common, especially in people with Type 1 diabetes and those with celiac disease [23]. Therefore, most guidelines recommend routine measurement of total IgA to exclude IgA deficiency. The other recommended method is to first measure IgA if the initial screening test using only a-TG-A and/or EmA is negative. If the child has IgA deficiency, IgG-specific antibody tests (a-TG or EmA IgG or both) should be used for screening [24]. In our clinic, we use IgA and a-TG-A together in the first screening. İn our study; Anti-TGA IgA antibodies were positive in 6 (10%) of the 60 patients; 4 of these patients were female (66.6%) and 2 were male (33.3%). 3 of 6 patients with a-TGA Ab positivity were diagnosed with CD by a small bowel biopsy by pediatric gastroenterology. All 3 patients were girls. The mean age of these 3 patients diagnosed with CD was 13.3. The mean age at T1DM diagnosis of the patients was found to be 7 years. The mean plasma IgA level was within the normal range. Both of the patients diagnosed with CD had hypothyroidism and were using medication.
İn Polish children is reported that the prevalence of at least one diabetes associated Ab was found in 87%, with the highest prevalence of 64% for zinc transporter 8 (ZnT8 Ab), islet cell autoimmunity was 34%, Thyroid Ab was 26% (42% in girls vs. 8% in boys), tTG Ab was 11% patients. In patients with a duration >10 years, 50% had at least one antibody [24]. In a study conducted with adolescents and adults, it was reported that 96.7% of the patients were positive for GAD, 53.3% for islet autoantibodies, 80% for insulin autoantibodies, and 23.3% for TPOAb positive. It was determined that 16.7% of the patients were positive for both TPOAb and TGAb [25]. As seen in the Polish study, although zinc antibody positivity is very common, it cannot be studied in our hospital. In our study, as expected, autoantibody positivity was found to be less than in adolescent and adult studies due to the lower median age. Therefore, our study emphasizes the importance of long-term follow-up of patients with T1DM.
Limitation
The limitation of the study is the lack of long-term follow-up to evaluate the susceptibility of patients with anti-GAD and anti-TTG antibodies to celiac disease or type-1 diabetes mellitus. Additionally, since our study was single-center, multicenter studies with larger patient numbers are needed.
Conclusion
OT recordings and CD tend to be highly elevated in T1DM patients compared to those without. Serological screening for CD in children with T1DM is recommended annually, in the first 5 years of diabetes, and then every 2 years after T1DM diagnosis. In addition, we emphasize the importance of using such autoantibodies, which we can use clinically, for screening purposes in early diagnosis. In the near future, further research should be conducted regarding these two autoimmune conditions, especially for girls with T1DM.
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.
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Onur Sivas, Damla Geçkalan, Veysel Nijat Baş. Evaluation of autoimmune diseases in pediatric patients with type 1 diabetes mellitus. Ann Clin Anal Med 2025;16(6):401-405
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The effect of chewing gum on intestinal functions, postoperative pain, and early discharge after isolated coronary bypass surgery
Habibe Çevik 1, Rahşan Çam 2, Mesut Engin 3, Senol Yavuz 3
1 Department of Nursing, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, 2 Department of Surgical Nursing, Faculty of Nursing, Adnan Menderes University, Aydin, 3 Department of Cardiovascular Surgery, University of HealthSciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
DOI: 10.4328/ACAM.22416 Received: 2024-09-22 Accepted: 2024-12-16 Published Online: 2025-01-11 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):406-409
Corresponding Author: Mesut Engin, Department of Cardiovascular Surgery, University of HealthSciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey. E-mail: mesut_kvc_cor@hotmail.com P: +90 224 295 50 00 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2418-5823
Other Authors ORCID ID: Habibe Çevik, https://orcid.org/0000-0003-2286-6211 . Rahşan Çam, https://orcid.org/0000-0002-0659-4861 . Senol Yavuz, https://orcid.org/0000-0001-5246-0808
This study was approved by the Ethics Committee of Adnan Menderes University, Faculty of Nursing Non-Interventional Clinical Research (Date: 2020-09-07, No: 50107718-050.04.04)
Aim: Abdominal distension is a significant problem that may occur after coronary artery bypass graft surgery (CABG). In this study, we aimed to investigate the effects of postoperative gum chewing on bowel function, pain levels, and early discharge in patients who underwent isolated CABG surgery.
Material and Methods: Patients who underwent isolated CABG surgery at the Health Sciences University were prospectively included in this non-randomized study between June 2021 and December 2021. The study group (single-use gum chewed for at least 15 minutes (min) and a maximum of 30 minutes each time, at the 4th, 6th, 8th, and 10th hours after checking for swallowing reflex and orientation 4 hours after extubation) included 24 patients. With 24 controls, 48 patients were thus included in the study.
Results: There was no difference between the groups regarding gender, hypertension (HT), body mass index, diabetes mellitus, chronic obstructive pulmonary disease rates, education levels, and defecation habits. A significant increase in bowel sounds and a significant decrease in pain levels were detected 15 to 30 minutes after chewing gum at all times, during the 4th, 6th, 8th, and 10th postoperative hours (P < 0.001 for all parameters).
Discussion: Chewing gum early after CABG may allow bowel functions to return earlier. It can also reduce pain levels. However, there was no significant effect on early discharge.
Keywords: Coronary Artery Bypass Graft, Postoperative Term, Chewing Gum, Postoperative Care
Introduction
Today, coronary artery bypass graft (CABG) surgery is successfully applied in the treatment of atherosclerotic heart disease. Most of these operations are performed with cardiopulmonary bypass (CPB) [1]. Although CPB systems are technologically advanced, these operations involve serious surgery with prolonged anesthesia times. Therefore, various postoperative complications that affect all organ systems may occur [2].
Abdominal distension is a significant problem that may occur after coronary artery bypass graft surgery (CABG). It may occur due to prolonged bed rest and mobilization issues [3]. Although abdominal distention is a painful condition in the postoperative period, serious clinical problems such as paralytic ileus and gastric dilation may occur if the duration is prolonged [4]. There are suggestions such as early mobilization, fluid consumption, chewing gum, and hot application, to avoid abdominal distention. Postoperative gum chewing is highly recommended practice because it is easy for patients to adapt to, it can be easily applied, and it is economical [5]. Studies have shown that chewing gum at the 4th hour after the operation as the first oral nutrition reduces the ileus development [6].
In this study, we aimed to investigate the effects of postoperative gum chewing on bowel function, pain level, and early discharge in patients who underwent isolated CABG surgery.
Material and Methods
Patients who underwent isolated CABG surgery at the Health Sciences University between June 2021 and December 2021 were prospectively included in this study. Patients with a left ventricular ejection fraction greater than 40%, who had underwent elective isolated CABG surgery, and who did not have an impediment to chewing gum, were included in the study. Patients with preoperative dyspeptic complaints, combined surgery, or a history of abdominal surgery, were not included in the study. Patients who developed early postoperative mortality or morbidity (e.g., prolonged ventilation for12 hours, use of intra-aortic balloons) during this period and who refused to chew gum, were excluded from the study. Demographic data of the patients (age, gender, educational status, body mass index, etc.), operative data (operation time), and postoperative data (total hospitalization time of the patient, time to start oral intake, first flatus passing and stool output time, postoperatively evaluated bowel sound, postoperatively evaluated pain level, postoperative first mobilization time, hospitalization period), were recorded. The total hospital stay was calculated by considering the entire period between preoperative preparation and the time of the patient’s discharge.
Sample Size Calculation
The sample included 48 patients undergoing isolated CABG surgery. To detect a statistically significant difference between the two groups with 96% power, a significance level of 0.05, and the possibility of type I error below 5%, the required sample size was calculated to be 24 patients per group. As gender differences were not significant difference in the reference studies, no distinction was made between men and women in the volunteer patients to be included in the study. All patients who met the inclusion criteria and volunteered to participate were included in the sample until the specified sample size was reached.
Chewing Gum (Study) Group
Following the removal of the intubation tube, patients were assessed for their ability to swallow and orientation after four hours. They were then instructed to chew a single-use gum for a minimum of 15 minutes and a maximum of 30 minutes at the 4th, 6th, 8th, and 10th hours). This group consisted of 24 patients.
Control Group
The chewing gum group was determined first within the specified date range. Then, 24 consecutive patients meeting the inclusion criteria were assigned to the control group. The study continued until both groups had 24 patients within the study period.
The timing for the patients to start chewing gum was based on the ERAS (Enhanced Recovery After Surgery) guidelines [5]. Swallowing reflex control was initiated once researchers observed that the patients could swallow without aspiration, by giving them swallow a small amount of water. Bowel sounds before and after each chewing were verified by the researcher with a stethoscope. To determine the duration of the first flatus after chewing gum, the patients were asked to verbally state. Pain assessments were assessed using the Visual Analogue Scale (VAS) at the postoperative 4th, 6th, 8th, and 10th hours for all patients [7]. Participants were provided with a 10-cm line representing a continuum from “no pain” and “worst possible pain”. Participants were then asked to indicate their level of pain by making a handwritten mark on the line, with “no pain” being represented by a mark at the left end of the line and “worst possible pain” being represented by a mark at the right end of the line.
Statistical Analysis
Statistical analyses were performed in the JASP (Jeffrey’s Amazing Statistics Program) software, (an open-source program developed by the University of Amsterdam that does not require a license) . Descriptive statistics of qualitative variables in the study were reported as frequency and percentage; while quantitative variables were presented with mean, standard deviation, median, minimum, and maximum values. The normality of quantitative variables was assessed using the Shapiro-Wilk test. The Mann-Whitney U test was used to compare two independent groups of quantitative variables. The quantitative variables were analyzed using the Wilcoxon test to compare two dependent groups. The Yates, Fisher, and Pearson chi-square tests were used for independent group comparisons of qualitative variables. Results below 0.05 were considered statistically significant in all statistical analyses.
Ethical Approval
This study was approved by the Ethics Committee of Adnan Menderes University, Faculty of Nursing Non-Interventional Clinical Research Ethics Committee (Date: 2020-09-07, No: 50107718-050.04.04). After obtaining the ethics committee’s approval, written permission (Date: 2020-10-26, No: 31234050-799) was obtained from the management of Health Sciences University, Bursa Yuksek Ihtisas Training and Research Hospital.
Results
A total of forty-eight patients were included in the study; and their preoperative characteristics and demographic data are presented in Table 1. There were twenty-four patients in the study group with a median age of 57.5 (31-68), and there were twenty-four patients in the control group with a median age of 63 (30-76) (P= 0.042). There was no difference between the groups in terms of gender, hypertension (HT), body mass index (BMI), diabetes mellitus (DM), chronic obstructive pulmonary disease rates (COPD), education levels, and defecation habits. Operative and postoperative data of the patients are presented in Table 2. There was no significant differences between the groups in operation times, perfusion times, postoperative first mobilization hours, pain levels at the 4th hour after extubation, or total hospital stay. The first postoperative bowel sound, time to first flatus, and time to first defecation were significantly earlier in the study group (P < 0.001 for all parameters). Table 3 presents the evaluation of pain and bowel sounds in the gum-chewing group before and 15 to 30 minutes after chewing gum. A significant increase in bowel sounds and a significant decrease in pain levels were observed 15 to 30 minutes after chewing gum at all times, at the 4th, 6th, 8th, and 10th postoperative hours (P < 0.001 for all parameters).
Discussion
CABG surgeries with cardiopulmonary bypass are commonly performed, and technological advances, mortality rates have reduced mortality rates to 1% [8]. However, morbid complications affecting multiple organ systems may still occur after these operations. Gastrointestinal complications occur in up to 6% after cardiac surgeries [4]. Abdominal distention is one such complication and can be painful, potentially leading to ileus. In this prospective non-randomized single-center study, we demonstrated that early gum chewing positively affects bowel function after CABG surgery and reduces postoperative pain levels.
Advanced age plays a role in the development and prognosis of many diseases. Because our study was not a randomized controlled trial, age was slightly higher in our control group (P = 0.042). This may affect the study results. However, there are also studies indicating that advanced age does not affect postoperative bowel sounds [9,10]. Auscultation of bowel sounds is an important manual assessment method, but it lacks objectivity. In our study, bowel sound assessments were performed manually. An electronic bowel sound recording system has been developed and is safely used in bowel sound analyses [11].
Most studies investigating postoperative outcomes with gum chewing have focused on abdominal surgery. In a study by Turkay et al. [12], the effect of postoperative gum chewing on pain and bowel movements in patients who underwent laparoscopic total hysterectomy was investigated. In the study group (N = 58), patients began chewing sugarless gum every two hours for fifteen minutes, beginning at the second postoperative hour. The control group (N = 51) did not chew gum and patients received standard postoperative care. The study demonstrated the positive and significant effects of chewing gum on pain and bowel movements. In a meta-analysis study by Roslan et al. [13], the effect of chewing gum on the ileus after colorectal surgery was investigated. The meta-analysis, which included 970 patients across 10 studies, concluded that postoperative gum chewing significantly reduced the incidence of ileus. Unlike these patient groups, our study focused on patients who underwent CABG surgery. No cases of ileus were observed in our study. We demonstrated that chewing gum had positive and significant effects on pain and bowel movements.
There have been studies investigating the effects of chewing gum on postoperative outcomes following surgical operations without peritoneal incisions. A study conducted on adolescent idiopathic scoliosis patients scheduled for posterior spinal fusion surgery, the effectiveness of chewing gum in promoting bowel function recovery was investigated. Although the study did not find a positive effect of postoperative gum chewing on intestinal functions, it did report a positive effect on postoperative pain [14]. Another study, the effect of postoperative gum chewing on the development of ileus was investigated in patients over 65 years of age with hip fractures. The study concluded that postoperative gum chewing reduced the incidence of ileus [15].
In cardiovascular surgery, a study investigating the effect of chewing gum on intestinal function was conducted on transperitoneal abdominal aortic surgery patients. This study included 44 patients, divided into a control group (N = 21) and a study group (N = 23), that chewed gum three times a day. In this study, the authors found that flatus was passed on postoperative day (POD) 1.49 in the gum group and on POD 2.35 in the control group (P = 0.0004) and the time to oral intake was 3.09 days in the gum group and 3.86 days in the control group (P = .023). At the end of their study, the authors emphasized that chewing gum after abdominal aortic surgery positively affects intestinal function [16]. Unlike this study, we performed coronary artery surgery on our patients and the abdomen was not opened.
ERAS is a perioperative management protocol originally designed to improve patient recovery after colorectal surgery [17]. A study by Hendy et al. [6], it was revealed that the ERAS protocol can also be applied to cardiac surgery patients. However, the protocol covers a diverse group of cardiac surgery patients. A protocol suitable for the characteristics of this patient group is necessary [5]. Chewing gum is one of the items that should be applied postoperatively in the ERAS protocol. Further studies are needed in the field of cardiac surgery.
In our study, the number of bowel sounds before chewing gum in the 10th postoperative hour [6 (5-14)] was significantly lower than that after chewing in the 8th postoperative hour [10 (7-20)], but it was not much different from that before chewing [6 (3-14)] in the 8th postoperative hour. This result indicates that the stimulating effect of chewing gum on bowel sounds is short-lived.
Limitation
The most important limitation of our study is that it was a single-center which limited the number of patients. We found that postoperative gum chewing significantly reduced postoperative pain levels, which is important as it may help prevent complications like postoperative atrial fibrillation. In our study, bowel sounds were recorded by one person using a stethoscope. Automatic systems could not be used [18].
Conclusion
It is crucial to reduce morbid outcomes after CABG surgery. Chewing gum early after these surgeries may allow bowel functions to return earlier. It can also reduce pain levels. However, there was no significant effect on early discharge. Our study is the first to investigate the effects of early gum chewing after isolated CABG operations with cardiopulmonary bypass. Multi-center studies using electronic bowel sound recording systems and larger patient populations 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
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Habibe Çevik, Rahşan Çam, Mesut Engin, Senol Yavuz. The effect of chewing gum on intestinal functions, postoperative pain, and early discharge after isolated coronary bypass surgery. Ann Clin Anal Med 2025;16(6):406-409
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Determinants of participation of children with diplegic cerebral palsy in educational, home, and social settings
Hasan Bingöl 1, Dilan Demirtaş Karaoba 2
1 Department of Physiotherapy and Rehabilitation, Faculty of Physical Therapy and Rehabilitation, Bingöl University, Bingöl, 2 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Iğdır University, Iğdır, Türkiye
DOI: 10.4328/ACAM.22444 Received: 2024-10-08 Accepted: 2024-12-24 Published Online: 2025-01-10 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):410-414
Corresponding Author: Hasan Bingöl, Department of Physiotherapy and Rehabilitation, Faculty of Physical Therapy and Rehabilitation, Bingöl University, Bingöl, Türkiye. E-mail: hesenbingol@gmail.com P: +90 507 232 81 00 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3185-866X
Other Authors ORCID ID: Dilan Demirtaş Karaoba, https://orcid.org/0000-0002-6754-9335
This study was approved by the Ethics Committee of Bingöl University (Date: 2024-01-23, No:24/01)
Aim: Although most children with spastic diplegic cerebral palsy (SDCP) achieve independent walking levels, they are still prone to participation restrictions due to impairments in body functions, activity limitations, and child factors. This study aimed to verify a structural model of the determinants of participation of children with SDCP.
Material and Methods: A convenience sample of 40 children with SDCP (mean 9.13 standard deviation 3.2) was recruited. Body function parameters were measured using the five-times-sit-to-stand test, Timed Up and Go test, and Pediatric Balance Scale. Activity measures were Gross Motor Function Measure-88, The Gillette Functional Assessment Questionnaire 22-item skill, and the One-Minute Walk Test. Participation was measured using the Child and Adolescent Scale of Participation. A structural model of the determinants of participation was conceptualized based on the theoretical relationships available, common problems observed in spastic diplegic cerebral palsy, and the perspectives of researchers.
Results: Path analysis demonstrated that impairments in body function had a significant direct effect of 0.98 (P < 0.001) on the activity construct. The activity construct had a significant direct effect on participation (β weight = 0.26; P < 0.05). The child factors construct was revealed to influence the participation of children with spastic diplegic cerebral palsy significantly, with a direct effect of 0.10 (P < 0.05). Finally, the proposed structural model explained 30% of the variance in the participation outcomes of children with spastic diplegic cerebral palsy.
Discussion: The participation of children with SDCP is multidimensional and requires the consideration of various factors, including physical impairments, activity limitations, and child-related factors.
Keywords: Cerebral Palsy, Children, Diplegic, Participation, Structural Equation Modelling
Introduction
Participation in home, school, and community life is vital for children with cerebral palsy (CP), as it reflects both individual and societal aspects of functioning and plays a pivotal role in their development and quality of life [1]. It is essential for children with physical disabilities, such as those with CP, to participate in different life situations, like their typically developing peers. Participation in different life situations promotes all aspects of development, including the formation of friendships and social relationships, as well as the enhancement of intellectual, emotional, and physical well-being [2]. Research indicates that children with CP, including those with spastic diplegic CP (SDCP), are more likely to experience participation restrictions than their typically developing peers [3]. Participation is a multidimensional concept influenced by a range of internal and external factors, such as body functions, activity, and environmental and personal factor domains of the International Classification of Functioning, Disability, and Health (ICF). In children with SDCP, spastic walking patterns, poor functional balance, restricted lower-extremity mobility, reduced selective motor and postural control, and poor coordination have been reported to be the most significant impairments in body functions [4]. Several studies have been conducted to investigate the factors that influence the participation of children with CP [2, 5, 6], but none have specifically focused on the determinants of participation of children with SDCP. Therefore, obtaining data on the factors influencing the participation of children with SDCP would provide valuable insights into the specific issues that need to be addressed to improve their participation outcomes. Thus, this study aimed to validate a structural model based on theoretical relationships from the existing literature to identify potential factors responsible for low participation outcomes of children with SDCP in educational, home, and social settings.
Material and Methods
This study followed the guidelines established by the Declaration of Helsinki for conducting studies involving human participants. After providing extensive information about the study’s objectives and procedures, written informed consent was obtained from both participating children and their primary caregivers.
Participants
A convenience sample of 40 participants was determined using the principles of structural equation modeling (SEM), which recommends five to ten participants per estimated parameter, such as paths and covariances [6]. Children who met the following criteria were included in the study: a diagnosis of SDCP according to the Surveillance of Cerebral Palsy in Europe (SCPE) criteria, an age range of 5–14 years, the ability to comprehend instructions (IQ > 0.70), the ability to walk (GMFCS I-III), and had not received BoNT-A injections in the lower extremities within the past six months. Children with uncontrolled seizures, severe comorbidities, or no clear diagnosis of SDCP were excluded from the study.
Assessment
The gross motor function was evaluated using the Gross Motor Function Measure-88 (GMFM-88). It has been suggested that GMFM-88 is a reliable tool for assessing gross motor function in children with CP [7]. Lower limb functional strength was quantified using the Five-Times Sit-to-Stand Test (FTSST), which measures the ability to rise from a seated position. The FTSST measures the amount of time required for an individual to perform the tasks of standing up and sitting back down five times. It has been shown to be a reliable test for measuring functional lower-extremity strength in children with CP [8]. The Timed Up and Go (TUG) test measured the dynamic balance of the study participants. The test measures the time it takes for the child to complete tasks, including standing up, walking 10 feet, turning around, and returning to the starting point, and sitting back down. TUG has been demonstrated to be a reliable and responsive test for measuring dynamic balance in children with CP [9]. The Pediatric Balance Scale (PBS), a modified version of Berg’s Balance Scale, was used to assess functional balance in the context of everyday activities. The PBS has been shown to be reliable for describing the functional balance of children with CP [10]. The Gillette Functional Assessment Questionnaire 22-item skill set (FAQ-22 skill set) was used to describe several locomotor activities using a five-point Likert difficulty scale. Measurement properties of the FAQ-22 questionnaire for assessing ambulatory function in children with CP have been established [11]. Walking or functional ability was evaluated using the One-Minute Walk Test (1MWT). It measures the distance covered by a child during a fast 1-minute walk and has been shown to be reliable for use in children with bilateral spastic cerebral palsy, including SDCP [12]. Finally, the Child and Adolescent Scale of Participation (CASP) was used to assess participation in the home, school, and community settings. The CASP demonstrates appropriate measurement properties and is effective in evaluating the participation outcomes of children with disabilities [13].
Conceptualizing A Structural Model of Determinants of Participation
A conceptual model was developed based on theoretical relationships identified in published sources, common issues observed in spastic diplegia, and the perspectives of researchers in the field (Figure 1). The model aims to achieve a thorough comprehension of children’s participation by considering the various dimensions of ICF. Specifically, the proposed model includes both measurement and structural models. In the measurement model, the validity of the indicators of the latent variables (i.e., body function and activity, personal factors) that could not be directly measured was investigated. A structural model was established to predict various factors contributing to the participation of children with SDCP. A list of both the dependent and independent variables is summarized in Table 2.
Statistical Analysis
Regression analysis was performed using the IBM SPSS v. 25 package program, while Structural Equation Modelling (SEM) was performed with IBM AMOS (Analysis of Moment Structures version 20). SEM is an advanced statistical method that combines path and factor analysis. The proposed model of the determinants of participation by children with SDCP involves measurement and structural models. Measurement models of body function and activity and child/personal factors were confirmed using factor analysis, whereas the structural model of the direct effects of the independent variables on the dependent variables was evaluated through path analysis. In the measurement model, an acceptable factor loading or regression weight for the indicators of the construct was ≥ 0.60 [14]. In the structural model, the significance of a standardized path coefficient (β weight) with an α level below 0.05 was examined to determine whether a construct/independent variable had a significant impact on the dependent variable. The verification of the structural model of the determinants of participation (measurement model and direct and indirect paths) was investigated according to the goodness-of-fit indices. Goodness-of-fit indices were used to assess whether the proposed path model was an appropriate representation of the collected data. The following goodness-of-fit indices with specified acceptable values were investigated: X2/df: 3 < X2/df < 5, Root Mean Square Error of Approximation [RMSEA] < 0.08, Standardized Root Mean Residual [SRMR]: < 0.08, Comparative Fit Index [CFI]: > 0.90, Goodness of Fit Index [GFI] > 0.90, and Adjusted Goodness of Fit Index [AGFI] > 0.90 [15].
Ethical Approval
This study was approved by the Ethics Committee of Bingöl University (Date: 2024-01-23, No:24/01).
Results
The characteristics of the children with SDCP in this study are summarized in Table 1. Testing the Validity of Indicators of Constructs (Body Functions, Activity, and Child Factors)
Confirmatory factor analysis (CFA) revealed that a decrease in lower limb functional strength and impaired dynamic and functional balance were contributors to the impairment in body functions (factor loadings/regression weights from indicator variables to body functions: 0.89 –0.97). Similarly, CFA showed that gross motor function, functional locomotor activity, and walking ability significantly contributed to activity limitations. In other words, the factor loadings and regression weights of the indicator variables for the activity construct are higher than the acceptable threshold of 0.60, with estimates ranging from 0.90 to 0.91. The measurement model of child factors revealed that only indicators of age and The Number of Years Receiving Rehabilitation Services (NYRRS) had a factor loading more than 0.60 (factor loading/regression weight from the age and NYRRS to child factor: 0.64 and 0.62, respectively). In contrast, the factor loading/regression weight from gestational age and sex indicator variables to the child factor construct was found to be less than 0.60. (Factor loading/regression weight of gestational age, 0.11 and 0.24, factor loading/regression weight of gender: -0.01) (Table 2 and Figure 2).
Testing the Structural Model (Direct and Indirect Effects)
The results of the structural model are shown in both Figure 2 and Table 2. The results of the path analysis revealed that impairment in body functions had a significant direct effect of 0.98 (P < 0.001) on activity but had no significant direct effect on participation (β weight = 0.06 and P > 0.05). The activity construct had a significant direct effect on participation restriction (β weight = 0.26; P < 0.05). This implies that the effect of impaired body function on participation was not immediate; rather, it was mediated by activity restrictions. The Child Factors construct was revealed to influence the participation of children with SDCP significantly, with a direct effect of 0.10 (P<0.05). The goodness-of-fit indices indicated that the proposed structural model fit the data collected from the participants (X2/df = 3.840, RMSEA = 0.067, SRMR = 0.056, CFI = 0.93, GFI = 0.92, and AGFI = 0.95). Finally, the results of the regression analysis showed that the proposed structural model explained 30% of the variation in the participation of children with SDCP (Table 3).
Discussion
This study is uniquely describes the factors that influence the participation of children with SDCP by using the SEM statistical method. In other words, the proposed structural model sought to understand the multiple factors contributing to the participation of children with SDCP in home, school, and educational settings. The structural model indicated that physical impairments and activity limitations played a significant role in the participation restrictions of children with SDCP, whereas child-related factors had a relatively low impact. This suggests that the participation of children with SDCP is complex and influenced by multiple factors, including both CP and child-related factors.
Although this research lacked a comparative design and thus did not involve a comparable group of typically developing (TD) children, previous findings have already established that children with CP are generally at risk of lower participation outcomes than their TD peers [1, 2, 6, 16]. More specifically, a previous study conducted by Calley et al. [3] revealed that children with SDCP participate less in daily activities than TD children. The ICF establishes a framework for understanding the relationship between body function, activity, and participation within the context of personal and environmental factors. As predicted, the present study revealed that decreased lower-limb muscle strength and impaired dynamic and functional balance are essential impairments in the body function of children with SDCP. This is in line with previous findings that children with SDCP often exhibit impaired trunk control [17] and weakness and spasticity in the lower extremities [18], resulting in poor dynamic balance and functional mobility [19]. Additionally, trunk control is an essential component of postural control and balance reactions and plays a significant role in the development of upper and lower limb movements [20]. The relationship between lower-limb muscle strength and gross motor function has also been well established [21]. Consequently, impairments in body function led to activity limitations, including a reduction in gross motor functions, difficulties with functional locomotor activity, and a decrease in walking ability, as suggested by the structural model. Path analysis revealed that impairments in body function were the primary cause of activity limitation, as demonstrated by a direct effect of 0.98. This finding supports the concept of ICF, which proposes a relationship between body function, activity, and participation [22]. Moreover, a direct relationship between impairment in body function and participation restrictions was not found, whereas a direct relationship between activity limitations and participation restrictions was evident. This indicates that impairment of body function had an indirect effect on participation restrictions. Therefore, it can be argued that impairments in body function result in activity limitation and subsequent participation restriction. The measurement model of child factors indicated that both age and NYRRS were significant observed variables in explaining the construct of child factors. Importantly, the results of path analysis showed that childhood factors, including age and NYRRS, directly influenced the participation of children with SDCP. In contrast, as child factors, neither prematurity nor gender contributed to the participation of children with SDCP. It has been well documented that prematurity is closely related to deficient muscle strength, decreased muscle tone, and delayed motor function [23]. In addition, the relationship between spastic diplegia and prematurity is widely recognized [24]. Despite this, the results of the current study revealed that prematurity did not have a significant impact on the participation outcomes of children with SDCP. This implies that providing sufficient rehabilitation services to children with SDCP, regardless of whether they are born prematurely, may be critical for better participation outcomes. Finally, the proposed structural model explained 30% of the variance in participation, indicating that impairments in body function, activity limitations, and factors such as age and NYRRS were significant determinants of participation in children with SDCP. Although most children with SDCP attain independent walking skills with or without walking devices, they still tend to participate less in daily activities. Therefore, to achieve better participation outcomes in children with SDCP, pediatric physical or occupational therapists should consider the determinants of participation identified in the current study.
Limitation
A limitation of the present study is that it did not consider environmental, family, or some child factors (e.g., psychological and behavioral characteristics), which are known to play a role in the participation of children with CP. This was because the researchers focused more on CP-related factors that could affect the participation of SDCP children. Thus, further understanding of the participation of children with SDCP requires including more variables related to contextual factors.
Conclusion
This article discusses the participation of children with SDCP in relation to the ICF framework, demonstrating that the participation of children with SDCP is multidimensional and influenced by multiple factors. Children’s participation is influenced by impairments in body function, activity limitations, and child factors. The measurement model of impairments in body function indicated that deficient lower-limb muscle strength and poor dynamic and functional balance are the principal impairments in body functions in children with SDCP. The structural model indicated that impairments in body function had a direct effect on activity capacity and a subsequent indirect effect on participation outcome. This suggests that the activity capacity mediates the effects of impairments in body function on participation. Furthermore, child factors, such as age and NYRRS, were found to influence the participation of children with SDCP. Finally, the proposed structural model demonstrated that impairments in body function, activity capacity, and child factors predicted the participation of children with SDCP. Therefore, targeted rehabilitation programs that address impairments in body function and activity limitations are essential to enhance the participation of children with SDCP in various life 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.
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Hasan Bingöl, Dilan Demirtaş Karaoba. Determinants of participation of children with diplegic cerebral palsy in educational, home, and social settings. Ann Clin Anal Med 2025;16(6):410-414
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The expression of miR-22, miR-140, and miR-328 in breast cancer tissues: Implications for PET/CT imaging biomarkers
Elif Özlem Gökçe 1, Meliha Merve Cicekliyurt 1, 2, Oruç Numan Gökçe 3, Kenan Çetin 3
1 Department of Medical System Biology, Graduate School of Sciences, 2 Department of Medical Biology, Faculty of Medicine, 3 Department of General Surgery, Faculty of Medicine, Canakkale Onsekiz Mart University, Çanakkale, Turkiye
DOI: 10.4328/ACAM.22454 Received: 2024-10-24 Accepted: 2024-11-25 Published Online: 2025-01-02 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):415-419
Corresponding Author: Meliha Merve Çiçekliyurt, Department of Medical System Biology, Graduate School of Sciences, Canakkale Onsekiz Mart University, Çanakkale, Turkiye. E-mail: mervemeliha@comu.edu.tr P: +90 532 722 09 03 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4303-9717
Other Authors ORCID ID: Elif Özlem Gökçe, https://orcid.org/0000-0002-4288-433X . Oruç Numan Gökçe, https://orcid.org/0000-0002-9678-7818 . Kenan Çetin, https://orcid.org/0000-0002-8616-9784
This study was approved by the Ethics Committee of Çanakkale Onsekiz Mart University Clinical Research (Date: 2021-10-20, No: 2021-07)
Aim: To evaluate the correlation between microRNA (miRNA) expression and 18F-fluorodeoxyglucose (18F-FDG) uptake in breast cancer patients, focusing on the tumor-suppressor miRNAs miR-22, miR-140, and miR-328, and their potential as diagnostic biomarkers.
Material and Methods: Biopsies from 14 female breast cancer patients were analyzed, including both tumor and adjacent healthy tissues. The expression levels of miR-22, miR-140, and miR-328 were quantified using real-time PCR. SUVmax values from PET/CT imaging were obtained to assess metabolic activity in tumor tissues. Statistical analyses were performed to explore correlations between miRNA expression and PET/CT results.
Results: Our patients’ ages ranged from 38 to 74 years, with a mean of 59.5 years. The levels of miR-22, miR-328, and miR-140 were significantly lower in breast cancer tissues compared to healthy tissues. However, no statistically significant correlations were found between miRNA values and 18-FDG PET/CT SUVmax values.
Discussion: While miR-22, miR-140, and miR-328 show promise as potential diagnostic biomarkers for breast cancer due to their significant downregulation in tumor tissues, their expression does not correlate with metabolic activity as measured by SUVmax in PET/CT imaging. Further research is needed to explore the clinical applications of miRNAs in breast cancer diagnosis and prognosis.
Keywords: Breast Cancer, Glut, Mir-22, Mir-328, Mir-140, PET/CT
Introduction
Breast cancer represents a significant public health issue, with a lifetime risk of one in eight women developing the disease. Its development and progression are influenced by various factors, including genetics and environmental influences [1]. Biomarkers play a crucial role in distinguishing cancerous cells from normal cells; however, existing tumor markers in serum have limitations in specificity and sensitivity [2].
Various biochemical markers, including enzyme and hormone levels, as well as mRNA and microRNA (miRNA) expression, are associated with different cancer types. miRNAs are short, non-coding RNA molecules crucial for post-transcriptional gene regulation in nearly all biological processes. Dysregulation of the miRNA pathway is closely linked to cancer development and progression [3, 5]. Specifically, the up- or down-regulation of miRNAs can influence the initiation and advancement of breast cancer and other malignancies. The deletion of tumor-suppressor miRNAs or the overexpression of oncogenic miRNAs can promote tumorigenesis and metastasis, thus positioning miRNAs as potential diagnostic, prognostic, and therapeutic targets [6].
Glucose metabolism and uptake are increased in breast cancer. Moreover, the expression of metabolic enzymes, such as glucose transporter (GLUT) and hexokinase, modulates miRNA involvement in cell metabolism. The expression of glucose transporter-1 (GLUT-1) is elevated in poorly differentiated breast cancer [7], and GLUT-1 expression is influenced by tumor suppressor microRNAs, specifically miR-22, miR-140, and miR-328, which are decreased in breast cancer [8, 10].
Combining the glucose equivalent 18F-fluorodeoxyglucose (18-FDG) with positron emission tomography (PET) is a valuable tool in the assessment and management of many malignancies [11]. 18-FDG-PET relies on FDG uptake into the tumor cell by metabolic enzymes, including GLUT-1. The XbaI G>T single-nucleotide polymorphism in the GLUT-1 gene leads to higher 18-FDG uptake, which is linked to the stage of breast cancer [12]. 18-FDG-PET/X-ray computed tomography (PET/CT) is well-studied in breast cancer [13]. The standardized uptake value (SUV) in PET/CT images represents the radioactivity accumulated by 18-FDG uptake in tissue.
Numerous studies have investigated the etiology and prognosis of microRNAs (miRNAs) in breast cancer alongside various imaging techniques aimed at enhancing the detection and monitoring of the disease. However, no research has yet examined the relationship between these imaging modalities and miRNA expression profiles, which are linked to the biological mechanisms underlying imaging. The identification of novel biomarkers related to imaging biology presents intriguing opportunities for breast cancer detection. Notably, the downregulation of tumor-suppressor miR-22, miR-140, and miR-328 has been observed in breast cancer, influencing GLUT-1 expression. Positron emission tomography/computed tomography (PET/CT) scans measure cellular metabolic activity by assessing the uptake of 18-FDG, a glucose analog, which increases with heightened metabolic activity in cancer cells. We hypothesize that alterations in miRNA levels in cancerous tissue may affect GLUT protein levels, thereby influencing 18-FDG uptake and the maximum standardized uptake value (SUVmax) in tumor tissue. This study aims to evaluate the correlation between 18F-FDG uptake and the effects of tumor-suppressor miRNAs on GLUT-1 expression in breast cancer.
Material and Methods
Design and Patients
This comparative study involved biopsies from 14 female breast cancer patients aged 18 years and older, all eligible for surgery and capable of providing written consent. Fresh tumors and adjacent normal tissues were collected during surgery, ensuring clear surgical margins [14]. RNA extraction and miRNA measurements were conducted on both tissue types, and SUVmax values of the cancerous tissues were obtained from the patients’ PET/CT reports.
Sample Preparation and RNA Extraction
Samples were homogenized with ceramic beads for 45 seconds, vortexed, and incubated on ice for 5 minutes, then at room temperature. To facilitate phase separation, 200 µL of chloroform was added after centrifuging at 12,000 rpm for 20 minutes at 4°C. The RNA-containing aqueous phase was transferred to a new tube, and 500 µL of isopropanol was added for precipitation and incubated for 10 minutes, followed by centrifuging at 12,000 rpm. The RNA pellet was washed with 75% ethanol and centrifuged at 7,500 × g for 5 minutes at 4°C. After removing the supernatant, the ethanol was evaporated at 60°C, and the pellet was resuspended in 50-100 µL of RNase-free water.RNA quality and quantity were assessed via gel electrophoresis and spectrophotometric analysis (Thermo Scientific, USA), with total RNA standardized to 2 ng for qPCR.
PET/CT.
Before surgery, all patients underwent standardized PET/CT imaging. To minimize external influences, patients were instructed to avoid physical activity and cold exposure for two days before imaging and to fast for at least six hours. After confirming appropriate blood glucose levels with a capillary test, 8-12 mCi of FDG was administered via an angiocath. Patients then rested for 45-60 minutes to optimize biodistribution and tumor uptake. Following this resting period, they were asked to empty their bladders and lie supine with their arms positioned overhead on the PET/CT scanner bed. Initial guide tomograms were obtained, followed by non-contrast computed tomography (CT) scans, and then PET images captured at 2 mm intervals. The entire imaging procedure took approximately 25 minutes.
Complementary DNA (cDNA) procedure
A commercial kit (abmPoly-A Polymerase) was utilized to add a poly(A) tail to the microRNAs. Selected miRNAs were then reverse transcribed to cDNA using the OneScript® Plus cDNA Synthesis Kit. RNA samples were mixed with the provided reagents on ice and incubated at 25 °C for 10 minutes, followed by 50 °C for 15 minutes, and 85 °C for 5 minutes to ensure proper primer denaturation. The synthesized cDNA was stored at -20 °C for further analysis.
Real-time quantitative PCR
Real-time PCR was performed to assess miR-22, miR-140, and miR-328 expression in 28 samples (14 healthy, 14 cancerous). RNU6 was used as a normalization control [15-16]. The qPCR assays were conducted using the SensiFast Probe No-Rox kit on the Thermo Scientific™ PikoReal™ Real-Time PCR System, with triplicate reactions. Amplification conditions included initial denaturation at 94°C for 15 minutes, followed by 45 cycles of 94°C for 30 seconds, 59°C for 15 seconds, and 72°C for 30 seconds. Melting curve analysis confirmed product specificity. Expression levels were calculated using the 2^-ΔΔCt method (Livak ve Schmittgen 2001), and diagnostic potential was assessed with ROC curves and cluster analysis.
Statistics
Data were presented as mean ± standard deviation. Statistical significance was determined using Student’s t-test or ANOVA, while the Mann-Whitney U test was applied to evaluate PET/CT values. Changes in miRNA expression between healthy and cancerous tissues were assessed using the t-test, followed by ROC analysis for diagnostic grouping. Cluster analysis further explored the diagnostic potential of miRNAs. Pearson correlation analysis was used to examine the relationship between miRNA expression and PET/CT results, with p-values <0.05 considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of Çanakkale Onsekiz Mart University Clinical Research Ethics Committee (Date: 2021-10-20, No: 2021-07). Informed consent was obtained from all participants.
Results
Baseline information on study subjects
This study comprised 14 patients with a median age of 59.5 years (range: 38–74 years). Tumor staging was conducted using the TNM classification based on postoperative pathological data. According to this system, four patients (28.57%) were classified as Stage IA, six patients (42.85%) as Stage IB, two patients (14.28%) as Stage IIA, and one patient each as Stage IIB and IIIB (7.14% each). The median tumor size was 29.42 mm, with a range of 11 to 130 mm. Of the patients, nine had right-sided tumors, and five had left-sided tumors. Axillary metastases were present in six patients (Table 1).
PET/CT
FDG/PET is a method that has proven its sensitivity in palpable breast masses undergoing PET/CT, with SUVmax values related not only to the malignancy of the tumor but also to the size of the lesion. The average SUVmax value of healthy breast tissue was 0.8, based on previous studies [17], and this was used as the reference value for our analysis. In this study, the highest tumor SUVmax value observed was 17.3 in a Stage IB breast cancer patient, while the lowest was 1.2 in a Stage IA patient. The median SUVmax value for the tumors was 5.58. Tumor tissue SUVmax values were compared with the reference value of 0.8 for normal breast tissue. Statistical analysis using the Mann-Whitney U test indicated a significant difference, with a z-score of -2.40067 and p = 0.0164 (p < 0.05). Patient demographics, tumor staging, and SUVmax values are summarized in Table 1.
Expression profiling of select miRNAs
The study examined the expression levels of miR-22, miR-140, and miR-328 in breast cancer tissues compared to healthy tissues, revealing significant downregulation of all three miRNAs in cancerous samples. The median log values for miR-22, miR-140, and miR-328 in healthy tissues were -0.125, 0.78, and 0.03, respectively, while tumor tissues exhibited lower medians of -4.86, -2.85, and -4.91 (Figure 1).
ROC analysis identified cut-off values of -1.975, -2.780, and -3.535 for miR-22, miR-140, and miR-328, respectively, highlighting their potential as diagnostic biomarkers (Figure 2).
Cluster analysis further validated the diagnostic relevance of miR-22 and miR-140, although miR-328 showed some variability in differentiating between healthy and cancerous tissues (Table 2).
All miRNAs showed significant downregulation in cancer tissues (P < 0.001). Correlations between miRNAs are provided, indicating moderate relationships between miR-22 and miR-140 (r = 0.429) and a weaker relationship between miR-22 and miR-328 (r = 0.012). Negative correlations are observed between miR-140 and PET/CT SUVmax (r = -0.175) as well as miR-328 and SUVmax (r = -0.219).
Discussion
Our study highlights the significant downregulation of miR-22, miR-140, and miR-328 in breast cancer tissues, supporting their potential role as diagnostic biomarkers. Consistent with previous studies, miR-22 was significantly reduced in cancer tissues compared to healthy tissues. This miRNA targets GLUT-1. A key regulator of glucose metabolism and its downregulation has been associated with inhibited cancer cell proliferation and invasion [4], as well as enhanced metastasis potential [18]. We identified a diagnostic cut-off value of -1.975 for miR-22, reinforcing its potential to distinguish between healthy and cancerous tissues.
Similarly, miR-140 showed substantial downregulation in tumor tissues, with a cut-off value of -2.780 established through ROC analysis. miR-140 is known to exert antiglycolytic and antiproliferative effects by targeting GLUT-1 [9], and its downregulation has been linked to poor prognosis in breast cancer [5]. Our cluster analysis supported miR-140’s diagnostic value, showing clear differentiation between healthy and cancerous tissues.
miR-328 also exhibited significant downregulation, though it demonstrated some variability in cluster analysis, with a subset of healthy tissues misclassified as cancerous. This miRNA also directly targets GLUT-1[19] and plays a critical role in breast cancer. ROC analysis for miR-328 revealed a cut-off value of -3.535, indicating its potential as a diagnostic marker, although its clustering performance was less precise than miR-22 and miR-140.
Both miR-22 and miR-140 showed strong concordance with pathology results, while miR-328 exhibited variability in differentiating between healthy and cancerous tissues, as revealed by cluster analysis (Figure 4, Table 2). The expression levels of miR-22, miR-140, and miR-328 were significantly reduced in tumor tissues compared to healthy tissues (Figure 2, Table 2). The bar plot illustrates the relative expression ratios of miR-22 to miR-140 and miR-22 to miR-328 in both healthy and tumor tissues. In tumor samples, these ratios significantly altered, with a notable decrease in the miR-22/miR-140 and miR-22/miR-328 ratios, indicating dysregulation of these miRNAs in cancer. ROC analysis for all three miRNAs demonstrated that a greater distance between the blue line (representing miRNA expression) and the red line (representing pathology results) indicates higher diagnostic capability. The ROC plots showed the blue line forming an outer frame, highlighting their potential as diagnostic markers. Additionally, the expression levels of miR-22, miR-140, and miR-328 were correlated with tumor tissue SUVmax values.
PET/CT and miRNA expression
Our study demonstrated a significant downregulation of miR-22, miR-140, and miR-328-3p in breast cancer tissues, consistent with findings in the literature. Despite this, we did not observe a significant correlation between the expression levels of these miRNAs and SUVmax values from PET/CT scans. While glucose metabolism and FDG uptake are closely related to GLUT-1 expression [20], prior studies have reported mixed results regarding the relationship between GLUT-1 and FDG retention, suggesting that other proteins may influence FDG uptake [20, 21].
In this study, we aimed to explore whether miRNA expression changes in healthy and cancerous tissues correlate with PET/CT findings. Although significant downregulation of miR-22, miR-140, and miR-328 was observed in tumor tissues compared to healthy controls (p<0.05) (Table 3), Pearson correlation analysis revealed no statistically significant association between miRNA expression levels and PET/CT results (p>0.05). This suggests that while these miRNAs are downregulated in tumor tissues, their expression does not directly correspond with PET/CT imaging data in this context.
Conclusion
Identifying a correlation between miRNA expression and PET/CT data could facilitate the development of novel tumor markers for cancer monitoring and diagnosis. Our study found decreased expression of miR-22, miR-328, and miR-140 in malignant tissues compared to healthy tissues; however, no correlation was established with PET/CT scan results. The majority of our patients had early-stage breast cancer, with only two patients at Stage IIB and IIIB. This may explain the lack of correlation, as more advanced stages typically show higher metabolic activity and SUVmax values. Additionally, SUVmax can be influenced by various factors, including patient body mass index, blood glucose levels, and differences in PET/CT protocols [22]. Furthermore, the complexity of metabolic processes in tumors may involve additional regulatory mechanisms beyond miRNA expression, which could account for the lack of correlation between miRNA levels and 18F-FDG uptake. Breast tissue density directly affects SUV values, with denser tissues resulting in higher SUV values [17].
In conclusion, our findings corroborate the significant downregulation of miR-22, miR-140, and miR-328 in tumor tissues. However, the absence of a correlation with PET/CT SUVmax values suggests a need for further research to understand the complex interactions between miRNA expression, glucose metabolism, and imaging biomarkers in breast cancer. MiRNAs may serve as valuable diagnostic and prognostic tools, warranting exploration of larger sample sizes with diverse tumor stages and consideration of additional oncogenic or tumor-suppressive miRNAs in future studies.
Study Limitations
This study is limited by a small and heterogeneous sample size, predominantly consisting of participants with early-stage breast cancer, which may restrict the generalizability of the findings. Specifically, only one patient was at Stage IIB and another at Stage IIIB, limiting the applicability of the results to advanced breast cancer, where miRNA expression and metabolic activity may vary. The cross-sectional design further restricts causal inferences between miRNA expression levels and PET/CT SUVmax values, underscoring the need for longitudinal studies to elucidate this relationship. Additionally, variations in PET/CT imaging protocols and patient preparation factors, such as fasting state and body mass index, could affect SUVmax measurements. Lastly, potential confounding variables, including hormonal status and treatment history, were not controlled for, which may influence both miRNA expression and PET/CT outcomes.
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: This work was supported by Çanakkale Onsekiz Mart University’s Scientific Research Coordination Unit, Project number: TYL-2022-3842.
Conflict of Interest
The authors declare that there is no conflict of interest.
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Elif Özlem Gökçe, Meliha Merve Cicekliyurt, Oruç Numan Gökçe, Kenan Çetin. The expression of miR-22, miR-140, and miR-328 in breast cancer tissues: Implications for PET/CT imaging biomarkers. Ann Clin Anal Med 2025;16(6):415-419
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Topotecan–loaded niosomes: Characterization and pulmonary drug deposition in treating lung cancer
Abdulfattah Y Alhazmi 1, Mohammed S Alshammari 2
1 Department of Pharmaceutical Practices, College of Pharmacy, Umm Al-Qura University, Makkah, 2 Department of Pharmacy Practice, College of Pharmacy, Hafar Albaten University, Hafr Albaten, Saudi Arabia
DOI: 10.4328/ACAM.22474 Received: 2024-11-03 Accepted: 2024-12-09 Published Online: 2025-01-04 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):420-424
Corresponding Author: Abdulfattah Y Alhazmi, Department of Pharmaceutical Practices, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. E-mail: ayhazmi@uqu.edu.sa P: +966 56 230 6932 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5433-6322
Other Authors ORCID ID: Mohammed S Alshammari, https://orcid.org/0000-0002-3423-6199
Aim: To examine the stability, physicochemical properties, and cytotoxic efficacy of TPT-loaded niosomes on non-small cell lung cancer (H460 and A549) and assess in vitro drug deposition.
Material and Methods: TPT-loaded niosomes were prepared using hot melt emulsification and homogenization. Cytotoxicity was evaluated using clonogenic cell survival assays on H460 and A549 cells. TPT-loaded niosomes and TPT solution were nebulized for 1.20 minutes using a mesh nebulizer (Aerogen), with drug deposition and aerosol particle size distribution assessed via a Next Generation Impactor.
Results: TPT-loaded niosomes achieved an entrapment efficiency >76%, with particle sizes of 1191–1264 nm and zeta potential from -51 to -46 mV. TPT-loaded niosomes showed greater cytotoxicity than TPT solution, inhibiting H460 cell survival by 51% versus 31% (p < 0.0001) and A549 by 49% versus 38% (p < 0.001). The niosomal formulation also demonstrated higher drug deposition (FPF% 49.34%; 87.07 µg) compared to the TPT solution (36.41%; 60.04 µg).
Discussion: Niosomes, as non-ionic surfactant vesicles, offer an effective delivery system for hydrophilic drugs like topotecan (TPT), encapsulating it within aqueous layers to enhance stability and therapeutic efficacy. This study demonstrates that TPT-loaded niosomes provide higher cytotoxicity against lung cancer cells and improved deposition of respirable particles compared to TPT solution, highlighting their potential as targeted pulmonary drug carriers for lung cancer treatment.
Keywords: Topotecan, Nanoparticles, Inhalation, Non-Ionic Surfactant Vesicles, Stability
Introduction
Non-targeted chemotherapy has limited safety and efficacy due to inadequate drug delivery to cancer tumors or severe toxic effects in healthy tissues [1]. These limitations can be avoided by encapsulating the chemotherapeutic drug inside nanocarriers for targeted therapy [2].
Topotecan (TPT) is a semisynthetic chemotherapeutic agent approved by the FDA for lung cancer, acting as a topoisomerase I inhibitor [3]. TPT’s lactone ring is crucial for its biological activity [4], and encapsulating TPT in lipid vesicles can stabilize this ring [5].
Niosomes are vesicles containing non-ionic surfactants (NIVs) used as delivery systems to improve drug accumulation in target tissues and minimize toxicity [6]. Niosomes have a similar structure to liposomes but are more cost-effective, stable, and bioavailable, offering better control of drug release and greater protection of the encapsulated drug [7].
Physicochemical characteristics like particle size, distribution, surface charge (zeta potential), and entrapment efficiency are crucial for evaluating the stability of colloidal formulations [8, 9]. The particle size influences the stability of NIVs, and a high charge helps resist particle aggregation [10, 11].
Pulmonary drug delivery is more effective than parenteral injection for targeting lung diseases [12]. However, it requires a safe, stable formulation that can avoid innate lung defense mechanisms like mucociliary clearance and macrophage uptake [13]. The upper airways have a smaller surface area and minimal blood flow, while the smaller airways and alveolar space—making up 95% of the lung’s surface—are better connected to systemic circulation and can resist mucociliary clearance [14, 15]. Previous research shows that particle size and solubility affect drug deposition in the lungs during nebulization [16].
This study investigates the physicochemical properties of empty niosomes, TPT-loaded niosomes, and free TPT solution, focusing on particle size, surface charge, and entrapment efficiency post-preparation.
Material and Methods
Materials
TPT and diacetyl phosphate (DCP) were purchased from Sigma-Aldrich Inc., Dorset, UK. Cholesterol was obtained from Croda Chemicals Ltd., East Yorkshire, UK. Tetra-ethylene glycol mono n-hexadecyl ether (surfactant VIII) was purchased from Santa Cruz Biotechnology, USA.
Methods
1. Chromatographic conditions of the HPLC method for TPT detection
Acetonitrile-water (50:50, 0.1% trifluoroacetic acid) was run on a Phenomenex Luna C-18 column (150 x 4.60 mm) in isocratic mode at a flow rate of 0.4 mL/min with the wavelength on the UV detector set at 227 nm.
2. Production of TPT-loaded in niosomes
Lipid constituents (cholesterol, surfactant VIII, and DCP) were weighed in a 3:3:1 molar ratio, respectively, and then melted at 130°C in an oil bath for 5 mins. The formulation was then hydrated with 1mg/ml of TPT prepared in 5% tartaric acid in 0.9% NaCl, and a Silverson L4R homogenizer (Chesham, Buckinghamshire, UK) was used to homogenize the formulation at 8000 rpm for 15 minutes.
3. Determination of drug particle size, polydispersity index (PDI), and zeta potential
Approximately 0.1 ml of each niosomal preparation was suspended in 2.5 ml of distilled water. The suspension was then sampled in triplicate and placed in a cuvette to measure the size and ZP using a Nano ZS® (Malvern, UK).
4. Determination of drug entrapment efficiency (EE) for TPT niosomal formulation
0.5 ml TPT-loaded in niosomes was suspended in 4.5 ml of 5% tartaric acid in 0.9% NaCl w/v, then ultracentrifuged using an XL-90 ultracentrifuge (Beckman Optima, U.S.A.) at 60000 rpm for an hour. HPLC samples were prepared and diluted to a suitable concentration within the calibration range to determine the entrapment efficiency (EE%) using Equation 1, where Cp is the TPT concentration in the nano-niosomes and CT is the initial drug concentration added to the formulation.
EE% = (Cp/CT) * 100 (Eq. 1)
5. In vitro cytotoxicity evaluation of TPT-loaded niosomes
Aliquots containing A549 or H460 cells (non-small cell lung cancer cells) were cultured and treated at each indicated concentration and incubated for 7-9 days. After incubation, the dishes were washed with a phosphate-buffered solution and fixed in 100% methanol for 10 minutes, then stained with 10% Giemsa’s stain solution so that visible colonies could be counted. The number of colonies was then counted by eye, and the fraction of cells surviving (SF) was calculated by dividing the number of colonies of the experimental treatment group by the number of colonies of the control plates multiplied by plating efficiency (PE).
6. Stability studies of TPT-loaded niosomes
Aggregation or precipitation of the formulation was determined by the changes in the vesicle diameter using the Dynamic Light Scattering (DLS) technique. The formulations were stored at four °C or 25°C for one month and assessed for changes in entrapment efficiency, size, and ZP at two different temperatures (4°C and 25°C) every week over one month.
7. In vitro pulmonary drug deposition determination of TPT niosomal formulation
The nebulization efficiency of TPT niosomal formulation and TPT solution were evaluated using an in vitro simulated lung model NGI to determine the aerodynamic particle size distribution (APSD). An aerosol formulation containing 200 µg of either TPT niosomal formulation or TPT solution was nebulized over 1.20 minutes using a mesh nebulizer (Aerogen).
8. Statistical Analysis
All experiments were conducted in triplicate (N=3), with results reported as the mean (±SD). T-test was used during niosomes characterization and stability studies to determine if the effects were statistically significantly different over time compared with day 0. Two-way ANOVA analysis was used during the cytotoxicity assay to compare TPT niosomal formulation with TPT solution. To determine if the drug deposition of TPT niosomal formulation was statistically significantly different, t-test analysis was used. All statistical tests were carried out using GraphPad Prism software, version 6.0, 2014 (CA).
Ethical Approval
This study used commercially available cell lines (H460 and A549) for in vitro testing, which does not involve human participants or animal models and, therefore, does not require ethical approval under Umm Al-Qura University’s Ethical Committee’s guidelines.
Results
1. Validation of analytical procedures
The HPLC method for quantification of topotecan was validated for linearity (r2 = 0.999; y = 2.82x – 0.42), accuracy (100.42–101.6%), the Low Limit of Detection (LLD) (0.072 μg/mL), and the Low Limit of Quantitation (LLQ) (0.41 μg/ml).
2. Characterization and encapsulation of TPT in niosomes
The main characterization properties of the resulting TPT NIVs and empty NIVs are presented in Table 1. The size and ZP of TPT NIVs demonstrated a stable formulation. This negative charge indicates a stable formulation that resists the aggregation within the colloidal system. However, there was a significant increase in the particle size of TPT-loaded in niosomes when compared with empty niosomes (P > 0.001). This significant increase in the particle size of niosomes after encapsulation with TPT suggests an interaction between NIVs and the chemical structure of TPT, leading to an increase in the particle size after the encapsulation. The PdI values indicate that both formulations have a heterogeneous size distribution.
The encapsulation efficiency of TPT-loaded in niosomes ranged from 76.22% (± 2.50) on day 0 to 67.54% (± 9.372) on day 7 and showed no significant change (P > 0.05). Overall, the percentage entrapment efficiency showed a promising result for the TPT-loaded in niosomes.
3. In vitro cytotoxicity evaluation of TPT-loaded niosomes
Following exposure of H460 and A549 lung cancer cells to empty-niosomes (Figure 1), there were no significant differences in the clonogenic survival fraction of empty-niosomes when compared to untreated control, indicating that the used empty niosomes had no toxic effect on both cells. In both cell lines, the TPT niosomal formulation was superior in achieving greater cytotoxicity than the TPT solution over a dose range of 30-90 nM. At 90 nm concentration, following TPT niosomal formulation, there was a statistically significant inhibition by 51% (p < 0.0001) of H460 cells clonogenic survival compared with 31% survival inhibition by the TPT solution treatment group. Similarly, A549 cells exhibited significant differences in favor of TPT niosomal formulation. At a dose of 90nM, following treatment with TPT niosomal formulation, the survival fraction was inhibited by 49% (p < 0.001) when compared to 38% inhibition with the TPT solution treatment group. It was observed that A549 cells are less sensitive to TPT treatment than H460 cells.
4. Stability studies of TPT loaded in nanoparticles post-preparation
The mean size, PDI, and ZP of TPT NIVs at two different temperatures (4°C and 25°C) over 28 days post-preparation are presented in Table 2.
A stable niosomal formulation must display a constant particle size and a constant amount of entrapped drug, with no signs of flocculation or precipitation of the membrane components [3]. The physical appearance of TPT NIVs was evaluated to demonstrate that formulations at four °C and 25°C do not have unacceptable changes in homogenization, appearance, clarity, or color of solution. Over the 28 days, TPT NIV formulations appeared to be homogenized and consistent in their color, appearance, and clarity. There were no signs of flocculation or sedimentation observed in any of the NIVs. The PdI values indicated that both TPT niosomal formulations had a heterogeneous size distribution ranging from 0.86 on day 0 to 0.64 at four °C and 0.61 at 25 °C on day 28. The percentage entrapment efficiency results showed great entrapment efficiency of TPT niosomal formulation. There was a statistically significant decrease on day 28, where the EE decreased from 76.22% (± 4.51) on day 0 to 56.32% (± 3.97) for four °C and 52.85% (±2.99) for 25°C. These results indicate that temperature does not influence formulation entrapment efficiency, particle size, or ZP over the time course.
5. In vitro pulmonary drug deposition determination of TPT niosomal formulation
Significant differences in the amount and size distribution of the aerosols between the two formulations across NGI sections were found. It was observed at the throat and stage 3 (particle size > 5 µm) that the percentage of TPT solution deposition was significantly higher than that of TPT niosomal formulation (P < 0.0001); TPT solution deposition was 21.31% (± 1.14, 35.14 µg) and that of TPT niosomal formulation was 17.36% (± 0.238, 30.63 µg). Interestingly, it was observed that TPT niosomal formulation deposition increased as the aerodynamic particle size decreased (≤ 5 µm). There were statistically significant differences in the drug deposition of TPT NIVs (16.30%, 28.76 µg) compared with TPT solution (13.71%, 22.60 µg) at stage 5 (3.30-2.08 µm) (P < 0.05). In addition, at stage 7 (1.36-0.98 µm), there was a significantly higher deposition of TPT niosomal formulation (4.50% ± 0.031, 7.94 µg) when compared with free TPT solution (0.74% ± 0.65, 1.22 µg) (P < 0.001).
The FPF% of TPT niosomal formulation was 49.34% (87.07 µg, ± 6.12) and 36.41% (60.04 µg, ± 9.23) for the TPT solution. 49.34% of the TPT niosomal formulation had a particle size of ≤ 5 μm, indicating successful delivery of respirable particles via lung airways. The MMAD values of the TPT niosomal formulation and TPT solution were 4.70 microns and 5.63 microns, respectively. This indicates polydisperse aerosols that have wider size distributions.
Discussion
Both empty NIV and TPT NIV formulations showed a high negative residual charge due to the lipid matrix and surfactants. TPT incorporation reduced zeta potential, likely due to TPT’s positive residual charge at the dispersion pH [4]. Particle sizes remained stable over seven days, though TPT-loaded niosomes were significantly larger than empty ones, consistent with studies linking size increases to drug encapsulation and hydration properties [17]. High encapsulation efficiency (>76%) confirms that the lipid and surfactant composition effectively entrap TPT, with lipid vesicles stabilizing the TPT lactone ring [5].
Our stability studies showed consistent particle size and zeta potential over time, with no significant temperature effects (P > 0.05). The high negative charges minimized signs of colloidal instability, such as sedimentation.
NIV systems enhanced in vitro cytotoxicity via improved drug delivery and increased EPR effect, in line with findings by Li et al. [18] showing TPT nanoencapsulation enhances cytotoxicity.
NGI results indicated higher deposition of free TPT at the throat and larger particles (>5 µm), while TPT NIVs were better deposited in respirable-size particles (<5 µm), improving lung penetration. DCP and surfactants in the NIV formulation likely enhanced nebulization efficiency by reducing inertial impaction, similar to findings by Chimote and Banerjee [19] and Pilcer et al. [20].
Limitation
Stability studies spanned one month at 4 °C and 25°C, potentially limiting long-term insights. The study focused solely on pulmonary delivery of TPT, without considering other routes or drugs. The in vitro deposition model may not fully replicate human lung dynamics, and clinical scalability was not explored. Nevertheless, findings highlight TPT-loaded niosomes’ potential for targeted lung cancer therapy.
Conclusion
TPT-loaded niosomes effectively encapsulated TPT with stable, uniform properties, enhanced EPR effect in cancer cells, and favorable lung deposition, supporting their use in targeted lung therapy.
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.
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Abdulfattah Y Alhazmi, Mohammed S Alshammari. Topotecan–loaded niosomes: Characterization and pulmonary drug deposition in treating lung cancer. Ann Clin Anal Med 2025;16(6):420-424
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Human brucellosis in northern borders, Saudi Arabia: Epidemiologic features and common presentation
Hanaa E. Bayomy 1, 2, Nouf Faris Alanazi 3, Dimah Alanazi 3, Hanan Madallah Almatrafi 3, Bishri Almesned 3, 4, Nawaf Farhan Alrawili 5, Reef Faris Alanazi 6, Asma Altag Alabed Bashir 7
1 Department of Family and Community Medicine, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia, 2 Department of Community,Faculty of Medicine, Benha University, Benha, Egypt, 3 Department of Medicine, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia, 4 Department of Neurology, King Fahad Medical City, Riyadh, Saudi Arabia, 5 Department of Internal Medicine, College of Medicine, Northern Border University, Arar, Saudi Arabia, 6 Department of Emergency, Prince Abdulaziz Bin Musaad Hospital (PAMH), Ministry of Health, Saudi Arabia, 7 Department of Internal Medicine, Prince Abdulaziz Bin Musaad Hospital (PAMH), Ministry of Health, Saudi Arabia
DOI: 10.4328/ACAM.22488 Received: 2024-11-16 Accepted: 2024-12-16 Published Online: 2025-01-05 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):425-429
Corresponding Author: Hanaa E. Bayomy, Department of Family and Community Medicine, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia, Turkiye. E-mail: Hanaa.Sayed@nbu.edu.sa Corresponding Author ORCID ID: https://orcid.org/0000-0001-7273-7931
Other Authors ORCID ID: Nouf Faris Alanazi, https://orcid.org/0009-0003-1551-5138 . Dimah Alanazi, https://orcid.org/0009-0009-7855-9246 . Hanan Madallah Almatrafi, https://orcid.org/0009-0007-6033-5186 . Bishri Almesned, https://orcid.org/0009-0008-3978-6617 . Nawaf Farhan Alrawili, https://orcid.org/0009-0004-0998-8040 . Reef Faris Alanazi, https://orcid.org/0009-0003-2015-2220 . Asma Altag Alabed Bashir, https://orcid.org/00009-0009-5909-0489
This study was approved by the Ethics Committee of the Northern Border University (Date: 2023-07-05, No: 50/44/H) and the Institutional Review Board of the Ministry of Health, Arar, Saudi Arabia (Date: 2023-11-29, No: N1C-IRB-023-10-044)
Aim: Brucellosis is one of the major bacterial zoonoses that threatens the public health system in many countries in North Africa and the Middle East, including Saudi Arabia. This study aimed to identify the pattern of Brucellosis infection from 2020 to 2023 and to determine the demographic structure and clinical features of Brucellosis infection in the Northern Border region of Saudi Arabia.
Material and Methods: A retrospective review of hospital records for Brucellosis from 2020 to 2023 was obtained from the North Medical Tower and the Prince Abdul-Aziz bin Musaed Hospital in the Northern Border Region, Saudi Arabia. Patients’ demographic characteristics, including age, gender, nationality, presentation symptoms, and results of the Slide Agglutination Test for Brucellosis were obtained.
Results: A total of 647 samples were examined between 2020 and 2023. The number of Brucellosis cases was 98, which progressively decreased from 51 cases in 2020 to only one case in 2023. Male patients predominated (82.65%) with high frequency in the age groups of 30 to 40 years (34.69%) and 20 to 30 years (28.57%). The most common symptoms observed in the current study were swinging fever (53.1%), back pain (37.7%), rigor (33.7%), and joint pain (19.4%), while 28.6% were asymptomatic cases.
Discussion: The incidence of Brucellosis infection was progressively decreased with a predominance of male patients aged 20 to 40 years. This confirms the national public health interventions and highlights the importance of awareness campaigns and surveillance systems among high-risk individuals and livestock to prevent transmission and facilitate case detection, particularly in asymptomatic patients.
Keywords: Brucellosis, Demographics, Clinical Presentations, Slide Agglutination Test (SAT), Northern Border Region
Introduction
Brucellosis is one of the major bacterial zoonoses, and in humans, it is also known as Undulant fever, Malta fever, or Mediterranean fever [1]. It is a significant threat to the public health system in many countries in North Africa and the Middle East, including Saudi Arabia [2]. Globally, the annual incidence of brucellosis has been estimated as 2.1 million, with higher levels in Africa and Asia [3]. Saudi Arabia had the highest occurrence of human brucellosis among Eastern countries [4]. Based on data from the Ministry of Health (MOH), the reported cases of brucellosis demonstrate a fluctuating pattern over the period from 2019 to 2022. The number of reported brucellosis cases in Saudi Arabia showed the following pattern: In 2019, there were 4,257 reported cases, which decreased to 2,372 cases by the end of 2020 [5]. But by the end of 2021, the number of cases elevated to 2,400 [6]. However, in 2022, there was a noticeable increase, with reported cases rising to 2,543 [7]. The distribution of the disease is over the country, and the most prevalent part is Al-Qassim and Aseer in the south, followed by Hail and the North of Saudi Arabia [8]. According to the statistics provided by the Saudi Ministry of Health, the number of reported cases in the Northern Borders region showed an increase from 33 cases in 2021 to 40 cases in 2022 [6, 7]. Males suffer more frequently than females because of greater occupational exposure. According to the Saudi Ministry of Health, in 2022, the number of affected Saudi males was 1,176, and non-Saudi males were 761. The biggest numbers of cases were reportedly found between age 15-45 (n = 1,451 cases), while 793 cases were ≥ 45 years old. [7] Particularly, there are special risks for Farmers, Shepherds, Butchers, Abattoir workers, Veterinarians, and Laboratory workers [1].
Brucellosis is caused by Brucella species. It is classified as a biological agent because of how contagious it is and how it affects human health. Brucellae are Gram-negative, non-spore-forming, non-motile coccobacilli and facultative intracellular parasites that cause a chronic disease that usually persists for life. Four common species can infect humans, including B. abortus, B. melitensis, B. canis, and B. suis, and less commonly, B. inopinata. B.melitensis is the most virulent and invasive species [1]. Human brucellosis is spread either by direct or indirect contact with diseased animals or by eating tainted food. Due to inadequate hygiene and unprotected animal interaction, it is seen as a serious issue in endemic nations [8]. Brucellosis is most prevalent under conditions of advanced domestication of animals in the absence of correspondingly advanced standards of hygiene, overcrowding of herds, high rainfall [1]. However, in Saudi Arabia, the highest number of cases were reported in August, with 311 cases, followed by June, with 309 cases [7].
The epidemiology of brucellosis in Saudi Arabia is difficult to manage, and it differs from the situation in other nations. Since there are numerous distinct characters and determining elements, Saudi Arabia greets millions of pilgrims who come for Umrah and Hajj, including the importation of a substantial number of sheep to meet the demands of the Hajj season is one of the key factors causing the disease’s spread in the Kingdom. Furthermore, Saudi Arabia has a long transitional history of housing camels that has resulted in direct contact with diseased animals and the consequence that they drink raw, unpasteurized camel milk and consume camel meat. Although the management is difficult currently, there is improvement in the domestic livestock protective precautions beginning with a mass vaccination program for animals and strict legislation, and for that, nowadays, there has been an obvious decline in the incidence and occurrence of brucellosis [4].
Brucellosis causes a variety of clinical symptoms that can last from a few days to several years [9]. Disease in humans ranges from asymptomatic to acute disease. Clinical features typically characterized by non-specific flu-like illness manifesting as swinging pyrexia, rigors and sweating, arthralgia/arthritis, and headache in addition to the subsequent complications, e.g., splenomegaly, hepatomegaly, leucopenia with relative lymphocytosis [1, 10].
Brucellosis is difficult to diagnose due to the lack of distinctive symptoms, weak diagnostic procedures, inadequate diagnostic methodologies, and a lack of suitable reagents for diagnosis [8]. Brucellosis is routinely diagnosed by serology, Slide Agglutination Test (SAT), which is considered the first line test, yet it may cross-react with IgM of different organisms such as Salmonella enterica serotype Urbana, Francisella tularensis, and other [11].
Brucellosis has been endemic in Saudi Arabia since the early 1980s. Its spread has been studied in different regions, where certain areas and the presence of animals (sheep) have been identified as risks for brucellosis. Our study is the first to highlight the Northern Border Region, epidemiologic features, and a wide range of clinical manifestations and laboratory findings among patients to define the pattern from 2020 to 2023.
Description of the study
The present study aimed to retrospectively identify the most common clinical presentations of human brucellosis in Northern Borders, Saudi Arabia, between 2020 and 2023.
Objectives
• To identify the pattern of Brucellosis infection in the Northern Border Region from 2020 to 2023.
• To describe the most common clinical presentations of Brucellosis in the Northern Borders.
• To identify the demographic structure of Brucellosis cases in the Northern Border Region, Saudi Arabia.
Material and Methods
Study design and settings
A retrospective review of all hospital records (2020-2023) for Brucellosis patients obtained from two public tertiary hospitals in Arar City, the capital of the Northern Borders Region, with a population of about 200,000 in 2022. These are the North Medical Tower and the Prince Abdul-Aziz bin Musaed Hospital. The two hospitals serve people in Arar and other cities in the Northern Borders, namely Rafha, Turayf, and Al Uwayqilah. Both hospitals have highly qualified medical staff, good equipment and facilities, provide outpatient, inpatient, and emergency services, and receive referrals from other hospitals and health centers in the Northern Border region.
Data collection procedure
Medical records of patients with Brucellosis were reviewed for patients’ demographic characteristics in terms of age, gender, nationality, and symptoms at presentation. Results of Slide Agglutination Tests (SAT) were obtained. In Saudi Arabia, a titer of ≥1:320 was considered positive for Brucellosis, and a titer of 1:160 was considered positive if associated with clinical evidence of Brucellosis.
Data management
The collected data will be entered, described, and presented using the computerized statistical package STATA/SE version 11.2 for Windows (STATA Corporation, College Station, Texas) and MS Excel.
Ethical approval
This study was approved by the Ethics Committee of the Northern Border University (Date: 2023-07-05, No: 50/44/H) and the Institutional Review Board of the Ministry of Health, Arar, Saudi Arabia (Date: 2023-11-29, No: N1C-IRB-023-10-044).
Results
Over the period between 2020 and 2023, 647 subjects had Slide Agglutination Test (SAT) for Brucellosis at the North Medical Tower and the Prince Abdul-Aziz bin Musaed Hospital in Arar. Table 1 shows the results of SAT for Brucella abortus and Brucella melitensis. Antibodies for Br. melitensis were detected in all subjects, while Br. abortus antibodies were undetectable for 167 (25.81%) subjects.
In Saudi Arabia, a titer of 1:320 or higher is considered positive. A titer of 1:160 is borderline and is considered positive if there is clinical evidence of brucellosis. Table 2 shows the incidence of Brucellosis between 2020 and 2023 in Arar. The number of cases progressively decreased from 51 cases in 2020 to only one case in 2023.
Table 3 shows the frequency distribution of incident Brucellosis cases by gender, age, and nationality. Males accounted for 82.65% of Brucellosis cases. The highest frequency was recorded in the age group 30-40 years (34.69%), followed by the age group 20-30 (28.57%). The frequency of cases was higher among Saudi people (47.06%) in 2020 compared to other nationalities. However, Sudanese had the higher frequency from 2021 to 2023.
Figure 1 shows that swinging fever was the most frequent symptom of Brucellosis (53.1%), followed by back pain (37.7%), rigor (33.7%), joint pain (19.4%), and headache (17.3%) while 28.6% were asymptomatic.
Discussion
Brucellosis remains the most spread zoonotic disease. However, WHO ranked it as the seventh most neglected disease in endemic areas [12, 13]. This research offers a clear insight into the epidemiological trends, clinical presentations, and complications of human brucellosis in the Northern Border region of Saudi Arabia.
Prevalence of detected cases
We observed a consistent downward trend in the detected cases throughout the study duration. This finding aligned with the global decline in cases. Notably, the reported cases in Spain declined from 514 cases in 2000 to 75 in 2015 [14]. Likewise, Al Shehhi et al. reported that the overall crude notification rate was 3.3 per 100,000 population in the United Arab Emirates, indicating a decrease in the incidence of cases from 135 to 75 per 100,000 population from 2012 to 2015 [15]. This decline could be attributed to the comprehensive efforts of the Saudi national interventions to eliminate brucellosis by raising the awareness of healthcare providers and the population regarding the disease, risk factors, and prevention policies like hand hygiene in addition to livestock vaccination campaigns as a control measure among animals to prevent transmission to humans [4]. The distribution of Brucella species observed during the study indicated a shift, with a higher prevalence of positive tests for Br. melitensis compared to Br. abortus. This finding aligns with the livestock demographics reported by the Saudi Ministry of Agriculture in 2020, which stated that sheep and goats—known reservoirs of Br. melitensis—constitute over 90% of the Kingdom’s livestock, while cattle, the primary reservoir for B. abortus, account for only 3% [16, 17].
Demographics of the patients
The predominance of male patients (82.65%) in this study is consistent with findings from another research conducted in Saudi Arabia. Alkahtani et al. similarly reported that males constituted most brucellosis cases in a study conducted in southern Saudi Arabia, largely due to their engagement in high-risk occupations such as farming and livestock handling [11]. Moreover, the limited educational opportunities for women in the agricultural sector may further explain this trend. Additionally, cultural norms in Saudi society, particularly in rural areas, restrict women’s participation in farming activities, thereby reducing their exposure to potential sources of infection. The age distribution in this study, with most cases occurring in the 30-40 years, agrees with the results of Alkahtani et al., who reported a similar age-related risk, as individuals in this age group are more likely to engage in outdoor work and have greater exposure to livestock [11].
Clinical manifestations of patients
The most common symptoms observed in the current study were swinging fever, back pain, rigor, and joint pain, which are consistent with findings from previous studies by Elmoselhy et al. on the Egyptian population [18], and Alsayed et al. conducted a study on brucellosis in Syria [19]. What is notable about this result is that almost one-third of the cases were asymptomatic carriers. This underscores the importance of implementing large-scale screening among high-risk individuals to prevent the spread of the disease.
Strengths and Weaknesses
Our study has several strengths and limitations. The first strength is that it covers a comprehensive time (2020-2023), providing a detailed overview of the epidemiological trends of brucellosis in the Northern Border region of Saudi Arabia. Secondly, we recruited a relatively large sample size (647 subjects), which supports the generalizability of the findings and allows for a more accurate representation of brucellosis in this region. Thirdly, the study focused on asymptomatic cases, which are often underreported but play a significant role in disease transmission. However, our limitation is that the reliance on the retrospective design made us limited to the data in records only and couldn’t recruit more data from the patients to avoid recall bias. Furthermore, SAT was used as a primary diagnostic tool, which may have lower sensitivity and specificity compared to molecular techniques such as Polymerase Chain Reaction (PCR) and the modern automated blood culture, potentially leading to underdiagnosis, especially in chronic or asymptomatic cases. However, SAT remains the main diagnostic tool in developing countries [20]. Finally, the study did not follow up on the patients for relapse rates and chronic complications. Further research should be conducted to assess long-term complications of patients to understand the disease progression. Despite limitations, this study offers additional insight into the brucellosis trend in KSA and the clinical manifestations of patients.
Conclusion
Overall, the trend was comparable to the global rates, with predominance for males aged 20-40 years, which confirms the success of the national public health interventions and highlights the importance of spreading awareness campaigns and conducting surveillance systems among high-risk individuals and livestock to prevent transmission and facilitate case detection, particularly in asymptomatic 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.
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Download attachments: 10.4328.ACAM.22488
Hanaa E. Bayomy. Nouf Faris Alanazi. Dimah Alanazi. Hanan Madallah Almatrafi. Bishri Almesned. Nawaf Farhan Alrawili. Reef Faris Alanazi. Asma Altag Alabed Bashir. Human brucellosis in northern borders, Saudi Arabia: Epidemiologic features and common presentation. Ann Clin Anal Med 2025;16(6):425-429
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Evaluation of triglyceride-glucose index with cardiovascular risk scoring in schizophrenia patients
Muhammed Fuad Uslu 1, Muhammed Fatih Tabara 2, Sevler Yıldız 3, Alaaddin Hekim 3
1 Department of Internal Medicine, Elazığ Fethi Sekin City Hospital, 2 Department of Psychiatry, Fırat University Hospital, 3 Department of Psychiatry, Elazığ Fethi Sekin City Hospital, Elazığ, Turkey
DOI: 10.4328/ACAM.22493 Received: 2024-11-19 Accepted: 2024-12-24 Published Online: 2025-01-06 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):430-434
Corresponding Author: Muhammed Fuad Uslu, Department of Internal Medicine, Elazığ Fethi Sekin City Hospital, Elazığ, Turkey. E-mail: dr.fuslu@gmail.com P: +90 539 925 51 56 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6300-5130
Other Authors ORCID ID: Muhammed Fatih Tabara, https://orcid.org/0000-0002-7479-5622 . Sevler Yıldız, https://orcid.org/0000-0002-9951-9093 . Alaaddin Hekim, https://orcid.org/0000-0002-1771-7820
This study was approved by the Ethics Committee of Fırat University (Date: 2024-03-05, No: 2024/04-14)
Aim: Schizophrenia patients who are at risk for cardiovascular diseases are often hospitalized in forensic psychiatry wards due to crimes they have committed. In this study, we evaluated schizophrenia patients in a forensic psychiatry service regarding cardiovascular risk scoring using the triglyceride-glucose index.
Material and Methods: The study included 51 healthy controls and 51 patients with schizophrenia receiving treatment in a forensic psychiatry service, resulting in 102 participants. The Triglyceride-Glucose Index [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL) / 2] and the Framingham Risk Score were calculated for all participants. The relationship between these values and clinical variables was then analyzed.
Results: BMI, platelet count, triglyceride, and total cholesterol values were significantly higher, while urea and creatinine values were significantly lower in the case group compared to the control group. The Framingham score and 10-year CVD risk score of the case group were significantly higher than the control group, while the groups were similar in terms of Triglyceride-Glucose index (p<0.001; p<0.001; p=0.066, respectively). The groups were similar according to the type of crime committed (p>0.05). There was a significant positive correlation between the duration of schizophrenia and Framingham score and 10-year CVD risk score (p<0.001; p<0.001, respectively).
Discussion: We propose that close monitoring of schizophrenia patients for cardiovascular diseases in forensic psychiatry wards, where long-term hospitalizations are common, may contribute to reducing mortality and morbidity.
Keywords: Schizophrenia, Triglyceride-Glucose Index, Cardiovascular Risk, Framingham Scoring
Introduction
Schizophrenia is a psychiatric condition that impacts roughly 1% of individuals worldwide of the population and is characterized by cognitive and motor symptoms. This encompasses positive symptoms like hallucinations and delusions, along with negative symptoms such as social withdrawal and apathy [1-2]. While schizophrenia is primarily managed with outpatient medication, inpatient treatment may be required during acute episodes [3]. In certain cases, patients who commit crimes during these episodes may undergo long-term inpatient treatment in forensic psychiatry services, as mandated by court decisions [4].
The risk of developing metabolic syndrome is significantly higher in patients with schizophrenia compared to the general population [5]. While the underlying causes of this increased risk are not fully understood, contributing factors include a sedentary lifestyle, the use of antipsychotic medications, and the neglect of physical health due to mental health challenges [6, 7]. Patients with schizophrenia have a reduced life expectancy, with an average loss of at least 13–15 years [8]. The primary contributor to this reduced life expectancy is cardiovascular disease, emphasizing the importance of early prevention to mitigate physical morbidity and mortality [9]. Research has demonstrated that schizophrenia patients face higher mortality rates from preventable cardiometabolic diseases compared to the general population [10]. Furthermore, Bergman et al. reported that individuals receiving forensic psychiatric care often exhibit poor physical health coupled with high levels of stress and aggression [11].
Over time, population-based models for assessing cardiovascular disease (CVD) risk have been developed to estimate an individual’s likelihood of developing cardiovascular disease over the next decade. Ten-year CVD risk is defined as the probability of the first occurrence of atherosclerotic CVD, stroke, or coronary heart disease in individuals without a prior history of atherosclerotic CVD [12].
The Framingham model, one of the oldest and most widely used tools, primarily predicts the risk of coronary heart disease. This assessment considers factors such as gender, age, total cholesterol, HDL cholesterol levels, blood pressure, smoking history, and the presence or absence of diabetes [13]. In addition to the Framingham risk score assessment, the Triglyceride-glucose index, which has recently been used in studies, has been defined as an independent risk factor for coronary artery disease. Triglyceride-glucose index (TyG index): [Fasting triglyceride (mg/dl) × fasting glucose (mg/dl)]/2 and is a composite indicator consisting of fasting triglyceride (TG) and fasting glucose (FG) levels [14].
Research indicates that individuals with psychotic disorders hospitalized in forensic psychiatry services exhibit a higher prevalence of cardiometabolic disease indicators in comparison to the general population but with a comparable or even lower prevalence than individuals with psychotic disorders in the broader community [15].
The elevated risk of cardiovascular diseases among patients in forensic psychiatry wards may be influenced by factors such as prolonged hospitalization, a predominantly sedentary lifestyle during their stay, and the substantial stress associated with forensic legal processes. To date, the number of studies available remains limited in evaluating the TyG index alongside the Framingham risk score, a tool for predicting coronary heart disease, about 10-year CVD risk in patients with schizophrenia. The purpose of this study is to examine the clinical utility of the TyG index and Framingham risk score as a novel, simple, and cost-effective method potentially suitable for routine assessment of long-term inpatients with schizophrenia who have committed criminal offenses.
Material and Methods
This research was carried out in compliance with the ethical standards outlined in the Declaration of Helsinki. All participants provided informed consent before being included in the study. The sample size was calculated using G*Power software version 3.1.9.2 (Universität Kiel, Germany). Using a statistical power of 95%, a significance level of 0.07, and an effect size of 0.5, the required sample size for each group was determined to be 45 participants. This prospective study included 51 schizophrenia patients hospitalized in the forensic psychiatry service at Elazığ Fethi Sekin City Hospital and 51 healthy volunteers who attended the internal medicine outpatient clinic for routine check-ups and had no chronic diseases. Inclusion criteria for the case group consisted of schizophrenia patients aged 18 to 65 years, diagnosed according to the DSM-5 criteria. Illiterate patients had mental retardation, alcohol or substance use disorders, or personality disorders were excluded from the study. Additionally, individuals with poor general health, chronic conditions requiring medical treatment, cardiovascular disease, metabolic syndrome, diabetes mellitus, renal or hepatic dysfunction, known malignancies, or local/systemic inflammatory diseases were not included. Verbal and written informed consent were obtained from all participants, as well as from their guardians, when necessary. Following consent, a psychiatrist conducted assessments, and a sociodemographic and clinical data form was administered to all participants. This form collected demographic information such as age, marital status, and education level. Routine blood test results, obtained after an average fasting period of 12 hours, were retrieved from the hospital’s registration system after the case group was admitted to the ward. Triglyceride levels were extracted from the lipid panel, and the Triglyceride-Glucose Index was calculated using the formula: Fasting triglyceride (mg/dL)×Fasting plasma glucose (mg/dL)/2. Additionally, Framingham Risk Score and 10-year CVD risk scores (13) were computed based on participants’ gender, age, total cholesterol and HDL cholesterol levels, blood pressure, smoking history, and the presence or absence of diabetes. These values were then analyzed about clinical variables to assess their associations.
Statistical Analysis
Statistical analysis was conducted using Statistical Package for Social Sciences (SPSS, version 22.0). The normality of the data was assessed using the Shapiro-Wilk test, kurtosis-skewness values, and histogram plots. Categorical data were analyzed using the Chi-square test. Numerical data following a normal distribution were compared using the Student’s t-test, while the Mann-Whitney U test was applied for pairwise comparisons of non-normally distributed data. The Kruskal-Wallis test was used for comparisons among multiple groups. The Spearman correlation test was employed to assess relationships between variables. Statistical significance was determined at p-values less than 0.05.
Ethical Approval
This study was approved by the Ethics Committee of Fırat University (Date: 2024-03-05, No: 2024/04-14).
Results
In this research, 51 patients with schizophrenia were compared to 51 sociodemographically matched healthy controls. In the case group, 92.2% (n=47) were male, compared to 90.2% (n=46) in the control group, with no statistically significant difference observed between the groups (p>0.05). The mean age of the case group was 38.29 ± 10.45 years, while the mean age of the control group was 34.18 ± 10.77 years, showing no significant difference (p>0.05). Further comparisons of the participants’ sociodemographic characteristics are provided in Table 1. The mean duration of illness in the case group was 10.86 ± 5.79 years. The most common type of offense committed by individuals in the case group was assault, representing 33.3% (n=17) of the cases. Other types of offenses committed by the case group are illustrated in Figure 1. Comparison of body mass index (BMI) between the case and control groups, blood pressure values, and blood parameters are presented in Table 2. The case group exhibited significantly higher BMI, platelet count, triglyceride, and total cholesterol levels compared to the control group. Conversely, the case group had significantly lower urea and creatinine levels than the control group. The TyG index, Framingham score, and 10-year cardiovascular disease risk scores were assessed using nonparametric tests due to the non-normal distribution of the data. Framingham score and 10-year cardiovascular disease risk were notably higher in the case group when compared to the control group. No notable difference in the TyG index was found between the case and control groups. Detailed statistical comparisons are shown in Table 3. The Kruskal-Wallis test was used to evaluate whether scores varied according to the type of crime committed. No substantial differences were identified between the groups based on crime type (p>0.05).
The relationship between disease duration and risk scores was assessed using Spearman’s correlation analysis. No significant correlation was found between the TyG index and disease duration. However, a significant positive correlation was observed between disease duration and both the Framingham score and 10-year CVD risk score (Spearman’s rho: 0.535, p<0.001; Spearman’s rho: 0.511, p<0.001, respectively).
Discussion
In our study, schizophrenia patients hospitalized in forensic psychiatry services exhibited significantly higher BMI, platelet count, triglyceride, and total cholesterol levels compared to the control group. These findings suggest that schizophrenia patients are at an elevated risk for cardiovascular disease, both currently and over the next 10 years.
Smoking, a modifiable risk factor for the development of cardiovascular pathology and major cardiac events, was found to be more prevalent in the schizophrenia group in our study. A study by Kelly DL et al. reported that smoking patients with schizophrenia had a 12-fold higher risk of cardiogenic death compared to non-smoking patients [16]. Similarly, a study by Mohammed F et al. found that substance use was more common among schizophrenia patients who were noncompliant with antipsychotic medications [17]. In our study, both smoking and alcohol use were found to be higher in the case group, regardless of treatment compliance, which aligns with the findings of these previous studies.
Several studies have linked lipid profile disorders and weight gain in patients with schizophrenia to the use of second-generation antipsychotics [18]. However, some authors suggest that hypertriglyceridemia, at least in part, may be intrinsically associated with the pathobiology of schizophrenia, independent of medication use [19]. Similarly, in our study, triglyceride and total cholesterol levels were found to be significantly higher in the schizophrenia group compared to the control group, regardless of medication use.
In our study, both the Framingham score and the associated 10-year risk of CVD were found to be elevated in patients with schizophrenia. However, this finding appears to contradict the study by Rebecca C. Rossom et al., which reported no significant difference in the overall 10-year cardiovascular risk between patients with serious mental illness (including bipolar disorder, schizophrenia, and schizoaffective disorder) and those without serious mental illness, our study compared the schizophrenia group with healthy controls. We believe that more comprehensive results may emerge from studies that include other patient groups with psychiatric disorders beyond schizophrenia. In the same study, a higher BMI was also observed [20], which aligns with our findings. This suggests that the sedentary lifestyle of schizophrenia patients, combined with a higher risk of developing obesity and metabolic syndrome compared to the general population, may help explain the elevated cardiovascular risk in this population.
In a study by Komuro J et al. [21], the prevalence of obesity, hypertension, diabetes, dyslipidemia, and physical inactivity was found to be more common in both men and women with schizophrenia. The same study also demonstrated that schizophrenia was associated with an increased risk of cardiovascular disease (CVD) in both men and women, not only in those under 50 years of age but also in those over 50. Similarly, a study conducted in China (with 83 schizophrenia patients and 243 controls) reported that patients had a higher mean 10-year CVD risk compared to controls [22]. In our study, BMI, triglyceride, and total cholesterol levels were significantly higher in the schizophrenia group compared to the control group, which is consistent with the findings of these studies. Likewise, the 10-year CVD risk in schizophrenia patients, assessed using the Framingham risk score, was comparable to the results found in the aforementioned studies.
In the study by Yating Yang et al., triglyceride and TyG index levels were found to be significantly higher than those in the general population. The TyG index, which has recently gained attention as an independent risk factor for coronary artery disease, was assessed alongside the Framingham risk score [23]. Similarly, the study by Hu C et al. demonstrated that a high TyG index was significantly associated with an increased risk of cardiovascular events, regardless of diabetes status [24]. In another study by Si Y et al., the TyG index was identified as an independent risk factor for coronary artery disease [25]. Despite these studies linking the TyG index to a higher risk of cardiovascular disease, the lack of a significant difference between the groups in our study may be attributed to the relatively small sample size.
Limitation
The main limitation of our study is that it is the only center in our region as a high-security forensic psychiatric hospital. In addition, the patient group we selected as the population in our study is predominantly male and low in number. These limitations of the current study will help future studies on similar topics.
Conclusion
In conclusion, patients with schizophrenia have an elevated 10-year risk of developing cardiovascular disease, as assessed by the Framingham risk score. Additionally, smoking and high BMI are more prevalent in this population. However, the recently introduced triglyceride-glucose (TyG) index did not show significant differences in schizophrenia patients in our study. We anticipate more robust and meaningful results in future multicenter studies with larger patient populations.
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.
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Muhammed Fuad Uslu, Muhammed Fatih Tabara, Sevler Yıldız, Alaaddin Hekim.Evaluation of triglyceride-glucose index with cardiovascular risk scoring in schizophrenia patients. Ann Clin Anal Med 2025;16(6):430-434
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The relationship between oral hygiene and upper extremity fractures in children
Muhammet Zeki Gültekin 1, Burak Kuscu 2, Fatih Doğar 1, 3, Ahmet Sinan Sarı 1, Ahmet Tuğrul Küpeli 4
1 Department of Orthopedics and Traumatology, Faculty of Health Sciences, Konya City Hospital , Konya, 2 Department of Orthopedics and Traumatology, Special Bandırma Royal Hospital, Balıkesir 3, Department of Orthopedics and Traumatology, Faculty of Medicine, Kahramanmaras Sütçü Imam Hospital, Kahramanmaraş, 4 Department of Dentist, Faculty of Health Sciences, Konya City Hospital, Konya, Turkiye
DOI: 10.4328/ACAM.22498 Received: 2024-11-21 Accepted: 2024-12-24 Published Online: 2025-01-03 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):435-439
Corresponding Author: Burak Kuscu, Department of Orthopedics and Traumatology, Special Bandırma Royal Hospital, Balıkesir, Turkiye. E-mail: dr.burakkuscu@hotmail.com P: +90 507 192 73 13 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1082-2206
Other Authors ORCID ID: Muhammet Zeki Gültekin, https://orcid.org/0000-0003-2160-8237 . Fatih Doğar, https://orcid.org/0000-0003-3848-1017 . Ahmet Sinan Sarı, https://orcid.org/0000-0002-5429-1929 . Ahmet Tuğrul Küpeli, https://orcid.org/0009-0007-4563-8699
This study was approved by the Ethics Committee of Necmettin Erbakan University Faculty of Medicine (Date: 2022-11-16, No: 2022/4074)
Aim: Bone fracture studies, which may be metabolically and socioculturally related to oral care in children, are essential in preventing fractures, emphasizing the importance of oral care and psychosocial awareness. In this study, we aimed to investigate the relationship between oral hygiene and the incidence of fractures in school-age children with upper extremity fractures and healthy school-age children.
Material and Methods: This study included 102 patients. There were 20 (55.6%) male patients in the control group (n = 36) and 50 (75.8%) male patients in the fracture group (n = 66). DMFT index was used for assessing oral hygiene.
Results: The mean years of maternal and paternal education were higher in the control group than in the fracture group. Both differences were statistically significant, i.e., p < 0.001 and p = 0.0038 for maternal and paternal education, respectively. The DMFT values for deciduous teeth were higher in the fracture group compared to the control group, and this difference between the groups was statistically significant (p = 0.02), while the DMFT values for permanent teeth were higher in the control group than in the fracture group.
Discussion: In our study, the relationship between education level, socioeconomic status, and fractures was significant. The DMFT values showed that the risk of fracture increased in children with poor oral hygiene. However, the evaluation of permanent teeth also revealed no difference.
Keywords: Pediatric, Upper Extremity, Fracture, Dmft Index, Oral Hygiene
Introduction
Fractures are a major public health concern common in the pediatric age group. In childhood, fractures are observed at a rate of 12–36.1/1000 per year [1]. In childhood, the risk of fracture is 42%–64% in boys and 27%–40% in girls [2]. Despite being healthy, most children with fractures suffer from genetic, metabolic, and systemic diseases that affect bone metabolism, causing fractures. Furthermore, low bone mass and mineral density, low calcium intake, a high body mass index, inactivity, carbonated drinks, and drug use have been associated with fractures in children [3].
For more than 70 years, the decayed, missing, and filled teeth (DMFT) index has been the most important index used to assess dental and oral hygiene and, more importantly, to assess public health in epidemiologic studies [4]. This index determines the low number of teeth, the number of treated teeth, and the number of teeth lost due to caries [5]. Periodontitis, also called gum disease, is caused by specific pathogenic bacterial flora in the subgingival space. Chronic inflammation leads to gradual alveolar bone resorption and gingival recession. The bone destruction mechanism in periodontitis may cause tooth loss in adults [6]. In adults, osteoporosis and poor bone quality increase the risk of fractures. However, no clear evidence exists for this in children [7]. Also, studies in the literature need to investigate the relationship between oral hygiene and pediatric bone fractures. Bone fracture studies, which may be metabolically and socioculturally related to oral care in children, are essential in preventing fractures, emphasizing the importance of oral care and psychosocial awareness. Our study’s objective was to examine the connection between dental health and fracture rates in school-age children who have upper extremity fractures and those who are healthy.
Material and Methods
In this study, the patient population included children who were admitted to the Orthopedics and Traumatology outpatient clinic of Konya City Hospital due to upper extremity fractures and patients who had not received any psychopharmacological treatment in the last 6 months and who were admitted to the orthopedic outpatient clinic for reasons such as counseling and growth pain. The study group included 6–16-year-old patients with only upper extremity fractures. Patients with high-energy fractures and known comorbidities were excluded from the study. The control group included patients aged 6–16 who were admitted to the outpatient clinic for counseling or growing pains without any disease.
The DMFT index was used by our hospital dentist for oral hygiene assessment. In this index, the number of patients with decay in deciduous and permanent teeth, loss in deciduous and permanent teeth, and fillings in deciduous and permanent teeth were determined in the intraoral examination of each patient included in the study. The “d” represented decay in a deciduous tooth, the “D” represented decay in a permanent tooth, the “m” represented a missing deciduous tooth, the “M” represented a missing permanent tooth, the “f” represented filling in a deciduous tooth, and the “F” represented filling in a permanent tooth. The DMFT index was grouped into five classes: as very low, between 0.0–1.1, 1.2–2.6 as low, 2.7–4.4 as moderate, 4.5–6.5 as high, and >6.6 as very high. The calculation of the DMFT index was performed with the formula D + M + F/T. Here, “T” represents the number of people examined. The analyses were performed using the R 4.2.1 program.
Mean and standard deviation were used as descriptive statistics for numerical variables, and frequency and percentage statistics were used for nominal variables. Chi-square and Fisher’s exact tests were used to analyze nominal variables. The T-test and Poisson regression methods were used to compare numerical variables. A p-value of <0.05 was considered significant.
Ethical Approval
This study was approved by the Necmettin Erbakan University Faculty of Medicine Local Ethics Committee (Date: 2022-11-16, No: 2022/4074).
Results
This study included 102 patients. There were 20 (55.6%) male patients in the control group (n = 36) and 50 (75.8%) male patients in the fracture group (n = 66) (Table 1). The mean age of the control group was 11.67 ± 3.02 years, and the mean age of the fracture group was 10.74 ± 3.09 years (p = 0.15). In the fracture group, eight (12%) patients had recurrent upper extremity fractures.
The mean years of maternal and paternal education were higher in the control group than in the fracture group. Both differences were statistically significant, i.e., p < 0.001 and p = 0.0038 for maternal and paternal education, respectively. The difference between the monthly income distribution of the patients in the control and fracture groups was not statistically significant (p = 0.4) (Table 2).
The DMFT values for deciduous teeth were higher in the fracture group compared to the control group, and this difference between the groups was statistically significant (p = 0.02) (Figure 1), while the DMFT values for permanent teeth were higher in the control group than in the fracture group (Figure 2). However, the DMFT total values were higher in the fracture group compared to the control group, and no statistically significant difference was found (p = 0.43) (Table 3).
Discussion
The occurrence of fractures in childhood is a common condition, with an incidence ranging between 1.2% and 5% with variations [8]. Compared to the anatomical region, upper extremity fractures constitute approximately two-thirds of all childhood fractures [9]. It has been shown that the risk of refracture increases in children who have experienced a fracture [10] and have a lower bone mineral density (BMD) [11]. In one study, inadequate calcium intake was determined in children with recurrent fractures, and it was shown that this decreased BMD and increased the risk of fracture [8]. In addition, the skeletal system and teeth are similar structures originating from similar origins [12]. Based on this information, people with poor oral hygiene also have poor bone quality, which may increase the risk of fracture.
These differences in the rates of childhood fractures are influenced by the child’s health status, age, and social and environmental factors. The information in the literature on the epidemiology of fractures in different childhood periods is quite limited. Physical, cognitive, and social developments differ in different age groups of children, which may explain the differences in the mechanism of fracture [9]. A previous study has shown that boys are more at risk of fracture than girls and that two-thirds of the injuries are caused by low-energy trauma and are frequently seen in the upper extremities. The same study showed that the male/female ratio increased with age (due to increased participation in sports) [13]. A case-control study by Ma and Jones [14] showed that participation in sports increased the risk of upper extremity fracture in boys and decreased the risk of fracture in girls. A study by Clark et al. showed that increased participation in sports increased the incidence of fractures independently of bone densitometry changes [15].
In another study, no relationship was found between family educational status and the frequency of fracture formation [13]. Therefore, the relationship between socioeconomic level and fracture formation was analyzed. In the preschool period, unintentional domestic injuries were associated with the education level of the caregiver [16], whereas no relationship was found between parental education level and fracture risk in childhood [3]. In our study, the level of maternal education in the control group was significantly higher than in the fracture group (p < 0.001). Similar to the literature, it was found that the higher the level of maternal education, the fewer fractures occurred in children. In addition, the level of the father’s education was significantly higher in the control group than in the fracture group (p = 0.0038). These statistically significant values indicate that an increase in parental education level will decrease the risk of fracture occurrence.
In a study conducted by Williams et al., it was shown that the economic level of the parents was associated with injury incidents occurring in the adolescent period and affected the type and extent of risky behaviors [17]. However, our study showed that there was no significant difference in the monthly income distribution of the parents of the patients in the control and fracture groups (p = 0.4).
Oral health reflects the cultural characteristics of individuals [18]. Many epidemiologic studies show that oral health is related to the social and economic environment. The relationship between low socioeconomic status and poor oral health in children has been demonstrated in the literature [19]. Sociodemographic characteristics directly affect the knowledge and level of oral care in a population. As a result, low parental education levels directly affect the oral health of children [20].
The DMFT index is a simple and useful value used worldwide that shows oral hygiene about patients’ level of education. For example, Mattila et al. showed that young maternal age, cohabitation of parents, rural residence, poor care conditions of parents, poor dental health and hygiene of the mother, the introduction of children to sugar before 18 months of age, and headaches in children at the age of 5 years were primarily associated with the DMFT index [21].
Previous studies have shown that periodontitis due to poor oral hygiene decreases bone mass [22]. In one study, an inverse relationship was observed between tooth loss in the mouth and BMD [23]. Another study conducted with Brazilian women revealed a relationship between poor oral hygiene and low bone density [24]. In our study, the DMFT index for deciduous teeth was significantly lower in the control group than in the fracture group (p = 0.02). This statistical analysis shows that children with poor oral hygiene have a higher risk of upper extremity fractures from simple trauma. In another study conducted between 14–18 years of age, it was found that there was no relationship between DMFT and BMD [25]. The permanent DMFT values were higher in the control group than in the fracture group, but the permanent DMFT values of the groups were not statistically different (p = 0.43). The equalization of the DMFT index value in permanent teeth can be explained by the fact that as children grow old, personal care becomes independent from the family, and they are influenced by a common environment with more relationships with their friends at school.
In light of all this literature, we can conclude that simple trauma and related fractures are less common in children of families with higher levels of education due to better oral care, adequate calcium intake, and living in a safer environment. It can also be interpreted that parents with higher levels of education in Turkey are more protective of their children, and children of rural families spend more time outside the home without supervision, which increases the risk of fracture.
Conclusion
This is the first study of its kind, as there have been none in the literature. In conclusion, in our study, the relationship between education level, socioeconomic status, and fractures was significant, in line with the literature. Although publications are showing the relationship between DMFT and BMD, there is no clear consensus. In our study, the DMFT values showed that the risk of fracture increased in children with poor oral hygiene. However, the evaluation of permanent teeth also revealed no difference. For this reason, we recommend that patients with pediatric simple fractures be reminded to undergo routine dental examinations for oral care. Therefore, it will be advantageous to maintain good oral hygiene and reduce the likelihood of developing osteoporosis at an advanced age due to chronic inflammation.
Limitation
As to the limitations of this study, more studies are needed to evaluate the relationship between the DMFT index and fractures. The population of our study is single-centered and limited in number, and a larger number of samples and a population from various regions would yield more meaningful results. In our study, we used the DMFT index for oral care, but other indices evaluate oral care. Therefore, we recommend the use of more evaluation parameters in future studies.
Acknowledgment
Thanks to ENAGO for translation and edditing the manuscript.
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
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2. Donaldson LJ, Reckless IP, Scholes S, Mindell JS, Shelton NJ. The epidemiology of fractures in England. J Epidemiol Community Health. 2008;62(2):174-80.
3. Hallal PC, Siqueira FV, Menezes AM, Araújo CL, Norris SA, Victora CG. The role of early life variables on the risk of fractures from birth to early adolescence: A prospective birth cohort study. Osteoporos Int. 2009;20(11):1873-9.
4. Broadbent JM, Thomson WM. For debate: Problems with the DMF index pertinent to dental caries data analysis. Community Dent Oral Epidemiol. 2005;33(6):400-9.
5. Görgün E, Çağlayan F. The Relationship Between Submandibular Gland Size and Oral Health Status, Gender, Age, Body Mass Index in a Healthy Population: A Cross-Sectional Study. Türkiye Klinikleri J of Dent Sci. 2023;29(1):45-51
6. Lai YL. Osteoporosis and periodontal disease. J Chin Med Assoc. 2004;67(8):387-8.
7. Shah MA, Faheem HI, Hamid A, Yousaf R, Haris M, Saleem U, et al. The entrancing role of dietary polyphenols against the most frequent aging-associated diseases. Medicinal Research Reviews. 2024;44(1):235-44.
8. Cooper C, Dennison EM, Leufkens HG, Bishop N, van Staa TP. Epidemiology of childhood fractures in Britain: A study using the general practice research database. J Bone Miner Res. 2004;19(12):1976-81.
9. Rennie L, Court-Brown CM, Mok JY, Beattie TF. The epidemiology of fractures in children. Injury. 2007;38(8):913-22.
10. Sillence DO A dyadic nosology for osteogenesis imperfecta and bone fragility syndromes 2024. Calcified Tissue International. 2024:1-18.
11. Manias K, McCabe D, Bishop N. Fractures and recurrent fractures in children; varying effects of environmental factors as well as bone size and mass. Bone. 2006;39(3):652-7.
12. Famili P, Cauley J, Suzuki JB, Weyant R. Longitudinal study of periodontal disease and edentulism with rates of bone loss in older women. J Periodontol. 2005;76(1):11-5.
13. Valerio G, Gallè F, Mancusi C, Di Onofrio V, Colapietro M, Guida P et al. Pattern of fractures across pediatric age groups: Analysis of individual and lifestyle factors. BMC Public Health. 2010;10(1):656.
14. Omondi MP Epidemiology of orthopedic injuries among inpatients admitted at a tertiary teaching and referral hospital in Kenya: a retrospective cross-sectional study. BMC Musculoskeletal Disorders. 2024:25(1): 670.
15. Clark EM, Ness AR, Tobias JH. Bone fragility contributes to the risk of fracture in children, even after moderate and severe trauma. J Bone Miner Res. 2008;23(2):173-9.
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17. Blaabæk EH, Andersen LH, Fallesen P. From unequal injuries to unequal learning? Socioeconomic gradients in childhood concussions and the impact on children’s academic performance. Soc Sci Med. 2024:341(12);116524.
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24. Henriques PS, Pinto Neto AM. Association between tooth loss and bone mineral density in Brazilian postmenopausal women. J Clin Med Res. 2011;3(3):118-23.
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Download attachments: 10.4328.ACAM.22498
Muhammet Zeki Gültekin, Burak Kuscu, Fatih Doğar, Ahmet Sinan Sarı, Ahmet Tuğrul Küpeli. The relationship between oral hygiene and upper extremity fractures in children. Ann Clin Anal Med 2025;16(6):435-439
Citations in Google Scholar: Google Scholar
TEP vs. TAPP for inguinal hernia repair: A comparative analysis of short-term quality of life in the turkish population
Mehmet Alperen Avcı, Can Akgün, Sevgi Bay
Department of General Surgery, Faculty of Medicine, Samsun University, Samsun, Turkiye
DOI: 10.4328/ACAM.22605 Received: 2025-02-15 Accepted: 2025-03-19 Published Online: 2025-04-30 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):440-444
Corresponding Author: Mehmet Alperen Avcı, Department of General Surgery, Faculty of Medicine, Samsun University, Samsun, Turkiye. E-mail: dr.maavci@gmail.com P: +90 553 215 86 98 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3911-2686
Other Authors ORCID ID: Can Akgün, https://orcid.org/0000-0002-8367-0768 . Sevgi Bay, https://orcid.org/0009-0008-3295-5510
This study was approved by the Ethics Committee of Samsun University (Date: 2024-10-23, No: GOKAEK 2024/19/9)
Aim: In laparoscopic inguinal hernia surgery, the most commonly used techniques are total extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) repair, yet there is still no consensus regarding their superiority over one another. This study aims to evaluate the impact of TEP and TAPP techniques on quality of life in a heterogeneous population and compare their superiority. Additionally, it seeks to compare these findings with normative data from the Turkish population.
Material and Methods: The TEP and TAPP techniques were compared based on postoperative data and SF-36 quality-of-life questionnaire results from 184 patients. Additionally, the SF-36 questionnaire data were compared with the normative values of the Turkish population.
Results: There was no statistically significant difference between the TEP and TAPP techniques in terms of complications and operative time. However, a significant association was found between an increase in chronic pain scores and the TAPP technique. In the quality of life analysis, the TEP technique demonstrated statistical superiority in emotional well-being, social functioning, and general health. When compared with Turkish normative values, both techniques yielded similar results in female patients, whereas the TEP technique achieved superior outcomes in male patients.
Discussion: In this study, the TEP technique was found to be superior in terms of quality of life and chronic pain. In the Turkish population, both techniques appeared to be suitable for female patients, whereas the TEP technique was shown to be more advantageous for male patients. Surgeons are advised to carefully evaluate the patient’s clinical condition and their own surgical experience when determining the most appropriate surgical technique.
Keywords: Total Extraperitoneal Procedure, Transabdominal Preperitoneal Procedure, Inguinal Hernia, Quality Of Life, Short Form-36
Introduction
Inguinal hernia repair remains one of the most commonly performed surgical procedures worldwide, with nearly 20 million patients undergoing surgery for inguinal hernia each year [1]. Despite extensive research, there is still no consensus on the optimal surgical approach for inguinal hernia repair. Laparoscopic surgery, developed as an alternative to open repair, has gained importance with advancements in technology, leading to the adoption of new surgical techniques [2]. The main advantages of laparoscopic techniques include shorter recovery time, lower recurrence rates, reduced incidence of chronic pain, and improved quality of life [3, 4]. Currently, the two most widely used laparoscopic techniques are total extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) repair [5].
Several studies have compared TEP and TAPP techniques in recent years, but the findings remain inconsistent. A randomized study found no significant differences between the two techniques in terms of complications and time to return to work [6]. However, another study reported that the TEP technique was associated with a shorter hospital stay and less postoperative pain, whereas the TAPP technique resulted in a shorter operative time [7].
The primary goal of inguinal hernia repair is to prevent complications such as obstruction and strangulation while reducing pain and improving patients’ quality of life. One of the most commonly used tools for assessing quality of life is the SF-36 questionnaire [8]. However, studies providing a detailed comparison of the impact of different surgical techniques on quality of life are limited. Furthermore, previous studies have been criticized for the heterogeneity of their patient populations and inadequate analysis of the SF-36 subscales.
This study aims to investigate the superiority of TEP and TAPP techniques by focusing on a heterogeneous patient population treated by experienced surgeons and to conduct a detailed comparison of their impact on patients’ quality of life using the SF-36 questionnaire. Additionally, the study seeks to compare the quality-of-life findings obtained with the normative data of the Turkish population.
Material and Methods
This retrospective study included patients diagnosed with primary unilateral and bilateral inguinal hernia who underwent TEP and TAPP inguinal hernia repair between January 2022 and January 2024 at the General Surgery Clinic of Samsun Training and Research Hospital. All patients who underwent elective inguinal hernia surgery were included, while patients with emergency, recurrent, conversion, or giant scrotal inguinal hernias, those with a history of major abdominal and pelvic surgery, high-risk patients (ASA III-IV), and those who could not be reached or did not wish to participate in the study were excluded. The patients were divided into two groups: TEP and TAPP. All patients received information about inguinal hernia repair, and informed consent was obtained. All surgical procedures were performed by two surgeons with over eight years of experience in both techniques. All procedures performed in studies involving human participants 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.
The TEP and TAPP hernia repair techniques were performed in a standardized manner under general anesthesia using a three-port technique by two surgeons. In the TEP technique, direct access to the preperitoneal space was achieved, while in the TAPP technique, an intraperitoneal approach was used, incising the peritoneum covering the hernia sac to visualize the defect and mobilize the peritoneum. A 10 × 15 cm polypropylene mesh (Marlex) was appropriately shaped and placed in the preperitoneal space. One edge of the mesh was fixed to the Cooper’s ligament, and it was secured at three to four additional points using tacker (Auto Suture Protack).
Data on patient gender, age, inguinal hernia laterality, ASA score, type of operation performed, type of anesthesia administered, operative time, postoperative complications, and readmission rates were collected from hospital records. Patients who had undergone surgery more than 12 months prior were contacted via the hospital’s communication line by a blinded investigator for a questionnaire assessing chronic pain and quality of life. Participants were informed about the study, and informed consent was obtained. Chronic pain was defined as pain persisting for three months or longer after surgery, and patients were asked to score their pain from 0 to 9. Quality of life was assessed using the SF-36 (Turkish Version) questionnaire. The SF-36 scale consists of two main components evaluating physical and mental functions and includes parameters such as physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/vitality, mental health, social functioning, pain, and general health.
Descriptive statistics were used to analyze the general characteristics of the study groups. Quantitative data were presented as mean and standard deviation (⁻X ± SD), while categorical data were expressed as frequency (n) and percentage (%). Relationships between categorical variables were analyzed using the Chi-Square test. Differences between SF-36 mean scores and normative values were assessed using the One-Sample t-test, while intergroup differences in independent samples were evaluated using the Independent Samples t-test. Logistic Regression Analysis was conducted to examine the relationships between variables. A p-value of <0.05 was considered statistically significant. Statistical analyses were performed using IBM SPSS Statistics version 22 (SPSS Inc., an IBM Company, Somers, NY).
Ethical Approval
This study was approved by the Ethics Committee of Samsun University (Date: 2024-10-23, No: GOKAEK 2024/19/9).
Results
Between January 2022 and January 2024, a total of 271 patients aged 18–90 years underwent elective TEP and TAPP procedures for a preliminary diagnosis of inguinal hernia. A total of 38 patients were excluded from the study due to recurrent hernia, open conversion, giant hernia, high-risk status (ASA 3–4), or a history of major abdominal and pelvic surgery. Additionally, 49 patients who could not be reached for the questionnaire or who declined to participate were excluded. Consequently, the study included 184 patients (Figure I).
Among the 184 patients, 12 were female and 172 were male. The median age of the patients was 53.32 ± 14.60 years (range: 17–85). Of these, 113 patients underwent surgery for unilateral inguinal hernia, while 71 patients were operated on for bilateral inguinal hernia. The TEP procedure was performed in 133 patients, whereas 51 patients underwent the TAPP procedure.
Postoperatively, seroma was observed in 3 patients, scrotal edema in 2 patients, and recurrence in 4 patients. In the chronic pain assessment, using a scoring scale of 0–9, the most frequently reported scores were 3 points in 15 patients, 2 points in 14 patients, and 6 points in 7 patients.
When the SF-36 subcategory scores were compared between the two surgical techniques, mental health, social functioning and general health scores were found to be significantly higher in the TEP procedure compared to the TAPP procedure. No statistically significant difference was observed between the two groups in terms of complications (p = 0.898) and chronic pain (p = 0.165) (Table I).
When logistic regression analysis was performed between the two groups, a one-unit increase in chronic pain was found to increase the likelihood of the surgical procedure being the TAPP technique by 28.3% (p = 0.007) (OR > 1) (Table II).
When comparing the operative durations of surgical techniques based on the side of inguinal hernia, no statistically significant difference was observed. The operative times for unilateral TEP/TAPP techniques were 72.23 ± 21.32 / 78.92 ± 33.77 minutes (p = 0.269), while those for bilateral TEP/TAPP techniques were 92.08 ± 32.95 / 111.13 ± 49.77 minutes (p = 0.103).
When the SF-36 scores of patients in the TEP and TAPP groups were compared with the normative values of the Turkish population, the physical functioning score, energy/vitality score, and pain score were found to be significantly higher in females in both groups, while no significant differences were observed in the other SF-36 subcategories. In males, all SF-36 scores except for role limitations due to physical health were significantly higher in the TEP group. In the TAPP group, only the physical functioning score, energy/vitality score, and pain score were significantly higher, while the other values showed no significant differences (Table III).
Discussion
In our study, no statistically significant difference was found between the TEP and TAPP techniques in terms of complications and operative time. However, regarding chronic pain, patients who underwent the TAPP procedure had significantly higher chronic pain scores. In the quality-of-life analysis, the TEP technique was found to be statistically superior to the TAPP technique in terms of mental health, social functioning and general health. When the SF-36 scores were compared with Turkish normative values, similar results were observed in females for both groups, while in males, the TEP procedure was found to be statistically superior to the TAPP procedure.
With advancements in the last quarter-century, various laparoscopic techniques have been introduced for inguinal hernia repair. The superiority of TEP and TAPP techniques in terms of postoperative outcomes and quality of life remains controversial. Scrotal edema and hematoma are the most common complications following laparoscopic inguinal hernia repair [10]. One study reported similar complication rates between the TEP and TAPP techniques [11], another study indicated a higher complication rate in the TAPP technique [5], while another study found the TEP technique to be associated with significantly more complications [12]. In our study, no statistically significant difference was observed between the two techniques in terms of complications.
The incidence of chronic pain following minimally invasive inguinal hernia repair has been reported to be around 3% in the literature [13]. Additionally, multiple studies with follow-up periods exceeding 12 months have found no significant difference between TEP and TAPP techniques regarding chronic pain [13-14]. In our study, chronic pain scores did not show a statistically significant difference between the two groups. However, logistic regression analysis revealed that a one-unit increase in chronic pain score increased the likelihood of undergoing the TAPP procedure by 28.3% (p = 0.007).
A review of the literature shows that operative times for laparoscopic inguinal hernia repair vary due to the learning curve requirement. One study reported a longer operative time for the TEP technique [5], while another found the TAPP technique to be more time-consuming [1]. These differences may be attributed to variations in unilateral or bilateral inguinal hernias and studies including surgeons who had not yet completed their learning curve. In our study, no statistically significant difference was observed between the two groups in terms of operative time for unilateral and bilateral inguinal hernia repairs performed by experienced surgeons.
The impact of laparoscopic inguinal hernia repair techniques on quality of life and their relative superiority remain uncertain. One study reported no significant differences in quality of life outcomes between the two techniques [15]. Myers et al. [16] demonstrated significant improvements in all quality-of-life measures except for social functioning and mental health following TEP repair, concluding that the TEP technique was superior to the TAPP technique in terms of physical and mental quality-of-life assessments. Castro et al. [17] found similar late postoperative quality-of-life outcomes between TEP and TAPP techniques, reporting lower scores in energy/vitality, mental health, and general health subdomains. In our study, when SF-36 subscale analyses were compared between TEP and TAPP hernia repair patients, mental health, social functioning, and general health were significantly higher in the TEP technique, while other subdomains were similar. When SF-36 scores were compared with Turkish normative values, similar results were found in females for both groups. However, in males, the TEP technique demonstrated superiority over the TAPP technique in most subparameters.
Limitation
This study has several limitations. Its single-center, retrospective design, relatively small patient population, and short follow-up period are the primary constraints. Therefore, prospective, multicenter studies with larger patient cohorts are needed to validate the current findings.
Conclusion
In this study, the TEP technique was found to be superior to the TAPP technique in terms of quality of life and chronic pain. When compared with Turkish normative values, both techniques appeared to be suitable for female patients, while the TEP technique was found to be more advantageous for male patients. It is recommended that surgeons carefully evaluate the patient’s clinical condition and their own surgical experience when determining the most appropriate surgical technique.
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. International guidelines for groin hernia management. Hernia. 2018;22(1):1-165.
2. Sun L, Shen YM, Chen J. Laparoscopic versus Lichtenstein hernioplasty for inguinal hernias: A systematic review and meta-analysis of randomized controlled trials. Minim Invasive Ther Allied Technol. 2020;29(1):20-7.
3. Perez AJ, Al-Refaie WB, Temple LK, Misih SRA, Maithel SK, Cloyd JM. Nationwide analysis of inpatient laparoscopic versus open inguinal hernia repair. J Laparoendosc Adv Surg Tech A. 2020;30(3):292-8.
4. Aghayeva A, Benlice C, Bilgin IA, Bengur FB, Bas M, Kirbiyik E, et al. Laparoscopic totally extraperitoneal vs robotic transabdominal preperitoneal inguinal hernia repair: assessment of short- and long-term outcomes. Int J Med Robot. 2020;16(4):e21111.
5. Hidalgo NJ, Guillaumes S, Bachero I, Butori E, Espert J.J, Ginesta C, et al. Bilateral inguinal hernia repair by laparoscopic totally extraperitoneal (TEP) vs laparoscopic transabdominal preperitoneal (TAPP). BMC Surg. 2023;23(1):270.
6. Köckerling F, Bittner R, Jacob DA, Seidelmann L, Keller T, Adolf D, et al. TEP versus TAPP: Comparison of the perioperative outcome in 17,587 patients with a primary unilateral inguinal hernia. Surg Endosc. 2015;29:3750-60.
7. Vãrcuæ F, Duţă C, Dobrescu A, Lazãr F, Papurica M, Cristi T. Laparoscopic repair of inguinal hernia: TEP versus TAPP. Chirurgia (Bucur). 2016;111:308-12.
8. Ware JE Jr. SF-36 Health survey update. Spine (Phila Pa 1976). 2000;25(24):3130-9.
9. Demiral Y, Ergor G, Unal B, Semin S, Akvardar Y, Kivircik B, et al. Normative data and discriminative properties of short form 36 (SF-36) in Turkish urban population. BMC Public Health. 2006;6:1-8.
10. Chao TC, Tung HY, Tsai CH, Pen CM, Wu CC, Liao CH, et al. Laparoscopic versus robotic TAPP/TEP inguinal hernia repair: A multicenter, propensity score weighted study. Hernia. 2024;28(1):199-209
11. Jaiswal RK, Pandey NK, Tolat A, Kalwaniya SD, Gupta AK, Rohith VN, et al. A prospective comparative study of laparoscopic totally extraperitoneal (TEP) and laparoscopic transabdominal preperitoneal (TAPP) inguinal hernial repair. Cureus. 2023;15(7):e42209.
12. Hung TY, Wu CC, Chen LS, Kang YN. Safety of two common laparoscopic inguinal herniorrhaphy approaches: An updated systematic review with meta-analysis of randomized clinical trials. Transl Androl Urol. 2020;9:2007-21.
13. Aiolfi A, Cavalli M, Del Ferraro S, Simona D, Manfredini L, Bonitta G, et al. Treatment of inguinal hernia: Systematic review and updated network meta-analysis of randomized controlled trials. Ann Surg. 2021;274(6):954-61.
14. Chen LS, Chen WC, Kang YN, Wu CC, Tsai LW, Liu MZ. Effects of transabdominal preperitoneal and totally extraperitoneal inguinal hernia repair: An updated systematic review and meta-analysis of randomized controlled trials. Surg Endosc. 2019;33:418-28.
15. Andresen K, Rosenberg J. Transabdominal preperitoneal (TAPP) versus totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair. Cochrane Database Syst Rev. 2024;7.
16. Myers E, Katherine M, Kavanagh D, Hurley M. Laparoscopic (TEP) versus Lichtenstein inguinal hernia repair: A comparison of quality-of-life outcomes. World J Surg. 2010;34:3059-64.
17. Castro GRA, Zilles A, Gazzola LD, Barros RB, Sadowski JA, Guetter CR. Laparoscopic inguinal hernia repair: The long-term assessment of chronic pain and quality of life. ABCD Arq Bras Cir Dig. 2022;35:e1695.
Download attachments: 10.4328.ACAM.22605
Mehmet Alperen Avcı, Can Akgün, Sevgi Bay. TEP vs. TAPP for inguinal hernia repair: A comparative analysis of short-term quality of life in the turkish population. Ann Clin Anal Med 2025;16(6):440-444
Citations in Google Scholar: Google Scholar
Evaluation of the appropriateness and readability of chatgpt-4, claude, copilot and gemini responses to patient queries on eye health
Meltem Toklu 1, Gizem Yel 2
1 Department of Ophthalmology, Ezine State Hospital, Çanakkale, 2 Department of Ophthalmology, Gazipasa State Hospital, Antalya, Türkiye
DOI: 10.4328/ACAM.22622 Received: 2025-03-03 Accepted: 2025-04-07 Published Online: 06-05-2025 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):445-449
Corresponding Author: Meltem Toklu, Department of Ophthalmology, Ezine State Hospital, Çanakkale, Turkiye. E-mail: drmtunca@gmail.com P: +90 507 756 22 95 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0890-324X
Other Authors ORCID ID: Gizem Yel, https://orcid.org/0000-0003-0071-9296
Aim: This study aims to assess the appropriateness and readability of ChatGPT-4, Claude, Copilot, and Gemini’s responses to frequently asked questions about eye health.
Material and Methods: Four commonly used Large Language Model (LLM) chatbots were asked 30 questions frequently asked by patients in an ophthalmology clinic. The appropriateness of the answers was evaluated by 2 experienced ophthalmologists. Readability was evaluated with 6 different indexes.
Results: The Likert scale (5-1) was utilized to determine adequacy. The responses generated by ChatGPT-4 had the highest average score of 4,90, followed by Anthropic Claude with 4,23, Google Gemini with 3,87, and last was Microsoft Copilot with a score of 3,50. None of the chatbot responses were rated as “very poor” or classified as incorrect. With an average Flesch-Kincaid Grade Level readability score of 7.60, only Anthropic Claude met the level of readability that The American Medical Association recommends. An assessment of the remaining five parameters revealed that the responses generated by all four chatbots exhibited readability levels exceeding that of a sixth-grade.
Discussion: In this study, ChatGPT-4 was more precise in responses, while Anthropic Claude scored better in terms of readability. These findings suggest that while LLMs may offer more comprehensive information, their complexity can hinder the average patient’s comprehension.
Keywords: Ophthalmology, ChatGPT-4, Gemini, Copilot, Claude
Introduction
The internet is an essential repository of health-related information for individuals pursuing knowledge about their medical conditions. Recent estimates suggest that approximately 80% of Americans utilize the Internet for health searches [1]. Searching for health information online is believed to positively impact health information consumers, as they are more likely to adhere to treatment after acquiring sufficient knowledge about their health conditions [2].
Over the last few years with the growing utilization of artificial intelligence (AI) natural language processing models have quickly gained popularity. Large language models (LLM) are AI systems capable of understanding and generating human language by processing vast amounts of text data. These systems can engage in dialogue-like interactions and operate in a manner akin to conventional existing search engines. Among various models, ChatGPT, or Chat Generative Pre-Trained Transformer, stands out as the most well-known. A variety of applications that have recently adopted LLMs include Google’s Gemini, Microsoft’s Copilot, and Anthropic’s Claude. The training of these datasets utilizes a vast compilation of textual material, encompassing more than 400 billion words sourced from various online platforms, such as articles, books, and websites. The contribution of these LLMs has been remarkable for everyday users and the scientific research community. Numerous studies evaluated the effectiveness of chatbots in conducting medical assessments. For a significant number of individuals and their caregivers, these artificial intelligence tools function as a “remote health advisor.” Advancements in AI chatbot technology, notably in LLMs, create promising avenues for improving patient education through online platforms. Therefore, these LLM chatbots are required to present reliable, understandable, and extensive replies. The variation among Google search outcomes, AI-driven chatbots, and the knowledge of medical professionals prompts a fresh dialogue regarding the caliber of information that patients might find on the internet.
Previous research indicates that ChatGPT’s effectiveness in addressing patient inquiries varies within ophthalmology and medicine. Certain studies have revealed that ChatGPT’s responses contained accurate information, whereas other research pointed out the existence of misleading and possibly harmful content in its replies [3-6]. Studies evaluating LLMs in different clinical conditions revealed that the readability of LLMs surpasses recommendations, requiring a higher level of patient understanding [7, 8].
While considerable proof emphasizes the effectiveness and possible implementations of ChatGPT in the medical domain, there is a significant gap in research focused on evaluating its competitors. Current research assessing the capabilities of large language models (LLMs) in the field of ophthalmology lacks studies that compare the quality of responses generated by ChatGPT with those from Claude, Gemini, and Copilot regarding general eye health. The objective of the present research is to evaluate the relevance and comprehensibility of the outputs produced by ChatGPT-4, Microsoft Copilot, Anthropic’s Claude, and Google Gemini in response to comprehensive queries about eye health.
Material and Methods
This study focused on examining the relevance and readability of the content generated by LLM chatbots. A total of 30 questions emerged from discussions with clinicians, aimed at addressing the most prevalent concerns raised by patients in an ophthalmology setting. The phrasing of the questions employed terminology and language that a non-expert would understand, simulating the experience of patients interacting directly with the chatbots. Individual questions were directed at four frequently used AI chatbots: ChatGPT-4, Google Gemini, Microsoft Copilot, and Anthropic Claude. Researchers used each platform to start separate chat discussions to pose questions. Chatbot responses were recorded and extracted from their respective platforms and compiled into a list. These question-and-answer lists were then blinded and presented to the evaluators. The evaluators (MT, GY) graded the adequacy of AI-generated responses using a Likert scale (5-1): 5- excellent, 4-above average, 3-average, 2-below average, 1-very poor. Each grader had experience in clinical ophthalmology for ten years.
Readability was assessed using an online readability calculator with six different indices: Gunning Fog Index, Coleman- Liau Index, Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG) Index and Automated Readability Index. Every AI-generated response was evaluated and the means for each AI chatbot was calculated. The Gunning Fog Index assesses the occurrence of multi-syllable words in conjunction with the mean length of sentences. The simplicity and clarity of a given text are evaluated using this index score, which spans from 0 to 20. The Coleman Liau index uses sentences and letters as variables to evaluate the reading level of a text. It is used in addition to the other scores to assess particularly medical and law documents. FRES assigns a quantitative score ranging from 1 to 100, with a range of 60 to 70 generally regarded as satisfactory. For FRES a higher value corresponds with more readable text. The FKGL assigns a specific numerical score that reflects the corresponding educational grade level; for instance, a score of 8.2 suggests that a student reading at an 8th-grade level would be capable of comprehending the material. The SMOG score uses the frequency of polysyllabic words as a tool to assess the readability of text. It has been shown very useful in the healthcare sector, to evaluate patient comprehension of healthcare-related terms. Automated Readability Index relies on a factor of characters per word and produces an approximate representation of the US grade level needed to comprehend the text. The Coleman Liau Index, Automated Readability Index, and SMOG yield a score between 1 and 20 that is inversely proportional to the ease of readability of the text. The lower the score, the easier it is to read and comprehend the body of text [9]. Likewise, The Gunning Fog Index and FKGL reveal that a decrease in their respective values correlates with an increase in text clarity and readability.
Since the study was essentially a NonHuman Subjects Research, it was exempt from review by the Ethics Committee.
Statistical Analysis
Data were evaluated using the IBM SPSS Statistics Standard Concurrent User V 30 (IBM Corp., Armonk, New York, ABD) statistical package program. Descriptive statistics were given as several units (n), percentage (%), mean ± standard deviation, median, and interquartile distance values. The conformity of the data to normal distribution was evaluated with the Shapiro-Wilk normality test. The variance homogeneity of the chatbot groups was analyzed with the Levene test. For normally distributed data, Chatbot groups were compared with a one-way analysis of variance in repeated measures. For data that did not show normal distribution, Chatbot groups were compared using Friedman analysis. Bonferroni correction was made for all pairwise comparisons. A statistical significance threshold of p<0,05 was applied.
Results
Readability Assessments
Flesch-Kincaid Grade Level (FKGL) assesses grade level with a preferred grade reading level of 8. In these terms, according to Table 1, Anthropic Claude had the most preferred score with an average of 7,60, followed by Google Gemini with 9,05, ChatGPT-4 with 9,78, and Microsoft Copilot with 10.14. FKGL values were statistically different in chatbot groups (p<0.001). Anthropic Claude FKGL was statistically lower than other AI search engines. Google Gemini had FKGL statistically lower than Microsoft Copilot and ChatGPT-4. Analysis revealed that the scores for Microsoft Copilot and ChatGPT-4 were statistically comparable (Figure 1).
The Gunning Fog Index, SMOG Index, Automated Readability Index and Coleman-Liau Index scores of Anthropic Claude were statistically lower than other chatbots (p<0.001) (Figure 2). Flesch Reading Ease score for Anthropic Claude was statistically superior to other AI search engines. The Automated Readability Index score for Google Gemini was significantly lower than those of both Microsoft Copilot and ChatGPT-4, while ChatGPT’s score also fell below that of Microsoft Copilot. Microsoft Copilot, Google Gemini, and ChatGPT-4 did not demonstrate any statistically significant difference in The Gunning Fog Index, Flesch Reading Ease, and Coleman-Liau Index scores. The SMOG Index score for Google Gemini demonstrated a statistically significant reduction compared to both Microsoft Copilot and ChatGPT-4, whereas the scores for Microsoft Copilot and ChatGPT-4 were not statistically significant.
Analysis of the counts of words and characters revealed that ChatGPT-4 exhibited markedly greater figures compared to the other LLM chatbots, with a significance level of p metrics (Table 2). The analysis of word and character count metrics for Google Gemini demonstrated markedly elevated values compared to those observed for Anthropic Claude and Microsoft Copilot, which exhibited no statistically significant differences between them.
Adequacy of Information
The Likert scale was utilized to determine adequacy. The responses generated by ChatGPT-4 had the highest average score of 4,90, followed by Anthropic Claude with 4,23, Google Gemini with 3,87, and last was Microsoft Copilot with a score of 3,50 (Table 2). Google Gemini had a statistically higher score than Microsoft Copilot. Anthropic Claude had a score statistically higher than Google Gemini and Microsoft Copilot. The performance of ChatGPT-4 surpassed that of its counterparts, demonstrating a statistically significant score. (Figure 3).
Discussion
This research aimed to evaluate how various language models respond to frequently asked questions about prevalent eye disorders. Our research revealed that responses generated by ChatGPT-4 were rated as more accurate and were preferred by clinicians. In terms of adequacy, ChatGPT-4 had the highest average score of 4,90, followed by Claude with 4,23. The evaluation of the responses indicated that none were rated as “very poor” or classified as incorrect. It was noted that ChatGPT generated appropriate replies that comprehensively responded to all queries, using bullet points to facilitate clarity. Claude offered responses that met expectations, regularly using a bullet-point format to express ideas clearly. In all responses, Claude recommended that individuals seek the expertise of qualified medical professionals to properly assess their medical conditions. Among large language models, CoPilot uniquely features hyperlinks that serve as citations in its replies. A significant number of hyperlinks led users to non-academic sites, which compromised the reliability of the information presented.
The American Medical Association (AMA) advises that online patient education materials should be written at or below a 6th-grade reading level to ensure understandability among patients with lower health literacy [10]. Readability refers to how easily a reader can comprehend a written text, in this study six different indices were used for evaluation. The FKGL measure functions as an alternative indicator for determining the readability associated with specific grade levels. With an average FKGL readability score of 7.60, Anthropic Claude meets the level of readability that the AMA recommends. An assessment of the remaining five parameters revealed that the responses generated by all four chatbots exhibited readability levels exceeding that of a sixth-grade education potentially limiting their accessibility to a broader patient demographic.
While a recent study determined that ChatGPT produces incomplete and inaccurate information about common ophthalmic conditions our results support two prior studies which found that ChatGPT was largely effective in responding to patients’ eye care questions [5, 11, 12]. Research that compared Google and ChatGPT indicates that responses generated by ChatGPT were more accurate but written at a significantly higher grade level than responses generated by Google [12, 13]. In a different analysis examining ChatGPT’s communication skills with individuals diagnosed with glaucoma, researchers found that the model proficiently offers general information, encompassing definitions, and potential therapeutic strategies. However, the readability scores were high [14]. Ichhpujani et al compared the appropriateness and readability of Google Bard and ChatGPT-3.5 generated responses for surgical treatment of glaucoma, they found that the answers generated by ChatGPT-3.5 are more accurate than the ones given by Google Bard but reported that comprehension of ChatGPT-3.5 answers may be difficult for the public with glaucoma [15]. According to Guven et al., the responses produced by ChatGPT-4 were considered satisfactory, yet the complexity of these responses made them challenging to read in the context of frequently posed questions about strabismus and amblyopia [16]. In a recent study appropriateness and readability of responses provided by ChatGPT-3.5, Bard, and Bing Chat to frequently asked questions about keratorefractive surgery were assessed, it was reported that ChatGPT-3.5 had the highest accuracy but the readability scores were more challenging than the recommended level [17].
Limitation
The main limitation of our study was that it involved a small number of questions. Furthermore, we employed subjective grading to evaluate the appropriateness of the responses, which means our findings might not apply to other chatbots and similar technologies.
Conclusion
In this study, ChatGPT-4 was more precise in responses, while Anthropic Claude scored better in terms of readability. These findings suggest that while LLMs may offer more comprehensive information, they do not always improve accessibility for the average patient. LLMs represent an accurate information source for patients and can be utilized by providers as a patient educational tool but presently it does not meet the necessary standards without concurrent supervision from healthcare providers. Furthermore, acknowledging that the success of knowledge relies on the comprehension skills of the patient is crucial, further studies using different prompts and evaluation methods will be needed to better assess the accuracy and understandability of the information provided by LLMs in ophthalmology and other fields of medicine.
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.
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11. Bernstein IA, Zhang YV, Govil D, Majid I, Chang RT, Sun Y, et al. Comparison of Ophthalmologist and Large Language Model Chatbot Responses to Online Patient Eye Care Questions. JAMA Netw Open. 2023;6(8):e2330320.
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Meltem Toklu, Gizem Yel. Evaluation of the appropriateness and readability of chatgpt-4, claude, copilot and gemini responses to patient queries on eye health.Ann Clin Anal Med 2025;16(6):445-449
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Evaluating ChatGPT’s responses on schizophrenia: Accuracy, quality, and stigmatization
Onur Gökçen 1, Ahmet Kağan Misci 2
1 Department of Psychiatry, 2 Medical Student, Faculty of Medicine, Kütahya Health Science University, Kütahya, Turkey
DOI: 10.4328/ACAM.22665 Received: 2025-03-20 Accepted: 2025-05-05 Published Online: 2025-05-28 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):450-454
Corresponding Author: Onur Gökçen, Department of Psychiatry, Faculty of Medicine, Kütahya Health Science University, Kütahya, Turkey. E-mail: onurgokcen29@gmail.com P: +90 507 201 52 21 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2058-9855
Other Authors ORCID ID: Ahmet Kağan Misci, https://orcid.org/0009-0000-7794-0322
This study was approved by the Ethics Committee of Kütahya Health Sciences University (Date: 2024-10-24, No: 2024/12-28)
Aim: ChatGPT, developed by OpenAI, is an AI-powered language model widely used for online information retrieval. This study aims to assess the accuracy, sufficiency, and stigmatization of ChatGPT’s responses on schizophrenia as evaluated by psychiatrists using validated assessment scales.
Material and Methods: Common patient queries were identified based on frequently asked questions in clinical practice, relevant healthcare platforms, and previous patient experiences. The questions were formulated with input from ten psychiatry specialists and then posed to ChatGPT in a single session. Psychiatrists evaluated the responses using the Global Quality Scale (GQS), the DISCERN Scale, and a stigma-related question.
Results: Among 57 psychiatrists (12 residents, 45 specialists), GQS scores indicated “good to excellent” quality, with higher ratings for treatment-related questions. Responses were generally not perceived as stigmatizing. The DISCERN total score averaged 50, classifying responses as “good,” though the lowest ratings were given for source credibility and date information.
Discussion: To the best of our knowledge, this is the first study assessing ChatGPT’s reliability as an information source on schizophrenia. It provides a valuable reference for future research on the accuracy, reliability, and ethical considerations of evolving large language models in psychiatry.
Keywords: Schizophrenia, Artificial Intelligence, ChatGPT, Patient Information
Introduction
Schizophrenia is a complex and chronic neuropsychiatric disorder that affects approximately 1% of the global population. It is characterized by a variety of symptoms, including positive symptoms (such as hallucinations and delusions), negative symptoms (such as anhedonia and social withdrawal), and cognitive impairments (such as deficits in working memory and executive function) [1]. Schizophrenia typically emerges in early adulthood and leads to significant impairments in social and occupational functioning, resulting in a reduction in life expectancy by approximately 15 years compared to the general population [1, 2]. Schizophrenia patients seek information about their condition from various sources, including the internet, their doctors, other healthcare professionals, and their social networks. Lower educational attainment has been associated with increased misconceptions regarding the etiology of schizophrenia, often leading to supernatural attributions [3]. Access to accurate information plays a critical role in helping patients and their families understand the causes, treatment options, and coping strategies for schizophrenia [4]. Psychoeducation is an essential component of treatment that improves care quality by reducing stigma [5].
Despite increased awareness about schizophrenia, surveys show that stereotypical beliefs about patients, such as tendencies toward violence, maladaptive behaviors, and an inability to maintain employment, remain widespread. The media often portrays schizophrenia with negative stereotypes, influencing public perception. This association between schizophrenia and violence further reinforces stigma [6, 7]. As patients internalize this stigma, their social isolation may increase, leading to higher stress levels and worsening of symptoms [8]. This underscores the importance of reliable and accessible information to ensure a proper understanding of the illness [4].
The internet is used as a source of mental health information by more than 10% of the general population, and by over 20% of individuals who have experienced mental health issues [9]. Approximately 24% of users consider the internet to be one of the top three most reliable sources of information. Due to the accessibility and anonymity it provides, individuals at risk of stigma are more likely to turn to the internet for health information. Additionally, many individuals first identify their symptoms online before seeking medical assistance [10].
Recently, AI-powered language models have become an important tool for obtaining information online. One such model, ChatGPT, is a large language model developed by OpenAI that can generate human-like responses on various topics. Trained on vast datasets, ChatGPT typically produces accurate and informative answers using advanced machine learning techniques [11]. However, as AI chatbots inherently lack the ability to independently verify the accuracy of the information they provide, they cannot guarantee the most up-to-date or comprehensive information. Nevertheless, they are increasingly being used by patients to gather information about illnesses and treatments. The potential for generating inaccurate or misleading information remains a significant concern [12, 13].
Studies examining the use of AI language models as reliable sources of information have addressed topics such as vaccine and statin hesitancy, clinical psychiatry knowledge, and spinal surgery [11, 14, 15]. However, there is no research evaluating whether AI models can serve as a source of information on schizophrenia or examining the stigmatizing nature of ChatGPT’s responses. This study aims to evaluate the information provided by ChatGPT regarding schizophrenia, as assessed by psychiatrists in terms of accuracy, sufficiency, and stigmatization.
Material and Methods
In this study, the most frequently asked questions by patients with schizophrenia to obtain information were identified through the examination of websites created by schizophrenia associations, medical associations, and healthcare institutions that provide services, as well as by evaluating the patients’ previous experiences. Subsequently, the questions were refined based on the opinions of ten experienced psychiatrists. The questions are presented in Table 1.
Following this, these questions were individually directed to ChatGPT, developed by OpenAI, in a single session. For the evaluation of the responses, the Global Quality Scale (GQS) and the DISCERN scale were used, as in similar studies [16, 17].
DISCERN (Criteria for Quality of Consumer Health Information):
DISCERN is a scale developed to assist patients and healthcare providers in assessing the quality of health information. This scale consists of 15 questions in total, each scored on a scale from 1 (low quality) to 5 (high quality) [18]. The first eight questions assess the reliability of the information, while the following seven focus on treatment options. The final, 16th question is used to determine the overall quality of the information by considering all previous evaluations. The total score for the first 15 questions is classified as excellent (63-75), good (51-62), moderate (39-50), inadequate (28-38), and very inadequate (15-27) [19].
Global Quality Scale (GQS)
The GQS is another scale used to evaluate the quality and usefulness of health information from the patient’s perspective. This five-question scale assesses factors such as the integrity, clarity, and practical utility of the information (Table 1). The total quality score is calculated by summing the scores of each section. Content with a total GQS score of 3 or below is considered of low to medium quality, while content with scores above 3 is classified as good to excellent quality [20]. When used in conjunction with DISCERN, GQS provides a more holistic evaluation in terms of the comprehensibility and patient guidance of the information [17].
A form was created to allow separate evaluations of each question and its corresponding answer from ChatGPT using the GQS, and a collective assessment of the total responses using the Discern scale. Additionally, an extra evaluation question, created by the researchers, was added to the form to examine the responses to the eighth, ninth, and tenth questions in terms of “stigmatization.”
“Evaluate the responses to questions 8, 9, and 10 in terms of stigma:
Does not stigmatize
Partially stigmatizes
Stigmatizes
This form was distributed to psychiatry specialists via Google Forms. The responses provided by a total of 57 psychiatry specialists were analyzed in this study. Among them, 12 were residents, while the remaining 45 were specialists in the field.
Ethical Approval
This study was approved by the Ethics Committee of Kütahya Health Sciences University (Date: 2024-10-24, No: 2024/12-28).
Results
Answers to questions about schizophrenia were provided by ChatGPT. The quality of each answer was evaluated by psychiatrists using the Global Quality Scale (GQS) (table 1). The average Global Quality Scale (GQS) scores for the responses to the questions were found to be in the “good to excellent quality” range, with scores above 3. The responses to the sixth and seventh questions, which were related to treatment, had higher average GQS scores. A Kruskal-Wallis test was conducted to determine whether there was a statistically significant difference between the GQS scores for the responses. The analysis revealed a significant difference (p = 0.014). Epsilon-Squared (ε²) was calculated to be 0.0265, indicating a small effect size. A post-hoc Dunn’s test showed that a significant difference was only found between the responses to the first and sixth questions (p < 0.001).
Participants were instructed to evaluate the responses to the eighth, ninth, and tenth questions in terms of stigma. It was observed that, on average, participants did not find the responses to be stigmatizing (Table 2).
In the evaluation using the Discern scale, the average total score for the participants was found to be 50. According to the standards of this scale, this indicates that the responses were rated as “good.” The first eight questions assess the reliability of the information, while the following seven focus on treatment options. Among the first eight Discern items assessing the reliability of the information, the lowest scores were given to items four, five, and seven. These questions were related to the sharing of the sources and dates of the information (Table 2). Among the last seven questions, which focus on treatment options, the lowest score was given to the response to the eleventh question. This question inquired whether the risks of each treatment were clearly defined.
Discussion
In this study, the responses provided by ChatGPT regarding schizophrenia were evaluated by 57 psychiatrists using the Global Quality Scale (GQS) and DISCERN scales. The evaluation revealed that, overall, the responses provided by ChatGPT were sufficient. Thus, this research will contribute meaningfully to the ongoing discussions about the use of large language models in psychiatry and expand potential areas for future studies.
The use of artificial intelligence (AI) in psychiatry has attracted significant interest from researchers. In recent years, large language models (LLMs) have paved the way for many innovative studies in the field of psychiatry. Previous studies in this context have demonstrated the success of LLMs in generating new and analyzable data points from original data using data augmentation techniques on complex and imbalanced text-based data found on social media platforms [21].
Moreover, through a specially developed framework, the capacity of LLMs to analyze text-based data and detect mental health conditions, as well as provide personalized and sensitive commentary, has been assessed, showing significant achievements in this area [22]. Additionally, the potential applications of LLMs in psychodynamic analysis and psychoanalytic formulations have been explored using written expressions from patients with different psychiatric diagnoses [23].
Overall, the number of studies focusing on the use of LLMs in healthcare is increasing, and the results emerging from these studies appear to be consistent and promising. GPT models are standing out and are widely preferred in these studies. Moreover, each new study lays the groundwork for future research and contributes to the advancement of the field.
The use of large language models as a source of information in psychiatry is also of significant importance. This study is the first to evaluate the quality of ChatGPT’s responses regarding schizophrenia; however, several studies have evaluated ChatGPT as a source of information in various medical fields.
The average Global Quality Scale (GQS) scores of the responses to the questions were found to be in the “good to excellent quality” range. The highest score was given to the response to the question ‘In what situations might hospitalization be necessary?’, while the lowest score was given to the response to the question ‘What is schizophrenia, and what are its symptoms?’. The difference in scores between these two responses was found to be statistically significant. The question about the necessity of hospitalization may be seen as a more straightforward topic with fewer required details, whereas the definition and symptoms of schizophrenia can be described in a much broader and more detailed manner. Furthermore, certain pieces of information that may be considered minor details could have been deemed important by psychiatrists, and their absence in the responses might have led to those responses being rated as ‘insufficient’. Indeed, the literature emphasizes that GPT’s accuracy can be highly variable, especially on specific topics such as rare diseases, and that this variability may be related to the limitations of online sources and GPT’s difficulty in selecting appropriate references [11, 24]. Moreover, previous studies examining the capabilities and limitations of GPT have shown that, although the model can produce non-conspiratorial responses to questions about vaccines and statins, it generates text based on linguistic associations, and the way questions are phrased can influence the quality of the responses [11, 24]. Indeed, compared to a more open-ended question such as ‘What is schizophrenia?’, a question like ‘In what situations might hospitalization be necessary?’, which allows for a clear, itemized response, may lead to answers that are more straightforward and easier to evaluate.
Similarly, in different medical specialties, the success rate of GPT has shown variability. For example, in a study conducted in the field of otolaryngology, it was noted that GPT achieved vastly different success rates across sub-specialties, performing better in more popular sub-specialties while showing lower success rates in less popular ones [25].
In our study, generally, more common and frequently encountered questions were selected. Therefore, our study’s results do not provide sufficient confidence regarding the quality of responses to more specific and rare questions. Furthermore, upon examining the DISCERN scale results, it was observed that the sources of information were not sufficiently clear and detailed in the responses provided by ChatGPT. Like other AI-assisted language models, ChatGPT is continuously evolving, and there may have been advancements in the provision and sharing of sources since the time this study was conducted. The GPT-3.5 model used in our study is free and is actively preferred by approximately 180 million users. While it is anticipated that more advanced and consistent responses will be obtained with future models, it is not guaranteed that later versions such as GPT-4 will always produce better results.
Limitation
This study examined ChatGPT’s responses on schizophrenia using two evaluation scales. It also explored whether ChatGPT can be considered a reliable information source. However, the study does have some limitations. First and foremost, ChatGPT, like other AI-assisted language models, is continuously developing. Therefore, the model’s performance and the quality of its responses may vary over time. Moreover, the responses provided by ChatGPT may change depending on the updates to online sources, meaning that responses obtained after the time this study was conducted may differ. Another important limitation is that the study was conducted exclusively in Turkish. While ChatGPT is capable of multilingual output, its performance can vary significantly across languages due to differences in training data volume, linguistic structure, and cultural context. These language-specific variations may affect the quality, completeness, and nuance of responses. Therefore, the results of this study may not be generalizable to responses generated in other languages, particularly English, which tends to be more prominently represented in ChatGPT’s training data.
Conclusion
Despite these limitations, this study is the first to evaluate the potential of ChatGPT as a reliable source of information on schizophrenia. The findings highlight both the possible benefits and the points of caution when using AI-assisted language models in medical information. In this context, the study provides an important reference point that can lay the groundwork for future research. Future studies could provide valuable insights into how these technologies can be used more effectively in healthcare by evaluating various AI models more comprehensively in terms of medical accuracy, source usage, and reliability.
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.
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Onur Gökçen, Ahmet Kağan Misci. Evaluating ChatGPT’s responses on schizophrenia: Accuracy, quality, and stigmatization. Ann Clin Anal Med 2025;16(6):450-454
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Detection of critical coronary artery stenosis through computed tomographic aortogram in patients with suspected aortic dissection
Muhammed Yaşar Sever 1, Nedim Uzun 2, Hüseyin Mutlu 3, Hasan Erdoğan 4
1 Department of Emergency Medicine, Sincan State Hospital, Ankara, 2 Department of Emergency Medicine, Hamidiye Medical School, Health Sciences University, İstanbul, 3 Department of Emergency Medicine, School of Medicine, Aksaray University, Aksaray, 4 Department of Radiology, Kayseri City Hospital, Kayseri, Türkiye
DOI: 10.4328/ACAM.22727 Received: 2025-04-28 Accepted: 2025-05-28 Published Online: 2025-05-29 Printed: 2025-06-01 Ann Clin Anal Med 2025;16(6):455-459
Corresponding Author: Hüseyin Mutlu, Department of Emergency Medicine, School of Medicine, Aksaray University, Aksaray, Türkiye. E-mail: hmutlu70@hotmail.com P: +90 505 349 32 63 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1930-3293
Other Authors ORCID ID: Muhammed Yaşar Sever, https://orcid.org/0000-0001-5667-773X . Nedim Uzun, https://orcid.org/0000-0001-9593-5869
Hasan Erdoğan, https://orcid.org/0000-0001-8109-8537
This study was approved by the Ethics Committee of Aksaray University, Faculty of Medicine (Date: 2023-10-17, No: 2023-02/03)
Aim: Computed tomographic aortography (CTA) is standard for aortic dissection (AD) diagnosis, but not commonly used for acute coronary syndromes. In this study, we aimed to investigate the success of CTA in detecting critical stenosis in coronary arteries in patients with non-ST-elevation myocardial infarction (NSTEMI) diagnosed with suspected AD in the emergency department (ED).
Material and Methods: This retrospective study was conducted at a tertiary ED from January 2016 to May 2019. Among 6647 acute chest pain patients undergoing CTA for suspected aortic dissection, 50 NSTEMI cases with conventional coronary angiography (CCA) performed were included. Exclusion criteria included age <18, incomplete records, ST elevation on ECG, or confirmed AD on CTA. CTA was performed using a 64-detector CT scanner, and critical stenosis (>50%) in the coronary arteries was evaluated by a radiologist with eight years of cardiothoracic imaging experience.
Results: In this study, 200 coronary arteries of 50 patients were analyzed. Among the 50 patients included in the study, 29 (58%) were male and 21 (42%) female, with a mean age of 61.4 ± 14.1 years. CTA exhibited a high specificity of 98.71% and sensitivity of 88.89% in detecting critical stenosis within the coronary arteries. A statistically significant positive correlation was observed between the imaging findings of CTA and those of CCA (p<0.001).
Discussion: The results indicate that CTA is comparably effective to CCA in identifying critical stenosis within coronary arteries. Moreover, CTA demonstrates potential as an early diagnostic tool for identifying patients with NSTEMI in the ED.
Keywords: Aortic Dissection, Computed Tomographic Aortogram, Critical Stenosis in Coronary Arteries, Non-ST-Elevation Myocardial Infarction
Introduction
Acute chest pain (ACP) is the most common reason for presentation to the emergency department (ED) after abdominal pain [1, 2]. Identifying the etiology of ACP is still one of the most important problems for healthcare professionals working in EDs [3, 5]. Although the causes of ACP are often non-cardiac, its differential diagnosis should include acute coronary syndrome (ACS), pulmonary thromboembolism (PTE), esophageal rupture, pneumothorax, and aortic dissection (AD), which have a mortal course [6, 7]. Initial evaluation of a patient presenting to the ED with ACP consists of patient history, physical examination, electrocardiography, transthoracic echocardiography, laboratory studies, and imaging modalities.
Triple-rule-out coronary CT angiography provides non-invasive visualization of the coronary arteries, pulmonary arteries, and thoracic aorta [8]. Although it is efficient in the differential diagnosis of ACP, it is not generally available in most hospitals. In patients with exertional chest pain radiating to the left arm who also have elevated serum troponin levels, coronary CTA (CCTA) may be requested for the diagnosis of ACS [9-13]. However, CCTA is impractical to use in the ED due to disadvantages, including patient compliance, medication to keep the heart rate below 80 beats/minute, and ECG-triggered acquisition [14, 15]. Computed tomographic aortogram (CTA) is the initial diagnostic imaging modality for AD in patients presenting to the ED with hypertension and chest and back pain. In contrast, it is not in general clinical use for evaluating ACS. Emergent coronary catheterization is essential for high-risk patients with ACS. The laboratory tests and imaging results should be eventuated before conventional coronary angiography (CCA) for patients with non-ST-elevation myocardial infarction (NSTEMI). Further imaging modalities for the diagnosis and risk stratification of ACS, particularly in patients without changes in ECG, might be helpful for physicians in reducing the time to diagnose stenosis.
In this study, we aimed to investigate the success of CTA in detecting critical stenosis in coronary arteries in patients with non-ST-elevation myocardial infarction (NSTEMI) diagnosed with suspected AD in the emergency department (ED).
Material and Methods
Study design and participants
This retrospective study was conducted from January 2016 to May 2019 at a tertiary ED that receives an average of 30,000 patients per month. Written informed consent for CTA imaging was obtained from all patients. However, the requirement for informed consent was waived due to the retrospective design of the study.
Patients presenting to the emergency department of our hospital with chest and/or back pain undergo a detailed physical examination, followed by electrocardiography (ECG), cardiac enzyme measurements, D-dimer measurement, chest X-ray (CXR), transthoracic echocardiography (TTE), and CTA when necessary. When STEMI is suspected on ECG, cardiologists are consulted for antithrombotic treatment and coronary angiography. Patients without STEMI are placed on troponin monitoring for NSTEMI. Patients diagnosed with NSTEMI after troponin monitoring undergo coronary angiography and medical treatment within 24 hours. Severe chest and/or back pain, perfusion deficit (unilateral pulse deficit, difference in systolic blood pressure between extremities or neurologic focal signs), enlarged mediastinum on CXR, significant signs on TTE (intimal flap, dilatation of the thoracic aorta, pericardial effusion and aortic valve insufficiency), history of a known AD syndrome (Marfan, vascular Ehlers-Danlos, Loeys-Dietz or Turner) and elevated D dimer (500 ng/mL), CTA is performed to rule out AD. Patients over 18 years of age who were diagnosed with NSTEMI and underwent coronary angiography were included in the study. Patients younger than 18 years of age who underwent CTA with a prediagnosis of AD, those diagnosed with AD, those with ST elevation on ECG, those who underwent coronary angiography and were diagnosed with a lesion, and those whose records could not be accessed were excluded from the study. Assistive technologies such as artificial intelligence and machine learning are not used in our paper.
Data collection
Clinical data were obtained from the hospital’s electronic medical database and patient files. The patients’ age, chronic diseases (diabetes mellitus, hypertension, coronary artery disease, and hypercholesterolemia), vital signs, echocardiography findings (presence or absence of left ventricular wall motion abnormalities), angiography findings, and laboratory results were recorded.
Statistical analysis
All statistical analyses were performed using the Statistical Package for the Social Sciences version 22 (IBM, Armonk, NY) software. Descriptive statistics were expressed as mean, standard deviation, minimum–maximum, frequency, and percentile values. The results of the CT image analysis of the cases were compared with those of conventional coronary angiography analysis, which is accepted as the gold standard. The sensitivity, specificity, positive predictive, and negative predictive values, and test validity values of all arteries were calculated. Specificity and sensitivity were determined using the Youden index. P values of less than 0.05 were accepted as statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of Aksaray University, Faculty of Medicine (Date: 2023-10-17, No: 2023-02/03).
Results
The study included 200 coronary arteries from 50 patients who underwent CTA and CCA at the ED from January 2016 to May 2019. Of the 50 patients included in the study, 29 (58%) were male, and 21 (42%) were female. The mean age of the patients was 61.4 ± 14.1 years. The basic characteristics of the patients are given in Table 1. Before the CTA examination, all patients had a normal ECG. They were diagnosed with non-ST-elevation myocardial infarction (NSTEMI) due to elevated levels of troponin I during their follow-up and underwent CCA within 24 hours. In the coronary artery examination, no critical stenosis was determined in 158 (79%) arteries on the CTA and 155 (77.5%) on the CCA. There was a statistically significant positive correlation between the CTA and CCA findings (P < 0.001) (Table 2). The Pearson correlation coefficient was found to be 0.738. It was found that CTA had high specificity (98.71%), sensitivity (88.89%), positive predictive (96.84%), and negative predictive (95.24%) values in the detection of critical stenosis in coronary arteries (Table 3).
Computed tomography (CT) imaging and analysis
CTA was performed using a 64-detector row CT scanner (Revolution CT, GE Healthcare, Waukesha, Wisconsin, US). The examination protocol was as follows: 120 kV, 512 x 512 matrix, 64 x 0.6 mm collimation, 0.28 second gantry rotation time, and spiral mode with a pitch of 0.6. Non-ionic contrast medium containing 300 mg of iodine (Omnipaque ®, Nycomed Imaging AS, Oslo, Norway) was administered at a speed of 4–5 mL/s with an automatic injector system. Procedures were successfully completed in all patients without any complications.
All CT images were evaluated by a radiologist (HE) with eight years of experience in cardiothoracic imaging. CT images were evaluated using the Picture Archiving and Communication System (FONET PACS software version 4.1, Ankara, Turkey). Multiplanar reconstruction images (axial, sagittal, and coronal) were used in all cases. The following four major vascular segments were examined in each patient: the left main coronary artery, the left anterior descending coronary artery, the circumflex coronary artery, and the right coronary artery. A total of 200 vascular segments were examined in 50 patients. The patients were divided into two groups according to whether they had critical stenosis of the coronary arteries (more than 50% stenosis) [16]. Figures 1-2 show examples of the CTA and CCA images in patients with critical stenosis, and Figure 3 presents the images of a patient without critical stenosis.
Discussion
Identifying patients with ACP in the ED remains challenging, particularly patients without ECG changes. In order not to overlook a diagnosis of ACS, ED physicians order a 12-lead ECG, laboratory tests (such as troponin I and CKMB), and coronary artery imaging [14,17]. It has also been recently suggested that patients with non-specific chest pain in selected centers can be evaluated with a single CTA screening protocol, called “triple rule out” (TRO), to exclude ACS, PTE, and AD (8). However, CCA remains the gold standard for examining coronary arteries. In the current study, we investigated whether CTA taken at the ED was as effective as CCA in detecting stenosis in coronary arteries. To the best of our knowledge, this is the first study to investigate the correlation between CTA and CCA findings for this purpose.
In this study, CTA detected stenosis in 40 of the 45 patients who had critical stenosis in coronary arteries according to CCA, and there was a statistically significant positive correlation between the findings of the two imaging modalities (P < 0.001). CTA had a specificity of 98.71% and a sensitivity of 88.89% in detecting critical stenosis in coronary arteries. These findings suggest that CTA is a useful diagnostic imaging modality for detecting critical stenosis in coronary arteries.
In a study conducted with 113 patients with chest pain, Litmanovitch et al. compared TRO-CTA and CCA in the evaluation of coronary arteries and reported that the former detected coronary stenosis with a sensitivity of 93% and a specificity of 88% [18]. Similarly, in other studies, Johnson et al. showed that CCTA had a sensitivity of 98% and a specificity of 96% in 109 patients with chest pain, and Stefanini et al. reported 81-99% sensitivity and 64-93% specificity values [19,20]. Johnson et al. confirmed stenosis with CCA in 15 of 19 patients who had critical stenosis on CCTA and showed a positive correlation between the two methods [19]. In our study, CTA, which we used as a more practical imaging method to exclude AD, was found to have high specificity and sensitivity (98.71% and 88.89%, respectively) in detecting coronary stenosis, consistent with the literature results on TRO-CTA and CCTA. We also found a positive correlation between CTA and CCA in our study and calculated the Pearson correlation coefficient at 0.738. Similar to CCTA, CTA evaluated by an experienced radiologist can provide information about the coronary arteries and help decide whether to perform cardiac follow-up or emergency catheterization in patients with risk factors.
In addition, by reducing the time to diagnose stenosis at the ED, CTA seems to be a more practical method with a lower radiation load but similar safety compared to CCTA and TRO-CTA.
Limitation
This study has several limitations. First, its retrospective and single-center design may limit the generalizability of the findings. The sample size, while sufficient for preliminary analysis, may not capture the full spectrum of NSTEMI presentations or comorbid conditions. Furthermore, potential selection bias cannot be excluded, as patients undergoing both CTA and CCA might represent a more specific clinical subgroup. The diagnostic accuracy and interpretation of CTA could also be influenced by operator expertise and imaging quality, which were not standardized across all cases. Finally, while the results suggest that CTA may facilitate earlier decision-making, the study did not evaluate long-term clinical outcomes or the cost-effectiveness of this approach. Larger, prospective, multicenter studies are needed to confirm these findings and establish clinical guidelines.
Conclusion
Our study revealed that CTA proved to be equally effective to CCA in identifying critical stenosis within the coronary arteries of NSTEMI patients. Evaluating coronary artery stenosis on CTA imaging could also be crucial for patients admitted to the ED with acute chest pain (ACP), despite ECG stability, once AD diagnosis has been ruled out. This approach could potentially prompt immediate coronary catheterization decisions, thereby reducing the time required for NSTEMI diagnosis. Consequently, there could be a reduction in ACS-related morbidity and mortality. To validate our findings, further comprehensive multicenter prospective studies are warranted.
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.
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Download attachments: 10.4328.ACAM.22727
Muhammed Yaşar Sever, Nedim Uzun, Hüseyin Mutlu, Hasan Erdoğan. Detection of critical coronary artery stenosis through computed tomographic aortogram in patients with suspected aortic dissection. Ann Clin Anal Med 2025;16(6):455-459
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